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Obesity, Metabolic Syndrome, and Cardiovascular Disease
Abstract
Obesity is a major underlying risk factor for ASCVD. It is associated with multiple ASCVD risk factors, and it also is a risk factor for type 2 diabetes. Diabetes itself is a cardiovascular risk factor. Despite the strong association between obesity and ASCVD, the mechanisms underlying this relationship are not well understood. Our understanding of the connection between obesity and vascular disease is complicated by a plethora of possibilities. Obesity acts on so many metabolic pathways, producing so many potential risk factors, that it is virtually impossible to differentiate between the more important and less important. The possibilities for confounding variables are enormous. This complexity provides a great challenge for basic and clinical research. It also raises the possibility for new targets of therapy for the metabolic syndrome. With this said, the fundamental challenge is how to intervene at the public health level to reduce the high prevalence of obesity in the general population. This approach offers the greatest possibility for reducing the cardiovascular risk that accompanies obesity.
... Obesity can be defined as excess body fat, indicating a high percent body fat. 34 Body mass index (BMI) is usually used to assess body fat and has a higher feasibility and lower cost than the test of percent body fat. 34 A BMI of 25-29 kg/m 2 is called overweight, and a higher BMI (⩾30 kg/m 2 ) is called obesity. ...
... 34 Body mass index (BMI) is usually used to assess body fat and has a higher feasibility and lower cost than the test of percent body fat. 34 A BMI of 25-29 kg/m 2 is called overweight, and a higher BMI (⩾30 kg/m 2 ) is called obesity. In today's society, bad living habits and overeating make people more prone to obesity. ...
Across the globe, metabolic syndrome, hyperuric acid, and their related diseases, such as cardiovascular disease, diabetes, and insulin resistance, are increasing in incidence due to metabolic imbalances. Due to the pathogenesis, women are more prone to these diseases than men. As estrogen levels decrease after menopause, obesity and metabolic disorders are more likely to occur. Men are also affected by hyperuric acid. To provide ideas for the prevention and treatment of metabolic syndrome and hyperuricemia, this article reviews and analyzes the relationship between estrogen receptors, metabolic syndrome, and hyperuricemia.
... of these metabolic syndromes (2)(3)(4). Epidemiologic studies of COVID- 19 have identified obesity and diabetes as significant risk factors for increased disease severity, length of hospitalization, and death (5)(6)(7)(8)(9)(10). The immune and molecular mechanisms behind this increased risk of COVID-19 have yet to be fully determined. ...
... The etiology of type 2 diabetes (T2D) is closely linked with chronic inflamma tion induced by excess adipose tissue. Stressed adipocytes and adipose tissue mac rophages (ATMs) secrete numerous proinflammatory cytokines that result in chronic low-grade inflammation which alters homeostatic glucose regulation by decreasing cellular responsiveness to insulin (4). This results in hyperglycemia, hyperinsulinemia, and glucose intolerance characteristic of T2D. ...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), emerged in Wuhan, China, in December 2019. As of September 2023, there have been over 770 million confirmed cases of COVID-19, including over 6.9 million deaths. Epidemiologic studies have indicated that comorbidities of obesity and diabetes mellitus are associated with increased morbidity and mortality following SARS-CoV-2 infection. We determined how the comorbidities of obesity and diabetes affect morbidity and mortality following SARS-CoV-2 infection in unvaccinated and adjuvanted spike nanoparticle (NVX-CoV2373) vaccinated mice. We find that obese/diabetic mice infected with SARS-CoV-2 have increased morbidity and mortality compared to age-matched normal mice. Mice that were fed a high-fat diet (HFD) and then vaccinated with NVX-CoV2373 produce equivalent neutralizing antibody titers compared to those fed a normal diet (ND). However, the HFD mice have reduced viral clearance early in infection. Analysis of the inflammatory immune response in HFD mice demonstrates a recruitment of neutrophils that was correlated with increased mortality and reduced clearance of the virus. Depletion of neutrophils in diabetic/obese vaccinated mice reduced disease severity and protected mice from lethality. This model recapitulates the increased disease severity associated with obesity and diabetes in humans with COVID-19 and is an important comorbidity to study with increasing obesity and diabetes across the world.
IMPORTANCE
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a wide spectrum of diseases in the human population, from asymptomatic infections to death. It is important to study the host differences that may alter the pathogenesis of this virus. One clinical finding in coronavirus disease 2019 (COVID-19) patients is that people with obesity or diabetes are at increased risk of severe illness from SARS-CoV-2 infection. We used a high-fat diet model in mice to study the effects of obesity and type 2 diabetes on SARS-CoV-2 infection as well as how these comorbidities alter the response to vaccination. We find that diabetic/obese mice have increased disease after SARS-CoV-2 infection and they have slower clearance of the virus. We find that the lungs of these mice have increased neutrophils and that removing these neutrophils protects diabetic/obese mice from disease. This demonstrates why these diseases have increased risk of severe disease and suggests specific interventions upon infection.
... Our findings, which show a notable reduction in HR and blood pressure after weeks of Common Yoga Protocol practice, align with prior studies suggesting that yoga effectively lowers blood pressure [87,88]. Yoga interventions induce para-sympathomimetic effects, leading to reductions in SBP, DBP, as well as HR [89,90]. This study did not find any significant difference in systolic-diastolic BP in the comorbid group as compared to the naïve groups. ...
... Our findings, which show a notable reduction in HR and blood pressure after weeks of Common Yoga Protocol practice, align with prior studies suggesting that yoga effectively lowers blood pressure [87,88]. Yoga interventions induce para-sympathomimetic effects, leading to reductions in SBP, DBP, as well as HR [89,90]. This study did not find any significant difference in systolic-diastolic BP in the comorbid group as compared to the naïve groups. ...
Non-clinical approaches such as meditation, yoga, and mindfulness are popular traditional therapeutical interventions adopted by many educational institutions to improve the physical and mental well-being of learners. This study aimed to evaluate the effectiveness of yoga intervention in improving cardiopulmonary parameters such as blood pressure, heart rate, pulmonary function tests and psychosomatic symptoms such as depression, anxiety and stress in medical and dental students. Using the PRISMA protocol, a search from databases such as PubMed, Scopus, and Embase resulted in 304 relevant articles. After screening the title and abstracts, 47 papers were analyzed thoroughly and included in the qualitative analysis. 18 articles with homogenous statistical data on physiology and psychological parameters were included for meta-analysis. In comparison to the control group, the study showed a significant reduction of systolic blood pressure (SBP: 6.82 mmHg, z = -3.06, p = 0.002), diastolic blood pressure (DBP: 2.92 mmHg, z = -2.22, p = 0.03), and heart rate (HR: 2.55 beats/min, z = -2.77, p = 0.006). Additionally, data from 4 studies yielded a significant overall effect of a stress reduction of 0.77 on standardized assessments due to the yoga intervention (z = 5.29, p < 0.0001). Lastly, the results also showed a significant (z = -2.52, p = 0.01) reduction of 1.2 in standardized anxiety tests in intervention group compared to the control. The findings offer promising prospects for medical educators globally, encouraging them to consider reformation and policymaking in medical curricula to enhance academic success and improve the overall quality of life for medical students worldwide.
... While Cana induces alterations in pathways related to fatty acid metabolism, PI3K-Akt signaling, and neuropeptide signaling in females, the overall response was weaker and less consistent in gene clusters across age groups. The comparison of conserved genes among males at both age groups and aged 25-month-old females, despite exhibiting phenotypically similar metabolic effects on energy homeostasis, revealed only a limited set of genes with roles in various aspects of cellular metabolism [5,9,30,31,37,44]. Cana-treated males showed changes in pathways related to aging at 12 and 25 months of age while females showed changes only at 12 months of age. ...
The hypothalamus undergoes significant changes with aging and plays crucial roles in age-related metabolic alterations. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are anti-diabetic agents that promote glucose excretion, and metabolic homeostasis. Recent studies have shown that a SGLT2i, Canagliflozin (Cana), can extend the median survival of genetically heterogeneous UM-HET3 male mice and improve central metabolic control via increases in hypothalamic insulin responsiveness in aged males, as well as reduced age-associated hypothalamic inflammation. We studied the long- and short-term effects of Cana on hypothalamic metabolic control in UM-HET3 mice. Starting the treatment from 7 months of age, we show that 4 weeks of Cana treatment significantly reduced body weight and fat mass in male but not female mice that was associated with enhanced glucose tolerance and insulin sensitivity observed by 12 months. Indirect calorimetry showed that Cana treatment increased energy expenditure in male, but not female mice, at 12 months of age. Long-term Cana treatment increased metabolic rates in both sexes, and markedly increasing formation of both orexigenic and anorexigenic projections to the paraventricular nucleus of the hypothalamus (PVH) mostly in females by 25 months. Hypothalamic RNA-sequencing analysis revealed increased sex-specific genes and signaling pathways related to insulin signaling, glycogen catabolic pathway, neuropeptide signaling, and mitochondrial function upregulated by Cana, with males showing a more pronounced and sustained effect on metabolic pathways at both age groups. Overall, our data provide critical evidence for sex-specific mechanisms that are affected by Cana during aging suggesting key targets of hypothalamic Cana-induced neuroprotection for metabolic control.
... Abdominal obesity is associated with the development of enlarged and dysfunctional adipose cells (21), which secrete adipokines like adiponectin and inflammatory cytokines, including interleukins and tumor necrosis factor alpha, which contribute to insulin resistance as well as the proinflammatory and pro-hypertensive states associated with visceral obesity (22)(23)(24). Lipolysis from visceral fat deposits increases free fatty acid supply to the liver, leading to increased hepatic synthesis of very low density lipoproteins and thus, raised levels of triglycerides (20,25). Free fatty acids can also accumulate in the pancreas as well as other organs, leading to organ dysfunction, a process known as lipotoxicity (26). ...
Background
Metabolic syndrome is a group of metabolic abnormalities that increase predisposition to several diseases including ischemic heart disease and diabetes mellitus. The study aimed to investigate metabolic syndrome among patients with type-2 diabetes mellitus (DM), and its impact on pharmacotherapy outcomes.
Methods
An observational cross-sectional study was performed on 910 patients with type-2 DM between June and December 2023. Fasting blood sugar, triglycerides, high-density lipoproteins (HDL), blood pressure, and abdominal obesity were measured. Metabolic syndrome was identified according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Pharmacotherapy outcomes were assessed according to American Association of Clinical Endocrinologists and American Diabetes Association guidelines using the ability to achieve adequate glycemic control and normal levels of blood pressure and fasting plasma lipoproteins.
Results
In total, 87.5% of type-2 DM patients had metabolic syndrome; the prevalence increased with age and was higher among females. Metabolic syndrome showed the following distribution of risk factors: insulin resistance (100%), low HDL (95.3%), elevated blood pressure (83%), triglycerides dyslipidemia (80.1%), and abdominal obesity (62.5%). Majority of the patients had either 5 or 4 risk factors of metabolic syndrome. The most common comorbidities were dyslipidemia (97.7%) and hypertension (83%). Treatment outcomes were insufficient where adequate glycemic control was only achieved in 12% of type-2 DM patients, and proper management of comorbid dyslipidemia and hypertension was achieved in 29% and 40.9% of patients, respectively. Adequate blood pressure control was less achieved in patients with metabolic syndrome (34.4%) than those without metabolic syndrome (77.2%). Similarly, dyslipidemia was less controlled in patients with metabolic syndrome (26.9%) than in those without metabolic syndrome (47.3%).
Conclusion
Pharmacotherapy outcomes were inadequate for most patients with type-2 diabetes mellitus. Adopting early preventive and therapeutic interventions for metabolic syndrome is advised to improve treatment outcomes of the comorbid dyslipidemia and hypertension.
... In phase 4, group 4 and 5 showed a significant increase (p<0.05) in weight when compared to the positive control. (Grundy, 2004). These chemicals have been reported to influence enterohepatic circulation through sequestration and binding of bile acids (Behall, 1997). ...
The antidyslipidemic activity of Irvingia wombolu ethanol seeds extract was studied in high fat diet induced dyslipidemic rats.Forty five (45) Wstar rats were grouped into 5 groups of 9 rats each. The animals were allowed 7 days acclimatization period. Group 1 was the control group and it received normal rat chow and water throughout the study. Groups 2 to 5 were given high fat diet for 14 days after which they were given normal rat chow till the end of the study. At the end of the 14 days, group 2 was not treated while group 3-5 were treated with 250, 500 and 1000mg/kg b.w ethanol extract of Irvingia wombolu seeds respectively for 28 days. The lipid profile of animals was evaluated three times: first after 14 days induction period (phase 1) i.e day 0 of treatment, second was taken 14 days after treatment (phase 2), third was taken 28 days after treatment (phase 3). The study lasted for 49 days and dimethyl sulphoxide was used as a vehicle for the extract. In phase 1, all the groups fed with high fat diet showed an increase in low density lipoprotein (LDL) triglyceride, total cholesterol and a decrease in high density lipoprotein (HDL) levels. In phase 2 there was a decrease in LDL, triglyceride and total cholesterol level in addition to increase in HDL for animals in all the treatment groups. It was observed that in phase 3 only 250mg/kg group showed a progressive decrease in LDL, triglyceride, total cholesterol and an increase in HDL levels while 500 and 1000 mg/kg b.w showed an increase in LDL, triglyceride and total cholesterol level and a decrease in HDL. The result of the present study demonstrated the antidyslipidemic effect of ethanol extract of Irvingia wombolu seeds at lower dose.
... Some of the common risk factors for CVD are high blood pressure, elevated plasma cholesterol levels, obesity, and diabetes (CDC, 2022;AHA, 2023). These risk factors are similar to those seen for Metabolic Syndrome (MetS), which is defined as the simultaneous presence of at least 3 of the following metabolic risk factors: (I) abdominal obesity/increased adiposity, (II) atherogenic dyslipidemia, (III) hypertension, (IV) hyperglycemia with or without insulin resistance, (V) prothrombotic state, and (VI) proinflammatory state, all of which contributes to the prevalence of developing CVD and Type 2 Diabetes Mellitus (T2DM) (Grundy, 2004). A close link exists between T2DM and CVD as diabetes is associated with an increased risk of heart failure. ...
... The growth, development, and survival of multicellular organisms are not only controlled by genetic and nutritional factors but are also tightly integrated by endocrine signals. Disrupted interplays among hormones, growth factors, and their cellular responses are responsible for the genesis of diabetes, obesity, metabolic syndrome, ischemic heart disease, and heart failure (43)(44)(45). Melatonin is a key player in the central serotonergic pathway controlling growth hormone synthesis (46). Animal experiments and clinical studies have shown that pinealectomy retards the overall growth and development of sexual organs (47,48). ...
Endocrine modulation of various growth and survival mechanisms is at the helm of cellular homeostasis and impaired endocrine balance may potentially galvanize cardiovascular health to go haywire. Melatonin, an effective antioxidant and multipotent hormone has preponderant influence on the activities of several endocrine factors including growth hormones, thyroid hormones, gastro-intestinal hormones, and those controlling reproductive and metabolic functions. Many of these hormones tightly regulate cardiovascular functions while the mammalian heart has its own endocrine machinery. Endocrine disruptions severely affect cardiovascular integrity and hormonal therapies may instigate adverse cardiac events. Therefore, this review focuses on the cardioprotective potential of melatonin concerning endocrine instability-mediated cardiovascular dysfunction. Melatonin has been reported to effectively counteract sympathetic overstimulation and also reduce the cardiotoxic attributes of catecholamines and their derivatives. Melatonin suppresses the pernicious cardiovascular manifestation of thyrotoxicosis and autoimmune thyroiditis, which is possibly attributed to its antioxidant property and regulation of iodothyronine-deiodinase activity. Interestingly, being a circadian synchronizer melatonin potentially preserves the diurnal pattern of insulin secretion and thereby improves glucose tolerance and cardiac GLUT-4 expression. Besides, melatonin modulates insulin signaling pathway by enhancing the activation of insulin receptor-associated tyrosine kinase, thus protecting the heart against diabetogenic outcomes. Further, melatonin has demonstrated its beneficial action against non-dipper hypertension by regulating the RAAS function. However, there is a plethora of unresolved research question that necessitates additional investigation into the potential therapeutic effect of melatonin in endocrine dysfunctions that emanates during various physiological and pathological states and may have potentially harmful cardiovascular implications.
... In the case of monogenic obesity, genetic variants in single genes lead to large effects [62]. Furthermore, obesity can be classified into the following categories, such as overweight (BMI = 25 to < 30 kg·m −2 ), moderate obesity (BMI = 30 to <35 kg·m −2 ) and severe obesity (BMI ≥ 35 kg·m −2 ) [64]. Contributions of leptin, leptin receptor, proopiomelanocortin, prohormone convertase 1, melanocortin 4 receptor, single-minded homolog 1, brain-derived neurotrophic factor and neurotrophic tyrosine kinase receptor type 2 genes have been identified as causes for obesity [65,66]; however, more than 500 obesity-related genes were identified [67]. ...
Metabolic syndrome (MS) is defined by the outcome of interconnected metabolic factors that directly increase the prevalence of obesity and other metabolic diseases. Currently, obesity is considered one of the most relevant topics of discussion because an epidemic heave of the incidence of obesity in both developing and underdeveloped countries has been reached. According to the World Obesity Atlas 2023 report, 38% of the world population are presently either obese or overweight. One of the causes of obesity is an imbalance of energy intake and energy expenditure, where nutritional imbalance due to consumption of high-calorie fast foods play a pivotal role. The dynamic interactions among different risk factors of obesity are highly complex; however, the underpinnings of hyperglycemia and dyslipidemia for obesity incidence are recognized. Fast foods, primarily composed of soluble carbohydrates, non-nutritive artificial sweeteners, saturated fats, and complexes of macronutrients (protein-carbohydrate, starch-lipid, starch-lipid-protein) provide high metabolic calories. Several experimental studies have pointed out that dairy proteins and peptides may modulate the activities of risk factors of obesity. To justify the results precisely, peptides from dairy milk proteins were synthesized under in vitro conditions and their contributions to biomarkers of obesity were assessed. Comprehensive information about the impact of proteins and peptides from dairy milks on fast food-induced obesity is presented in this narrative review article.
... Metabolic Syndrome (MetS) is a cluster of interrelated metabolic and physiological disorders [1,2] often linked to insulin resistance [3]. The central components of the syndrome, namely, central obesity, high blood pressure, hyperglycaemia and dyslipidaemia [2][3][4], have been identified as risk factors for type 2 diabetes [5,6] and cardiovascular diseases (CVDs), including ischemic heart disease and stroke [3,7]. Individuals with MetS are two times more likely to suffer from stroke [8] and have a fivefold increased risk of developing type 2 diabetes compared to those without MetS [9]. ...
This review aimed to systematically quantify the differences in Metabolic Syndrome (MetS) prevalence across various ethnic groups in high-income countries by sex, and to evaluate the overall prevalence trends from 1996 to 2022. We conducted a systematic literature review using MEDLINE, Web of Science Core Collection, CINAHL, and the Cochrane Library, focusing on studies about MetS prevalence among ethnic groups in high-income countries. We pooled 23 studies that used NCEP-ATP III criteria and included 147,756 healthy participants aged 18 and above. We calculated pooled prevalence estimates and 95% confidence intervals (CI) using both fixed-effect and random-effect intercept logistic regression models. Data were analysed for 3 periods: 1996–2005, 2006–2009, and 2010–2021. The pooled prevalence of MetS in high-income countries, based on the NCEP-ATP III criteria, was 27.4% over the studied period, showing an increase from 24.2% in 1996–2005 to 31.9% in 2010–2021, with men and women having similar rates. When stratified by ethnicity and sex, ethnic minority women experienced the highest prevalence at 31.7%, while ethnic majority women had the lowest at 22.7%. Notably, MetS was more prevalent in ethnic minority women than men. Among ethnic minorities, women had a higher prevalence of MetS than men, and the difference was highest in Asians (about 15 percentage points). Among women, the prevalence of MetS was highest in Asians (41.2%) and lowest in Blacks/Africans (26.7%). Among men, it was highest in indigenous minority groups (34.3%) and lowest among in Blacks/Africans (19.8%). MetS is increasing at an alarming rate in high-income countries, particularly among ethnic minority women. The burden of MetS could be effectively reduced by tailoring interventions according to ethnic variations and risk profiles.
... 2 Individuals with obesity are predisposed to metabolic syndrome, which is associated with a multitude of chronic diseases including type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease and a variety of cancers. [3][4][5][6] Bariatric and metabolic surgery can achieve long-term weight reduction and improvements in glycemic control, resulting in metabolic changes which lead to improvements in insulin sensitivity and beta cell function. 7,8 Preoperative lifestyle interventions prior to bariatric and metabolic surgery are advocated by national guidelines including the American Society for Metabolic and Bariatric Surgery and the National Institute for Health and Care Excellence. ...
Introduction
Metabolic surgery is a sustainable intervention for obesity and type 2 diabetes. Preoperative education optimizes weight loss and glycemic control outcomes.
Objective
This study aimed to determine the effect of a generalized preoperative evaluation process (PEP) in patients who underwent bariatric surgery on weight loss and glycemic control pre‐ and post‐surgery.
Methods
Data were retrospectively collected and analyzed for patients with type 2 diabetes who underwent bariatric surgery between 2010 and 2016. Patients were categorized into two groups determined by participation in the PEP. The groups were named the PEP group and non‐PEP group. The correlation among engagement in the PEP was determined using the chi‐square test and t ‐test. Statistical analysis with p < 0.05 was deemed significant.
Results
129 patients were included in the study; 86 females (67%) and 43 males (33%). Fifty‐nine patients (46%) engaged in the PEP and 70 (54%) patients did not engage in the PEP. A greater reduction in weight loss was observed in the PEP group versus the non‐PEP group from initial enrollment to pre‐surgery (14.3 ± 9.2 kg vs. 11.6 ± 9.2 kg; p = 0.11), and from pre‐surgery to 2‐years post‐surgery (20.6 ± 14.8 kg vs. 16.9 ± 15.6 kg; p = 0.17). A greater reduction in HbA1c from initial enrollment to pre‐surgery was seen in the PEP group versus the non‐PEP group (0.90 ± 1.28% vs. 0.63 ± 1.07%); however, this was not maintained from pre‐surgery to 2‐year post‐surgery (0.51 ± 1.18% vs. 0.70 ± 1.73%). In both cases, the statistical difference was insignificant.
Conclusion
The PEP was not associated with improvements in short‐term weight loss or glycemic control pre‐surgery and a 2‐years post‐surgery. Patients may benefit from individually tailored preoperative weight management strategies.
... MetS is a collection of cardiometabolic risk factors that includes obesity, insulin resistance (IR), hypertension and dyslipidemia (4). A diagnosis of MetS can be made if a person has three of the following five features: Increased waist circumference (≥102 cm in men and ≥88 cm in women), elevated triglycerides (≥150 mg/dl), reduced HDL cholesterol (<40 mg/dl in men and < 50 mg/dl in women), elevated blood pressure (≥130/85 mm Hg or on treatment for hypertension) and elevated glucose (≥100 mg/dl) (5). The perpetuation of these metabolic dysfunctions affects negatively on life expectancy and can eventually lead to the development of type 2 diabetes (T2D) mellitus, cardiovascular diseases, non-alcoholic fatty liver disease, some types of cancer or autoimmune disorders (6). ...
BACKGROUND: Due to the high prevalence of obesity and metabolic disease caused by obesity, it is necessary to find an effective and useful training method to mitigate the adverse effects of excess adiposity. METHODS: 30 overweight and obese women (BMI=33.24±4.7) with no history of exercise or certain diseases were selected and randomly divided into two groups of TRX training (n=15) and control (n=15). The training protocol was performed three days a week on non-consecutive days for 12 weeks, and each session lasted 60 minutes. Body weight, waist circumferences, BMI, BAI, VAI, TyG, fasting blood glucose, HOMA-IR and HOMA-β were measured 48 hours before and after the training period. RESULTS: There were decrease in the weight (P = 0.001) and BMI (P = 0.001), TG (P = 0.001), VAI (P < 0.001), BAI (P < 0.001), TyG (P = 0.004), TyG-BMI (P < 0.001), and TyG-WC (P < 0.001) in the experimental group and HDL (P = 0.013) was improved. No changes observed in FBS (P = 0.165), Insulin (P = 0.084), HOMA-IR (P = 0.97), and HOMA-β cell (P = 0.128). CONCLUSIONS: Anthropometric indices and lipid profile are more sensitive to TRX training than blood-related factors. Thus, TRX training is an affective training protocol to control body composition and lipid profile and consequently lower MetS risk factors in overweight and obese women.
... 2014). Obesity may be related to other diseases (Grundy, 2004). Weight management and get rid of obesity based on reducing the intake of calories than the consuming (low calorie diets). ...
... This finding agrees with the results of the study about overweight and obesity among adolescence Children in Jordan: Prevalence and Associated Factors by [25] who find that the daily pocket money was associated with overweight, while family monthly income associated with obesity. Also this result in the same line with the results of the study about Obesity, metabolic syndrome, and cardiovascular disease in the USA by [26] who studied that the prevalence of obesity in the United States is lower among those of higher socioeconomic status. This may be high economic index were more likely to be overweight and obese. ...
Overweight and obesity are the fifth leading risk for global deaths. At least 2.8 million adults die each year as a result of being overweight or obese. The study aim to evaluate the effect of application of health belief model (HBM) among youth at high risk for obesity in Palestine (West Bank). Research design: A quasi-experimental design was used. Settings: The study was conducted at Faculty of Nursing /A-Najah National University which located in Nablus and IBN Sina College for Health Sciences, West Bank-Palestine. Subjects: A purposive sample of 117 students, from both previous setting at high risk for obesity was included. Tools, three tools were used to collect data. A self-administered questionnaire, it was composed of 4 parts; the health belief model (HBM) sub-constructs which used in this study and anthropometric measurement to detect body mass index & levels of risk for obesity. Results: Revealed that according to BMI and levels of risk for obesity shows, less than half of youth were obesity class1 (low risk) while more than one third was obesity class II (moderate risk). There was a highly significant difference between student's knowledge and their practices regarding obesity, healthy food, and exercises pre & post application of HBM. Conclusion: Application of health belief model was effective in improved knowledge and practices of the student at high risk for obesity and changing health behavior. Recommendations: Conducting routine screening for obesity, dieting, and other weight reduction practices as an integral part of the ongoing health care provided by all health services. HBM also suggests that the benefits and barriers of changing health behavior must be taken into consideration, as those who perceive more benefits than barriers are more likely to take action.
... However, Central American countries are not exempt from suffering from eating disorders due to bad eating habits that cause an imbalance between energy intake and expenditure (3)(4)(5)(6). Obesity is often accompanied by significant comorbidities such as diabetes and hypertension (7,8). It is important to identify these disorders early because when diabetes and hypertension become complicated, they can be extremely disabling and may lead to significant economic losses in the health sector due to long-term treatments. ...
Introduction
Hispanic immigrants are a fast-growing population in the United States of America (USA) that disproportionately suffer from chronic diseases. Despite the increasing prevalence of obesity in Latin-American countries, only a few studies have examined the onset of chronic diseases in Mexican and Central American migrants in Mexico.
Objective
The objective of this study is to determine the prevalence of obesity, diabetes, and hypertension in Central American immigrants who are in the process of traveling through northeastern Mexico to the United States.
Methods
An observational, descriptive, cross-sectional study was conducted among migrants, mostly Central Americans. Migrants who agreed to participate in the study were interviewed face-to-face by researchers to obtain their sociodemographic data. To obtain the prevalence, many health indicators related to obesity, diabetes, and hypertension, including weight, height, fasting glucose, and blood pressure, were measured.
Results
In total, 520 migrants were interviewed; sociodemographic data indicated that most participants were men (76%), from Honduras (72.6%), single (61.2%), and have elementary level of education (48.6%). The somatometric evaluation revealed that 28.9% were diagnosed as overweight, 10.7% with obesity, and 3.3% with malnutrition. Of less prevalence, 8.8% were detected with hypertension and 4.6% had fasting hyperglycemia. The mean participant age was 29.11 ± 10.00 years. For each participant, the average weight was 66.72 ± 13.09 kg; the average height was 1.64 ± 0.08 m; the average body mass index (BMI) was 24.59 ± 4.32; the mean systolic and diastolic pressures were 116.26 ± 15.13 and 74 ± 9.65, respectively; and the average glycemia was 100.97 ± 21.99. El Salvador showed the highest proportion of people with diabetes (14.7%). Women who participated in this study had a higher proportion of obesity (23.4%, p = 0.02) and overweight (36.2%) than men (8.4 and 29.2%, respectively). People from Mexico, Nicaragua, and Honduras reported a high prevalence of overweight participants (63.6, 47.4, and 30.7%, respectively), while people from El Salvador and Nicaragua had a high prevalence of obese participants (23.5 and 21.1%, respectively).
Conclusion
We found significant differences in the rates of obesity, diabetes, and hypertension between groups of Central American migrants and their place of origin, age, educational level, and gender. Our findings highlight the importance of exploring differences within groups of Central American migrants traveling through northeastern Mexico to the United States, which may explain several health indicators.
... Type 2 diabetes mellitus (T2DM), a metabolic disease complicatedly caused by insulin resistance, is oten eatured with hyperlipidemia and hyperglycemia (Grundy, 2004). Under the prolonged condition o hyperglycemia, pancreatic β-cells largely increase compensatory insulin secretion, which might ultimately lead to impaired sensitivity to insulin and thereby attenuate insulin-mediated biological responses in its target tissues such as adipose tissues, liver and skeletal muscle (Petersen and Shulman, 2018;Shrivastava et al., 2021;Wen et al., 2022). ...
... Obesity is a risk factor for various diseases such as cardiovascular disease, non-alcoholic fatty liver disease, type 2 diabetes, cancer, and COVID-19 (Grundy 2004;Avgerinos et al. 2019;Kwok et al. 2020). Recent studies have revealed that the gut microbiota is associated with obesity. ...
Obesity is a global health threat that causes various complications such as type 2 diabetes and nonalcoholic fatty liver disease. Gut microbiota is closely related to obesity. In particular, a higher Firmicutes to Bacteroidetes ratio has been reported as a biomarker of obesity, suggesting that the phylum Bacteroidetes may play a role in inhibiting obesity. Indeed, the genus Bacteroides was enriched in the healthy subjects based on metagenome analysis. In this study, we determined the effects of Bacteroides stercoris KGMB02265, a species belonging to the phylum Bacteroidetes, on obesity both in vitro and in vivo. The cell-free supernatant of B. stercoris KGMB02265 inhibited lipid accumulation in 3T3-L1 preadipocytes, in which the expression of adipogenic marker genes was repressed. In vivo study showed that the oral administration of B. stercoris KGMB02265 substantially reduced body weight and fat weight in high-fat diet induced obesity in mice. Furthermore, obese mice orally administered with B. stercoris KGMB02265 restored glucose sensitivity and reduced leptin and triglyceride levels. Taken together, our study reveals that B. stercoris KGMB02265 has anti-obesity activity and suggests that it may be a promising candidate for treating obesity.
... Obesity is recognized as one of the risk factors associated with metabolic abnormalities, including type 2 diabetes, hypertension, hyperlipidemia, and cardiovascular disease [1][2][3][4]. Recent studies have highlighted the important role of chronic inflammation in adipose tissue in the development of metabolic abnormalities [5][6][7][8]. ...
Obesity induces inflammation in the hypothalamus and adipose tissue, resulting in metabolic disorders. A novel hypothalamic neuropeptide, neurosecretory protein GM (NPGM), was previously identified in the hypothalamus of vertebrates. While NPGM plays an important role in lipid metabolism in chicks, its metabolic regulatory effects in mammals remain unclear. In this study, a novel Cre driver line, NPGM-Cre, was generated for cell-specific manipulation. Cre-dependent overexpression of Npgm led to fat accumulation without increased food consumption in male NPGM-Cre mice. Chemogenetic activation of NPGM neurons in the hypothalamus acutely promoted feeding behavior and chronically resulted in a transient increase in body mass gain. Furthermore, the ablated NPGM neurons exhibited a tendency to be glucose intolerant, with infiltration of proinflammatory macrophages into the adipose tissue. These results suggest that NPGM neurons may regulate lipid storage and inflammatory responses, thereby maintaining glucose homeostasis.
... Obesity increases the risks of chronic disease experience, depression due to physical dissatisfaction, and the burden on others, all of which can lead to suicidal ideation [29,30]. Obesity is a factor closely associated with metabolic syndrome [31] and nancial support is needed to treat any such illnesses. Unstable nancial circumstances due to unemployment can hence lead to potential suicidal ideation. ...
Background: Employment status is a key indicator of socioeconomic status, and unstable employment conditions can cause various social problems. However, research in Asian cultures for the association between employment status and mental health has been limited. This study investigated the association between employment status and suicidal ideation in general population in South Korea.
Methods: Using data from the 2015, 2017, and 2019 Korea National Health and Nutrition Examination Survey (KNHANES), 6,509 participants aged ≥ 20 years were analyzed. Suicidal ideation was characterized by individuals considering suicide seriously within the past year. Covariates were adjusted to account for factors such as sociodemographic, health behavior, and mental health factors. Multivariable logistic regression and subgroup analysis were performed.
Results: In our KNHANES data analysis, unemployed status demonstrated 1.85 times more suicidal ideation than employed (adjusted Odd Ratio (aOR) 1.85, 95% confidence interval (CI) 1.41-2.44, p < .001). Low educational attainment (aOR 2.12, 95% CI 1.51-2.98, p < .001), low income (aOR 1.61, CI 1.22 -2.14, p < .001), presence of stress recognition (aOR 3.06, 95% CI 2.33-4.02, p < .001), and depression (aOR 13.0, 95% CI 10.0-16.9, p < .001) were also associated with suicidal ideation. In subgroup analysis, all covariates, except women and low body mass index, demonstrated combined effects with employment status on suicidal ideation.
Conclusions: This study demonstrated a significant association between employment status and suicidal ideation. Comprehensive supportive measures, including policy interventions and a variety of assistance, are crucial to mitigate the risk of suicidal ideation among the unemployed.
... Recently, studies in human populations have associated mtDNA haplogroups with the risk of metabolic syndrome or its complications (Chinnery et al. 2010, Estopinal et al. 2014, Martikainen et al. 2015, and sequence variation in mtDNA has also been shown to influence the expression of stress response genes (Bellizzi et al. 2006). A higher risk of metabolic syndrome is strongly associated with weight gain due to high nutrient excess (Grundy 2004). The resulting aberrant distribution of fat, mainly in visceral and intra-abdominal depots (Vazquez et al. 2007, Castro et al. 2014), leads to lipotoxicity -ectopic fat storage in metabolically active tissues such as the liver, myocardium, or skeletal muscle (Unger 2002). ...
Metabolic syndrome is a growing concern in developed societies, and due to its polygenic nature, the genetic component is only slowly being elucidated. Common mitochondrial DNA sequence variants have been associated with symptoms of metabolic syndrome and may be relevant players in the genetics of metabolic syndrome.
We investigate the effect of mitochondrial sequence variation on the metabolic phenotype in conplastic rat strains with identical nuclear but unique mitochondrial genomes, challenged by high-fat diet. We find that the variation in mitochondrial rRNA sequence represents a risk factor in insulin resistance development, which is caused by diacylglycerols accumulation induced by tissue-specific reduction of the oxidative capacity. These metabolic perturbations stem from the 12S rRNA sequence variation affecting mitochondrial ribosome assembly and translation. Our work demonstrates that physiological variation in mitochondrial rRNA might represent a relevant underlying factor in the progression of metabolic syndrome.
Competing interests
The authors declare that no competing interests exist.
... Obesity is a complex metabolic disorder that is associated with several metabolic abnormalities, including dyslipidemia. Dyslipidemia is a condition characterized by abnormal levels of lipids (fats) in the blood, including high levels of low-density lipoprotein (LDL) cholesterol (commonly referred to as "bad" cholesterol), low levels of high-density lipoprotein (HDL) cholesterol (commonly referred to as "good" cholesterol), and high levels of triglycerides [62]. ...
Leptin, a hormone produced by fat cells, regulates energy balance and body weight by suppressing appetite and increasing energy expenditure. In obesity, there is often leptin resistance, reducing the hormone's effects due to factors such as inflammation and changes in leptin receptors. This resistance leads to an increased risk of weight gain and obesity. Leptin therapy shows promise in treating obesity and related metabolic disorders, such as dyslipidemia and type 2 diabetes mellitus. It can lower body weight, improve insulin sensitivity, and reduce blood glucose and lipid levels. However, its effectiveness may be limited by the development of leptin resistance. Leptin also exhibits anti-inflammatory and cardiovascular protective effects, with potential therapeutic value for obesity-related conditions. Nevertheless, further research is necessary to comprehend leptin's mechanisms and develop safe and effective therapies for these conditions, including those targeting dyslipidemia.
... Obesity is recognized as one of the risk factors associated with metabolic abnormalities, including type 2 diabetes, hypertension, hyperlipidemia, and cardiovascular disease [1][2][3][4]. Recent studies have highlighted the important role of chronic inflammation in adipose tissue in the development of metabolic abnormalities [5][6][7][8]. ...
Obesity induces inflammation in the hypothalamus and adipose tissue, resulting in metabolic disorders. A novel hypothalamic neuropeptide, neurosecretory protein GM (NPGM), was previously identified in the hypothalamus of vertebrates. While NPGM plays an important role in lipid metabolism in chicks, its metabolic regulatory effects in mammals remain unclear. In this study, a novel Cre driver line, NPGM-Cre, was generated for cell-specific manipulation. Cre-dependent overexpression of Npgm led to fat accumulation without increased food consumption in NPGM-Cre mice. Chemogenetic activation of NPGM neurons acutely promoted feeding behavior and chronically resulted in a transient increase in body mass gain. Furthermore, the ablated NPGM neurons exhibited a tendency to be glucose intolerant, with infiltration of proinflammatory macrophages into the adipose tissue. These results suggest that NPGM neurons may regulate lipid storage and inflammatory responses, thereby maintaining glucose homeostasis.
... On one hand, these studies mainly address the risk factors that lead to obesity, namely socioeconomical status, lifestyle habits, sleeping patterns and genetic influence. On the other hand, they may also evaluate the possibility of an association between anthropometric parameters, such as body mass index (BMI), waist-to-height ratio or waist circumference, and the prevalence of CVD, insulin resistance, chronic kidney disease or dyslipidaemia [10,14,15]. ...
The increasing prevalence of overweight and obesity is a worldwide problem, with several well-known consequences that might start to develop early in life during childhood. The present research based on data from children that have been followed since birth in a previously established cohort study (Generation XXI, Porto, Portugal), taking advantage of State-of-the-Art (SoA) data science techniques and methods, including Neural Architecture Search (NAS), explainable Artificial Intelligence (XAI), and Deep Learning (DL), aimed to explore the hidden value of data, namely on electrocardiogram (ECG) records performed during follow-up visits. The combination of these techniques allowed us to clarify subtle cardiovascular changes already present at 10 years of age, which are evident from ECG analysis and probably induced by the presence of obesity. The proposed novel combination of new methodologies and techniques is discussed, as well as their applicability in other health domains.
... In comparison to those without the syndrome, those with metabolic syndrome have a higher risk of cardiovascular disease, myocardial infarction, stroke, and death from these conditions. The primary pathophysiological factor driving the clustering is thought to be insulin resistance [4]. When insulin activity intensifies, enhanced lipolysis generates more fatty acids, and this further reduces insulin's antilipolytic impact. ...
Introduction
Metabolic syndrome is a group of aberrant metabolic indicators including hypertension, dyslipidemia, impaired fasting blood glucose, and obesity. It has been reported that thyroid hormones have a strong influence on the cardiovascular system, and hypothyroidism has been linked to metabolic syndrome components. The objective of the study was to find out the association of thyroid function with lipid profile in patients with metabolic syndrome.
Methods
A prospective cross-sectional study was conducted in an apparently healthy adult population visiting the outpatient Department of Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar, India. Metabolic syndrome was diagnosed according to the International Diabetes Federation (IDF) criteria. Fasting blood glucose, triglyceride, and HDL levels were tested using the enzymatic photometric method. Thyroid-stimulating hormone (TSH), free T4, free T3, and insulin assays were performed using chemiluminescence immunoassay (CLIA).
Results
Out of 197 subjects recruited, 86 (51 males and 35 females) were diagnosed with metabolic syndrome according to the IDF criteria, and the rest 111 without metabolic syndrome were considered to be the controls. The mean age of subjects with and without metabolic syndrome was 45.8±8.5 and 46.4±9.6 years, respectively. The prevalence of thyroid dysfunction in the present study was 22%. In subjects with metabolic syndrome, most of the clinical and hormonal parameters (waist circumference, waist-height ratio, fasting blood sugar, fasting insulin, triglycerides, T3, and TSH) were significantly higher (p<0.001) as compared to those without metabolic syndrome. In case of lipid profile, the triglycerides in those with metabolic syndrome (262.8±112.3 mg/dL) were significantly higher (p<0.001) than those without metabolic syndrome (137.9±19.01 mg/dL), while the serum levels of HDL were significantly higher (p<0.001) in group without metabolic syndrome (50.5±3.9 mg/dL) as compared to those with metabolic syndrome (43.4±5.2 mg/dL). Also, the TSH levels were significantly higher (p<0.001) in subjects with metabolic syndrome (5.3±3.4 μl/mL) as compared to those without metabolic syndrome (2.6±1.4 μl/mL). Among all the components of metabolic syndrome, waist circumference and HDL showed a significant strong positive correlation (r=0.51) with TSH, and systolic blood pressure (r=0.39), diastolic blood pressure (r=0.39), and fasting blood sugar levels (r=0.44) showed significantly moderate positive correlation with TSH levels. T4 (OR=8.82; 95% CI: 1.56-49.8) and TSH (OR=1.61; 95% CI: 1.19-2.18) levels were observed to have significantly higher odds as risk factors for metabolic syndrome.
Conclusion
There is a significant association of thyroid function with lipid profile in metabolic syndrome. It was observed that along with metabolic alterations, cardiovascular symptoms of hypothyroidism and subclinical hypothyroidism are possible. Therefore, while evaluating people with metabolic syndrome, it may be appropriate to look into how well their thyroid glands are functioning.
... Additionally, fQRS has been associated with increased arrhythmia and sudden cardiac mortality in patients with idiopathic dilated cardiomyopathy (2). Various studies have shown an association between obesity and Cardiovascular diseases (CV) such as acute myocardial infarction, heart failure, arrhythmia (heart rhythm disorders), Sudden Cardiac Death (SCD), and Coronary Artery Disease (CAD) (3,4). Excess myocardial fat deposits may develop the ventricular arrhythmias. ...
Background: Fragmented QRS (fQRS) on electrocardiography is a marker of myocardial fibrosis and scar formation. We aimed to investigate whether the fQRS complex in children with and without obesity correlates with Body Mass Index (BMI). Methods: In this cross-sectional study, 104 children (5 to 17 years) referred to the pediatric clinic were studied. We divided participants into normal and obese groups. Standard 12-lead ECGs, anthropometric data, and blood pressure were recorded. All ECGs were analyzed blindly by two independent clinicians. Surveyed parameters of the ECG included heart rate, QRS duration, QT interval, presence of Q waves, and fQRS. Results: Among 104 participants, 52 patients had normal BMI and 52 cases were obese. Systolic blood pressure (p=0.001), pulse pressure (p=0.007), mean blood pressure (p=0.006), and heart rate (p=0.009) were meaningfully different between the two groups. We found fQRS in four children with obesity. The frequency of fQRS was significantly different between children with obesity and children in the control group (p=0.041). We have found that each unit change of weight and BMI at 1.07 and 1.45, respectively, could be useful in prediction of the occurrence of fQRS complex in children. Conclusion: This study suggested a significant association between the fQRS in children’s ECG and their weight and BMI. It would appear that each unit increasing weight and BMI predicts an increasing the occurrence of fQRS. The ECG may consider using fQRS as a cardiac risk marker in children with obesity.
... Thirty-three men with metabolic syndrome (age: 46.2 ± 4.6 years; body mass index (BMI): 35.4 ± 1.9 kg/m 2 ) participated in this study. Participants who met at least 3 of the 5 following criteria were classified as having metabolic syndrome: a waist circumference of ≥102 cm, a triglyceride level of ≥150 mg/dl, an high density lipoprotein cholesterol level of <40 mg/dl, a blood pressure of ≥130/80 mmHg, and a glucose level of ≥100 mg/dl (Grundy, 2004). Moreover, if the level of physical activity of participants was below 150 min per week, they were considered to be inactive (Füzéki & Banzer, 2018). ...
Objective:
This study aimed to investigate the effects of aerobic interval training and resistance training on anti-inflammatory adipokines, high sensitivity C-reactive protein, and clinical outcomes in sedentary men with metabolic syndrome.
Methods:
A total of 33 sedentary men with metabolic syndrome (age: 46.2 ± 4.6 years; body mass index: 35.4 ± 1.9 kg.m2) were randomly assigned to one of 3 groups: aerobic interval training (n = 12), resistance training (n = 10), or control (n = 11). Participants in the exercise groups completed a 12-week training program, 3 sessions per week, while those in the control group maintained their sedentary lifestyle. The levels of high sensitivity C-reactive protein (hs-CRP), omentin-1, adiponectin, lipid profiles, blood pressure, glucose metabolism, body composition, and peak oxygen uptake (VO2peak) were measured at baseline and after the intervention.
Results:
Both aerobic interval training and resistance training significantly improved the levels of omentin-1 and adiponectin, as well as reduced inflammation, as indicated by a decrease in hs-CRP levels. Exercise training also led to significant improvements in lipid profiles, blood pressure, glucose metabolism, and body composition. Specifically, the aerobic interval training group had significantly greater increases in high-density lipoprotein cholesterol and VO2peak, as well as greater reductions in low-density lipoprotein cholesterol, triglycerides, and total cholesterol compared to the resistance training group.
Conclusion:
Exercise training, particularly aerobic interval training and resistance training, can be an effective non-pharmacological intervention for managing inflammation and improving cardiovascular health in metabolic syndrome patients.
Hepatocellular carcinoma is one of the deadliest and fastest‐growing cancers. Among HCC etiologies, metabolic dysfunction‐associated fatty liver disease (MAFLD) has served as a major HCC driver due to its great potential for increasing cirrhosis. The obesogenic environment fosters a positive energy balance and results in a continuous rise of obesity and metabolic syndrome. However, it is difficult to understand how metabolic complications lead to the poor prognosis of liver diseases and which molecular mechanisms are underpinning MAFLD‐driven HCC development. Thus, suitable preclinical models that recapitulate human etiologies are essentially required. Numerous preclinical models have been created but not many mimicked anthropometric measures and the course of disease progression shown in the patients. Here we review the literature on adipose tissues, liver‐related HCC etiologies and recently discovered genetic mutation signatures found in MAFLD‐driven HCC patients. We also critically review current rodent models suggested for MAFLD‐driven HCC study.
Metabolic dysfunction of metabolic syndromes (MetS) has been widely reported to be a significant risk factor for heart failure (HF). While this interaction is well studied, what combinations of MetS factors pose the greatest risk for HF are not well defined. We hypothesize that some components of MetS are of higher risk of HF compared to others. We explored the relationship between the independent components of MetS and their combinatory effect on the risk of HF. All metabolic syndrome components except hypertriglyceridemia were significant individually (P-value<0.001), while hypertension (HTN) and diabetes or insulin resistance (IR) had the higher risk of developing heart failure when taken collectively. The odds of heart failure among the individuals who had HTN and IR was 7.7 times those who didn't have any MetS components. We observed the additive effect of number of metabolic components on HF, for the individuals who had only one MetS symptom, the odds of HF was 5.4 time compared to those who didn't have any of MetS symptoms. Similarly, these odds of HF were 6.4 and 7.4 times for those who had at least 2 or at least 3 symptoms respectively. Even though obesity is a significant risk factor for cardiovascular diseases, we found the protective effect of obesity on heart failure, which is an interesting result and needs further investigation.
Keywords: Retrospective case-control study, metabolic syndrome, heart failure, obesity, hypertension, insulin resistance, risk analysis
Information mining is a methodology of bringing huge models utilizing recorded information. It is normally utilized in different real applications to be express web records, double dealing distinctive confirmation talk attestation, human organizations, and so forth. Reenacted insight includes are utilized in information mining to imagine the future occasion subject to the models conveyed utilizing solid information. All the highlights got during information assortment may not be altogether important to the objective class of the model. Highlight choice is a system which picks the best subset of highlights in dataset to upgrade the demonstration of an information mining or AI estimation. As of now, observational assessment is driven on Naïve Bayesian classifier utilizing Pima Indian Type II Diabetes dataset with all the highlights what's more the subset of the highlights picked by predefined python libraries. The presentation of Naïve Bayesian classifier is assessed on all of things to come subset of the dataset to consider the effect of the high dimensionality on the presentation of Naïve Bayes Classifier.
Metabolic syndrome is a public health problem that has been rapidly increasing over the last century. Oxidative stress plays a major pathological role in the development of metabolic diseases such as obesity, hypertension and type 2 diabetes. Oxidative stress is an imbalance between reactive oxygen species (ROS), reactive nitrogen species (RNS), free radicals and antioxidant defences (superoxide nitric oxide, hydroxyl radical, glutathione peroxidase). Oxygen is essential for the living system. At the same time, oxygen may also be dangerous to the same biological system. ROS can injure cellular macromolecules leading to apoptosis and necrosis. ROS plays a vital role in physiological processes and a favourable role in the immune system. This review discusses the effects of oxidative stress and possible biomarkers that can be employed to determine the degree of development of metabolic diseases. The growth in the formation of oxidizing species in the metabolic syndrome has been considered as a main underlying mechanism for mitochondrial dysfunction, accumulation of protein and lipid oxidation merchandise, as well as an impairment of the antioxidant systems. These oxidative modifications are recognized as applicable oxidative stress biomarkers and are probably capable of clarifying the position of reactive oxygen and the examination of the severity of the condition aided by the nitrogen species involved in the metabolic syndrome's aetiology.
Context
Ectopic fat depots are related to the deregulation of energy homeostasis, leading to diseases related to obesity and metabolic syndrome (MS). Despite significant changes in body composition over women's lifespan, little is known about the role of breast adipose tissue (BrAT) and its possible utilization as an ectopic fat depot in women of different menopausal statuses.
Objective
We aimed to assess the relationship between BrAT and metabolic glycemic and lipid profiles and body composition parameters in adult women.
Methods
In this cross-sectional study, we enrolled adult women undergoing routine mammograms to perform history and physical examination, body composition assessment, semi-automated assessment of breast adiposity (BA) from mammograms and fasting blood collection for biochemical analysis. Correlations and multivariate regression analysis were used to examine the associations of the BA with metabolic and body composition parameters.
Results
Of the 101 participants included in the final analysis, 76.2% were in menopause, and 23.8% were in premenopause. The BA was positively related with fasting plasma glucose, glycated hemoglobin, homeostasis model assessment of insulin resistance, body mass index, waist circumference, body fat percentage, abdominal visceral and subcutaneous fat when adjusted for age among women in postmenopause. Also, the BA was an independent predictor of hyperglycemia and metabolic syndrome. These associations were not present among women in premenopause.
Conclusion
The BA was related to different adverse body composition and metabolic factors in women in postmenopause. The results suggest that there might be a relevant BrAT endocrine role during menopause, whose mechanisms are yet to be clarified, which thus opens up research perspectives on the subject as well as on clinical settings.
Adiponectin is a hormone, secreted from adipose tissue. It is inversely correlated with body fat mass. This hormone has also anti-inflammatory and ant-iatherogenic properties. This study was purposed to explore the relationship between serum adiponectin concentration and lipid profile. This cross-sectional analytical study was carried out in the Department of Biochemistry, Bangabandhu Sheikh Mujib Medical University (BSMMU) from March 2016 to February 2017. By non-probability sampling, a total of 156 study subjects were selected from apparently healthy adult individuals attending outpatient department of BSMMU. Serum adiponectin level positively correlated with serum HDL cholesterol (r=0.246, p value 0.002) concentrations and negatively correlated with serum total cholesterol (r=-0.171, p value 0.033) and serum triacylglycerol level (r=-0.3, p value 0.00). So, from this study it can be concluded that adiponectin has an important role in the metabolism of lipid profile components and responsible for controlling the concentration of serum lipid profile components. When adiponectin concentration of blood increases it is responsible for raised serum HDL-C concentration and decreased total cholesterol and triacylglycerol concentration. Bangladesh J Med Biochem 2019; 12(1): 6-10
Aim: The aim of this study is to evaluate the prevalence of Subclinical Hypothyroidism in the patientswith Metabolic syndrome.To find the correlation of Subclinical hypothyroidism with the variouscomponents of metabolic syndrome.Methodology: Cross sectional study- a single centre observational study over 100 patients and 50controls of the age group of 20 to 75 years.Results: Observations for metabolic syndrome patients (cases) versus Healthy controls.Observationsof thyroid function tests in Metabolic syndrome Vs Healthy controls.Observations for SubclinicalHypothyroidism in Metabolic syndrome Vs Healthy controls.Corelation of various components ofMetS with Subclinical Hypothyroidism.Conclusions: study clearly indicates and emphasizes a diehard need for investigating the presence ofthyroid dysfunction while managing patients with MetS.
Macrophages, a heterogeneous population of innate immune cells, exhibit remarkable plasticity and play pivotal roles in coordinating immune responses and maintaining tissue homeostasis within the context of metabolic diseases. The activation of inflammatory macrophages in obese adipose tissue leads to detrimental effects, inducing insulin resistance through increased inflammation, impaired thermogenesis, and adipose tissue fibrosis. Meanwhile, adipose tissue macrophages also play a beneficial role in maintaining adipose tissue homeostasis by regulating angiogenesis, facilitating the clearance of dead adipocytes, and promoting mitochondrial transfer. Exploring the heterogeneity of macrophages in obese adipose tissue is crucial for unraveling the pathogenesis of obesity and holds significant potential for targeted therapeutic interventions. Recently, the dual effects and some potential regulatory mechanisms of macrophages in adipose tissue have been elucidated using single-cell technology. In this review, we present a comprehensive overview of the intricate activation mechanisms and diverse functions of macrophages in adipose tissue during obesity, as well as explore the potential of drug delivery systems targeting macrophages, aiming to enhance the understanding of current regulatory mechanisms that may be potentially targeted for treating obesity or metabolic diseases.
Perfluorodecanoic acid (PFDA), an enduring and harmful organic pollutant, is widely employed in diverse food-related sectors. Our previous studies have provided evidence that PFDA has the potential to facilitate obesity and hepatic fat accumulation induced by high-fat diet (HFD) intake. Epigallocatechin-3-gallate (EGCG), a polyphenol found in green tea, has been suggested to possess potential preventive effects against metabolic abnormalities and fatty liver. The purpose of this research was to investigate the effects of EGCG on PFDA-exacerbated adiposity and hepatic lipid accumulation in HFD-fed mice. The results showed that EGCG reduced body weight gain; tissue and organ weights; blood glucose, serum insulin, HOMA-IR, leptin, and lipid parameters; serum inflammatory cytokines (IL−1β, IL−18, IL−6, and TNF−α); and hepatic lipid accumulation in PFDA-exposed mice fed an HFD. Further work showed that EGCG improved liver function and glucose homeostasis in mice fed an HFD and co-exposed to PFDA. The elevated hepatic mRNA levels of SREBP-1 and associated lipogenic genes, NLRP3, and caspase−1 in PFDA-exposed mice fed an HFD were significantly decreased by EGCG. Our work provides evidence for the potential anti-obesity effect of EGCG on co-exposure to HFD and PFDA and may call for further research on the bioactivity of EGCG to attenuate the endocrine disruption effects of long-term exposure to pollutants.
Purpose of Review
This article sumarizes pathopysiological consequencies between obesity and dyslipidemia and aims to bring some practical approach.
Recent Findings
Dyslipidemia is often present in individuals with obesity and simultaneusly, many obese individuals have lipid metabolism disorders. Especially the abdominal obesity increases the cardiometabolic risk because of the presence of atherogenic dyslipidemia while the total low density lipoprotein cholesterol (LDL-C) may be normal. LDL-C is the primary goal in dyslipidemia treatment. Apoliprotein B (Apo B) and non – high density lipoprotein cholesterol (non-HDL-C) should be estimated to precise the cardiovascular risk and represents the secondary goal in treatment. Weight loss either with diet or antiobestic medication induces the decrease in triglycerides (TG) and LDL-C and the increase in HDL-C. Composition of nutrients, esp. fatty acids, influences lipid levels. Bariatric surgery is efficient in weight loss and has a significant effect on serum lipids.
Summary
Dyslipidemia and obesity present common diseases that must be managed to decrease the cardiovascular risk and the risk of obesity-related complications.
Objective: Previous studies showed that the levels of micro elements may have a contribution to weight loss. Nevertheless, it is not possible to find many comprehensive studies analysing the potential relation between micro elements found in water used for drinking purposes and body composition. The present study aims to assess the relation between micro element levels of drinking water and body composition in normal, fat and obese subjects. Methods: The study consisted of 345 female participants, who were divided into 3 groups of 115, according to body mass index (BMI) for leanness, overweight, and obesity; and who applied to Diet Polyclinic of State Hospital. Water samples were analysed with mass spectrometry; and body composition measurements were conducted via bioelectrical impedance analysis. Results: The obesity percentage in females demonstrated statistically positive correlations with cobalt (Co) and selenium (Se) in water for drinking. Also, it was found that the BMI values of females significantly positively correlated with chromium (Cr). Conclusion: It may be suggested that women who consume drinking water containing high levels of Co, Se and Cr might be at a greater risk of developing obesity. On the other hand, the lack of knowledge about influence of levels of micro elements in drinking water on blood parameters associated with obesity or tissue remains unclear and deserves more investigation.
Obesity is a major global public health issue involving dyslipidemia, oxidative stress, inflammation, and increased risk of CVD. Weight loss reduces this risk, but the biochemical underpinnings are unclear. We explored how obesity and weight loss after bariatric surgery influence LDL interactions that trigger proatherogenic versus antiatherogenic processes. LDL was isolated from plasma of six patients with severe obesity before (basal) and 6–12 months after bariatric surgery (basal BMI = 42.7 kg/m²; 6-months and 12-months postoperative BMI = 34.1 and 30 kg/m²). Control LDL were from six healthy subjects (BMI = 22.6 kg/m²). LDL binding was quantified by ELISA; LDL size and charge were assessed by chromatography; LDL biochemical composition was determined. Compared to controls, basal LDL showed decreased nonatherogenic binding to LDL receptor, which improved postoperatively. Conversely, basal LDL showed increased binding to scavenger receptors LOX1 and CD36 and to glycosaminoglycans, fibronectin and collagen, which is proatherogenic. One year postoperatively, this binding decreased but remained elevated, consistent with elevated lipid peroxidation. Serum amyloid A and nonesterified fatty acids were elevated in basal and postoperative LDL, indicating obesity-associated inflammation. Aggregated and electronegative LDL remained elevated, suggesting proatherogenic processes. These results suggest that obesity-induced inflammation contributes to harmful LDL alterations that probably increase the risk of CVD. We conclude that in obesity, LDL interactions with cell receptors and extracellular matrix shift in a proatherogenic manner but are partially reversed upon postoperative weight loss. These results help explain why the risk of CVD increases in obesity but decreases upon weight loss.
Chronic low-grade inflammation has been recognized as an underlying event linking obesity to cardiovascular disease (CVD). However, inflammatory alterations in individuals who are overweight remain understudied. To provide insight, we determined the levels of key circulating biomarkers of endotoxemia and inflammation, including lipopolysaccharide-binding protein (LBP), CRP, IL-6, leptin, and adiponectin in adult female subjects (n = 20) who were lean or overweight and had high cholesterol and/or high blood pressure - two important conventional risk factors for CVD. Plasma levels of LBP (a recognized marker of metabolic endotoxemia in obesity) were significantly higher in the overweight group compared with the lean group (P = 0.005). The levels of CRP, a general marker of inflammation, were also significantly higher in overweight subjects (P = 0.01), as were IL-6 (P = 0.02) and leptin (P = 0.002), pro-inflammatory mediators associated with cardiovascular risk. Levels of adiponectin, an adipokine with anti-inflammatory and anti-atherogenic functions, were significantly lower in the overweight group (P = 0.002). The leptin/adiponectin ratio, a preferential atherogenic marker was significantly increased in women who are overweight (P = 0.02). LBP, CRP, leptin, and adiponectin levels significantly correlated with BMI, but not with age. These results reveal the presence of subclinical endotoxemia and a pro-inflammatory state in overweight women and are of interest for further studies with the goal for improved understanding of women’s cardiovascular health.
Background:
Previous studies have reported that oxidative stress contributes to obesity characterized by adipocyte hypertrophy. However, mechanism has not been studied extensively. In the current study, we evaluated role of extracellular vimentin secreted by oxidized low-density lipoprotein (oxLDL) in energy metabolism in adipocytes.
Methods:
We treated 3T3-L1-derived adipocytes with oxLDL and measured vimentin which was secreted in the media. We evaluated changes in uptake of glucose and free fatty acid, expression of molecules functioning in energy metabolism, synthesis of adenosine triphosphate (ATP) and lactate, markers for endoplasmic reticulum (ER) stress and autophagy in adipocytes treated with recombinant vimentin.
Results:
Adipocytes secreted vimentin in response to oxLDL. Microscopic evaluation revealed that vimentin treatment induced increase in adipocyte size and increase in sizes of intracellular lipid droplets with increased intracellular triglyceride. Adipocytes treated with vimentin showed increased uptake of glucose and free fatty acid with increased expression of plasma membrane glucose transporter type 1 (GLUT1), GLUT4, and CD36. Vimentin treatment increased transcription of GLUT1 and hypoxia-inducible factor 1α (Hif-1α) but decreased GLUT4 transcription. Adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), diacylglycerol O-acyltransferase 1 (DGAT1) and 2 were decreased by vimentin treatment. Markers for ER stress were increased and autophagy was impaired in vimentin-treated adipocytes. No change was observed in synthesis of ATP and lactate in the adipocytes treated with vimentin. Conclusion: We concluded that extracellular vimentin regulates expression of molecules in energy metabolism and promotes adipocyte hypertrophy. Our results show that vimentin functions in the interplay between oxidative stress and metabolism, suggesting a mechanism by which adipocyte hypertrophy is induced in oxidative stress.
Lipid-rich diet is the major cause of obesity, affecting 13% of the worldwide adult population. Obesity is a major risk factor for metabolic syndrome that includes hyperlipidemia and diabetes mellitus. The early phases of metabolic syndrome are often associated with hyperexcitability of peripheral small diameter sensory fibers and painful diabetic neuropathy. Here, we investigated the effect of high-fat diet-induced obesity on the activity of dorsal root ganglion (DRG) sensory neurons and pain perception. We deciphered the underlying cellular mechanisms involving the acid-sensing ion channel 3 (ASIC3). We show that mice made obese through consuming high-fat diet developed the metabolic syndrome and prediabetes that was associated with heat pain hypersensitivity, whereas mechanical sensitivity was not affected. Concurrently, the slow conducting C fibers in the skin of obese mice showed increased activity on heating, whereas their mechanosensitivity was not altered. Although ASIC3 knockout mice fed with high-fat diet became obese, and showed signs of metabolic syndrome and prediabetes, genetic deletion, and in vivo pharmacological inhibition of ASIC3, protected mice from obesity-induced thermal hypersensitivity. We then deciphered the mechanisms involved in the heat hypersensitivity of mice and found that serum from high-fat diet-fed mice was enriched in lysophosphatidylcholine (LPC16:0, LPC18:0, and LPC18:1). These enriched lipid species directly increased the activity of DRG neurons through activating the lipid sensitive ASIC3 channel. Our results identify ASIC3 channel in DRG neurons and circulating lipid species as a mechanism contributing to the hyperexcitability of nociceptive neurons that can cause pain associated with lipid-rich diet consumption and obesity.
Diabetes is a chronic condition that could lead to a global health care disaster. 382 million people worldwide have diabetes, according to the International Diabetes Federation. This will double to 592 million by 2035. Diabetes is a condition brought on by elevated blood glucose levels. The symptoms of this elevated blood sugar level include frequent urination, increased thirst, and increased hunger. One of the main causes of stroke, kidney failure, heart failure, amputations, blindness, and kidney failure is diabetes. Our bodies convert food into sugars, such as glucose, when we eat. Our pancreas is then expected to release insulin. Insulin acts as a key to unlock our cells, allowing glucose to enter and be used by us as fuel. However, this mechanism does not function in diabetes. The most prevalent forms of the disease are type 1 and type 2, but there are other varieties as well, including gestational diabetes, which develops during pregnancy. Data science has an emerging topic called machine learning that studies how machines learn from experience. The goal of this study is to create a system that, by fusing the findings of several machine learning approaches, can more accurately conduct early diabetes prediction for a patient. K closest neighbour, Logistic Regression, Random Forest, Support Vector Machine, and Decision Tree are some of the techniques employed. Each algorithm's accuracy is calculated along with the model's accuracy. The model for predicting diabetes is then chosen from those with good accuracy.
Background
In the United States, the relationship between visceral obesity and the risk of developing atherosclerosis cardiovascular disease (ASCVD) for the first time in 10 years is unclear.
Methods
Data for this cross-sectional study came from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020. We collected variable information related to 10-year ASCVD risk and visceral obesity reliable indicators [Visceral obesity index (VAI) and Lipid accumulation product (LAP)]. And we used multiple logistic regression to analyze the correlation of visceral obesity indicators (VAI and LAP) with 10-year ASCVD risk. In addition, we assessed the linear relationship between VAI or LAP and 10-year ASCVD risk by smoothing curve fitting. Finally, we conducted subgroup analysis and sensitivity analysis after excluding participants with extreme VAI and LAP values to ensure that we obtained accurate and reliable results.
Results
Our study included a total of 1,547 participants (mean age: 56.5 ± 10.1, 60% of males). The results of the multiple logistic regression showed that compared with participants with the lowest VAI in the 1st Quartile (≤0.79), the adjusted OR values for VAI and elevated 10-year ASCVD risk in Q3 (1.30–2.14), and Q4 (≥2.15) were 2.58 (95% CI: 1.24–5.36, P = 0.011), 15.14 (95% CI: 6.93–33.05, P < 0.001), respectively. Compared with participants with the lowest LAP in the 1st Quartile (≤28.29), the adjusted OR values for VAI and elevated 10-year ASCVD risk in Q3 (46.52–77.00), and Q4 (≥77.01) were 4.63 (95% CI: 2.18–9.82, P < 0.001), 16.94 (95% CI: 6.74–42.57, P < 0.001), respectively. Stratified analysis showed that the association between VAI or LAP and the first ASCVD event was more pronounced in males.
Conclusion
Higher VAI or LAP scores are significantly associated with elevated 10-year ASCVD risk in adults aged 40 to 79 in the USA, which suggested that monitoring visceral obesity is crucial to reduce the risk of a first ASCVD event.
Both type I and type II diabetes are powerful and independent risk factors for coronary artery disease (CAD), stroke, and peripheral arterial disease. Atherosclerosis accounts for virtually 80% of all deaths among diabetic patients. Prolonged exposure to hyperglycemia is now recognized a major factor in the pathogenesis of atherosclerosis in diabetes. Hyperglycemia induces a large number of alterations at the cellular level of vascular tissue that potentially accelerate the atherosclerotic process. Animal and human studies have elucidated three major mechanisms that encompass most of the pathological alterations observed in the diabetic vasculature: 1) Nonenzymatic glycosylation of proteins and lipids which can interfere with their normal function by disrupting molecular conformation, alter enzymatic activity, reduce degradative capacity, and interfere with receptor recognition. In addition, glycosylated proteins interact with a specific receptor present on all cells relevant to the atherosclerotic process, including monocyte-derived macrophages, endothelial cells, and smooth muscle cells. The interaction of glycosylated proteins with their receptor results in the induction of oxidative stress and proinflammatory responses 2) oxidative stress 3) protein kinase C (PKC) activation with subsequent alteration in growth factor expression. Importantly, these mechanisms may be interrelated. For example, hyperglycemia-induced oxidative stress promotes both the formation of advanced glycosylation end products and PKC activation.
Human adipose tissue expresses and releases the proinflammatory cytokine interleukin 6, potentially inducing low-grade systemic inflammation in persons with excess body fat.
To test whether overweight and obesity are associated with low-grade systemic inflammation as measured by serum C-reactive protein (CRP) level.
The Third National Health and Nutrition Examination Survey, representative of the US population from 1988 to 1994.
A total of 16616 men and nonpregnant women aged 17 years or older.
Elevated CRP level of 0.22 mg/dL or more and a more stringent clinically raised CRP level of more than 1.00 mg/dL.
Elevated CRP levels and clinically raised CRP levels were present in 27.6% and 6.7% of the population, respectively. Both overweight (body mass index [BMI], 25-29.9 kg/m2) and obese (BMI, > or =30 kg/m2) persons were more likely to have elevated CRP levels than their normal-weight counterparts (BMI, <25 kg/m2). After adjustment for potential confounders, including smoking and health status, the odds ratio (OR) for elevated CRP was 2.13 (95% confidence interval [CI], 1.56-2.91) for obese men and 6.21 (95% CI, 4.94-7.81) for obese women. In addition, BMI was associated with clinically raised CRP levels in women, with an OR of 4.76 (95% CI, 3.42-6.61) for obese women. Waist-to-hip ratio was positively associated with both elevated and clinically raised CRP levels, independent of BMI. Restricting the analyses to young adults (aged 17-39 years) and excluding smokers, persons with inflammatory disease, cardiovascular disease, or diabetes mellitus and estrogen users did not change the main findings.
Higher BMI is associated with higher CRP concentrations, even among young adults aged 17 to 39 years. These findings suggest a state of low-grade systemic inflammation in overweight and obese persons.
Low plasma concentrations of high density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apoA-I) are major risk factors for coronary heart disease (CHD). Low HDL levels are common in patients with hypertriglyceridemia, but they also occur in those with normal plasma lipids; the latter include obese patients and cigarette smokers, though other patients with low HDL levels are neither obese nor smokers. The present study was designed to define metabolic causes of low apoA-I levels in normal-weight, normolipidemic patients. ApoA-I tracer studies were carried out in two groups of normolipidemic patients having low HDL levels to determine input rates and residence times for ApoA-I; these patients included 11 nonobese nonsmokers and 11 nonobese cigarette smokers. Their results were compared to those of 20 normal-weight, normolipidemic controls with normal HDL levels and 12 obese nonsmokers also having low HDL. In all three groups manifesting low HDL-cholesterol and low apoA-I levels, residence times for plasma apoA-I were reduced by approximately 30%, compared to control subjects with normal HDL levels. In contrast, average input rates for apoA-I were similar among the three low-HDL patients and control subjects. No differences in apoA-I kinetics were observed among any of the three groups with low apoA-I concentrations. Within each of the four groups of the study, however, input rates for apoA-I were highly correlated with plasma concentrations of apoA-I. Thus, for individuals with normal levels of plasma lipids, both residence times and input rates for apoA-I appeared to be important determinants of apoA-I levels. Residence times for apoA-I were reduced in almost all patients with low apoA-I levels, regardless of concomitant factors, whereas input rates were highly variable among individuals.
The relative impacts of regional and generalized adiposity on insulin sensitivity have not been fully defined. Therefore, we investigated the relationship of insulin sensitivity (measured using hyperinsulinemic, euglycemic clamp technique with [3-3H]glucose turnover) to total body adiposity (determined by hydrodensitometry) and regional adiposity. The latter was assessed by determining subcutaneous abdominal, intraperitoneal, and retroperitoneal fat masses (using magnetic resonance imaging) and the sum of truncal and peripheral skinfold thicknesses. 39 healthy middle-aged men with a wide range of adiposity were studied. Overall, the intraperitoneal and retroperitoneal fat constituted only 11 and 7% of the total body fat. Glucose disposal rate (Rd) and residual hepatic glucose output (rHGO) values during the 40 mU/m2.min insulin infusion correlated significantly with total body fat (r = -0.61 and 0.50, respectively), subcutaneous abdominal fat (r = -0.62 and 0.50, respectively), sum of truncal skinfold thickness (r = -0.72 and 0.57, respectively), and intraperitoneal fat (r = -0.51 and 0.44, respectively) but not to retroperitoneal fat. After adjusting for total body fat, the Rd and rHGO values showed the highest correlation with the sum of truncal skinfold thickness (partial r = -0.40 and 0.33, respectively). We conclude that subcutaneous truncal fat plays a major role in obesity-related insulin resistance in men, whereas intraperitoneal fat and retroperitoneal fat have a lesser role.
Malonyl-CoA is an allosteric inhibitor of carnitine palmitoyltransferase (CPT) I, the enzyme that controls the transfer of long-chain fatty acyl (LCFA)-CoAs into the mitochondria where they are oxidized. In rat skeletal muscle, the formation of malonyl-CoA is regulated acutely (in minutes) by changes in the activity of the beta-isoform of acetyl-CoA carboxylase (ACCbeta). This can occur by at least two mechanisms: one involving cytosolic citrate, an allosteric activator of ACCbeta and a precursor of its substrate cytosolic acetyl-CoA, and the other involving changes in ACCbeta phosphorylation. Increases in cytosolic citrate leading to an increase in the concentration of malonyl-CoA occur when muscle is presented with insulin and glucose, or when it is made inactive by denervation, in keeping with a diminished need for fatty acid oxidation in these situations. Conversely, during exercise, when the need of the muscle cell for fatty acid oxidation is increased, decreases in the ATP/AMP and/or creatine phosphate-to-creatine ratios activate an isoform of an AMP-activated protein kinase (AMPK), which phosphorylates ACCbeta and inhibits both its basal activity and activation by citrate. The central role of cytosolic citrate links this malonyl-CoA regulatory mechanism to the glucose-fatty acid cycle concept of Randle et al. (P. J. Randle, P. B. Garland. C. N. Hales, and E. A. Newsholme. Lancet 1: 785-789, 1963) and to a mechanism by which glucose might autoregulate its own use. A similar citrate-mediated malonyl-CoA regulatory mechanism appears to exist in other tissues, including the pancreatic beta-cell, the heart, and probably the central nervous system. It is our hypothesis that by altering the cytosolic concentrations of LCFA-CoA and diacylglycerol, and secondarily the activity of one or more protein kinase C isoforms, changes in malonyl-CoA provide a link between fuel metabolism and signal transduction in these cells. It is also our hypothesis that dysregulation of the malonyl-CoA regulatory mechanism, if it leads to sustained increases in the concentrations of malonyl-CoA and cytosolic LCFA-CoA, could play a key role in the pathogenesis of insulin resistance in muscle. That it may contribute to abnormalities associated with the insulin resistance syndrome in other tissues and the development of obesity has also been suggested. Studies are clearly needed to test these hypotheses and to explore the notion that exercise and some pharmacological agents that increase insulin sensitivity act via effects on malonyl-CoA and/or cytosolic LCFA-CoA.
Overweight and obesity are increasing dramatically in the United States and most likely contribute substantially to the burden of chronic health conditions.
To describe the relationship between weight status and prevalence of health conditions by severity of overweight and obesity in the US population.
Nationally representative cross-sectional survey using data from the Third National Health and Nutrition Examination Survey (NHANES III), which was conducted in 2 phases from 1988 to 1994.
A total of 16884 adults, 25 years and older, classified as overweight and obese (body mass index [BMI] > or =25 kg/m2) based on National Institutes of Health recommended guidelines.
Prevalence of type 2 diabetes mellitus, gallbladder disease, coronary heart disease, high blood cholesterol level, high blood pressure, or osteoarthritis.
Sixty-three percent of men and 55% of women had a body mass index of 25 kg/m2 or greater. A graded increase in the prevalence ratio (PR) was observed with increasing severity of overweight and obesity for all of the health outcomes except for coronary heart disease in men and high blood cholesterol level in both men and women. With normal-weight individuals as the reference, for individuals with BMIs of at least 40 kg/m2 and who were younger than 55 years, PRs were highest for type 2 diabetes for men (PR, 18.1; 95% confidence interval [CI], 6.7-46.8) and women (PR, 12.9; 95% CI, 5.7-28.1) and gallbladder disease for men (PR, 21.1; 95% CI, 4.1-84.2) and women (PR, 5.2; 95% CI, 2.9-8.9). Prevalence ratios generally were greater in younger than in older adults. The prevalence of having 2 or more health conditions increased with weight status category across all racial and ethnic subgroups.
Based on these results, more than half of all US adults are considered overweight or obese. The prevalence of obesity-related comorbidities emphasizes the need for concerted efforts to prevent and treat obesity rather than just its associated comorbidities.
Obesity is associated with profound alterations of the cardiovascular system including an increase in systemic blood pressure. Several vasoactive factors, including non-esterified fatty acids, angiotensin II, prostaglandins, and nitric oxide are known to be produced by adipose tissue, and are therefore of particular interest regarding their potential role for the regulation of vascular tone and structure. In addition, central nervous system actions of the adipose tissue-derived hormone leptin may contribute to increased sympathetic nervous system activity that is typically found in obesity. Enhanced leptin-driven renal sympathetic out-flow, in combination with low atrial natriuretic peptide plasma levels possibly due to over-expression of the natriuretic peptide clearance receptor in adipocytes, may enhance sodium retention and volume expansion, both key features in the pathophysiology of obesity-associated hypertension. In this review, we discuss these and other possible contributions of adipose tissue to the regulation of cardiovascular-renal function and speculate on the role of adipose tissue for the development of obesity-associated hypertension.
Epidemiologic studies provide increasing evidence that hypertriglyceridemia is a risk factor for cardiovascular disease. A meta-analysis of 17 population-based studies of triglyceride levels and cardiovascular disease identified a 76% increase in cardiovascular disease risk in women and a 31% increase in men associated with a 1 mmol/L increase in triglyceride levels. Additional epidemiologic studies have shown that plasma triglyceride levels and low-density lipoprotein particle sire predict subsequent coronary artery disease. Taken together, the existing epidemiologic data may help identify a group of patients who may benefit from interventions aimed at decreasing triglyceride levels associated with an increased risk of cardiovascular disease. (C) 1999 by Excerpta Medica, Inc.
Low levels of high-density lipoprotein cholesterol (HDLC), and elevated total cholesterol-to-HDL-C ratios are independently associated with increased risk of coronary artery disease. In observational studies, every 1-mg/dL increment in HDL-C is associated with a 2% decreased risk of coronary artery disease in men and 3% decreased risk in women. On average, HDL-C levels are lower in men than in women, and are lower in whites than in blacks. Low HDL-C has also been found to be linked to higher risk of ischemic stroke, degree of carotid atherosclerosis, increased atherosclerotic progression as measured by coronary arteriography, higher coronary mortality among people with cardiovascular disease, and the development of coronary artery disease among patients with diabetes mellitus. (C) 2000 by Excerpta Medica, Inc.
Background— Nuclear magnetic resonance (NMR) offers an alternative, spectroscopic means of quantifying LDL and of measuring LDL particle size.
Methods and Results— We conducted a prospective nested case-control study among healthy middle-aged women to assess LDL particle size (NMR) and concentration (NMR) as risk factors for future myocardial infarction, stroke, or death of coronary heart disease. Median baseline levels of LDL particle concentration (NMR) were higher (1597 vs 1404 nmol/L; P = 0.0001) and LDL particle size (NMR) was lower (21.5 vs 21.8 nm; P =0.046) among women who subsequently had cardiovascular events (n=130) than among those who did not (n= 130). Of these 2 factors, LDL particle concentration (NMR) was the stronger predictor (relative risk for the highest compared with the lowest quartile=4.17, 95% CI 1.96–8.87). This compared with a relative risk of 3.11 (95% CI 1.55–6.26) for the ratio of total cholesterol to HDL cholesterol and a relative risk of 5.91 (95% CI 2.65–13.15) for C-reactive protein. The areas under the receiver operating characteristic curves for LDL particle concentration (NMR), total cholesterol to HDL cholesterol ratio, and C-reactive protein were 0.64, 0.64, and 0.66, respectively. LDL particle concentration (NMR) correlated with several traditionally assessed lipid and nonlipid risk factors, and thus adjustment for these tended to attenuate the magnitude of association between LDL particle concentration (NMR) and risk.
Conclusions— In this cohort, LDL particle concentration measured by NMR spectroscopy was a predictor of future cardiovascular risk. However, the magnitude of predictive value of LDL particle concentration (NMR) was not substantively different from that of the total cholesterol to HDL cholesterol ratio and was less than that of C-reactive protein.
Received May 20, 2002; revision received July 18, 2002; accepted July 19, 2002.
background Cardiovascular disease causes severe morbidity and mortality in type 1 diabetes, al- though the specific risk factors and whether chronic hyperglycemia has a role are un- known. We examined the progression of carotid intima-media thickness, a measure of atherosclerosis, in a population with type 1 diabetes. methods As part of the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the long-term follow-up of the Diabetes Control and Complications Trial (DCCT), 1229 patients with type 1 diabetes underwent B-mode ultrasonography of the internal and common carotid arteries in 1994-1996 and again in 1998-2000. We assessed the inti- ma-media thickness in 611 subjects who had been randomly assigned to receive con- ventional diabetes treatment during the DCCT and in 618 who had been assigned to re- ceive intensive diabetes treatment. results At year 1 of the EDIC study, the carotid intima-media thickness was similar to that in an age- and sex-matched nondiabetic population. After six years, the intima-media thick- ness was significantly greater in the diabetic patients than in the controls. The mean progression of the intima-media thickness was significantly less in the group that had received intensive therapy during the DCCT than in the group that had received con- ventional therapy (progression of the intima-media thickness of the common carotid artery, 0.032 vs. 0.046 mm; P = 0.01; and progression of the combined intima-media thickness of the common and internal carotid arteries, ¡0.155 vs. 0.007; P=0.02) after adjustment for other risk factors. Progression of carotid intima-media thickness was associated with age, and the EDIC base-line systolic blood pressure, smoking, the ratio of low-density lipoprotein to high-density lipoprotein cholesterol, and urinary albumin excretion rate and with the mean glycosylated hemoglobin value during the mean du- ration (6.5 years) of the DCCT. conclusions Intensive therapy during the DCCT resulted in decreased progression of intima-media thickness six years after the end of the trial. abstract
To estimate the prevalence of and the cardiovascular risk associated with the metabolic syndrome using the new definition proposed by the World Health Organization
A total of 4,483 subjects aged 35-70 years participating in a large family study of type 2 diabetes in Finland and Sweden (the Botnia study) were included in the analysis of cardiovascular risk associated with the metabolic syndrome. In subjects who had type 2 diabetes (n = 1,697), impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) (n = 798) or insulin-resistance with normal glucose tolerance (NGT) (n = 1,988), the metabolic syndrome was defined as presence of at least two of the following risk factors: obesity, hypertension, dyslipidemia, or microalbuminuria. Cardiovascular mortality was assessed in 3,606 subjects with a median follow-up of 6.9 years.
In women and men, respectively, the metabolic syndrome was seen in 10 and 15% of subjects with NGT, 42 and 64% of those with IFG/IGT, and 78 and 84% of those with type 2 diabetes. The risk for coronary heart disease and stroke was increased threefold in subjects with the syndrome (P < 0.001). Cardiovascular mortality was markedly increased in subjects with the metabolic syndrome (12.0 vs. 2.2%, P < 0.001). Of the individual components of the metabolic syndrome, microalbuminuria conferred the strongest risk of cardiovascular death (RR 2.80; P = 0.002).
The WHO definition of the metabolic syndrome identifies subjects with increased cardiovascular morbidity and mortality and offers a tool for comparison of results from diferent studies.
LR: 20061115; JID: 7501160; 0 (Antilipemic Agents); 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 57-88-5 (Cholesterol); CIN: JAMA. 2001 Nov 21;286(19):2401; author reply 2401-2. PMID: 11712930; CIN: JAMA. 2001 Nov 21;286(19):2400-1; author reply 2401-2. PMID: 11712929; CIN: JAMA. 2001 Nov 21;286(19):2400; author reply 2401-2. PMID: 11712928; CIN: JAMA. 2001 Nov 21;286(19):2400; author reply 2401-2. PMID: 11712927; CIN: JAMA. 2001 May 16;285(19):2508-9. PMID: 11368705; CIN: JAMA. 2003 Apr 16;289(15):1928; author reply 1929. PMID: 12697793; CIN: JAMA. 2001 Aug 1;286(5):533-5. PMID: 11476650; CIN: JAMA. 2001 Nov 21;286(19):2401-2. PMID: 11712931; ppublish
Writing Group I of Prevention Conference V reviewed the role of medical office assessment in the detection of risk factors and estimation of total cardiovascular risk. The primary focus was on identification of known risk factors for coronary heart disease (CHD). In the following discussion, the major risk factors and risk markers for CHD that can be detected in medical office assessment are reviewed. The different categories of risk are then considered. Finally, the special characteristics of each risk factor in relation to global risk assessment are reviewed. Special groups, including older patients and those with diabetes, are considered, and suggestions are made for modifying the existing guidelines for risk assessment.
There is increasing evidence that alterations in metabolism of triglyceride-rich lipoproteins are of importance in the pathogenesis of atherosclerosis and its clinical consequences. Particles with the characteristics of triglyceride-rich lipoprotein remnants have been related to the extent and severity of atherosclerosis in humans and in animal models. These particles can be identified using ultracentrifugal procedures as small, very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) with Svedberg flotation rates (Sf) of 12-60. Postprandial triglyceride levels also have been related to risk of coronary artery disease, consistent with a pathologic role for remnant lipoproteins. In studies in which measurements of lipoprotein subfractions have been carried out, levels of IDL have been more predictive than low-density lipoprotein (LDL) of atherosclerosis progression as assessed by coronary artery angiography or carotid artery ultrasonography. These findings suggest that a considerable portion of the coronary disease risk attributed to LDL may be accounted for by the IDL particles included in standard LDL measurements. Other metabolic changes associated with increased levels of plasma triglyceride may also adversely affect cardiovascular disease risk. These include reductions in HDL-cholesterol and apoprotein A1, increased levels of small dense LDL particles, redistribution of apoC-III from HDL to apoB-containing lipoproteins, diminished insulin sensitivity, and procoagulant changes, including increased levels of the fibrinolysis inhibitor, plasminogen-activator inhibitor-1 (PAI-1). A predominance of small dense LDL (subclass pattern B) is a discrete marker for this cluster of interrelated abnormalities and is found in 40-50% of patients with coronary artery disease. Therapeutic interventions with favorable effects on components of this dysmetabolic profile appear to be of value in decreasing atherosclerosis risk in a substantial proportion of the population.
The hypothesis that obesity-related hypertension is relatively innocuous was explored by an examination of cardiovascular events over 34 years of follow-up when related to biennially measured weights and blood pressures using time-dependent covariate proportional hazards analysis. The 5209 participants were also classified by age, cigarette smoking, and antihypertensive treatment at each of four baseline examinations with 8-year follow-up periods. Over the period of follow-up, there were 978 cardiovascular events in men and 836 in women. Risk of cardiovascular morbidity and mortality in general and of CHD in particular was as strongly related to hypertension at all levels of body mass index. This was also found to apply when adjustment was made for possible confounding by cigarette smoking. Age and smoking-adjusted absolute risks of cardiovascular events were found to be higher in hypertensive individuals with high than with low BMIs. Furthermore, the relative risk of cardiovascular disease did not vary significantly with BMI. Thus hypertension is at least as dangerous in obese as in lean persons at all ages in either sex, providing no support for the hypothesis that hypertension in the obese is more benign. This is important, since obesity predisposes to hypertension and most who have hypertension are obese. This report examines the hypothesis for CVD outcomes considered by previous reports and also the subcategories of CVD disease such as myocardial infarction and stroke, and includes data on both men and women and on young and old.
To determine the effect of obesity on prognosis in hypertensive subjects, a population of 1727 men 50 to 79 years of age was dichotomized by baseline body mass index (less than 27 and greater than or equal to 27 kg/m2) and systolic blood pressure (less than 160 and greater than or equal to 160 mm Hg). After 9 years of follow-up, age-adjusted all-cause, cardiovascular, and ischemic heart disease mortality rates were highest in the nonobese hypertensive subjects. The relative risk for mortality associated with a systolic blood pressure of 160 mm Hg or higher was significantly increased only in the nonobese group, with the largest difference in relative risk between obese and nonobese for ischemic heart disease. Results were consistent after separately excluding those with a history of heart disease, diabetes, current use of antihypertensive medication, and cigarette smoking, and those who died within 2 years of the baseline examination. When the independent effect of risk factors, including age, plasma cholesterol level, cigarette smoking, use of antihypertensive medication, and personal history of heart disease or diabetes was assessed with the Cox model, systolic blood pressure was a significant independent predictor of all-cause, cardiovascular, and ischemic heart disease death only in the nonobese subjects. We do not exclude an adverse effect of raised blood pressure in the obese. However, these data suggest that the prognosis is poorer in leaner hypertensive patients than in those who are overweight.
Lipoprotein classes isolated from the plasma of two patients with apolipoprotein AI (apo AI) and apolipoprotein CIII (apo CIII) deficiency were characterized and compared with those of healthy, age- and sex-matched controls. The plasma triglyceride values for patients 1 and 2 were 31 and 51 mg/dl, respectively, and their cholesterol values were 130 and 122 mg/dl, respectively; the patients, however, had no measurable high density lipoprotein (HDL)-cholesterol. Analytic ultracentrifugation showed that patients' S degrees f 0-20 lipoproteins possess a single peak with S degrees f rates of 7.4 and 7.6 for patients 1 and 2, respectively, which is similar to that of the controls. The concentration of low density lipoprotein (LDL) (S degrees f 0-12) particles, although within normal range (331 and 343 mg/dl for patients 1 and 2, respectively), was 35% greater than that of controls. Intermediate density lipoproteins (IDL) and very low density lipoproteins (VLDL) (S degrees f 20-400) were extremely low in the patients. HDL in the patients had a calculated mass of 15.4 and 11.8 mg/dl for patients 1 and 2, respectively. No HDL could be detected by analytic ultracentrifugation, but polyacrylamide gradient gel electrophoresis (gge) revealed that patients possessed two major HDL subclasses: (HDL2b)gge at 11.0 nm and (HDL3b)gge at 7.8 nm. The major peak in the controls, (HDL3a)gge, was lacking in the patients. Gradient gel analysis of LDL indicated that patients' LDL possessed two peaks: a major one at 27 nm and a minor one at 26 nm. The electron microscopic structure of patients' lipoprotein fractions was indistinguishable from controls. Patients' HDL were spherical and contained a cholesteryl ester core, which suggests that lecithin/cholesterol acyltransferase was functional in the absence of apo AI. The effects of postprandial lipemia (100-g fat meal) were studied in patient 1. The major changes were the appearance of a 33-nm particle in the LDL density region of 1.036-1.041 g/ml and the presence of discoidal particles (12% of total particles) in the HDL region. The latter suggests that transformation of discs to spheres may be delayed in the patient. The simultaneous deficiency of apo AI and apo CIII suggests a dual defect in lipoprotein metabolism: one in triglyceride-rich lipoproteins and the other in HDL. The absence of apo CIII may result in accelerated catabolism of triglyceride-rich particles and an increased rate of LDL formation. Additionally, absence of apo CIII would favor rapid uptake of apo E-containing remnants by liver and peripheral cells. Excess cellular cholesterol would not be removed by the reverse cholesterol transport mechanism since HDL levels are exceedingly low and thus premature atherosclerosis occurs.
A common, genetically influenced lipoprotein subclass profile characterized by a predominance of small, dense low density lipoprotein (LDL) particles is associated with relative increases in plasma triglyceride and apolipoprotein (apo) B-100, and reduced levels of high density lipoprotein cholesterol and apoAI. Recently, this phenotype has also been associated with the insulin resistance syndrome and familial combined hyperlipidemia. Case-control studies of patients with myocardial infarction and angiographically documented coronary artery disease (CAD) have demonstrated that 40-50% of patients have the small, dense LDL phenotype and that this is associated with a 2- to 3-fold increase in disease risk. However, because of strong statistical correlations among the multiple features of the phenotype, it has been difficult to determine whether > or = 1 of its metabolic alterations are primarily responsible for increased CAD susceptibility. More direct evidence for enhanced atherogenicity of lipoproteins in this trait derives from a recent report that LDL-cholesterol lowering by diet and drug treatment resulted in reduced coronary angiographic progression in CAD subjects with predominantly dense LDL, but that an equivalent lowering of LDL cholesterol in subjects with more buoyant LDL was not associated with angiographic benefit. Further, in vitro findings have indicated increased susceptibility of small, dense LDL to oxidative modification and relatively greater binding of these particles to arterial wall proteoglycans. Thus, the small, dense LDL trait may underlie familial predisposition to CAD in a large proportion of the population, and its presence may indicate the potential for benefit from specific therapeutic interventions.
A cohort of 2181 men and women, aged 40 to 79 years, without evidence of coronary heart disease or cancer at entry to the Tecumseh Study was evaluated.
Subjects were defined as lean if their Metropolitan Life Insurance table relative weight was < 110 (n = 584) and as obese if their relative weight was > or = 120 (n = 1024). There were 688 subjects with hypertension at study entry (systolic blood pressure > or = 160, diastolic blood pressure > or = 95, or treated). The 29-year relative risk (RR) of mortality from ischemic heart disease (IHD) or cardiovascular disease (CVD) associated with systolic blood pressure level was significant for both lean and obese subjects. Among hypertensive subjects, the RR of fatal IHD for lean versus obese hypertensive subjects was 1.87 (95% confidence interval, 1.21 to 2.88) and the RR of fatal CVD was 1.56 (95% confidence interval, 1.10 to 2.20) using a Cox proportional-hazards model to adjust for the independent effects of age and traditional CVD risk factors. The findings are consistent with other studies in men showing lean hypertensive subjects to be at greater risk of IHD or CVD mortality than obese hypertensive subjects. A similar finding is now observed in women.
Associations do not prove causality or dictate management. Nevertheless, the unexplained higher mortality in lean versus obese hypertensive subjects has now been reported with sufficient frequency to suggest that the association is real (if unexplained). Determining the reasons for this association may improve targeted prevention and treatment strategies.
The incidence of coronary heart disease (CHD) was assessed via the Prospective Cardiovascular Münster (PROCAM) study in 19,698 volunteer subjects aged between 16 and 65 years. An adequate incidence of atherosclerotic CHD was only found in male subjects greater than 40 years of age. The analysis and subsequent 6 year follow-up period was, therefore, confined to 4559 male participants aged 40-64 years. In the follow-up period, 186 study participants developed atherosclerotic CHD (134 definite non-fatal myocardial infarctions (MIs) and 52 definite atherosclerotic CHD deaths including 21 sudden cardiac deaths and 31 fatal MIs). Univariate analysis revealed a significant association between the incidence of atherosclerotic CHD and high-density lipoprotein cholesterol (P < 0.001), which remained after adjustment for other risk factors.
Cardiovascular disease is increased 2- to 4-fold in non-insulin-dependent diabetes mellitus (NIDDM); yet in most studies, there is a relatively weak relationship between the frequency of coronary heart disease (CHD) and the duration of diabetes and severity of hyperglycaemia. A number of authors have suggested that the prediabetic stage may contribute to the risk of CHD in NIDDM. Hyperinsulinaemia and insulin resistance have been strongly associated with the development of NIDDM. Data are less conclusive about the relationship of hyperinsulinaemia to the development of CHD in nondiabetic subjects. Relatively little data are available on hyperinsulinaemia and/or insulin resistance to CHD in NIDDM subjects. Tight control of glycaemia with exogenous insulin improves cardiovascular risk factors in NIDDM subjects and therefore is unlikely to increase the risk of CHD. Although the relation of insulin to CHD in the general population is somewhat controversial, insulin is clearly related to multiple cardiovascular risk factors (especially elevated triglyceride, decreased high-density lipoprotein, small dense low-density lipoprotein, impaired glucose tolerance and increased plasminogen activator inhibitor 1 (PAI-1)). However, the relation of insulin resistance to hypertension remains controversial.
Abdominal obesity, particularly excess intraperitoneal fat, is considered to play a major role in causing insulin resistance and NIDDM. To determine if NIDDM patients accumulate excess intraperitoneal fat, and whether this contributes significantly to their insulin resistance, 31 men with mild NIDDM with a wide range of adiposity were compared with 39 nondiabetic, control subjects for insulin sensitivity (measured using euglycemic-hyperinsulinemic clamp technique with [3-3H]glucose turnover) and total and regional adiposity (assessed by hydrodensitometry and by measuring subcutaneous abdominal, intraperitoneal, and retroperitoneal fat masses using magnetic resonance imaging [MRI], and truncal and peripheral skinfold thicknesses using calipers). MRI analysis revealed that intraperitoneal fat was not increased in NIDDM patients compared with control subjects; in both groups it averaged 11% of total body fat. NIDDM patients, however, had increased truncal-to-peripheral skinfolds thickness ratios. In NIDDM patients, as in control subjects, amounts of truncal subcutaneous fat showed a stronger correlation with glucose disposal rate than intraperitoneal or retroperitoneal fat; however, NIDDM patients were more insulin resistant at every level of total or regional adiposity. Further, no particular influence of excess intraperitoneal fat on hepatic insulin sensitivity was noted. We conclude that NIDDM patients do not have excess intraperitoneal fat, but that their fat distribution favors more truncal and less peripheral subcutaneous fat. Moreover, for each level of total and regional adiposity, NIDDM patients have a heightened state of insulin resistance.
Hypertriglyceridemic patients commonly have low levels of HDL cholesterol. Elevated triglycerides per se may be one cause of low HDL levels, but other factors also may be involved. The current study was designed to define the role of cholesterol-ester transfer protein (CETP) in causation of a low HDL cholesterol in hypertriglyceridemic patients; in addition other factors-lecithin cholesterol acyl transferase (LCAT), hepatic triglyceride lipase (HTGL), and lipoprotein lipase (LPL)-were examined. Plasma activities of CETP and LCAT were measured in 137 male patients with moderate hypertriglyceridemia (plasma triglycerides [TGs] 200 to 500 mg/dL and LDL cholesterol < 160 mg/dL). Results were compared with those from 50 normolipidemic men of similar age and body habitus. In addition, lipase activities in postheparin plasma were measured in 118 of the subjects with hypertriglyceridemia. The activities of CETP and LCAT were 17% (P < .01) and 7% (P < .05), respectively, higher in the hypertriglyceridemic group than in control subjects. By stepwise regression analysis CETP appeared to contribute 15.2% and LCAT 9.8% to variation in HDL-cholesterol levels. Activities of LPL and HTGL together contributed an additional 14.1% to HDL-cholesterol variation. In contrast, levels of plasma TG accounted for only 5.4% of the variation. There were no differences in relative contributions of these parameters in patients with and those without coronary heart disease. This study indicates that several factors contribute to the variation in HDL-cholesterol levels in hypertriglyceridemic patients, and five factors-CETP, LCAT, HTGL, LPL, and triglyceride levels-account for almost half of this variation.
Plasminogen activator inhibitor type 1 (PAI-1) contributes to the pathogenesis of atherothrombosis. Its plasma level is strongly correlated with parameters that define the insulin resistance syndrome, in particular with BMI and visceral accumulation of body fat, suggesting that PAI-1 may be an adipose tissue-derived circulating peptide. The present study was designed to investigate PAI-1 expression by human adipose tissue and its different cellular fractions. Special interest has been paid to the amount of PAI-1 antigen produced by omental versus subcutaneous fat. PAI-1 protein detected by immunolocalization was present at the stromal and adipocyte levels. PAI-1 mRNA was detected in stromal vascular cells freshly isolated and under culture conditions. It was also detected in whole adipose tissue and adipocyte fraction under culture conditions. The mRNA signal from the adipocyte fraction was detected as early as 2 h of incubation. The increase in PAI-1 mRNA was followed by an increase in PAI-1 antigen in the conditioned medium that was suppressed by treatment with cycloheximide. Transforming growth factor-beta1 significantly increased PAI-1 antigen production by the adipocyte fraction, whereas tumor necrosis factor-alpha did not have any effect. Interestingly, after 5 h of incubation, omental tissue explants produced significantly more PAI-1 antigen than did subcutaneous tissue from the same individual, whereas similar production of leptin by the two territories was observed. These results strongly suggest that human adipose tissue, in particular visceral tissue, can be an important contributor to the elevated plasma PAI-1 levels observed in central obesity.
The Münster Heart Study (PROCAM) was initiated in 1979 in order to examine cardiovascular risk factors, cardiovascular events including myocardial infarction and stroke, and mortality in people at work. Examination at entry comprised a standardized case history, measurement of blood pressure and anthropometric data, a resting electrocardiogram, and measurement of more than 20 laboratory parameters in a fasting blood sample. The prevalence data in this report are based upon a single examination of 17,437 men aged 40.4 +/- 11.3 years (mean +/- SD) and 8065 women aged 35.7 +/- 12.1 years, which took place between 1979 and 1991. Severe hypercholesterolaemia (> 300 mg.dl-1) was seen in 5% of men and 8% of women aged 45 to 64 years. In men, the prevalence of hypertriglyceridaemia (> 200 mg.dl-1) rose from 5% at age 20 to 20% at age 45 and remained constant thereafter; in women the prevalence of hypertriglyceridaemia increased linearly from 2% at age 20 to 7% at age 60. The LDL/HDL ratio was higher in men than in women at all age groups; in the age group 45 to 64 years, LDL/HDL ratios > 5 were approximately twice as common in men. Lipoprotein(a) levels were distributed in a highly skewed fashion. In men, a slight rise in the geometric mean lipoprotein(a) concentration occurred with age, whereas in women a dramatic increase was seen after age 40. Using multivariate analysis by the multiple logistic function method, total cholesterol, HDL cholesterol, LDL cholesterol and log-transformed triglycerides showed a significant (P < 0.001) age-adjusted correlation with the presence of major coronary events. A risk algorithm has been developed for men aged 40 to 65 years which takes into account the independent risk factors of HDL cholesterol, LDL cholesterol, triglycerides, fibrinogen, age, systolic blood pressure, cigarette smoking, presence of diabetes mellitus and family history of myocardial infarction and angina pectoris. This algorithm can be used in clinical practice to calculate the 8-year risk of an individual suffering a myocardial infarction.
The objective of this study was to examine the association of Joint National Committee (JNC-V) blood pressure and National Cholesterol Education Program (NCEP) cholesterol categories with coronary heart disease (CHD) risk, to incorporate them into coronary prediction algorithms, and to compare the discrimination properties of this approach with other noncategorical prediction functions.
This work was designed as a prospective, single-center study in the setting of a community-based cohort. The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up. During the 12 years of follow-up, a total of 383 men and 227 women developed CHD, which was significantly associated with categories of blood pressure, total cholesterol, LDL cholesterol, and HDL cholesterol (all P<.001). Sex-specific prediction equations were formulated to predict CHD risk according to age, diabetes, smoking, JNC-V blood pressure categories, and NCEP total cholesterol and LDL cholesterol categories. The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used. After adjustment for other factors, approximately 28% of CHD events in men and 29% in women were attributable to blood pressure levels that exceeded high normal (> or =130/85). The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol (> or =200 mg/dL) was 27% in men and 34% in women.
Recommended guidelines of blood pressure, total cholesterol, and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample. A simple coronary disease prediction algorithm was developed using categorical variables, which allows physicians to predict multivariate CHD risk in patients without overt CHD.
The degree of clustering for common metabolic coronary disease risk factors is not well known, the antecedents of clustering are not well studied, and the impact of such clusters on coronary risk has not been assessed systematically.
Prospective community sample of 2406 men and 2569 women aged 18 to 74 years at baseline. The 6 metabolically linked risk factors considered were the lowest sex-specific quintile of high-density lipoprotein cholesterol and the highest quintiles of body mass index, systolic blood pressure, triglycerides, glucose, and serum total cholesterol.
At baseline the risk factor sum, represented as integer values, ranged from 0 to 6, and clusters of 3 or more risk factors occurred at twice the rate predicted by chance. After adjustment for age and obesity level, a 2.25-kg (5-lb) weight increase over 16 years was associated with an increased risk factor sum in men (+20%; P=.002) and women (+37%; P<.001), and a 2.25-kg weight loss was associated with a decreased risk factor sum in men (-48%; P<.001) and women (-40%; P<.001). Clusters of 3 or more risk factors were associated with a 2.39 (95% confidence interval, 1.56-3.36) and 5.90 (95% confidence interval, 2.54-13.73) times greater risk of coronary heart disease in men and women, respectively (both P<.001).
Atherogenic risk factor clustering is common in both sexes, worsens with weight gain, and is associated with greatly increased risk of coronary disease risk in both sexes.
Epidemiologic studies provide increasing evidence that hypertriglyceridemia is a risk factor for cardiovascular disease. A meta-analysis of 17 population-based studies of triglyceride levels and cardiovascular disease identified a 76% increase in cardiovascular disease risk in women and a 31% increase in men associated with a 1 mmol/L increase in triglyceride levels. Additional epidemiologic studies have shown that plasma triglyceride levels and low-density lipoprotein particle size predict subsequent coronary artery disease. Taken together, the existing epidemiologic data may help identify a group of patients who may benefit from interventions aimed at decreasing triglyceride levels associated with an increased risk of cardiovascular disease.
Hepatic lipase catalyses the hydrolysis of triglycerides and phospholipids in all major classes of lipoproteins. Genetic deficiency of this enzyme is associated with a unique plasma lipoprotein profile, characterized by hypertriglyceridemia and elevated concentrations of intermediate density lipoproteins and HDL. Recent studies have identified common polymorphisms in the hepatic lipase gene that are associated with low hepatic lipase activity and increased concentrations of large HDL. Association studies using these polymorphisms are elucidating the effects of variation in hepatic lipase activity on plasma lipoprotein concentrations and susceptibility to coronary atherosclerosis.
Data have revealed interactions between baseline concentration of hs-CRP and the efficacy of common pharmacologic therapies in primary and secondary prevention, suggesting not only that it may be possible to modify the increased risk associated with elevated hs-CRP, but also that inflammatory markers may be useful in targeting preventive therapies. Inflammatory markers may become a valuable component of routine cardiovascular risk assessment.
It is estimated that by the year 2020 there will be approximately 250 million people affected by type 2 diabetes mellitus worldwide (1). Although the primary factors causing this disease are unknown, it is clear that insulin resistance plays a major role in its development. Evidence for this comes from (a) the presence of insulin resistance 10–20 years before the onset of the disease (2, 3); (b) cross-sectional studies demonstrating that insulin resistance is a consistent finding in patients with type 2 diabetes (3–6); and (c) prospective studies demonstrating that insulin resistance is the best predictor of whether or not an individual will later become diabetic (2, 3). Here, I focus on some recent advances in our understanding of human insulin resistance that have been made using nuclear magnetic resonance spectroscopy (NMR). This technique takes advantage of the spin properties of the nuclei of certain isotopes, such as 1H, 13C, and 31P, which endow the isotopes with a magnetic component that can be used to measure the concentration of intracellular metabolites noninvasively and to assess biochemical differences between normal and diabetic subjects. Drawing on NMR studies from my laboratory and others, I first consider the control of glucose phosphorylation and transport in regulating muscle responses to insulin. I then turn to the effects of fatty acids on insulin responses, showing that commonly accepted models that attempt to explain the association of insulin resistance and obesity are incompatible with recent findings. Finally, I propose an alternative model that appears to fit these and other available data.
To examine relationships of normal blood pressure (BP), hypertension and degree of BP control with cardiovascular disease (CVD) risk factors and predicted 10-year risks for coronary heart disease (CHD) and stroke.
Cross-sectional survey.
107 Marks and Spencer retail stores in the UK.
14,077 women, aged 30-64 years, screened for CVD risk factors between 1988 and 1991.
Systolic (SBP) and diastolic (DBP) BP; total, high-(HDL) and low-density lipoprotein (LDL) cholesterol, ratio of total to HDL cholesterol (TC/HDL-C); triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein (a), glucose, body mass index, antihypertensive medication and predicted risks for CHD and stroke. Hypertension was defined as SBP > or = 140 mmHg and/or DBP > or = 90 mmHg and/or taking anti-hypertensive medication. Subjects were divided into normotensives with optimal (n = 6,599), normal (n = 3,170) and high normal (n = 2,184) BP levels, and hypertensives with adequate BP control (n = 228), untreated (n = 1,729) and inadequate BP control (n = 291).
BP level was associated with other CVD risk factors among both normotensives and hypertensives. Women with inadequately controlled BP had the worst risk profile, followed by untreated hypertensives, those with adequately controlled BP and normotensives. Odds ratios for being in the top quintile of predicted 10-year CHD and stroke risks were 1, 2.7, 4.2, 8.5, 13.0, 18.9 for CHD; 1, 1.1, 5.8, 18.7, 20.6, 756 for stroke, for optimal, normal, high normal, adequate BP control, untreated and inadequate BP control groups respectively.
Untreated hypertensives and women taking anti-hypertensive medication but with BP > or = 140/90 mmHg have the most atherogenic risk factor profiles. Effective management of BP and the associated CVD risk requires a multi-factorial approach, rather than addressing BP control in isolation.
It is proposed that an important function of leptin is to confine the storage of triglycerides (TG) to the adipocytes, while limiting TG storage in nonadipocytes. Excess TG deposition in nonadipocytes leads to impairment of functions, increased ceramide formation, which triggers nitric oxide-mediated lipotoxicity and lipoapoptosis. The fact that TG content in nonadipocytes normally remains within a very narrow range irrespective of excess caloric intake, while TG content of adipocytes rises, is consistent with a system of fatty acid (FA) homeostasis in nonadipose tissues. When leptin is deficient or leptin receptors are dysfunctional, TG content in nonadipose tissues such as pancreatic islets, heart and skeletal muscle, can increase 10-50-fold, suggesting that leptin controls the putative homeostatic system for intracellular TG. The fact that function and viability of nonadipocytes is compromised when their TG content rises above normal implies that normal homeostasis of their intracellular FA is critical for prevention of complications of obesity. FA overload of skeletal muscle, myocardium and pancreatic islets cause, respectively, insulin resistance, lipotoxic heart disease and adipogenic type 2 diabetes. All can be completely prevented by treatment with antisteatotic agents such as troglitazone. In diet-induced obesity, leptin signaling is normal initially and lipotoxic changes are at first prevented; later, however, post-receptor leptin resistance appears, leading to dysfunction and lipoapoptosis in nonadipose tissues, the familiar complications of obesity.
The rising prevalence of obesity is accompanied by an increasing number of patients with the metabolic complications of obesity. The major complications come under the heading of the metabolic syndrome. This syndrome is characterized by plasma lipid disorders (atherogenic dyslipidemia), raised blood pressure, elevated plasma glucose, and a prothrombotic state. The clinical consequences of the metabolic syndrome are coronary heart disease and stroke, type 2 diabetes and its complications, fatty liver, cholesterol gallstones, and possibly some forms of cancer. At the heart of the metabolic syndrome is insulin resistance, which represents a generalized derangement in metabolic processes. Obesity is the predominant factor leading to insulin resistance, although other factors play a role. The mechanistic link between insulin resistance and the metabolic syndrome is complex. The relationship is modulated by yet other factors, such as physical activity, body fat distribution, hormones, and a person's genetic polymorphic architecture. A better understanding of the molecular basis of this relationship is needed to suggest new targets for prevention and treatment of the complications of obesity. In addition, understanding at the clinical level will lead to improved management of these complications.
Recent epidemiological evidence suggests that although lowering low-density lipoprotein (LDL) cholesterol is important in decreasing cardiovascular disease morbidity and mortality, it accounts only for part of the coronary artery disease (CAD) improvement with lipid-lowering therapy. In the last decade, it has become evident that the atherogenicity of LDL particles is associated not only with their plasma levels, but also with their size and density. The presence of small, dense LDL particles is associated with a three fold increase in CAD risk. Hepatic lipase (HL), a key enzyme in the formation of small, dense LDL particles, modulates their phospholipid and triglyceride contents. The higher the HL activity, the smaller, denser, and more atherogenic the resulting lipoprotein particle. It is, therefore, plausible to hypothesize that at least part of the CAD benefits observed in the recent CAD-prevention pharmacological trials, which are not accounted for by the decrease in LDL-C (LDL-cholesterol), might be explained by a pharmacological effect on LDL size and density, possibly mediated by changes in hepatic lipase activity. By studying patients with dyslipidemia and CAD, we have been able to provide strong evidence that regression of coronary atherosclerosis results from at least two independent effects of lipid-lowering therapy on lipoprotein metabolism: the well known one that leads to changes in LDL-C and apo B levels, and a new pathway of HL-mediated improvement in LDL buoyancy. Finally, HL activity and LDL density appear to be significantly affected by the presence of a common C-->T substitution at position -514 with respect to the transcription start site of the HL gene, raising the possibility that the -514 C-->T polymorphism may significantly contribute to differences in individual CAD response to lipid-lowering treatment, as seen in the recent major primary and secondary CAD-prevention clinical trials.
Alterations in nutritional status, such as obesity, markedly influence insulin, leptin, GH secretion, and free fatty acid (FFA) levels. We measured every hour for 24 h circulating leptin, insulin, GH, and FFA levels in lean and obese adolescents to determine: 1) the impact of adolescent obesity on the diurnal changes in leptin concentrations; and 2) the temporal relationships between the diurnal patterns of circulating leptin levels and insulin, GH, and FFA levels. During puberty, we found that the 24-h profile of circulating plasma leptin levels follows a bimodal pattern with minimal concentrations occurring early in the afternoon and a nocturnal elevation starting after midnight and culminating early morning. The time course of the diurnal variation in leptin levels in the obese adolescents was not different from that in lean controls. Of note, however, in obese girls leptin 24-h excursion and leptin night to day ratio were lower than those found in lean girls. In obese adolescents, mean GH levels varied significantly less during the day and night than lean controls. During the day, there were distinct preprandial increases and postprandial decreases in FFA levels, whereas after midnight FFA levels rose in both lean and obese adolescents. A significant positive correlation was found between mean plasma insulin levels between 0800 h and 2000 h and peak in leptin in lean and obese girls and boys (r = 0.63, P: < 0.001). Peak leptin was inversely correlated with the area under the nocturnal GH levels in all groups (r = -0.31, P: < 0.0003), whereas it was positively correlated with the nocturnal peak in FFA levels (r = 0.45, P: < 0.004). In summary, we report in obese adolescent girls a blunted relative diurnal excursion in leptin levels. This abnormal rhythmicity may, in part, explain their leptin resistance state. The nocturnal rise in leptin was paralleled by a nocturnal rise in GH and FFA levels. Additional studies are needed to test the potential link between the adipose-derived peptide and GH axis in humans.
Biological amines react with reducing sugars to form a complex family of rearranged and dehydrated covalent adducts that are often yellow-brown and/or fluorescent and include many cross-linked structures. Food chemists have long studied this process as a source of flavor, color, and texture changes in cooked, processed, and stored foods. During the 1970s and 1980s, it was realized that this process, called the Maillard reaction or advanced glycation, also occurs slowly in vivo. Advanced glycation endproducts (AGEs) that form are implicated, causing the complications of diabetes and aging, primarily via adventitious and crosslinking of proteins. Long-lived proteins such as structural collagen and lens crystallins particularly are implicated as pathogenic targets of AGE processes. AGE formation in vascular wall collagen appears to be an especially deleterious event, causing crosslinking of collagen molecules to each other and to circulating proteins. This leads to plaque formation, basement membrane thickening, and loss of vascular elasticity. The chemistry of these later-stage, glycation-derived crosslinks is still incompletely understood but, based on the hypothesis that AGE formation involves reactive carbonyl groups, the authors introduced the carbonyl reagent aminoguanidine hydrochloride as an inhibitor of AGE formation in vivo in the mid 1980s. Subsequent studies by many researchers have shown the effectiveness of aminoguanidine in slowing or preventing a wide range of complications of diabetes and aging in animals and, recently, in humans. Since, the authors have developed a new class of agents, exemplified by 4,5-dimethyl-3-phenacylthiazolium chloride (DPTC), which can chemically break already-formed AGE protein-protein crosslinks. These agents are based on a new theory of AGE crosslinking that postulates that alpha-dicarbonyl structures are present in AGE protein-protein crosslinks. In studies in aged animals, DPTC has been shown to be capable of reverting indices of vascular compliance to levels seen in younger animals. Human clinical trials are underway.
The role of the ATP-binding cassette transporter 1 (ABCA1) in cellular lipid efflux and high density lipoprotein metabolism has been recently documented by mutations in genetic HDL deficiency syndromes such as classical Tangier disease. Analysis of ABCA1 knockout mice and overexpression studies have established the importance of ABCA1 as a major determinant of HDL cholesterol in plasma. These studies also indicate that ABCA1 is critically involved in cellular trafficking of cholesterol and choline-phospholipids and in total body lipid homeostasis, such as intestinal cholesterol and fat-soluble vitamin absorption and in the modulation of steroidogenesis. First insights into the upregulation of ABCA1 gene expression by cellular cholesterol and cAMP have identified critical ABCA1 promoter elements, which bind the transcription factors liver X receptor, retinoid X receptor, Sp1 and E-box proteins. The finding that a lipid sensitive subgroup of ABC transporters is able to translocate cholesterol and phospholipids supports the concept that in ABCA1 deficiency, compensatory mechanisms possibly involving MDR1, MDR3 and MRP-family members could be active. This suggests that a network of ABC transporters involved in cellular lipid transport exists, which is under the tight control of energy pathways directly linked to high density lipoprotein metabolism and atherogenesis.
The Hypertension Optimal Treatment (HOT) Study provided information about cardiovascular events in 18,790 hypertensives, subjected to pronounced blood pressure lowering for a mean of 3.8 years.
The HOT Study data have been further analysed after risk stratification of the patients (1999 World Health Organization and International Society of Hypertension guidelines criteria): (i) no patients of the HOT Study were classified as low risk, 50% were classified as medium risk, 20.2% as high risk and 29.8% as very high risk; (ii) incidence of cardiovascular events in these patients with excellent blood pressure control [92% had diastolic blood pressure (DBP) < or = 90 mmHg] remained proportional to pretreatment risk. The relative risk of very high- versus medium-risk strata was between two and three both when HOT Study patients were considered independently of, or within the DBP target group they had been randomized to; and (iii) event rates in all risk strata were calculated to be much lower (possibly 60% lower) than rates expected from baseline risk calculated approximately by the Framingham equation.
The low event rate in HOT Study patients is likely to result from pronounced blood pressure lowering, and is not explained by a lower risk profile than in previous controlled trials of antihypertensive treatment. The persistence of a risk gradient despite intensive blood pressure lowering suggests a combination of blood pressure control with other strategies of risk correction and the need to initiate antihypertensive therapy before complications develop.
Low levels of high-density lipoprotein cholesterol (HDL-C), and elevated total cholesterol-to-HDL-C ratios are independently associated with increased risk of coronary artery disease. In observational studies, every 1-mg/dL increment in HDL-C is associated with a 2% decreased risk of coronary artery disease in men and 3% decreased risk in women. On average, HDL-C levels are lower in men than in women, and are lower in whites than in blacks. Low HDL-C has also been found to be linked to higher risk of ischemic stroke, degree of carotid atherosclerosis, increased atherosclerotic progression as measured by coronary arteriography, higher coronary mortality among people with cardiovascular disease, and the development of coronary artery disease among patients with diabetes mellitus.
Obesity is a major risk factor for insulin resistance and type 2 diabetes mellitus. Adipocytes secrete numerous substances that might contribute to peripheral insulin sensitivity. These include leptin, tumor necrosis factor alpha, Acrp30/adiponectin/adipoQ and interleukin 6, the potential roles of which are briefly reviewed here. Thiazolidinedione (TZD) antidiabetic drugs regulate gene transcription by binding to peroxisome proliferator activated receptor gamma, a nuclear hormone receptor found at its highest levels in adipocytes. A search for genes that are downregulated by TZDs in mouse adipocytes led to the discovery of an adipose-specific secreted protein called resistin. Resistin circulates in the mouse, with increased levels in obesity, and has effects on glucose homeostasis that oppose those of insulin. Thus, resistin is a potential link between TZDs, obesity and insulin resistance in the mouse. Future studies must address the mechanism of action and biological role of resistin and related family members in mice and humans.
The Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) highlights the importance of treating patients with the metabolic syndrome to prevent cardiovascular disease. Limited information is available about the prevalence of the metabolic syndrome in the United States, however.
To estimate the prevalence of the metabolic syndrome in the United States as defined by the ATP III report.
Analysis of data on 8814 men and women aged 20 years or older from the Third National Health and Nutrition Examination Survey (1988-1994), a cross-sectional health survey of a nationally representative sample of the noninstitutionalized civilian US population.
Prevalence of the metabolic syndrome as defined by ATP III (>/=3 of the following abnormalities): waist circumference greater than 102 cm in men and 88 cm in women; serum triglycerides level of at least 150 mg/dL (1.69 mmol/L); high-density lipoprotein cholesterol level of less than 40 mg/dL (1.04 mmol/L) in men and 50 mg/dL (1.29 mmol/L) in women; blood pressure of at least 130/85 mm Hg; or serum glucose level of at least 110 mg/dL (6.1 mmol/L).
The unadjusted and age-adjusted prevalences of the metabolic syndrome were 21.8% and 23.7%, respectively. The prevalence increased from 6.7% among participants aged 20 through 29 years to 43.5% and 42.0% for participants aged 60 through 69 years and aged at least 70 years, respectively. Mexican Americans had the highest age-adjusted prevalence of the metabolic syndrome (31.9%). The age-adjusted prevalence was similar for men (24.0%) and women (23.4%). However, among African Americans, women had about a 57% higher prevalence than men did and among Mexican Americans, women had about a 26% higher prevalence than men did. Using 2000 census data, about 47 million US residents have the metabolic syndrome.
These results from a representative sample of US adults show that the metabolic syndrome is highly prevalent. The large numbers of US residents with the metabolic syndrome may have important implications for the health care sector.
I review evidence that leptin is a liporegulatory hormone that controls lipid homeostasis in nonadipose tissues during periods of overnutrition. When adipocytes store excess calories as triacylglycerol (TG), leptin secretion rises so as to prevent accumulation of lipids in nonadipose tissues, which are not adapted for TG storage. Whenever leptin action is lacking, whether through leptin deficiency or leptin resistance, overnutrition causes disease of nonadipose tissues with generalized steatosis, lipotoxicity, and lipoapoptosis. Examples of such disorders of liporegulation include generalized lipodystrophies, mutations of leptin and leptin receptor genes, and diet-induced obesity. Lipotoxicity of pancreatic beta-cells, myocardium, and skeletal muscle leads, respectively, to type 2 diabetes, cardiomyopathy, and insulin resistance. In humans this constellation of abnormalities is referred to as the metabolic syndrome, a major health problem in the United States. When lipids overaccumulate in nonadipose tissues during overnutrition, fatty acids enter deleterious pathways such as ceramide production, which, through increased nitric oxide formation, causes apoptosis of lipid-laden cells, such as beta-cells and cardiomyocytes. Lipoapoptosis can be prevented by caloric restriction, by thiazolidinedione treatment, and by administration of nitric oxide blockers. There is now substantial evidence that complications of human obesity may reflect lipotoxicity similar to that described in rodents.
There is increasing evidence for the existence of a condition consisting of a cluster of metabolic disorders which include insulin resistance, alterations in glucose and lipid metabolism, increased blood pressure and visceral obesity. The metabolic syndrome is now the favoured definition of the cluster. Each single component of the cluster increases the cardiovascular risk, but the combination of factors is much more important. Insulin resistance is the most frequently associated factor to the singular components of the syndrome: most authors believe that it may be the common aetiological factor. However, visceral obesity seems to be the main driving factor by means of the increased production of free fatty acids whose activity, in turn, might interfere with the action of insulin. Some questions exist about the syndrome because of the frequent lack in the cluster of one of the factors. This does not mean that the missing factor does not belong to the syndrome, but only that it is not yet clinically evident. Weight gain has been shown to be a strong predictor of the metabolic syndrome. This aspect gives strength to treatment and prevention because it means that losing weight or stopping weight increase might reduce the risk of a future appearance of a factor that is still not evident. Interventions to treat visceral obesity by means of losing weight seem to be the most efficacious way to treat the metabolic syndrome thus improving the most widespread cardiovascular risk factor in western countries.
A workshop was convened by the International Diabetes Federation to review the latest information relating to the risks associated with impaired glucose tolerance (IGT) and impaired fasting glycaemia (IFG) for future diabetes and cardiovascular disease (CVD). The workshop sought to address three questions: (i) are the current definitions of IGT and IFG appropriate; (ii) are IFG and IGT risk factors, risk markers or diseases; (iii) what interventions (if any) should be recommended for people with IFG and IGT? The determinants of elevated fasting glucose and 2-h plasma glucose in an oral glucose tolerance test (2-HPG) levels differ. Raised hepatic glucose output and a defect in early insulin secretion are characteristic of the former, and peripheral insulin resistance is most characteristic of the latter. Therefore, it is not surprising that the concordance between the categories of IFG and IGT is limited. In all prevalence studies to date only half or less of people with IFG have IGT, and even a lower proportion (20-30%) with IGT also have IFG. In the majority of populations studied, IGT is more prevalent than IFG, and there is a difference in phenotype and gender distribution between the two categories. IFG is substantially more common amongst men and IGT slightly more common amongst women. The prevalence of IFG tends to plateau in middle age whereas the prevalence of IGT rises into old age. Both IFG and IGT are associated with a substantially increased risk of developing diabetes, with the highest risk in people with combined IFG and IGT. Because IGT is commoner than IFG in most populations it is more sensitive (but slightly less specific) for identifying people who will develop diabetes. In most populations studied, 60% of people who develop diabetes have either IGT or IFG 5 years or so before, with the other 40% having normal glucose tolerance at that time. The limited published data suggest that both isolated IFG (I-IFG) and isolated IGT (I-IGT) are similarly associated with cardiovascular risk factors, such as hypertension and dyslipidaemia, with the highest risk in those with combined IFG and IGT. However, some data have suggested that I-IGT is more strongly associated with hypertension and dyslipidaemia (features of the metabolic syndrome) than I-IFG. In unadjusted analyses both IFG and IGT are associated with CVD and total mortality. In separate analyses for fasting and 2-HPG adjusted for other cardiovascular risk factors (from the DECODE study) there remains a continuous relationship between 2-HPG and mortality, but an independent relationship with fasting glucose is only found above 7.0 mmol/l. Glycated haemoglobin (HbA1c) levels are continuously and positively associated with CVD and total mortality independent of other CVD risk factors. Life style interventions, including weight loss and increased physical activity, are highly effective in preventing or delaying the onset of diabetes in people with IGT. Two randomized controlled trials of individuals with IGT found that life style intervention studies reduce the risk of progressing to diabetes by 58%. The oral hypoglycaemic drugs metformin and acarbose have also been shown to be effective, but less so than the life style measures. Similar data do not yet exist for the effectiveness of such interventions in people with I-IFG. Larger studies are required to evaluate the effects of interventions on cardiovascular outcomes in people with IGT. Cost effective strategies to identify people with IGT for intervention should be developed and evaluated. The use of simple risk scores to assess who should undergo an oral glucose tolerance test is one promising approach, although these will need to be population-specific. In conclusion, IGT and IFG differ in their prevalence, population distribution, phenotype, and risk of total mortality and CVD. The consensus of the workshop was: 1. The diagnostic thresholds for all categories of glucose intolerance should be revisited in the light of the latest evidence. There was no clear consensus (with current evidence) on whether IFG and IGT should be classified as diseases, but they clearly represent risk factors and risk markers for diabetes and CVD, respectively. 2. Both IGT and IFG are similarly associated with an increased risk of diabetes, but IGT is more strongly associated with CVD outcomes. 3. Risks are higher when IGT and IFG coexist. 4. Life style interventions are highly effective in delaying or preventing the onset of diabetes in people with IGT and may reduce CVD and total mortality, but the latter requires formal testing.