Ernesto Maddaloni

Sapienza University of Rome | la sapienza · Department of Experimental Medicine

Introduction: Young-onset type 2 diabetes (T2D) is associated with premature complications and death. Aim: To assess whether long-term complications and mortality rates differed with younger age at T2D diagnosis over UKPDS 30-year follow-up. Methods: Using 1977-2007 data from UKPDS participants with newly-diagnosed T2D without diabetes autoantibodi...

The global escalation of obesity has made it a worldwide health concern, notably as a leading risk factor for cardiovascular disease (CVD). Extensive evidence corroborates its association with a range of cardiac complications, including coronary artery disease, heart failure, and heightened vulnerability to sudden cardiac events. Additionally, obes...

Introduction: Despite the improvements of insulin therapy, people with type 1 diabetes (T1D) still suffer from a decreased quality of life and life expectancy. The search toward a cure for T1D is therefore still a scorching open field of research. Areas covered: Tackling the immune checkpoint signaling pathways has gained importance in the field...

Aim To compare the efficacy and safety of saxagliptin/dapagliflozin and insulin glargine in people with latent autoimmune diabetes in adults (LADA). Methods In this phase 2b multicentre, open‐label, comparator‐controlled, parallel‐group, non‐inferiority study, we randomly assigned 33 people with LADA who had a fasting C‐peptide concentration ≥0.2...

Chitotriosidase (CHIT), a mammalian chitinase secreted by neutrophils and activated macrophages, is increased in both cardiovascular disease (CVD) and type 2 diabetes (T2D). Arterial stiffness rises early in T2D and increases the risk of CVD. The aim of this study is to evaluate CHIT activity as an early biomarker of arterial stiffness in people wi...

Autoimmune diabetes is a heterogeneous disease, encompassing both type 1 diabetes, characterized by fast progression towards an insulin-dependent state, and latent autoimmune diabetes in adults (LADA), considered a less severe form of autoimmune diabetes with a mild metabolic decompensation. An extensive genetic, phenotypic, and humoral heterogenei...

Background: Autoimmune diabetes (AD) results from a loss of immune tolerance leading to the destruction of β-cells in the pancreas. Heterogeneity in severity of β-cell damage among people with AD is well-recognized, with some patients retaining a certain amount of insulin-producing cells for years despite the presence of pancreatic autoimmunity. Ce...

In the past, indications for total pancreatectomy (TP) were rare, with several concerns about patients’ postoperative quality of life due to exocrine and endocrine post-pancreatectomy management [...]

Background: Little is known about the changes in organs and tissues that may make elder patients more vulnerable to acute stressors such as SARS-CoV-2 infection. Methods: In 80 consecutive elderly patients with SARS-CoV-2 infection, we evaluated the association between the descending thoracic aorta calcium score, L1 bone density and T12 skeletal...

Background: Novel biomarkers of vascular disease in diabetes could help identify new mechanistic pathways. Osteocalcin, osteoprotegerin and osteopontin are key molecules involved in bone and vascular calcification processes, both compromised in diabetes. We aimed to evaluate possible associations of osteocalcin, osteoprotegerin and osteopontin wit...

Aims: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce renal and heart failure (HF) events. Although their glycaemic efficacy depends on kidney function, it remains unclear to what extent baseline kidney function influences the magnitude of cardiorenal effects. Methods: We searched randomized, placebo-controlled trials testing SGLT2i ef...

Effects of novel glucose-lowering agents on cardiac autonomic function and structure in type 2 diabetes Ilaria Cavallari, Ernesto Maddaloni, Francesco Veneziano, Carla Indennidate, Maria Valeria Giaccari, Dario Tuccinardi, Silvia Pieralice, Nicola Napoli, Raffaella Buzzetti, Francesco Grigioni Background Novel glucose-lowering agents, such as sodi...

Background Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have demonstrated to reduce heart failure (HF) and renal outcomes irrespective of diabetes status. The cardiovascular efficacy and the mortality benefit of these agents in patients without HF and across the spectrum of left ventricular ejection fraction (EF) are a matter of debate. Meth...

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce renal and heart failure (HF) events in people with and without diabetes. Although their glycemic efficacy is dependent on kidney function, it remains unclear to what extent baseline kidney function influences the magnitude of SGLT2i cardiorenal effects. Methods...

Introduction: Diabetes mellitus worsens the prognosis of SARS-CoV-2 infection, vaccination has been the major tool for reducing the risk of hospitalization, and mortality. The primary aim of this study was to evaluate the response to the SARS-CoV-2 vaccine in subjects with diabetes and controls. Differences between type 1 (T1D) and type 2 (T2D) di...

Sodium–glucose co-transporter-2 inhibitors or gliflozins, the newest anti-hyperglycemic class, induce cardioprotective benefits in patients with type 2 diabetes (T2D). As platelet activation and oxidative stress play a key role in atherothrombotic-related complications, we hypothesized that gliflozins might modulate oxidative stress, platelet activ...

Background: This is a proof of concept, as a pilot study, with the aim to evaluate continuous glucose monitoring metrics (CGM) in subjects with type 2 diabetes (T2DM), treated with nutritional therapy and metformin, before and after testosterone replacement therapy (TRT). Methods: In this longitudinal observational study, subjects affected by T2...

Adult-onset autoimmune (AOA) diabetes pathophysiology starts with immune changes, followed by dysglycaemia and overt disease. AOA diabetes can occur as classic type 1 diabetes when associated with severe loss of insulin secretion. More frequently, it is diagnosed as latent autoimmune diabetes in adults, a slowly progressing form with late onset, a...

Patients with diabetes have a prothrombotic state and a 2 to 4 times higher risk of cardiovascular events than those without diabetes. Aspirin is the cornerstone of treatment in patients with cardiovascular disease, irrespective of diabetes status, being able to confer a 19% relative risk reduction per year in serious vascular events compared with...

Impaired beta‐cell function is a recognised cornerstone of diabetic pathophysiology. Estimates of insulin secretory capacity are useful to inform clinical practice, helping to classify types of diabetes, complication risk stratification, and to guide treatment decisions. Since C‐peptide secretion mirrors beta‐cell function, it has emerged as a valu...

Background: Intensive glycemic control reduces the risk of diabetic retinopathy (DR) in people with type 1 diabetes (T1D) . However, the impact of glycemic control during the peri-diagnostic period on the long-term risk of DR is not known.Aim: To evaluate the association between the glycemic control obtained within the first year after T1D diagnosi...

Background Insulin resistance (IR) can increase atherosclerotic and cardiovascular risk by inducing endothelial dysfunction, decreasing nitric oxide (NO) production, and accelerating arterial inflammation. The aim is to determine the mechanism by which insulin action and NO production in endothelial cells can improve systemic bioenergetics and decr...

Introduction: IDegLira was shown to maintain glycemic control while reducing risk of hypoglycemia and body weight gain. The REX study was designed to generate real-world evidence on the use of IDegLira in Italian clinical practice in two different subgroups of patients, those switching to IDegLira from a basal insulin-supported oral therapy (BOT g...

Antibodies (Abs) against intracellular epitopes of the tyrosine-phosphatase 2 (IA-2) are detected in type 1 diabetes. Abs directed against the IA-2(256-760) portion, with both intra- and extracellular epitopes, are present in people with latent autoimmune diabetes in adults (LADA) and in obese subjects with normal glucose tolerance (NGT). We aim to...

Aim To evaluate early, before the onset of cardiovascular events and of chronic renal insufficiency, the association between CKD-mineral bone disorder biomarkers and vascular stiffness (Cardio Ankle Vascular Index, CAVI) in the course of type 2 diabetes (T2DM). Method we evaluated 174 T2DM patients (median age 56 y; M/F = 100/74) with diabetes dur...

Objective: To build a clinical risk score to aid risk stratification among hospitalised COVID-19 patients. Methods: The score was built using data of 417 consecutive COVID-19 in patients from Kuwait. Risk factors for COVID-19 mortality were identified by multivariate logistic regressions and assigned weighted points proportional to their beta co...

The relation between diabetes mellitus (DM) and bleeding complications after percutaneous coronary intervention (PCI) is controversial. This study investigates the role of low platelet reactivity (LPR) in the bleeding risk stratification of patients who underwent PCI according to DM status. A total of 472 patients who underwent PCI on aspirin and c...

Background: Ranolazine is a second-line drug for the management of chronic coronary syndromes (CCS). Glucose-lowering and endothelial effects have also been reported with this agent. However, whether ranolazine may improve short-term glycemic variability (GV), strictly related to the prognosis of patients with type 2 diabetes (T2D), is unknown. Th...

Introduction Immunotherapies for type 1 diabetes mellitus (T1D) have been the focus of intense research over the past few decades; nevertheless, the results of clinical trials have not matched expectations. However, thanks to the recent and promising results on T1D prevention, among all the different immune-intervention tested strategies, clinical...

Heart failure (HF) represents a major global health and economic burden with still unacceptably high morbidity and mortality rates. In recent decades, novel therapeutic opportunities with a significant impact on HF outcomes have been introduced in addition to angiotensin-converting enzyme (ACE) inhibitors, β-blockers, and mineralocorticoid receptor...

Background The association between diabetes mellitus (DM) and bleeding complications following percutaneous coronary intervention (PCI) is controversial. We hypothesized that on-treatment platelet reactivity may have a role in the bleeding risk stratification of such patients. Purpose To investigate the role of low platelet reactivity (LPR) in the...

Aims/hypothesis The β-cell stress hypothesis suggests that increased insulin demand contributes to the development of type 1 diabetes. In the TRIGR trial we set out to assess the profile of plasma glucose and HbA1c before the diagnosis of clinical diabetes compared to nondiabetic children. A cohort of children (N = 2159) with an affected first-degr...

Background A growing body of evidence suggests a potential link between bone metabolism and cardiovascular disease. Aim of this study was to investigate the relationship between levels of circulating bone turnover biomarkers and advanced atherosclerosis. Methods Klotho (KL), sclerostin (SOST), osteopontin (OPN) and osteoprotegerin (OPG) were measu...

In patients with autoimmune diabetes no significant differences were observed in glucose control, expressed as time in range evaluated by continuous glucose monitoring comparing the 3 days after Sars-Cov2 vaccine with the 14 days preceding the vaccine.

Contrasting data have been published about the impact of cardiovascular disease on Covid-19. A comprehensive synthesis and pooled analysis of the available evidence is needed to guide prioritization of prevention strategies. To clarify the association of cardiovascular disease with Covid-19 outcomes, we searched PubMed up to 26 October 2020, for st...

Hyperglycemia has been evaluated extensively as risk factors for cardiovascular disease (CVD) in people with type 1 diabetes (T1DM). However, the effects of the autoantibody on atherosclerosis and immunogenic trigger are not well understood in T1D. Using the generated several mice models of atherosclerosis including NOD, congenic ApoE-/-/NOD (NDM a...

In type 2 diabetes, anti-thrombotic management is challenging, and current anti-platelet agents have demonstrated reduced efficacy. Old and new anti-diabetic drugs exhibited—besides lowering blood glucose levels—direct and indirect effects on platelet function and on thrombotic milieu, eventually conditioning cardiovascular outcomes. The present re...

Purpose Angiotensin converting enzyme 2 (ACE2) is the door for SARS-CoV-2, expressed in critical metabolic tissues. So, it is rational that the new virus causes pleiotropic alterations in glucose metabolism, resulting in the complication of pre-existing diabetes’s pathophysiology or creating new disease mechanisms. However, it seems that less atten...

Aims: The outbreak of coronavirus disease 2019 (COVID-19) forced several countries to adopt measures of lockdown constraining people at home, with a relevant impact on those with chronic diseases such as type 2 diabetes (T2D). Therefore, the aim of this study was to assess the effect of lockdown on glycaemic control in T2D. Material & methods: i...

The risk of ischemic events carried by different clusters of type 2 diabetes mellitus (DM) in the setting of secondary prevention is not definite and the association between DM and bleeding complications is controversial. We explored these issues in the START-ANTIPLATELET, a multicenter Italian registry including acute coronary syndrome (ACS) patie...

Aims The aim of this real-world study is to evaluate the effect of glucagon-like peptide1 receptor-agonist (GLP1 RA) and sodium-glucose co-transporter2 inhibitor (SGLT2i) on coronary heart disease (CHD) risk, in patients with type 2 diabetes (T2D) in primary cardiovascular prevention. Methods Data from 312 patients with T2D, without CHD history, s...

Aims Microvascular complications' risk differs between people with latent autoimmune diabetes in adults (LADA) and people with type 2 diabetes. We aimed to investigate whether the prevalence of cardiac autonomic neuropathy, a life‐threatening complication of diabetes, also varies depending on diabetes type. Methods In this cross‐sectional study, 4...

Background: Cardiometabolic disorders may worsen Covid-19 outcomes. We investigated features and Covid-19 outcomes for patients with or without diabetes, and with or without cardiometabolic multimorbidity. Methods: We collected and compared data retrospectively from patients hospitalized for Covid-19 with and without diabetes, and with and witho...

Aims: To evaluate whether subjects with diabetes hospitalized for Coronavirus disease-19 (Covid-19) represent a subgroup of patients with high-risk clinical features compared to patients with diabetes without Covid-19. Methods: In this case-control study 79 patients with type 2 diabetes out of 354 adults hospitalized for Covid-19 and 158 control...

In a nationwide study of 3818 charts from patients with fatal COVID-19, we found that geographical differences in Dipeptidyl peptidase 4 (DPP4) inhibitors use did not correlate with diabetes prevalence among COVID-19 deaths, thus not supporting the hypothesis of a clinically relevant involvement of DPP4 inhibition in COVID-19 development and progre...

Introduction: Thyroid ultrasound (US) is crucial for clinical decision in the management of thyroid nodules. In this cross-sectional study, we aimed to test if the evaluation of thyroid nodules' vascularization could improve the risk stratification ability of the American College of Radiology (ACR) TI-RADS classification system. Methods: A total...

Context Diabetes and heart failure (HF) are two deadly and strictly related epidemic disorders. Aim of this review is to present an updated discussion of the epidemiology, pathophysiology, clinical presentation and treatment options for HF in diabetes. Evidence Acquisition Relevant references published up to February 2020 were identified through s...

Hyperglycemia, hyperlipidemia and hypertension have been evaluated extensively as risk factors for cardiovascular disease (CVD) in people with type 1 diabetes (T1DM). However, the impact of autoimmunity in T1DM on CVD has not been determined. We have generated several mice models of atherosclerosis including ApoE-/-/NOD, ApoE-/-/NOD (congenic non d...

Background: The efficacy of increasing dietary fiber intake (DFI) to ameliorate glycemic control in patients with type 2 diabetes (T2D) is still controversial. In this randomized open-label comparator-controlled study we tested the effect of high-fiber diet and fiber supplement on glycemic control in patients with T2D on metformin monotherapy. Meth...

Background and Aim: Our previous data showed that transition from pediatric to an adult care center (ACC) improves glycaemic control in youth with type 1 diabetes (T1D). However, factors that might impact the success of transition are still unclear. In this study we aimed to evaluated whether metabolic control after transition differs by different...

Novel markers of vascular disease in diabetes could help identify new disease pathways and enhance risk stratification. Osteoprotegerin (OPG) and osteopontin (OPN) are key molecules involved in bone and vascular calcification processes, both compromised in diabetes. To evaluate whether OPG and/or OPN are associated with diabetic vascular complicati...

The original version of this article unfortunately contained a mistake in the authorgroup section. The authors' given and family names were inadvertently interchanged.

An increasing number of new cases of autoimmune diabetes occur during adulthood. Most are cases of latent autoimmune diabetes in adults (LADA), a form of autoimmune diabetes with older mean age at onset, slower rate of beta-cell loss and longer period of insulin independence after onset when compared with type 1 diabetes. Unfortunately, patients wi...

Purpose of review: Genetic, socioeconomic and clinical features vary considerably among individuals with type 2 diabetes (T2D) influencing disease development, progression and response to therapy. Although a patient-centred approach to pharmacologic therapy of T2D is widely recommended, patients are often treated similarly, irrespective of the dif...

A novel RNA betacoronavirus causing coronavirus disease 2019 (Covid‐19) has now been declared pandemic disease by WHO. Guo W et al published the first report of biochemical features in patients with diabetes and the further risk that this disease can determine to the progression of Covid‐19. Among different cytokines found significantly higher in p...

Background: Latent autoimmune diabetes of adulthood (LADA) differs in clinical features from type 2 diabetes. Whether this difference translates into different risks of complications remains controversial. We examined the long-term risk of microvascular complications in people enrolled in the UK Prospective Diabetes Study (UKPDS), according to the...

Purpose To evaluate the effect of oral alpha-lipoic acid (ALA) ± palmitoyl-ethanolamide (PEA) on neuropathic symptoms in patients with diabetic peripheral neuropathy (DPN) and to identify factors related to the efficacy of the treatment. Methods This is a retrospective observational pilot study evaluating 49 patients with diabetes and positive Neu...

Sommario Il diabete mellito di tipo 2 (DM2) è una patologia multifattoriale altamente prevalente nella popolazione anziana. Più del 65% della popolazione affetta da DM2 ha infatti un’età maggiore di 65 anni ed esiste uno stretto legame fisiopatologico e clinico tra invecchiamento, DM2 e complicanze vascolari. Ciò impone un’attenta riflessione sui r...

Purpose To evaluate the relationship between wrist circumference, markers of adipose dysfunction, and cardiovascular risk in youths with obesity. Methods In this cross-sectional study, we measured body mass composition by dual-energy X-ray absorptiometry, wrist circumference, waist-to-height ratio, fasting blood insulin, glucose, lipid profile, ad...

Background: Latent Autoimmune Diabetes of Adults (LADA) is a mild form of autoimmune diabetes which can be identified in 3-12% of adults who have a clinical diagnosis of T2D. LADA differs in genetic and clinical features with T2D, but whether this translates into a different risk for complications remains controversial. Aim: We examined the long-te...

Aims: Filipino people are one of the largest immigrant populations in Italy. Aim of this study was to assess differences in T2D, prediabetes and obesity between native Italians and Filipino immigrants living in Rome. Changes in metabolic characteristics and dietary habits between first-generation immigrants and their descendants were examined. Meth...

Normal sleep is characterized by increased glycogen stores and reduced glucose turnover by metabolically active tissues, thus it is a state of decreased metabolism. It has been reported that reduced sleep quality is associated with disrupted glucose metabolism. However, the relationship between Sleep Metabolic Rate (SMR) and prediabetes defined by...

Background and Aim: Chitotriosidase (Chit), a mammalian chitinases secreted by monocytes and epithelial cells, is increased in both cardiovascular disease (CVD) and type 2 diabetes (T2D). Arterial stiffness rises early in T2D and increases the risk of CVD. Aim of the study was to evaluate Chit activity as a precocious biomarker of arterial stiffnes...

Although metabolic risk factors that accelerate atherosclerosis are shared between people with type 1 (T1D) and 2 (T2D) diabetes, it remains unknown whether autoimmunity in T1D contribute to cardiovascular pathologies, which have been reported for other autoimmune diseases. In order to determine the role of autoimmunity with and without overt diabe...

Aims Latent Autoimmune Diabetes of Adults (LADA) is diagnosed in up to 12% of adults with clinically‐diagnosed type 2 diabetes (T2D). LADA tend to have healthier cardiovascular (CV) risk profiles than T2D, but it remains uncertain whether their risk of CV events differ. We examined the risk of CV events in patients enrolled in the United Kingdom Pr...

Objective: To determine clinical diabetes-related risk factors for fragility fractures in type 1 diabetes (T1D). Research design and methods: History of bone fragility fractures occurring after T1D diagnosis was assessed by questionnaire in this cross-sectional study in 600 T1D subjects. Glycated hemoglobin A1c (HbA1c) over the previous 5 years...

Obesity in childhood and adolescence continues to be a major health issue due to significant health implications and to the economic burden that arise from treating this disease and its complications. Current data shows that childhood obesity is no longer just a concern for developed countries, but more significantly affecting developing countries....

Aim/hypothesis Antibodies to post‐translationally modified insulin (oxPTM‐INS‐Ab) are a novel biomarker of type 1 diabetes (T1D). Here, we evaluated whether oxPTM‐INS‐Ab can improve T1D prediction in children with positive standard islet‐autoantibodies (AAB). Methods We evaluated sensitivity, specificity, accuracy and risk for progression to T1D a...

The recent results of the DECLARE‐TIMI 58 trial forces a profound reflection about the cardiovascular protection conferred by SGLT‐2 inhibitors. DECLARE‐TIMI 58, the largest cardiovascular outcome trial in diabetes, failed to show a significant reduction in the risk of major cardiovascular events (MACE) conferred by dapagliflozin compared to placeb...

Purpose of the Review To summarize available evidence regarding lipid-lowering interventions for the prevention of cardiovascular disease in patients with diabetes. Recent Findings Statins and non-statin therapies that act through upregulation of LDL receptor expression are associated with similar cardiovascular risk reduction per decrease in LDL...

Diabetes mellitus is an important risk factor for a first cardiovascular event and for worse outcomes after a cardiovascular event has occurred. This situation might be caused, at least in part, by the prothrombotic status observed in patients with diabetes. Therefore, contemporary antithrombotic strategies, including more potent agents or drug com...

Purpose of Review To describe the main pathways involved in the interplay between bone and cardiovascular disease and to highlight the possible impact of physical activity and medical nutrition therapy on the bone-vascular axis. Recent Findings Diabetes increases the risk of both cardiovascular disease and bone fragility fractures, sharing common...

Transition from paediatric to adult diabetes clinics for type 1 diabetes (T1D) patients represents a critical phase often characterized by worsening effects on diabetes outcomes as care visit attendance, metabolic control and diabetes related complications. Aim of this study was to evaluate metabolic control of 122 T1D patients [82/40 M / F, mean (...

Background: Palmitoylethanolamide (PEA) is an amide with “autacoid local inflammation antagonism” effects, protecting nerve degeneration due to mast cell degranulation. PEA add-on to alpha-lipoic acid (ALA) is successfully used as treatment of neuropathic pain, but there are no data in diabetic peripheral neuropathy (DPN) specifically. Aim: To eval...

Normal sleep is characterized by increased glycogen stores and reduced glucose turnover by metabolically active tissues, thus it is a state of decreased metabolism. It has been reported that reduced sleep quality is associated with increased insulin-resistance and disrupted metabolism. However, the relationship between energy expenditure during sle...

Objective: Thyroid ultrasound is crucial for clinical decision in the management of thyroid nodules. In this study we aimed to estimate and compare the performance of ATA, AACE/ACE/AME and ACR TI-RADS ultrasound classifications in discriminating nodules with high-risk cytology. Design: Cross sectional study Methods 1077 thyroid nodules undergoin...

Vitamin D has been suggested as a protective compound for diabetes mellitus. Several mechanisms linking vitamin D to the regulation of the immune response support a role for vitamin D in the pathogenesis of autoimmune diabetes. Epidemiological evidence and observational studies suggesting that adequate vitamin D status is related to decreased risk...

Objective: The objective of this study is to evaluate whether exogenously induced hyperinsulinemia may increase the development of atherosclerosis. Approach and results: Hyperinsulinemia, induced by exogenous insulin implantation in high-fat fed (60% fat HFD) apolipoprotein E-deficient mice (ApoE(-/-)) mice, exhibited insulin resistance, hypergl...

Background Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes (T1D). A pro-calcific drift of circulating monocytes has been linked to vascular calcification and is marked by the surface expression of osteocalcin (OCN). We studied OCN+ monocytes in a unique population with ≥50 years of T1D, the 50-Year Joslin Medalists (J5...

Adult-onset autoimmune diabetes is a heterogeneous disease that is characterized by a reduced genetic load, a less intensive autoimmune process and a mild metabolic decompensation at onset compared with young-onset type 1 diabetes mellitus (T1DM). The majority of patients with adult-onset autoimmune diabetes do not require insulin treatment for at...

Madagascar is a geographically isolated country considered a biodiversity hotspot with unique genomics. Both the low-income and the geographical isolation represent risk factors for the development of diabetes. During a humanitarian health campaign conducted in Ambanja, a rural city in the northern part of Madagascar, we identified 42 adult subject...