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Inflammation and insulin resistance
... Several studies have demonstrated the connection between inflammation and insulin resistance, linking inflammatory mediators to insulin signalling pathway disruption and glucose homeostasis impairment [1,2]. These mediators include cytokines, chemokines, and adipokines. ...
... TNF-α has been identified as a crucial mediator between inflammation and insulin resistance. Through the activation of serine kinases including c-Jun N-terminal kinase (JNK) and IκB kinase (IKK), which phosphorylate insulin receptor substrate (IRS) proteins and interfere with downstream insulin signalling, TNF-α has been shown in experimental experiments to block insulin signalling pathways [1,2]. Clinical research has demonstrated increased TNF-α levels in patients with type 2 diabetes mellitus (T2DM) and obesity, further linking TNF-α to the aetiology of insulin resistance [2,8]. ...
... Through the activation of serine kinases including c-Jun N-terminal kinase (JNK) and IκB kinase (IKK), which phosphorylate insulin receptor substrate (IRS) proteins and interfere with downstream insulin signalling, TNF-α has been shown in experimental experiments to block insulin signalling pathways [1,2]. Clinical research has demonstrated increased TNF-α levels in patients with type 2 diabetes mellitus (T2DM) and obesity, further linking TNF-α to the aetiology of insulin resistance [2,8]. ...
A common component of metabolic diseases including metabolic syndrome and type 2 diabetes, insulin resistance is now known to be closely linked to persistent low-grade inflammation. This chapter explores the intricate connection between insulin resistance and inflammatory pathways, clarifying the molecular processes that underlie inflammation-induced insulin resistance. We examine the part that important inflammatory mediators play in upsetting insulin signalling pathways and encouraging insulin resistance, including cytokines, chemokines, and adipokines. We also go over how inflammatory signalling cascades, like the JNK and NF-κB pathways, affect insulin sensitivity and cellular metabolism. Understanding the interaction between insulin resistance and inflammation can help to better understand the pathogenesis of metabolic diseases and identify possible treatment targets. In people who are at risk of developing issues associated with insulin resistance, strategies targeted at reducing inflammatory responses may be able to reduce insulin resistance and enhance metabolic health.
... De este modo, es necesario que se desarrolle tolerancia específica para evitar una respuesta inmune innecesaria contra antígenos "inofensivos" que se están eliminando, pero también es necesario el desarrollo de una respuesta inmune eficiente contra patógenos que sí son "peligrosos". Se sabe que la presentación antigénica que realizan las células macrofágicas hepáticas como las Células de Kupffer (CK) y las células endoteliales sinusoidales hepáticas (CES), es críticamente responsable tanto de la inducción de la respuesta inmune local, como así también la inducción de tolerancia (1,2,3). Varios mecanismos de tolerancia pueden operar simultáneamente en el hígado, como el control de la presentación antigénica (ignorancia inmune), deleción clonal y la desviación inmune. ...
... Funcionan como una barrera que separa las macromoléculas y los leucocitos presentes en el lumen del sinusoide con los hepatocitos, previniendo, de esta manera, el contacto directo entre ambos tipos celulares (22). Las CES expresan en su superficie PRRs (receptores de reconocimiento de patógenos) como el RM y los receptores basureros que le permiten remover de la circulación desechos coloidales o macromoleculares solubles (menores que 100 nm) de manera rápida y eficiente (3,6). Otra característica importante de las CES es que expresan toda la maquinaria necesaria para realizar la presentación antigénica como son las moléculas de CMH tipo I y II y moléculas coestimulatorias CD40, CD80 y CD86. ...
... Otra característica importante de las CES es que expresan toda la maquinaria necesaria para realizar la presentación antigénica como son las moléculas de CMH tipo I y II y moléculas coestimulatorias CD40, CD80 y CD86. Estas CES realizan la endocitosis de antígeno mediada por receptores y o la fagocitosis, el procesamiento y la presentación antigénica con la misma eficacia que lo hacen las CDs (1,3,6). Sin embargo, cuando se las activa con ligandos del receptor TLR-4, liberan la citoquina IL-10 y disminuyen sus funciones de CPA, generando como efecto final Li T tolerogénicos (2). ...
... Indeed, an overweight or obese status is observed in nearly one in five children with CD [12]. The association between obesity and chronic inflammation has been extensively studied in non-IBD populations [13,14]. Obesity is associated with a low grade inflammatory state [15,16], which may be triggered by adipocyte hypertrophy and consequent secretion of pro-inflammatory markers, including interleukin (IL)-6, IL-8, IL-1β, C-reactive protein (CRP) [17], tumour necrosis factor-α (TNF-α) [18] and monocyte chemoattractant factor [19]. ...
... Another study by the same group in a paediatric population showed no relationship between obesity and disease progression as defined by a clinically complicated disease phenotype [36]. In contrast, prior IBD-related surgery was associated with overweight and obesity in a cohort of 1598 children with CD [14]. However, the present study found no association between obesity and a complicated disease behaviour. ...
... However, the present study found no association between obesity and a complicated disease behaviour. It is important to note that previous studies defined obesity based on the World Health Organisation (WHO) child growth chart standards [33], or defined their at-risk population as one with a BMI ≥85th percentile [14] or BMI > 30 kg/m 2 [36], while we employed a more conservative approach of defining our at-risk population as one with a BMI of >25 kg/m 2 . Concomitant medication usage is a surrogate of disease severity that may be utilised along with hospitalisation and surgery. ...
Background
The evidence on the relationship between adiposity and disease outcomes in paediatric Crohn’s disease (CD) is limited and lacks consensus.
Aim
To investigate the relationship between (a) body mass index (BMI) and clinical CD outcomes (hospitalisation, surgery, disease behaviour, biologic use, extra-intestinal manifestations (EIMs)) and (b) the age of CD onset with clinical outcomes.
Design
Clinical outcomes were examined in CD patients diagnosed at age <17 years and enroled in the National Institute for Health Research IBD-UK BioResource at a median age of 24 years. All outcomes and BMI were recorded at the time of enrolment. Participants were categorised into normal (<25 kg/m²) and high (≥25 kg/m²) BMI. Age at disease diagnosis was categorised into pre-puberty/early puberty (<11 years), puberty (11–14 years) and post-puberty (15–17 years). Spearman rank correlation was used to test the associations between continuous variables and chi-square test to compare categorical variables.
Results
848 participants with CD were included (51.8% males) and median age at diagnosis was 14 years. Participants with high BMI experienced a greater frequency of EIMs (P = 0.05) than those with low BMI (1 type of EIM: 18.5% vs. 13.2%, respectively; ≥2 types of EIMs: 7.8% vs. 5.6%, respectively). Age at diagnosis and BMI showed weak correlations with corticosteroid use (ρ = 0.08, P = 0.03 and ρ = −0.09, P = 0.01; respectively). An early diagnosis (<11 years) was associated with higher occurrence of stenosing and penetrating disease behaviour (P = 0.01) and hospitalisations (P < 0.001).
Conclusions
A higher BMI and an earlier age of disease onset are associated with worse CD clinical presentation.
... Elevated levels of inflammatory cytokines are thought to be key contributors to beta cell impairment and insulin resistance (50,51) . Our results showed a significant difference in CRP at week 16 between groups, supporting a potential link between prebiotic fibre, inflammation, and metabolic health (Fig. 2f). ...
... In this manner, SCFAs influence the expression of pro-and anti-inflammatory cytokines, which further regulates both local and systemic inflammation. This is particularly relevant in pre-diabetes where the control and regulation of inflammatory cytokines are likely to play a role in the advancement of insulin resistance and type 2 diabetes (50,58,59) . Additionally, the SCFA butyrate promotes GLP-1 secretion in the colonic epithelium (via FFAR2/3 receptors) and intestinal gluconeogenesis, both of which may indirectly promote glucose homeostasis and insulin sensitivity (23,24,60) . ...
Prebiotic fibre represents a promising and efficacious treatment to manage pre-diabetes, acting via complementary pathways involving the gut microbiome and viscosity-related properties. In this study, we evaluated the effect of using a diverse prebiotic fibre supplement on glycaemic, lipid, and inflammatory biomarkers in patients with pre-diabetes. Sixty-six patients diagnosed with pre-diabetes (yet not receiving glucose-lowering medications) were randomised into treatment (n = 33) and placebo (n = 33) interventions. Participants in the treatment arm consumed 20g per day of a diverse prebiotic fibre supplement and participants in the placebo arm consumed 2g per day of cellulose for 24 weeks. A total of 51 and 48 participants completed the week 16 and week 24 visits, respectively. The intervention was well-tolerated, with a high average adherence rate across groups. Our results extend upon previous work, showing a significant change in glycated haemoglobin (HbA1c) in the treatment group, but only in participants with lower baseline HbA1c levels (<6% HbA1c) ( P = 0.05; treatment -0.17 ± 0.27 vs. placebo 0.07 ± 0.29, mean ± SD). Within the whole cohort, we showed significant improvements in insulin sensitivity ( P = 0.03; treatment 1.62 ± 5.79 v. placebo -0.77 ± 2.11), and C-reactive protein ( P FWE = 0.03; treatment -2.02 ± 6.42 vs placebo 0.94 ± 2.28) in the treatment group compared with the placebo. Together, our results support the use of a diverse prebiotic fibre supplement for physiologically relevant biomarkers in pre-diabetes.
... Clinical and experimental studies suggest that the transcriptomic response to bariatric surgery is critically implicated in restoring metabolic homeostasis [15][16][17][18][19][20][21][22][23][24]. Type 2 diabetes in adults with obesity is characterized by low-grade inflammation, insulin resistance, and progressive loss of β cells [25][26][27][28]. In rodent models that recapitulate obesity-linked type 2 diabetes, duodenal-jejunal bypass surgery results in reduced inflammation, improved glucose tolerance and insulin sensitivity, and increased regeneration and proliferation of β cells [20][21][22]. ...
... Insulin resistance is a characteristic feature of type 2 diabetes and obesity [27]. One of the mechanisms that contributes to insulin resistance is chronic inflammation [28]. Consequently, caloric restriction and bariatric surgery have been used to mitigate inflammation, despite contrasting outcomes [19,74]. ...
Context
Bariatric surgery has been shown to be effective in inducing complete remission of type 2 diabetes in adults with obesity. However, its efficacy in achieving complete diabetes remission remains variable and difficult to predict before surgery.
Objectives
We aimed to characterize bariatric surgery-induced transcriptome changes associated with diabetes remission and the predictive role of the baseline transcriptome.
Patients and Methods
We performed a whole genome microarray in peripheral mononuclear cells at baseline (before surgery) and 2 and 12 months after bariatric surgery in a prospective cohort of 26 adults with obesity and type 2 diabetes. We applied machine learning to the baseline transcriptome to identify genes that predict metabolic outcomes. We validated the microarray expression profile using a real-time polymerase chain reaction.
Results
Sixteen patients entered diabetes remission at 12 months and ten did not. The gene expression analysis showed similarities and differences between responders and nonresponders. The difference included the expression of critical genes (SKT4, SIRT1, and TNF superfamily), metabolic and signaling pathways (Hippo, Sirtuin, ARE-Mediated mRNA Degradation, MSP-RON, and Huntington), and predicted biological functions (beta cell growth and proliferation, insulin and glucose metabolism, energy balance, inflammation, and neurodegeneration). Modeling the baseline transcriptome identified ten genes that could hypothetically predict the metabolic outcome before bariatric surgery.
Conclusions
The changes in the transcriptome after bariatric surgery distinguish patients in whom diabetes enters complete remission from those who do not. The baseline transcriptome can contribute to the prediction of bariatric surgery-induced diabetes remission preoperatively.
... Patients with metabolic syndrome and insulin resistance are also susceptible to the development of type 2 diabetes mellitus 4,5 . Studies of obesity in the clinic and in mouse models have linked chronic low-grade WAT inflammation to insulin resistance and the development of type 2 diabetes mellitus [6][7][8] . However, the underlying causes of adipose tissue inflammation in mammals remain poorly understood. ...
... In mouse models of diet-induced obesity (DIO) and genetic obesity, inflammation of the WAT and liver is associated with an increase in proinflammatory cytokine and exosomal microRNA release by adipose CD11c + inflammatory macrophages that can promote the development of systemic insulin resistance 7,[9][10][11] . These findings are supported by studies demonstrating that loss of these proinflammatory factors (that is, IL-6, IL-1β, tumour necrosis factor-α) or inducible deletion of total CD11c + cells leads to improved glucose homeostasis during DIO 9,[11][12][13] . ...
Obesity is associated with chronic low-grade white adipose tissue (WAT) inflammation that can contribute to the development of insulin resistance in mammals. Previous studies have identified interleukin (IL)-12 as a critical upstream regulator of WAT inflammation and metabolic dysfunction during obesity. However, the cell types and mechanisms that initiate WAT IL-12 production remain unclear. Here we show that conventional type 1 dendritic cells (cDC1s) are the cellular source of WAT IL-12 during obesity through analysis of mouse and human WAT single-cell transcriptomic datasets, IL-12 reporter mice and IL-12p70 protein levels by enzyme-linked immunosorbent assay. We demonstrate that cDC1s contribute to obesity-associated inflammation by increasing group 1 innate lymphocyte interferon-γ production and inflammatory macrophage accumulation. Inducible depletion of cDC1s increased WAT insulin sensitivity and systemic glucose tolerance during diet-induced obesity. Mechanistically, endocytosis of apoptotic bodies containing self-DNA by WAT cDC1s drives stimulator of interferon genes (STING)-dependent IL-12 production. Together, these results suggest that WAT cDC1s act as critical regulators of adipose tissue inflammation and metabolic dysfunction during obesity.
... It became clear from the past published studies that not only tumor necrosis factor alpha over expressed in obesity but also many other inflammatory mediators elevated. In obesity, inflammatory response is triggered predominantly in adipose tissue and later in other sites such as liver [43]. ...
... Insulin receptors belong to the tyrosine kinase receptor kinase family and to mediate it signaling pathway use docking proteins. Among the large number of substrates, insulin receptor substrate proteins are used to bind with receptors of insulin [43,44,45]. Insulin by stimulating tyrosine phosphorylation of insulin receptor substrate protein mediates its pathway. ...
... Recent observations suggest that inflammation, immunological dysregulation, alterations in gut microbiota, and cytokine dysregulation are the key pathophysiological contributors to T2DM 3 [3,4,814]. The focus of many recent investigations has been on unraveling the molecular bases, of metabolic inflammation and its association with cardiometabolic disease and T2DM [19,20]. This inflammatory nexus has been a hallmark of obesity and MS [21,22]. ...
... Several studies have revealed key pathophysiological aspects of T2DM, including inflammation, chemokine dysregulation, gut microbiome alterations, and immunological dysregulation [3,4,8,14]. Many inflammatory cytokines and other variables contribute to the inflammatory nexus that is characteristic of obesity and MS [19,23,24]. Pro-inflammatory chemokines have been linked to the etiology of T2DM, although the results have been mixed and inconsistent [22][23][24]. ...
Background. Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in poorer nations. The high prevalence of obesity and the ensuing diabetes is attributed to rapid economic progress, physical inactivity, consumption of high-calorie foods, and changing lifestyles. Objectives. We investigated the role of pro-inflammatory chemokines; CCL1, 2, 4 and 5 with varying levels of obesity in T2DM in the Asir region of Saudi Arabia. Materials and methods. 170 confirmed T2DM patients and a normal control group were enrolled. The demographic data, serum levels CCL-1, 2, 4 and 5 and the biochemical indices were assessed in patients and control groups by standard procedures. Results. T2DM patients were divided into four groups: A (normal body weight), B (Overweight), C (obese), and D (highly obese). n controls. We observed that male and female control patients had similar mean serum concentrations of pro-inflammatory chemokines CCL 1, 2, 4, and 5. Chemokines CCL1, CCL2, and CCL4 in the serum of Type 2 Diabetes Mellitus patients with normal or overweight body weights were significantly higher than the control group, regardless of gender. In T2DM individuals with obesity and severe obesity, the rise was most significant. There was a progressive rise in the concentrations of CCL1, 2, and 4 in T2DM) patients with increasing BMI. Serum CCL5 levels increased significantly in all T2DM patient groups. The increase in CCL5 was more predominant in normal-weight people as compared to overweight and obese T2DM patients. Conclusions. Male and female control patients had similar serum levels of pro-inflammatory chemokines CCL 1, 2, 4, and 5. The progressive rise in blood concentrations of three Pro-inflammatory chemokines; CCL1, 2, and 4 in T2DM patients with increasing BMI supports the idea that dyslipidemia and obesity contribute to chronic inflammation and insulin resistance. Serum CCL5 levels increased significantly in all T2DM patient groups. The selective and more pronounced increase of CCL5 in the T2DM group with normal BMI as compared to patients with varying degrees of obesity, was rather surprising. Further research is needed to determine if CCL5 under-expression in overweight and obese T2DM patients is due to some unexplained counterbalancing processes.
... Many studies in the literature have shown that diabetes is associated with inflammation [19,20]. Although the molecular mechanisms leading to IR formation are still unclear, epidemiological studies have demonstrated that systemic inflammation and IR coexistence play a role in the pathogenesis of diabetes [20]. ...
... Many studies in the literature have shown that diabetes is associated with inflammation [19,20]. Although the molecular mechanisms leading to IR formation are still unclear, epidemiological studies have demonstrated that systemic inflammation and IR coexistence play a role in the pathogenesis of diabetes [20]. Increased neutrophil and decreased lymphocyte count indicate the immune system's response to different physiological diseases, and the neutrophil/lymphocyte ratio (NLR) is now considered an important inflammatory marker for evaluating the degree of disease [19,21,22]. ...
... Moreover, adipose tissue dysfunction exacerbates insulin resistance by leading to aberrant secretion of adiponectin, an adipokine with insulin-sensitizing properties. Reduced adiponectin levels in obesity further perpetuate insulin resistance, underscoring the intricate connections between adipose tissue function, inflammation, and metabolic dysfunction [30,31,35]. ...
Obesity has become a global epidemic, intricately linked with metabolic dysfunction and posing significant health risks. This article presents a comprehensive investigation into the complex dynamics of obesity and metabolic disorders, focusing on adipose tissue as an active endocrine organ and its role in chronic inflammation and insulin resistance. Through a thorough literature review and analysis of epidemiological data, this study explores the socioeconomic, lifestyle, and environmental factors influencing obesity prevalence and its associated complications. Case studies from countries with successful intervention programs, expert interviews, and a comparative analysis of strategies implemented worldwide provide valuable insights into effective approaches for addressing obesity and metabolic dysfunction. Drawing on these findings, evidence-based recommendations are proposed for healthcare systems, policymakers, and public health practitioners to combat the multifaceted challenges posed by obesity and promote population health.
... The reduction of muscle mass leads to impaired physical function, high risk of falls and fractures, and worsening of glycemic control, since skeletal muscle mass represents the largest insulinsensitive tissue of the body (Kalyani et al., 2014). Moreover, the concomitant increase of fat mass is directly associated with insulin resistance and chronic inflammation in T2DM patients (Shoelson et al., 2006;Donath and Shoelson, 2011). ...
... Insulin resistance is a hallmark feature of T2DM, particularly in the elderly, in which excess blood glucose impairs insulin receptor sensitivity, leading to blood glucose dysregulation (hyperglycemia) and dyslipidemia (Fig. 1A). Insulin resistance additionally can induce inflammation, and vice versa (Shoelson et al., 2006). T2DM and insulin resistance are well-established risk factors for neurodegenerative diseases, and markers of brain insulin resistance have been observed in neurodegenerative disease patients both with and without a T2DM diagnosis (Talbot et al., 2012). ...
... IR is a pathophysiological disorder that manifests itself primarily in the form of decreased insulin sensitivity of muscle and liver tissues, resulting in a reduced bioavailability of insulin, a diminished capacity to uptake glucose, and ultimately hyperglycemia [36]. The hyperglycemic state further induces inflammation, as evidenced by elevated inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-8, the production of which further leads to smooth muscle cell proliferation and collagen deposition, ultimately leading to vascular senescence and vascular sclerosis [37][38][39]. IR also inhibits the expression of adiponectin, which has been reported to increase the risk of coronary artery disease in male patients with hypoadiponectinemia [40]. IR also promotes the production of fibrinogen activator inhibitor-1, which further contributes to thrombosis [41], in addition to elevated expression of adhesion-inducing factor and thromboxane A2-dependent tissue factor in platelets, which further promotes platelet activation [42]. ...
Background
Although studies have demonstrated the value of the triglyceride–glucose (TyG) index for cardiovascular disease (CVD) and cardiovascular mortality, however, few studies have shown that the TyG index is associated with all-cause or CVD mortality in young patients with diabetes. This study aimed to investigate the association between the TyG index and all-cause and CVD mortality in young patients with diabetes in the United States.
Methods
Our study recruited 2440 young patients with diabetes from the National Health and Nutrition Examination Survey (NHANES) 2001–2018. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Cox regression modeling was used to investigate the association between TyG index and mortality in young patients with diabetes. The nonlinear association between TyG index and mortality was analyzed using restricted cubic splines (RCS), and a two-segment Cox proportional risk model was constructed for both sides of the inflection point.
Results
During a median follow-up period of 8.2 years, 332 deaths from all causes and 82 deaths from cardiovascular disease were observed. Based on the RCS, the TyG index was found to have a U-shaped association with all-cause and CVD mortality in young patients with diabetes, with threshold values of 9.18 and 9.16, respectively. When the TyG index was below the threshold value (TyG index < 9.18 in all-cause mortality and < 9.16 in CVD mortality), its association with all-cause and CVD mortality was not significant. When the TyG index was above the threshold (TyG index ≥ 9.18 in all-cause mortality and ≥ 9.16 in CVD mortality), it showed a significant positive association with all-cause mortality and CVD mortality (HR 1.77, 95% CI 1.05–2.96 for all-cause mortality and HR 2.38, 95% CI 1.05–5.38 for CVD mortality).
Conclusion
Our results suggest a U-shaped association between TyG index and all-cause and CVD mortality among young patients with diabetes in the United States, with threshold values of 9.18 and 9.16 for CVD and all-cause mortality, respectively.
... The only manipulation was selecting young pigs with high plasma cholesterol levels (> 95 mg/dl) into the C and HFHS groups. The high energy diet led to the development of type 2 diabetes as confirmed by the increase of triglycerides and glucose in the blood plasma concomitant with characteristic chronic systemic signs (elevated WBC) [21][22][23] and local tissue inflammation (rise in oxidative stress and DNA damage) 4 . Several months were required to develop T2D in the experimental pigs, mimicking the situation of overweight and obese children gaining insulin resistance at young age 24 . ...
To reveal the sources of obesity and type 2 diabetes (T2D) in humans, animal models, mainly rodents, have been used. Here, we propose a pig model of T2D. Weaned piglets were fed high fat/high sugar diet suppling 150% of metabolizable energy. Measurements of weight gain, blood morphology, glucose plasma levels, cholesterol, and triglycerides, as well as glucose tolerance (oral glucose tolerance test, OGTT) were employed to observe T2D development. The histology and mass spectrometry analyses were made post mortem. Within 6 months, the high fat-high sugar (HFHS) fed pigs showed gradual and significant increase in plasma triglycerides and glucose levels in comparison to the controls. Using OGTT test, we found stable glucose intolerance in 10 out of 14 HFHS pigs. Mass spectrometry analysis indicated significant changes in 330 proteins in the intestine, liver, and pancreas of the HFHS pigs. These pigs showed also an increase in DNA base modifications and elevated level of the ALKBH proteins in the tissues. Six diabetic HFHS pigs underwent Scopinaro bariatric surgery restoring glycaemia one month after surgery. In conclusion, a high energy diet applied to piglets resulted in the development of hyperlipidaemia, hyperglycaemia, and type 2 diabetes being reversed by a bariatric procedure, excluding the proteomic profile utill one month after the surgery.
... In ISR, insulin downregulates the PI3K/AKT pathway, primarily stimulating the MAPK pathway, resulting in decreased NO release, which in turn promotes smooth muscle proliferation, cellular migration, and plaque formation. Secondly, IR-induced release of pro-inflammatory factors and free fatty acids may also contribute to the pathophysiology of ISR [23,24]. ...
Background
Insulin resistance (IR) can lead to cellular metabolic disorders, activation of oxidative stress, and endothelial dysfunction, contributing to in-stent restenosis (ISR). The triglyceride-glucose index (TyG index), a new indicator reflecting IR, is extensively researched in the cardiovascular field. This study, through a meta-analysis, aimed to utilize a larger combined sample size and thereby enhance the overall test efficacy to explore the TyG index-ISR relationship.
Methods
A thorough search was conducted in the PubMed, EMBASE, Web of Science, and Cochrane Library databases to find original papers and their references published between 1990 and January 2024. This search included both prospective and retrospective studies detailing the correlation between the TyG index and ISR in individuals with coronary heart disease (CHD).
Outcomes
The five included articles comprised 3,912 participants, and the odds ratio (OR) extracted from each study was combined using the Inverse Variance method. Results showed that, in the context of CHD patients, each incremental unit in the TyG index, when treated as a continuous variable, corresponded to a 42% elevation in ISR risk (95% CI 1.26–1.59, I²=13%, p < 0.005). When analyzing the TyG index categorically, the results revealed a higher ISR risk in the highest TyG index group compared to the lowest group (OR: 1.69, 95% CI 1.32–2.17, I²=0). Additionally, in patients with chronic coronary syndrome (CCS), each unit increase in the TyG index, the risk of ISR in patients increased by 37% (95% CI 1.19–1.57, I²=0%, p < 0.005). This correlation was also observable in acute coronary syndrome (ACS) patients (OR:1.48, 95% CI 1.19–1.85, I²=0, p < 0.005).
Conclusions
The TyG index, an economical and precise surrogate for IR, is significantly linked with ISR. Furthermore, this correlation is unaffected by the type of coronary heart disease.
... These larger fat cells promote the secretion of a range of inflammatory molecules [351,354,357,[367][368][369][370][371][372][373][374][375], including the cytokines (8 in Fig. 1.12) which act on the liver, pancreas, skeletal muscles, and brain to interfere with insulin signalling, worsening IR, and producing central obesity. ...
... These larger fat cells promote the secretion of a range of inflammatory molecules [351,354,357,[367][368][369][370][371][372][373][374][375], including the cytokines (8 in Fig. 1.12) which act on the liver, pancreas, skeletal muscles, and brain to interfere with insulin signalling, worsening IR, and producing central obesity. ...
... While emerging clinical epidemiological studies have proved the good predicting performance of the TyG index in the onset and progress of diseases, the exact underlying biological mechanisms remained less studied. Compelling evidence indicated that insulin resistance was closely related to endothelial dysfunction, oxidative stress, and inflammatory response of the systemic metabolism [60][61][62]. As early signs of insulin resistance, TyGrelated indices could help to inflect the pro-inflammatory condition of the participants and indicate the vulnerability to the severity and progress of diseases. ...
Background
Triglyceride-glucose (TyG) index has been determined to play a role in the onset of metabolic syndrome (MetS). Whether the TyG index and TyG with the combination of obesity indicators are associated with the clinical outcomes of the MetS population remains unknown.
Method
Participants were extracted from multiple cycles of the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 years. Three indicators were constructed including TyG index, TyG combining with waist circumference (TyG-WC), and TyG combining with waist-to-height ratio (TyG-WHtR). The MetS was defined according to the National Cholesterol Education Program (NCPE) Adult Treatment Panel III. Kaplan-Meier (KM) curves, restricted cubic splines (RCS), and the Cox proportional hazard model were used to evaluate the associations between TyG-related indices and mortality of the MetS population. The sensitive analyses were performed to check the robustness of the main findings.
Results
There were 10,734 participants with MetS included in this study, with 5,570 females and 5,164 males. The median age of the study population was 59 years old. The multivariate Cox regression analyses showed high levels of TyG-related indices were significantly associated with the all-cause mortality of MetS population [TyG index: adjustedhazard ratio (aHR): 1.36, 95%confidence interval (CI): 1.18–1.56, p < 0.001; TyG-WHtR index: aHR = 1.29, 95%CI: 1.13–1.47, p < 0.001]. Meanwhile, the TyG-WC and TyG-WHtR index were associated with cardiovascular mortality of the MetS population (TyG-WC: aHR = 1.45, 95%CI: 1.13–1.85, p = 0.004; TyG-WHtR: aHR = 1.50 95%CI: 1.17–1.92, p = 0.002). Three TyG-related indices showed consistent significant correlations with diabetes mortality (TyG: aHR = 4.06, 95%CI: 2.81–5.87, p < 0.001; TyG-WC: aHR = 2.55, 95%CI: 1.82–3.58, p < 0.001; TyG-WHtR: aHR = 2.53 95%CI: 1.81–3.54, p < 0.001). The RCS curves showed a non-linear trend between TyG and TyG-WC indices with all-cause mortality (p for nonlinearity = 0.004 and 0.001, respectively). The sensitive analyses supported the positive correlations between TyG-related indices with mortality of the MetS population.
Conclusion
Our study highlights the clinical value of TyG-related indices in predicting the survival of the MetS population. TyG-related indices would be the surrogate biomarkers for the follow-up of the MetS population.
... Existing literature highlights the high prevalence of insulin resistance in patients with RA compared to the general population [4,5], which has also been demonstrated in a recent meta-analysis by Cai et al. [6]. Insulin resistance is not just a parallel condition but is directly implicated in the exacerbation of RA symptoms; further investigation of this relationship has revealed insulin resistance as a mechanistic component of RA flares, contributing to the further debilitation of the patient's quality of life [7,8]. While several inflammatory cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNF-α) have been implicated in the etiology and pathogenesis of RA [9], TNF-α has also been found to impairinsulin sensitivity and promote insulin resistance by causing defects in the insulin signaling cascade [10]. ...
Background and aim: Increasing evidence demonstrates a link between the chronic inflammatory state in patients
with rheumatoid arthritis (RA) and the development of insulin resistance. It is thought that anti-TNF-α biologic
therapy may improve insulin sensitivity and ameliorate insulin resistance by the downregulation of inflammatory
cytokines, however, pre-clinical and clinical studies have yielded conflicting results. A meta-analysis on this topic
is necessary to summarize current evidence and generate hypotheses for future research.
Methods: Literature search was performed in four databases, namely PubMed, EMBASE, Scopus, and The
Cochrane Library, from inception till April 9, 2023, querying studies reporting peripheral insulin resistance with
and without anti-TNF-α use in patients with RA. Peripheral insulin resistance or sensitivity was quantified by the
Homeostasis Model Assessment of Insulin Resistance (HOMA) index or the Quantitative Insulin Sensitivity Check
Index (QUICKI) respectively. The difference in insulin resistance or sensitivity between the treatment and control
group was calculated using standardized mean difference (SMD) for the purposes of the meta-analysis.
Results: Twelve articles were reviewed, with 10 longitudinal studies with a total of 297 patients included in the
meta-analysis. The pooled standardized mean difference (SMD) from baseline HOMA was − 0.82 (95% CI: − 1.38
to − 0.25) suggesting significant beneficial effects of anti-TNF-α therapy on insulin resistance.
Conclusion: Current evidence supports the significant clinical efficacy of anti-TNF-α biologics in alleviating insulin
resistance and improving insulin sensitivity in patients with active RA.
... Diabetes mellitus (DM) has been reported to affect the male gonad negatively, with a decrease in fertility rate (11,12) Mounting evidence from both clinical and experimental studies have demonstrated decreased fertility rates which has been linked with testicular inflammation (13) . The role of the immune system in development of T2D has gained interest in recent years such that a growing number of studies have highlighted the involvement of inflammatory biomarkers in the pathogenesis of T2D (14,15) . Studies have shown that adiposity, insulin resistance, and hyperglycemia can induce systemic inflammation through stimulating the production of proinflammatory proteins such as C-reactive protein and cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) (16) . ...
In vascularized tissues, inflammation is a complex and dynamic defensive response to cell injury, infection by bacteria, trauma, or toxins. Inflammatory biomarkers are molecules that regulate the inflammatory response in all immune system cells. Numerous mediators are released from the attack site, and different host immune system cells infiltrate the area during inflammation. Without the combination of regulated leukocyte population migration, different inflammatory mediators, inflammatory biomarkers (acute or systemic inflammatory marker), and subsequent physiologic changes that carry inflammatory responses, it would be impossible to assemble and regulate inflammatory responses. This study focuses on the attenuating potential of modified diets on testicular inflammatory biomarkers in streptozotocin-induced diabetic Wistar rats. Ninety-six adults male Wistar rats were divided into four units, of four groups/unit and each group consisting of six rats. Unit 1 is non-diabetic unit, whereas Units 2, 3, and 4 were induced with type 2 diabetes. While the rats in group one in all the units were fed with standard rat chaw, group 2 received HFD, group three received HPD, while groups four received HCD. Alpha lipoic acid (200 mg/kg body weight) and metformin (50 mg/kg body weight) were also given to the rats in units three and four, respectively. After 12 weeks of treatment and feeding, each rat was euthanized and testes were excised for biochemical analysis. Data were examined using GraphPad Prism. Two-way analysis of variance (ANOVA) was used to examine the mean variations between groups. The Tukey post hoc test was then performed, with p-values of 0.05 being deemed statistically significant. According to the current study's findings, high-protein meals, both by themselves and in conjunction with ALA, reduce blood glucose levels and the inflammatory damage brought on by streptozotocin toxicity. For this reason, they may be utilized to treat diabetes mellitus and autoimmune-induced inflammation.
... Inflammatory processes have been identified as possible risk factors for obesity, insulin resistance, type 2 diabetes (T2D) and cardiovascular disease (16,17) . However, studies assessing the associations between different types of dairy and inflammatory biomarkers are scarce and have been mainly conducted in adults (18) . ...
OBJECTIVE
The aim of this analysis was to investigate whether habitual intake of total dairy (TD) or different dairy types (liquid, solid, fermented, not-fermented, low-fat, high-fat, low-sugar and high-sugar dairy) during adolescence is associated with biomarkers of low-grade inflammation as well as risk factors of type 2 diabetes in young adulthood.
DESIGN
Multivariable linear regression analyses were used to investigate prospective associations between estimated TD intake as well as intake of different types of dairy and a pro-inflammatory score, based on hsCRP, IL-6, IL-18, leptin and adiponectin, and insulin resistance assessed as HOMA2-IR in an open cohort study.
SETTING
Dortmund, Germany
PARTICIPANTS
Data from participants (n=375) of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study were included, for whom at least two 3-day weighed dietary records during adolescence (median age: 11 years) and one blood sample in young adulthood (>18 years) were available.
RESULTS
There was no statistically significant association between TD intake or intake of any dairy type and the pro-inflammatory score (all p>0.05). TD intake as well as each dairy type intake and insulin resistance also showed no association (all p>0.05).
CONCLUSIONS
The habitual intake of dairy or individual types of dairy during adolescence does not seem to have a major impact on low-grade systemic inflammation and insulin resistance in the long term. There was no indication regarding a restriction of dairy intake for healthy children and adolescents in terms of diabetes risk reduction.
... Other sources include the highly cited work of Monteiro and Azevedo [110] (14%), the NIH's 2022 updated definition of atherosclerosis [111] (12%), and a chapter by Tornheim and Ruderman [112] (10%). The remaining components come from the highly cited overview of Bastien et al. [113], a classic study by Mayer-Davis et al. [114], the authoritative review of Mottillo et al. [115], and the well-known work of Shoelson et al. [116]; previous subsections completed this subsystem (black arrows). Relationships causing an increase are depicted by plain arrows, while those causing a decrease are depicted by dashed arrows. ...
The Provincial Health Services Authority (PHSA) of British Columbia suggested that a paradigm shift from weight to well-being could address the unintended consequences of focusing on obesity and improve the outcomes of efforts to address the challenges facing both individuals and our healthcare system. In this paper, we jointly used artificial intelligence (AI) and participatory modeling to examine the possible consequences of this paradigm shift. Specifically, we created a conceptual map with 19 experts to understand how obesity and physical and mental well-being connect to each other and other factors. Three analyses were performed. First, we analyzed the factors that directly connect to obesity and well-being, both in terms of causes and consequences. Second, we created a reduced version of the map and examined the connections between categories of factors (e.g., food production, and physiology). Third, we explored the themes in the interviews when discussing either well-being or obesity. Our results show that obesity was viewed from a medical perspective as a problem, whereas well-being led to broad and diverse solution-oriented themes. In particular, we found that taking a well-being perspective can be more comprehensive without losing the relevance of the physiological aspects that an obesity-centric perspective focuses on.
... The significant health and economic impact of T2D has led to intense interest over the past 4 decades in the molecular mechanisms that underlie the development of T2D (Shoelson et al., 2006). Multiple mechanisms that have strong supporting evidence have been proposed. ...
It is now well-accepted that obesity-induced inflammation plays an important role in the development of insulin resistance and type 2 diabetes. A key source of the inflammation is the murine epididymal and human visceral adipose tissue. The current paradigm is that obesity activates multiple proinflammatory immune cell types in adipose tissue, including adipose-tissue macrophages (ATMs), T Helper 1 (Th1) T cells, and natural killer (NK) cells, while concomitantly suppressing anti-inflammatory immune cells such as T Helper 2 (Th2) T cells and regulatory T cells (Tregs). A key feature of the current paradigm is that obesity induces the anti-inflammatory M2 ATMs in lean adipose tissue to polarize into proinflammatory M1 ATMs. However, recent single-cell transcriptomics studies suggest that the story is much more complex. Here we describe the single-cell genomics technologies that have been developed recently and the emerging results from studies using these technologies. While further studies are needed, it is clear that ATMs are highly heterogeneous. Moreover, while a variety of ATM clusters with quite distinct features have been found to be expanded by obesity, none truly resemble classical M1 ATMs. It is likely that single-cell transcriptomics technology will further revolutionize the field, thereby promoting our understanding of ATMs, adipose-tissue inflammation, and insulin resistance and accelerating the development of therapies for type 2 diabetes.
... Body iron stores are commonly assessed by serum ferritin, a widely available clinical biomarker to evaluate iron status 8,12 . Cross-sectional studies indicate an independent link between high iron stores and T2DM occurrence 13,14 . And found Ferritin, a reliable marker, has been linked to glycemic status and complications of Diabetes Mellitus, including Retinopathy, Nephropathy, Neuropathy, and Vascular dysfunction 15 . ...
Background: Type 2 diabetes mellitus (T2DM) is a global health concern. Around 56% of subjects in Bangladesh go undiagnosed, increasing the risk of stroke and cardiovascular issues. Iron stores' impact on diabetes is gaining attention, with ferritin as a key biomarker. Hyperferritinemia probably contributes to insulin resistance and subsequently to decreased insulin secretion, causing the development of insulin resistance. The link between ferritin and insulin resistance (IR) varies based on ethnicity, gender, and glycemic state. Objectives: This study investigates serum ferritin levels in different glycemic stages and explores potential correlations between ferritin and insulin resistance markers (blood glucose, serum insulin, and HOMA-IR) Methods: The study was conducted at the Department of Biochemistry, Sir Salimullah Medical College, Dhaka, Bangladesh, from March 2018 to February 2019. A total of 140 subjects were included to conduct this study. Participants were categorized into three groups: those with normal fasting glucose (NFG group), impaired fasting glucose (IFG group), and newly diagnosed type 2 diabetes mellitus (Diabetic group) according to WHO (2006) criteria. A purposive convenient sampling method was used, focusing on adults aged 25 to 55 years. Exclusion criteria were applied to eliminate individuals with inflammatory diseases, chronic conditions, major cardiovascular events, anemia, or specific medications that could affect ferritin levels. Results: The study found that serum ferritin levels significantly differed among three glycemic groups (NFG, IFG, and T2DM) with higher levels in T2DM. IFG and T2DM groups also had elevated serum insulin and HOMA-IR. Serum ferritin correlated strongly with fasting blood glucose, serum insulin, HOMA-IR, and BMI. The highest tertile of ferritin levels were associated with the IFG & diabetic group. Conclusion. Elevated serum ferritin levels in IFG and type 2 diabetes may significantly impact glucose regulation. Compared to NFG, there are high insulin resistance markers (fasting insulin, glucose, HOMA-IR) in T2DM and IFG. They have crucial implications for both therapy and prognosis in these conditions. Mugda Med Coll J. 2023; 6(2): 57-63
... Activation of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), CRPs, interleukin-6, plasminogen activation factor inhibitor-1, and leptin has been understood as a core pathophysiology in the mechanism by which obesity (including severe subcutaneous fat) causes systemic inflammation [33][34][35][36], which ultimately leads to IR and T2DM [37]. In these process, activation of the nuclear factor-κB (NF-κB) pathway and c-Jun NH2-terminal kinase (JNK) pathway due to endoplasmic reticulum (ER) stress, reactive oxygen species, and ceramide was found to play a underlying key role [38][39][40][41][42][43]. IR and NAFLD are cross-talked with each other [10], and the relationship may be independent of the severity of obesity [44,45]. ...
It has been generally accepted that insulin resistance (IR) and reduced insulin secretory capacity are the basic pathogenesis of type 2 diabetes mellitus (T2DM). In addition to genetic factors, the persistence of systemic inflammation caused by obesity and the associated threat of lipotoxicity increase the risk of T2DM. In particular, the main cause of IR is obesity and subjects with T2DM have a higher body mass index (BMI) than normal subjects according to recent studies. The prevalence of T2DM with IR has increased with increasing BMI during the past three decades. According to recent studies, homeostatic model assessment of IR was increased compared to that of the 1990s. Rising prevalence of obesity in Korea have contributed to the development of IR, non-alcoholic fatty liver disease and T2DM and cutting this vicious cycle is important. My colleagues and I have investigated this pathogenic mechanism on this theme through clinical and experimental studies over 20 years and herein, I would like to summarize some of our studies with deep gratitude for receiving the prestigious 2023 Sulwon Award.
... Some studies show a significant increment in blood glucose level after vaccination, and no studies till date have shown a significant decrease in blood glucose level after vaccination. Shoelson et al. [28] described that the extent of activation of inflammatory pathways by vaccination is generally insufficient to produce tangible effects on mean blood glucose levels or glucose variability. Even though Heald has reported that the COVID-19 vaccination can cause temporary relative hyperglycaemia in people with T1DM, the need for insulin dose adjustment in these patients is almost non-existent. ...
Objective
COVID-19 vaccination is recommended in diabetic patients since diabetes is associated with worse clinical outcomes in COVID-19 infection. The safety profile of different types of COVID-19 vaccines, especially on glycemic control, can be explored due to availability of data from continuous glucose monitoring (CGM) devices. This meta-analysis aimed to quantify the impact of COVID-19 vaccination on glycemic control in patients with type 1 diabetes mellitus (T1DM).
Methods
A systematic search of PubMed, Embase, and Google Scholar was conducted using a search strategy for studies published till January 2023 in English language. Comparative observational studies reporting glycemic control obtained from CGM before and after COVID-19 vaccination in T1DM patients were included. The primary outcome was time in range (TIR) metric of proportion of glucose results falling within the range: 3.9–10 mmol/L. Other outcomes were time above range (TAR) (>10 mmol/L), time below range (TBR) (<3.9 mmol/L), coefficient of variation (CV), and mean blood glucose levels. The pooled outcomes were compared pre- and post-vaccination using Hedges’ g (HG) with 95% confidence interval (CI).
Results
A total of seven studies (632 participants) were included in the meta-analysis. COVID-19 vaccination caused small and statistically insignificant decrease in TIR after both the first (HG = 0.21, 95% CI: -0.02-0.44, P =0.07) and second dose (HG = 0.09, 95% CI: -0.04-0.21, P = 0.19). Likewise, TAR was not affected after neither first (HG = -0.09, 95% CI: -0.22-0.03, P = 0.12) nor second vaccine dose (HG = -0.07, 95% CI: -0.21-0.06, P = 0.30). Likewise, TBR, mean blood glucose levels, and CV were not significantly altered following uptake of either of the doses.
Conclusion
COVID-19 vaccination has an excellent safety profile in in T1DM patients owing to its minimal impacts on immediate glycemic control.
... It is well known that obesity is linked to systemic inflammation, which further triggers systemic and tissue insulin resistance [42,43]. Next, we examined the inflammatory profiles of myeloid-specific Ghsrdeficient mice under DIO. ...
Objective
Obesity-associated chronic inflammation, aka meta-inflammation, is a key pathogenic driver for obesity-associated comorbidity. Growth hormone secretagogue receptor (GHSR) is known to mediate the effects of nutrient-sensing hormone ghrelin in food intake and fat deposition. We previously reported that global Ghsr ablation protects against diet-induced inflammation and insulin resistance, but the site(s) of action and mechanism are unknown. Macrophages are key drivers of meta-inflammation. To unravel the role of GHSR in macrophages, we generated myeloid-specific Ghsr knockout mice (LysM-Cre;Ghsrf/f).
Methods
LysM-Cre;Ghsrf/f and control Ghsrf/f mice were subjected to 5 months of high-fat diet (HFD) feeding to induce obesity. In vivo, metabolic profiling of food intake, physical activity, and energy expenditure, as well as glucose and insulin tolerance tests (GTT and ITT) were performed. At termination, peritoneal macrophages (PMs), epididymal white adipose tissue (eWAT), and liver were analyzed by flow cytometry and histology. For ex vivo studies, bone marrow-derived macrophages (BMDMs) were generated from the mice and treated with palmitic acid (PA) or lipopolysaccharide (LPS). For in vitro studies, macrophage RAW264.7 cells with Ghsr overexpression or Insulin receptor substrate 2 (Irs2) knockdown were studied.
Results
We found that Ghsr expression in PMs was increased under HFD feeding. In vivo, HFD-fed LysM-Cre;Ghsrf/f mice exhibited significantly attenuated systemic inflammation and insulin resistance without affecting food intake or body weight. Tissue analysis showed that HFD-fed LysM-Cre;Ghsrf/f mice have significantly decreased monocyte/macrophage infiltration, pro-inflammatory activation, and lipid accumulation, showing elevated lipid-associated macrophages (LAMs) in eWAT and liver. Ex vivo, Ghsr-deficient macrophages protected against PA- or LPS-induced pro-inflammatory polarization, showing reduced glycolysis, increased fatty acid oxidation, and decreased NF-κB nuclear translocation. At molecular level, GHSR metabolically programs macrophage polarization through PKA-CREB-IRS2-AKT2 signaling pathway.
Conclusions
These novel results demonstrate that macrophage GHSR plays a key role in the pathogenesis of meta-inflammation, and macrophage GHSR promotes macrophage infiltration and induces pro-inflammatory polarization. These exciting findings suggest that GHSR may serve as a novel immunotherapeutic target for the treatment of obesity and its associated comorbidity.
... FFA and hepatic TG stimulate the reduction in insulininduced glucose uptake and cause intracellular inflammation [38,39]. In addition, a subacute inflammatory response with oxidative stress in the endoplasmic reticulum (ER) could trigger hepatic steatosis [40]. Moreover, hyperinsulinemia and hypoglycemia resulting from insulin resistance led to imbalances in lipid input relative to lipid output and promoted hepatic steatosis [41,42]. ...
Nonalcoholic fatty liver disease (NAFLD), which can manifest as nonalcoholic steatohepatitis (NASH) or severe fibrosis, is the most prevalent chronic liver disease in children and adolescents. However, there is no proven cure for it so far. This study was conducted to determine whether adolescents with NAFLD would improve with treatment intervention with orlistat. This study is a randomized controlled trial (RCT). Fifty-three adolescents with overweight/obese as well as with NAFLD randomly allocated to receive orlistat (n = 27) or placebo as control (n = 26) for 12 weeks. In addition, NAFLD activity score, anthropometric factors, biochemical parameters including serum levels of lipid profiles, liver enzyme, and glucose metabolism taken from subjects at baseline and end of the study were investigated. The findings of our article indicated that orlistat improves liver enzymes (alanine transaminase and aspartate transaminase) (P = < 0.001), steatosis score (P = 0.001), NAFLD activity score (P = < 0.001), weight (P = < 0.001), body mass index (BMI) (P = < 0.001), waist circumferences (WC) (P = < 0.001), BMI-Z score (P = < 0.001), glucose metabolism (P = 0.001), total cholesterol (TC) (P = 0.009), low density lipoprotein-cholesterol (LDL) (P = < 0.001), and high density lipoprotein-cholesterol HDL levels (P = 0.014) compared to the control group after adjusting for possible confounders for 12 weeks. However, no significant changes were observed on triglyceride (TG) following intake of orlistat compared to placebo after adjusting for confounders.
Conclusion: The findings of our study reported that orlistat improved NAFLD-related factors and metabolic syndrome-related factors compared to placebo for 12 weeks.
... Notably, as far back as 1876, Ebstein demonstrated the potential benefits of sodium salicylate in alleviating symptoms of diabetes [3]. Over the past few decades, diabetes and its associated vascular complications have been increasingly recognized as chronic low-grade inflammatory conditions [4][5][6][7]. Proinflammatory cytokines, such as tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and nuclear factor B (NF-B), have been implicated in the activation of various intracellular inflammatory signaling pathways, including JNK and IKK, which can lead to glucose and insulin resistance [4,6,8]. Moreover, the involvement of inflammasomes like NLRP3, critical components of inflammatory activation, in the production of interleukin-1 beta (IL-1) has been linked to islet-cell mass and function [4,9,10]. ...
Purpose
There have been limited studies examining the prospective association between the Systemic Immune-Inflammation Index (SII), a novel inflammatory marker, and mortality among individuals with diabetes in the United States.
Methods
We utilized data from the National Health and Nutrition Examination Survey (NHANES), a representative sample of US adults, linked with information from the National Death Index.
Results
Our study included 8697 individuals from NHANES spanning the years 1999 to 2018. SII was calculated by dividing the platelet count by the neutrophil count and then dividing that result by the lymphocyte count. We employed multivariable Cox proportional hazards regression analysis to investigate the associations between SII levels and all-cause as well as cause-specific mortality, while adjusting for potential confounding factors. SII levels were categorized into quartiles based on the study population distribution. Over a median follow-up period of 94.8 months (with a maximum of 249 months), we observed a total of 2465 all-cause deaths, 853 deaths from cardiovascular causes, 424 deaths from cancer, and 88 deaths related to chronic kidney disease. After adjusting for multiple variables, higher SII levels were significantly and non-linearly associated with an increased risk of all-cause mortality in Quartile 4 (HR 1.74, 95% CI 1.15–2.63, P for trend = 0.043) when Quartile 1 was used as the reference group. Additionally, we identified a linear association between SII and cardiovascular mortality, with a 70% higher risk of cardiovascular mortality in Quartile 4 (HR 1.70, 95% CI 1.18–3.30, P for trend = 0.041) compared to Quartile 1.
Conclusion
Our findings indicate that SII is significantly associated with an elevated risk of all-cause and cardiovascular mortality in US adults with diabetes.
... (44,45) On the other hand, MUFAs are considered to be a healthy type of fat that can help lower cholesterol levels, improve insulin sensitivity, impact positively on fat distribution, and reduce oxidative stress and inflammation. (46)(47)(48) However, the specific relationship between Zn and MUFA intake and the development of multiple chronic conditions, particularly in the context of multimorbidity, is not well established and requires further research. Understanding the intricate interplay between Zn and MUFA intake and their impact on underlying biological processes, such as inflammation, oxidative stress, and immune function, could provide crucial insights for developing targeted dietary interventions aimed at mitigating the burden of multimorbidity and/or specific chronic diseases. ...
Research on the link between diet and multimorbidity is scarce, despite significant studies investigating the relationship between diet and individual chronic conditions. This study examines the association of dietary intake of macro- and micronutrients with multimorbidity in Cyprus's adult population. It was conducted as a cross-sectional study, with data collected using a standardised questionnaire between May 2018 and June 2019. The questionnaire included sociodemographic information, anthropometrics, medical history, dietary habits, sleep quality, smoking habits, and physical activity. The participants were selected using a stratified sampling method from adults residing in the five government-controlled municipalities of the Republic of Cyprus. The study included 1137 adults with a mean age of 40⋅8 years, of whom 26 % had multimorbidity. Individuals with multimorbidity consumed higher levels of sodium ( P = 0⋅009) and vitamin A ( P = 0⋅010) compared to those without multimorbidity. Additionally, higher fibre and sodium intake were also observed in individuals with at least one chronic disease of the circulatory system or endocrine system, compared to those with no chronic diseases in these systems ( P < 0⋅05). Logistic regression models revealed that individuals with ≥2 chronic diseases compared to 0 or 1 chronic disease had higher fat intake (OR = 1⋅06, 95 % CI: 1⋅02, 1⋅10), higher iron intake (OR = 1⋅05, 95 % CI: 1⋅01, 1⋅09), lower mono-unsaturated fat intake (OR = 0⋅91, 95 % CI: 0⋅86, 0⋅96), and lower zinc intake (OR = 0⋅98, 95 % CI: 0⋅96, 0⋅99). Future research should replicate these results to further explore the intricate relationships between nutrient intake and multimorbidity. Our study's findings suggest that specific dietary components may contribute to preventing and managing multimorbidity.
... However, iInsulin resistance may overwork the β cell function and combined with iron toxicity, can lead to IGT and DM(Flynn et al 1976 ;Chern et al 2001 ;Suvarna et al 2006).Moreover, this insulin resistance may be mediated through ironmediated activation of inflammation and release of inflammatory markers that induce insulin resistance in the liver and other body tissues.(Rabinovitch et al 1998;Reimers et al 1998;Senn et al 2002;Steven et al 2006 ;Morabito et al 2007;Mahachoklertwattana et al 2010;Park et al 2010). ...
Objective:
Both insulin deficiency and insulin resistance are reported in patients with β thalassemia major (TM). The use of continuous blood glucose monitoring system (CGMS) among the different methods for early detection of glycaemic abnormalities has not been studied thoroughly in these patients.
Aims of the study:
The aims of this study were: 1. to evaluate glycaemic abnormalities, if any, in young adult patients with TM using oral glucose tolerance test (OGTT) and 72-h continuous glucose concentration by CGMS, And to compare the results of these two methods in evaluating glycemic abnormalities.
2. To calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) in these patients.
In order to evaluate whether glycaemic abnormalities are due to insulin deficiency and /or resistance.
Materials and methods:
In this study, 14 TM patients were selected randomly. All patients were investigated using a standard 75 gm oral glucose tolerance test (OGTT) and 72-h continuous glucose concentration by CGM system (Medtronic system). Fasting serum insulin and C-peptide concentrations were also measured. HOMA-B, HOMA-IR were calculated using what? And QUICKI index.
Results:
Using OGTT, 5 patients had impaired fasting glucose (IFG) only, 2 had both IFG and IGT (glucose < 11.1 mmol/L) and 1 had diabetes. In contrast, by CGMS 6 patients had IFG only (Check), 8 patients had (57%) (IGT) 4 patients (28.5%) were Diabetics with glucose level ≥11.1 mmol/L.
The mean values of HOMA and QUICKI in patients with TM were < 2.6 (1.6± 0.8) ( Mean +/- SD and > 0.33 (0.36±0.03) respectively ruling out significant insulin resistance in these adolescents. There was a significant negative correlation between the β-cell function (B %) and the Fasting and the 2- h BG (r= -0.6, and - 0.48, P< 0.01 respectively). Serum insulin concentrations were not correlated with fasting BG or ferritin levels. The average and maximum BG levels recorded by CGMS were significantly correlated with the fasting BG (r= 0.69 and 0.6 respectively with P < 0.01) and with the BG at 2-hour after oral glucose intake (r= 0.87and 0.86 respectively with P < 0.01). Ferritin concentrations were positively correlated with the fasting BG and the 2-h BG levels in the OGTT (r= 0.69, 0.43 respectively, P < 0.001) as well as with the average and the maximum BG recorded by CGM (r =0.75, and 0.64 respectively with P < 0.01). Ferritin concentrations were negatively correlated with the β-cell function (r= -0.41, P< 0.01).
Conclusion:
Our data suggest that CGMS is more sensitive than OGTT in detecting glycaemic abnormalities in young adult patients with β thalassemia major furthermore our data suggest that defective β-cell function rather than insulin resistance appears to be the cause for these abnormalities in our patients.
... La sarcopenia entre sus teorías explicativas; se asocia a la ocurrencia del estado inflamatorio persistente, resistencia a la insulina secundaria y el aumento de tejido adiposo muscular 9, 10 . ...
Objetivos: El presente estudio plantea caracterizar la relación entre la elevación de la Gama Glutamil Transferasa sérica y sarcopenia en pacientes adultos mayores con fracturas hospitalizados en el Hospital Clínico Viedma durante los meses de diciembre 2021 a mayo del 2022. Material y Métodos: Se realizó un estudio observacional analítico de cohorte, prospectivo, longitudinal; con enfoque positivista cuantitativo, donde se validó clínicamente el Riesgo Relativo de ocurrencia de fractura ante la elevación de Gama Glutamil Transferasa sérica. Resultados: En una población de 22 pacientes ancianos hospitalizados con diagnostico de fractura; se estableció la relación de riesgo relativo de 2.2 [IC: 1.15 – 4.20] entre la elevación de gamaglutamil trasnferasa sérica y la ocurrencia de sarcopenia. Asi como se demostró que la elevación de los niveles séricos de gama glutamil transferasa representa mayor riesgo de disminución de la fuerza muscular a partir del análisis de regresión Log-lin entre las variables género y severidad de elevación de gama glutamil transferasa, demostrando una mayor relación predictiva de sarcopenia entre el género femenino en los niveles leves y severos de elevación de la GGT, con un valor de frecuencia esperada de predominio en mujeres para leve (recuento esperado 5.5) [p<0.05] y un predominio en mujeres para grave (recuento esperado de 4.5) [p<0.05]
... In the early stages of CKD, patients typically have elevated levels of circulating inflammatory cytokines, such as tissue necrosis factor alpha (TNF-α), interleukin-6, interferon gamma, and lipopolysaccharide. These circulating inflammatory cytokines are produced by various organs in the body, including the kidneys, adipocytes, liver, or muscles [36,Fig. 3 Forest plot showing the predictive power for incident chronic kidney disease by subgroups according to sex and diabetes mellitus, hypertension, smoking, and obesity status. ...
Background
Chronic kidney disease (CKD) has emerged as a mounting public health issue worldwide; therefore, prompt identification and prevention are imperative in mitigating CKD-associated complications and mortality rate. We aimed to compare the predictive powers of the homeostatic model assessment for insulin resistance (HOMA-IR) and the metabolic score for insulin resistance (METS-IR) for CKD incidence in middle-aged and older adults.
Methods
This study used longitudinal prospective cohort data from the Korean Genome and Epidemiology Study. A total of 10,030 participants, aged 40–69 years, residing in the Ansung or Ansan regions of the Republic of Korea, were recruited between 2001 and 2002 through a two-stage cluster sampling method. We compared the predictive powers of METS-IR and HOMA-IR for CKD prevalence and incidence, respectively. CKD prevalence was measured by the area under the receiver operating characteristic (ROC) curve (AUC), and the indices’ predictive performance for CKD incidence were assessed using Harrell’s concordance index and time-dependent ROC curve analysis.
Results
A total of 9261 adults aged 40–69 years at baseline and 8243 adults without CKD were included in this study. The AUCs and 95% confidence intervals (CIs) of HOMA-IR and METS-IR for CKD prevalence at baseline were 0.577 (0.537–0.618) and 0.599 (0.560–0.637), respectively, with no significant difference (p = 0.337). The Heagerty’s integrated AUC for METS-IR in predicting CKD incidence was 0.772 (95% CI 0.750–0.799), which was significantly higher than that of HOMA-IR (0.767 [95% CI 0.742–0.791], p = 0.015).
Conclusion
METS-IR surpassed HOMA-IR in predicting CKD incidence and was as effective as HOMA-IR in predicting CKD prevalence. This implies that METS-IR could be a valuable indicator for early detection and prevention of CKD among Korean adults.
... In our study, individuals with higher TyG index were more likely to be smokers, overweight, and have higher prevalence rates of diabetes, hyperlipidemia, cardiovascular disease, and chronic kidney disease. Second, as mentioned earlier, the TyG index is a favorable biomarker of IR which is associated with chronic inflammation, oxidative stress, and endothelial dysfunction of the vascular wall [38,50]. All of these contribute to the development and progression of hypertension and stiffness [22]. ...
Background
Prior research has established the correlation between insulin resistance (IR) and hypertension. While the association between triglyceride-glucose (TyG) index, a reliable surrogate marker of IR, and uncontrolled hypertension as well as arterial stiffness among individuals with hypertension remains undisclosed.
Methods
In this study, a total of 8513 adults diagnosed with hypertension from the National Health and Nutrition Examination Survey 1999–2018 were included. The primary outcome of the study are arterial stiffness (represented with estimated pulse wave velocity, ePWV) and uncontrolled hypertension. Logistic regression model, subgroup analysis, restricted cubic spine, and smooth curve fitting curve were conducted to evaluate the association between the IR indicators and uncontrolled hypertension and arterial stiffness in individuals with hypertension.
Results
Among included participants, the overall prevalence of uncontrolled hypertension was 54.3%. After adjusting for all potential covariates, compared with the first quartile of TyG index, the risk of uncontrolled hypertension increased about 28% and 49% for participants in the third quartile (OR, 1.28; 95% CI 1.06–1.52) and the fourth quartile (OR, 1.49; 95% CI 1.21–1.89) of TyG index, respectively. The higher OR of TyG index was observed in participants taking antihypertensive medication [fourth quartile versus first quartile (OR, 2.03; 95% CI 1.37–3.11)]. Meanwhile, we explored the potential association between TyG index and arterial stiffness and found that TyG index was significantly associated with increased arterial stiffness (β for ePWV, 0.04; 95% CI 0.00–0.08; P = 0.039). However, traditional IR indicator HOMA-IR showed no significant positive correlation to uncontrolled hypertension as well as arterial stiffness in US adults with hypertension.
Conclusion
Elevated levels of the TyG index were positive associated with prevalence of uncontrolled hypertension and arterial stiffness among US adults with hypertension.
... Increases in body fat alter the body's response to insulin, potentially leading to insulin resistance. Increased fat also creates a proinflammatorystate [24,25] and a prothrombotic state [23,26]. This studied aimed to matured some inflammatory and Biochemical parameter and compared results between lean and obese women. ...
The present study aims to detecting several biochemical markers and cytokines in obese and normal lean Iraqi women. Forty women (20 obese and 20 lean) were chosen from different areas in Baghdad city there ages ranges between 20-37 years and body mass index (BMI) between 20.75-35.6 Kg/m². The study showed a high significant increment in Fasting Blood Glucose (FBG), serum cholesterol and Homeostasis Model Assessment (HOMA) in obese women as compared with lean and a significant increment in HDL (High Density Lipoprotein) in lean women when compared with obese ones. A significant correlation coefficient (r) was noticed between BMI and studied parameters, FBG, cholesterol, triglyceride, insulin, HOMA, high sensitive C Reactive Protein (hs-CRP), Tumor Necrosis Factor alfa (TNF-α) and IL-6.
... Consequentemente, o risco de câncer de mama, endométrio e possivelmente outros cânceres na pós-menopausa é aumentado (Giovannucci et al., 2010). A inflamação causada pelo aumento da resistência à insulina contribui ainda mais para a formação da complexa interação de câncer e DCV (Shoelson, Lee & Goldfine, 2006). ...
One of the main priorities in the cardiovascular care of cancer patients is to reduce morbidity and mortality and improve the quality of life of cancer survivors through interdisciplinary efforts. The survival rate in cancer patients has improved dramatically over the last few decades. Even in the midst of achievements and advances, survivors may be more likely to die from long-term cardiovascular disease secondary not only to the potential toxicity of cancer therapy but also to cancer biology. In this context, cardio-oncology has been highlighted as a promising field of medicine, obtaining, through studies in this area, relevant information and promising results. Among the initial data, researchers have highlighted the importance of dietary interventions represented by a healthy diet and correct supplementation, and the practice of physical exercises by cancer survivors, with the aim not only of preventing, but also of treating cardiotoxicity and its consequences in the long term.
... Some studies have reported that lymphocytes regulate the production of inflammatory mediators by macrophages and are also essential for obesity-associated inflammation. 29 Lymphocytes are increased in adipose tissue in individuals with diet-induced obesity, insulin resistance, and diabetes. 30 31 It has been suggested that lymphocytes appear to be the major leucocyte subpopulation associated with the development of diabetes. ...
Introduction
There is little bulk clinical evidence on nutritional status and mortality in patients with diabetes. The purpose of this study was to examine the relationship between prognostic nutritional index (PNI) and all-cause mortality and cardiovascular mortality in adults with diabetes.
Research design and methods
This study included 5916 adult patients with diabetes from the National Health and Nutrition Examination Survey 1999–2018. Cox proportional risk models were used to estimate risk ratios (HRs) and 95% CIs for all-cause mortality, cardiovascular disease (CVD) mortality.
Results
During a mean follow-up of 8.17 years, there were 1248 deaths from all causes and 370 deaths from CVD. After multivariate adjustment, the risk of all-cause mortality was reduced by 24%, 38%, and 28% in Q2 (49.0–52.99), Q3 (53.0–57.99), and Q4 (≥58.0), respectively, compared with Q1 (PNI<49.0). The risk of cardiovascular mortality was reduced by 30%, 27%, and 26%, respectively. Consistent results were observed in the subgroup analysis.
Conclusions
Lower serum PNI levels were significantly associated with higher all-cause and CVD mortality. These findings suggest that maintaining an appropriate range of serum PNI status may reduce the risk of death in patients with diabetes.
... Both pathways are simultaneously stimulated by cytokines such as TNF-α and IL -6, but also by lipids. It has been convincingly demonstrated in experimental studies that genetic or chemical inhibition of these pathways can reduce inflammation and improve insulin resistance (for review, see [55] ) (Figure 14.4 ). In obesity, JNK activity is elevated not only in adipose tissue, but also in the liver and muscle. ...
Weight problems are defined as a not unusual chronic sickness of excessive frame fat and has grown to be a global epidemic that is no longer the handiest gift within industrialized international but also in many growing and even underdeveloped nations. At gift, the prevalence of weight problems (described as body mass index [BMI] ≥ 30 kg/m2) is within the range of 15-30% in the growing populations in Europe, North America, and many Arabic international locations, with an unequivocal trend for in addition, increases [1]. This circumstance will increase the risk of growing diffusion of negative results to human health ranging from metabolic disturbances, type 2 diabetes mellitus (T2DM), and cardiovascular headaches to problems with locomotor machines and many types of cancer [2]. In addition, weight problems impair the subjective nice of life in affected human beings and can reduce existence expectancy [3]. Although there is a very specific relationship between excessive frame weight and the risk of diabetes, obesity may additionally result in many other disturbances that can aggravate the diabetic state.
... Because MCP-1 and other cytokines, such as 9 TNF-, IL-6, resistin, leptin, adiponectin, MCP-1, PAI-1, and angiotensinogen, are proteins produced by adipocytes and macrophages, pinpointing precise sites of production is difficult. [10] As a result, adipocytes experience greater lipolysis and reduced triglyceride synthesis. Excessive circulatory free fatty acids (FFAs) and triglyceride buildup in skeletal muscle, liver, and -cells disturb normal activities. ...
... The degree of inflammation may vary within individuals and between tissues and does not necessarily reflect the degree of systemic inflammation. Potential mechanisms involved in this inflammatory response are hypoxia and cell death in the expanding adipose tissue, activation of the inflammation-and stress-induced kinases IκB kinase-β (IKKβ) and JUN N-terminal kinase (JNK), which further stimulate inflammation and insulin resistance [62]. ...
Peripheral artery disease (PAD) is a major health problem with increased cardiovascular mortality, morbidity and disabling critical limb threatening ischemia (CLTI) and amputation. Diabetes mellitus (DM) and cigarette smoke are the main risk factors for the development of PAD. Although diabetes related PAD shows an accelerated course with worse outcome regarding complications, mortality and amputations compared with non-diabetic patients, current medical treatment does not make this distinction and includes standard antiplatelet and lipid lowering drugs for all patients with PAD. In this review we discuss the pathophysiologic mechanisms of PAD, with focus on differences in thrombo-inflammatory processes between diabetes-related and smoking-related PAD, and hypothesize on possible mechanisms for the progressive course of PAD in DM. Furthermore, we comment on current medical treatment and speculate on alternative medical drug options for patients with PAD and DM.
... [13][14][15] Growing studies have emphasized ncRNAs in DM and its complications, proposing that ncRNAs can interact with insulin. 16 Furthermore, there is evidence indicating that ncRNAs might act as diagnostic markers and modulators of diabetic cardiovascular disease. 17-20 Impaired glucose tolerance in T2D is associated with insulin resistance, and insulin shortage impacts glucose consumption in the liver, adipose tissues, and skeletal muscle. ...
Cytokine storms, oxidative stress, and hyperglycemia can enhance the risk of type 2 diabetes (T2D). Moreover, T2D may change the functional and structural heart. However, some signaling pathways, such as insulin resistance, dyslipidemia, and hyperglycemia, can play in T2D, and various pathomechanics and pathophysiology involved in T2D are not understood. Moreover, it is well documented that the non-coding RNAs are potentially pivotal molecules in oxidative stress, inflammation, and cell death signaling pathways. Hence, long non-coding RNAs (lncRNAs) and microRNAs may have vital roles in oxidative stress, inflammation, metabolism, T2D, and cardiovascular systems. Non-coding RNAs can target hub gene networks and suppress or trigger various cascades. Furthermore, lifestyle is the other factor that may affect the prevalence of T2D. A sedentary lifestyle and excessive sitting can enhance inflammation, oxidative stress, and hyperglycemia. Here, we attempt to comprehend the role of hub genes, non-coding RNAs, and unhealthy lifestyles on the pathomechanics and pathophysiology of diabetic vascular complications.
White adipose tissue is not only a highly heterogeneous organ containing various cells, such as adipocytes, adipose stem and progenitor cells, and immune cells, but also an endocrine organ that is highly important for regulating metabolic and immune homeostasis. In individuals with obesity, dynamic cellular changes in adipose tissue result in phenotypic switching and adipose tissue dysfunction, including pathological expansion, WAT fibrosis, immune cell infiltration, endoplasmic reticulum stress, and ectopic lipid accumulation, ultimately leading to chronic low‐grade inflammation and insulin resistance. Recently, many distinct subpopulations of adipose tissue have been identified, providing new insights into the potential mechanisms of adipose dysfunction in individuals with obesity. Therefore, targeting white adipose tissue as a therapeutic agent for treating obesity and obesity‐related metabolic diseases is of great scientific interest. Here, we provide an overview of white adipose tissue remodeling in individuals with obesity including cellular changes and discuss the underlying regulatory mechanisms of white adipose tissue metabolic dysfunction. Currently, various studies have uncovered promising targets and strategies for obesity treatment. We also outline the potential therapeutic signaling pathways of targeting adipose tissue and summarize existing therapeutic strategies for antiobesity treatment including pharmacological approaches, lifestyle interventions, and novel therapies.
The role of inflammation in disease promotion is significant, yet the precise association between a newly identified inflammatory biomarker and insulin resistance (IR) and mortality remains uncertain. We aim to explore the potential correlation between systemic immune-inflammation index (SII) and these factors. We used data from 2011 to 2016 of National Health and Nutrition Examination Survey, and multivariate logistic regression and restricted cubic spline were employed. Subgroup and interaction analysis were conducted to recognize the consistency of the results. The association between SII and mortality was described by survival analysis. 6734 participants were enrolled, of whom 49.3% (3318) exhibited IR and 7.02% experienced mortality. Multivariate logistic regression revealed that individuals in the highest quartile (Q4) of SII had a significantly increased risk of IR compared to those in the lowest quartile (Q1). We then identified a linear association between SII and IR with an inflection point of 407, but may be influenced by gender. Similarly, compared to Q1, people whose SII at Q4 showed a higher all-cause and cardiovascular mortality. It showed a significant association between SII and both all-cause and cardiovascular mortality, but the results need to be interpreted with caution.
Introduction
Subcutaneous fat wasting in HIV therapy is primarily associated with the use of stavudine (d4T) and zidovudine (AZT). We hypothesized that C-reactive protein (CRP) might have an additive effect on nucleoside reverse transcriptase inhibitor (NRTI)-mediated peripheral fat loss.
Methods
3T3-F442A cells were exposed to AZT (6 μM), d4T (3 μM) and/or CRP (0.5 μg/ml) during differentiation. Differentiation was assessed by real-time PCR measurement of peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding protein (C/EBP)α, by quantification of triglyceride accumulation and by determination of adiponectin expression and secretion. In addition, parameters of lipid accumulation, lipolysis, cell viability and apoptosis were examined.
Results
When preadipocytes were induced to differentiate in the presence of only AZT, d4T or CRP, only AZT significantly impaired adipogenic differentiation. When combined, d4T+CRP also led to reduced triacylglycerol accumulation, an effect not explained by CRP-induced apoptosis or cell death, but instead confirmed by reduced PPARγ and C/EBPα expression and decreased expression of factors involved in lipogenesis, such as fatty acid synthase and acetyl-coenzyme A carboxylase. We observed further reduction in adiponectin expression and secretion when adipocytes were differentiated in the presence of AZT or d4T together with CRP. Addition of rosiglitazone (1 μM) had no effect on reduced adipogenesis, but partially rescued the effects of d4T and d4T+CRP on adiponectin production.
Conclusions
We conclude that CRP at levels circulating in patients with HIV infection might promote the anti-adipogenic potential of d4T, a cooperative effect that could account for the in vivo observed variability in the development of lipoatrophy.
Diabetes is the leading cause of chronic kidney disease (CKD) and kidney failure worldwide. CKD frequently coexists with heart failure and atherosclerotic cardiovascular disease in the broader context of cardio-kidney-metabolic syndrome. Diabetes and CKD are associated with increased risk of all-cause and cardiovascular death as well as decreased quality-of-life. The role of metabolic and hemodynamic abnormalities has long been recognized as important contributors to the pathogenesis and progression of CKD in diabetes, while a more recent and growing body of evidence support activation of both systemic and local inflammation as important contributors. Current guidelines recommend therapies targeting pathomechanisms of CKD in addition to management of traditional risk factors such as hyperglycemia and hypertension. Sodium-glucose cotransporter-2 inhibitors are recommended for treatment of patients with CKD and type 2 diabetes (T2D) if eGFR is >20 ml/min/173m2 on a background of renin-angiotensin system inhibition. For patients with T2D, CKD, and atherosclerotic cardiovascular disease, a glucagon-like peptide-1 receptor agonist is recommended as additional risk-based therapy. A non-steroidal mineralocorticoid receptor antagonist is also recommended as additional risk-based therapy for persistent albuminuria in patients with T2D already treated with renin-angiotensin system inhibition. Implementation of guideline directed medical therapies is challenging in the face of rapidly accumulating knowledge, high cost of medications, and lack of infrastructure for optimal healthcare delivery. Furthermore, studies of new therapies have focused on T2D and CKD. Clinical trials are now planned to inform the role of these therapies in people with T1D and CKD.
In the current scenario, the incidence of non-communicable diseases (NCDs) - cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes - is increasing globally. Diabetes is one of the most common NCD diseases in low- and middle-income countries and the main causes are population aging, economic growth, urbanization, unhealthy dietary habits, and sedentary lifestyles. Complications of diabetes have become a serious public health problem. [1]. For 2,000 years, diabetes has been recognized as a devastating and deadly disease. The first-century Greek physician Aretaeus explained the destructive nature of sadness, named "siphon" from the Greek word "siphon". [2] Clinical features similar to diabetes were described by the ancient Egyptians 3,000 years ago. The term "diabetes" was first coined by Aretaus of Cappadocia (a Greek physician). Then, the word mellitus (Honeysweet) was added after Thomas Willis
England) rediscovered the sweetness of urine and blood in patients (first noted by ancient Indians). Only in
1776 Dobson (England) first confirmed the presence of excess sugar in urine and blood as a cause of diabetes. The history of modern diabetes has coincided with the development of experimental drugs. An important stage in the history of diabetes is the overproduction of glucose. Claude Bernard (France) in 1857. A low-calorie diet prolongs life but leaves them weak and hungry. But in 1921, a Canadian doctor treated a dying diabetic patient with insulin and was able to bring his blood sugar back to normal. Since then, medical advances have continued to extend and improve the lives of people with diabetes. [2] The role of the pancreas in the pathogenesis of diabetes was discovered in 1889 by Mering and Minkowski (Austria). This discovery became the basis for the isolation and clinical use of insulin by Banting and Best (Canada) in 1921. In 1995, the development of an oral hypoglycemic agent was released with the first marketing of tolbutamide and carbetamide [3]. In the 1950s, two types of diabetes were identified: "insulin-sensitive" (type I) and "insulin-insensitive" (type II). [2] However, none of these features distinguish one form of diabetes from another and do not
account for the entire spectrum of diabetes phenotypes. There are several reasons to revisit the classification of diabetes. First, the phenotypes of T1DM and T2DM are different, with obesity
increasing at a young age and the incidence of T1DM in adulthood and T2DM occurring in young adults being less different. Second, advances in molecular genetics allow doctors to identify more
common forms of diabetes, which in some cases have important implications for treatment options. In addition, increasing knowledge of pathophysiology has led to the development of
Insulin is a critical hormone that promotes energy storage in various tissues, as well as anabolic functions. Insulin resistance significantly reduces these responses, resulting in pathological conditions, such as obesity and type 2 diabetes mellitus (T2DM). The management of insulin resistance requires better knowledge of its pathophysiological mechanisms to prevent secondary complications, such as cardiovascular diseases (CVDs). Recent evidence regarding the etiological mechanisms behind insulin resistance emphasizes the role of energy imbalance and neurohormonal dysregulation, both of which are closely regulated by autophagy. Autophagy is a conserved process that maintains homeostasis in cells. Accordingly, autophagy abnormalities have been linked to a variety of metabolic disorders, including insulin resistance, T2DM, obesity, and CVDs. Thus, there may be a link between autophagy and insulin resistance. Therefore, the interaction between autophagy and insulin function will be examined in this review, particularly in insulin-responsive tissues, such as adipose tissue, liver, and skeletal muscle.
There are reports of link of osteoprotegerin (OPG) gene polymorphism to type-2 diabetes (T2D) and hypertension (HTN). The objective of the study was to assess the allele frequency of OPG (rs2073618) gene polymorphism and its association with heart rate variability (HRV) and blood pressure variability profile as CVD risks in diabetes mellitus patients with hypertension undergoing treatment. T2D patients on treatment without hypertension (n = 172), with hypertension (n = 177) and 191 healthy volunteers were recruited for the study. Their blood pressure variability including baroreflex sensitivity (BRS), heart rate variability (HRV), OPG, insulin, lipid profile, receptor-activator for NFkB (RANK), receptor-activator for NFkB-Ligand (RANKL), and tumor necrosis factor-α (TNF-α) were estimated. Allele frequency of OPG (rs2073618) gene polymorphism was assessed from the DNA samples. BRS and HRV indices were decreased, and RANKL/OPG and TNF-α were increased in T2D and T2D + HTN groups, respectively compared to healthy control group. The reduction in BRS was contributed by increased inflammation and reduced SDNN of HRV in GG genotype in T2D + HTN. In GG + GC subgroup, it was additionally contributed by rise in RANKL/OPG level (β − 0.219; p 0.008). Presence of mutant GG genotype contributed to the risk of hypertension among T2D patients (OR 3.004) as well as in general population (OR 2.79). It was concluded that CV risks are more in T2D patients with HTN expressing OPG rs2073618 gene polymorphism.
Objectives
The extent to which observed associations between high-sensitivity C-reactive protein (hs-CRP) and incident diabetes are explained by obesity and hypertension remains unclear. This study aimed to investigate the association of hs-CRP with developing diabetes in a Norwegian general population sample.
Design
A cohort study using two population-based surveys of the Tromsø Study: the sixth survey Tromsø6 (2007–2008) as baseline and the seventh survey Tromsø7 (2015–2016) at follow-up.
Setting
Tromsø municipality of Norway, a country with increasing proportion of older adults and a high prevalence of overweight, obesity and hypertension.
Participants
8067 women and men without diabetes, aged 30–87 years, at baseline Tromsø6 who subsequently also participated in Tromsø7.
Outcome measures
Diabetes defined by self-reported diabetes, diabetes medication use and/or HbA1c≥6.5% (≥48 mmol/mol) was modelled by logistic regression for the association with baseline hs-CRP, either stratified into three quantiles or as continuous variable, adjusted for demographic factors, behavioural and cardiovascular risk factors, lipid-lowering medication use, and hypertension. Interactions by sex, body mass index (BMI), hypertension or abdominal obesity were assessed by adding interaction terms in the fully adjusted model.
Results
There were 320 (4.0%) diabetes cases after 7 years. After multivariable adjustment including obesity and hypertension, individuals in the highest hs-CRP tertile 3 had 73% higher odds of developing diabetes (OR 1.73; p=0.004; 95% CI 1.20 to 2.49) when compared with the lowest tertile or 28% higher odds of incidence per one-log of hs-CRP increment (OR 1.28; p=0.003; 95% CI 1.09 to 1.50). There was no evidence for interaction between hs-CRP and sex, hypertension, BMI or abdominal obesity.
Conclusions
Raised hs-CRP was associated with future diabetes development in a Norwegian adult population sample. The CRP-diabetes association could not be fully explained by obesity or hypertension.
Objectives
Insulin resistance is a well-established contributor to inflammation; however, the specific association between the triglyceride glucose (TyG) index, a biomarker reflecting insulin resistance, and arthritis remains unexplored. As a result, the main aim of this study was to examine the correlation between the TyG index and arthritis.
Methods
This observational study used data from the National Health and Nutrition Examination Survey (NHANES), which was conducted between 2007 and 2018. To investigate the relationship between the TyG index and arthritis, various statistical analyses were employed, including weighted multivariable logistic regression analysis, subgroup analysis, curve fit analysis, and threshold effect analysis.
Results
In total, 14,817 patients were enrolled in the trial, with 4,191 individuals (28.29%) diagnosed with arthritis. An increased risk of arthritis was found to be significantly correlated with higher TyG index values (odds ratio OR = 1.15, 95% confidence interval CI: 1.07–1.23), according to the results of multivariable logistic regression analysis after full adjustment. Subgroup analysis and interaction tests further indicated that the TyG index exhibited an additive effect when combined with other established risk factors, including age (OR = 1.29; 95% CI: 1.17–1.41), body mass index (BMI) (OR = 1.43; 95% CI: 1.24–1.69), and diabetes (OR = 1.20; 95% CI: 1.11–1.31). Additionally, curve fit analysis and threshold effect analysis demonstrated a nonlinear relationship with a breakpoint identified at 8.08 µmol/L.
Conclusion
The TyG index was positively correlated with arthritis in adults under 60 years of age in the United States who had normal weight and no diabetes. Further large-scale prospective studies are warranted for a comprehensive analysis of the role of the TyG index in arthritis.
Diabetes mellitus is a chronic disease that leads to complications including heart disease, stroke, kidney failure, blindness and nerve damage. Type 2 diabetes, characterized by target-tissue resistance to insulin, is epidemic in industrialized societies and is strongly associated with obesity; however, the mechanism by which increased adiposity causes insulin resistance is unclear. Here we show that adipocytes secrete a unique signalling molecule, which we have named resistin (for resistance to insulin). Circulating resistin levels are decreased by the anti-diabetic drug rosiglitazone, and increased in diet-induced and genetic forms of obesity. Administration of anti-resistin antibody improves blood sugar and insulin action in mice with diet-induced obesity. Moreover, treatment of normal mice with recombinant resistin impairs glucose tolerance and insulin action. Insulin-stimulated glucose uptake by adipocytes is enhanced by neutralization of resistin and is reduced by resistin treatment. Resistin is thus a hormone that potentially links obesity to diabetes.
Obesity is closely associated with insulin resistance and establishes the leading risk factor for type 2 diabetes mellitus, yet the molecular mechanisms of this association are poorly understood. The c-Jun amino-terminal kinases (JNKs) can interfere with insulin action in cultured cells and are activated by inflammatory cytokines and free fatty acids, molecules that have been implicated in the development of type 2 diabetes. Here we show that JNK activity is abnormally elevated in obesity. Furthermore, an absence of JNK1 results in decreased adiposity, significantly improved insulin sensitivity and enhanced insulin receptor signalling capacity in two different models of mouse obesity. Thus, JNK is a crucial mediator of obesity and insulin resistance and a potential target for therapeutics.
Microorganisms that invade a vertebrate host are initially recognized by the innate immune system through germline-encoded pattern-recognition receptors (PRRs). Several classes of PRRs, including Toll-like receptors and cytoplasmic receptors, recognize distinct microbial components and directly activate immune cells. Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of overlapping and unique genes involved in the inflammatory and immune responses. New insights into innate immunity are changing the way we think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity.