Lorenza Santi

The Metabolic Syndrome is an independent predictor of cardiovascular disease in Type 2 diabetic subjects. Prospective data from the Verona Diabetes Complications Study

Aims  To evaluate the cardiovascular risk associated with the presence of the Metabolic Syndrome in Type 2 diabetic subjects.

Relationship between fasting insulin and cardiovascular risk factors is already present in young men : the Verona Young Men Atherosclerosis Risk Factors Study

The associations between fasting plasma insulin concentration and risk factors for cardiovascular diseases were examined in 979 18‐year‐old men participating in the Verona Young Men Atherosclerosis Risk Factors Study, a cross‐sectional population‐based study. Body mass index (BMI), waist‐to‐hip ratio (WHR), plasma triglycerides and uric acid concentrations, and blood pressure values significantly increased, and the high‐density lipoprotein (HDL)–total cholesterol ratio decreased, across quartiles of fasting insulin. Total and low‐density lipoprotein cholesterol concentrations did not change significantly with the increase in fasting insulin levels. After adjustment for BMI, WHR, smoking, alcohol intake and physical activity, only plasma triglycerides significantly increased across insulin quartiles (F =7.1; P <0.001). However, systolic blood pressure and uric acid were close to statistical significance (P =0.06–0.07). Multiple linear regression analysis confirmed that plasma insulin was independently correlated with plasma triglycerides and, to a lesser extent, with blood pressure and uric acid concentration. This analysis pointed out that BMI was a stronger independent predictor of all cardiovascular disease risk factors than fasting insulin. When subjects were categorized according to the number of metabolic and haemodynamic disorders occurring within the same individual, subjects with multiple disorders (i.e. three or four) had higher plasma insulin levels than those with none or few disorders, even after adjusting for BMI, WHR and behavioural variables (F =4.0; P <0.01). These results indicate that hyperinsulinaemia is already associated with a cluster of cardiovascular disease risk factors in young adulthood, the strongest independent association being with plasma triglycerides.

Prevalence of Cardiovascular Autonomic Neuropathy in a Cohort of Patients With Newly Diagnosed Type 2 Diabetes: The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS).

OBJECTIVE Cardiovascular autonomic diabetic neuropathy (CAN) is a serious complication of diabetes. No reliable data on the prevalence of CAN among patients with newly diagnosed type 2 diabetes are available. Therefore, the aim of this study was to estimate the prevalence of CAN among patients with newly diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS A cohort of 557 patients with newly diagnosed type 2 diabetes with cardiovascular autonomic test results available was selected. Early and confirmed neuropathy were assessed using a standardized methodology and their prevalences determined. A multivariate logistic regression analysis was modeled to study the factors associated with CAN. RESULTS In the entire cohort, the prevalence of confirmed CAN was 1.8%, whereas that of early CAN was 15.3%. Prevalence did not differ between men and women. In the multivariate analyses BMI results were independently and significantly associated with CAN after adjusting for age, sex, hemoglobin A1c, pulse pressure, triglyceride-to-HDL cholesterol ratio, kidney function parameters, and antihypertensive treatment. CONCLUSIONS CAN could be detected very early in type 2 diabetes. This study may suggest the importance of performing standardized cardiovascular autonomic tests after diagnosis of type 2 diabetes.

Is common genetic variation at IRS1, ENPP1 and TRIB3 loci associated with cardiometabolic phenotypes in type 2 diabetes? An exploratory analysis of the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 5

BACKGROUND AND AIMS Insulin resistance is a hallmark of type 2 diabetes (T2DM), it is often accompanied by defective beta-cell function (BF) and is involved in the pathophysiology of cardiovascular disease (CVD). Commonalities among these traits may recognize a genetic background, possibly involving the genetic variation of insulin signaling pathway genes. We conducted an exploratory analysis by testing whether common genetic variability at IRS1, ENPP1 and TRIB3 loci is associated with cardiovascular risk traits and metabolic phenotypes in T2DM. METHODS AND RESULTS In 597 drug-naïve, GADA-negative, newly-diagnosed T2DM patients we performed: 1) genotyping of 10 independent single-nucleotide polymorphisms covering ∼ 90% of common variability at IRS1, ENPP1 and TRIB3 loci; 2) carotid artery ultrasound; 3) standard ECG (n = 450); 4) euglycaemic insulin clamp to assess insulin sensitivity; 5) 75 g-OGTT to estimate BF (derivative and proportional control) by mathematical modeling. False discovery rate of multiple comparisons was set at 0.20. After adjustment for age, sex and smoking status, rs4675095-T (IRS1) and rs4897549-A (ENPP1) were significantly associated with carotid atherosclerosis severity, whilst rs7265169-A (TRIB3) was associated with ECG abnormalities. Rs858340-G (ENPP1) was significantly associated with decreased insulin sensitivity, independently of age, sex and body-mass-index. No consistent relationships were found with BF. CONCLUSION Some associations were found between intermediate phenotypes of CVD and common genetic variation of gatekeepers along the insulin signaling pathway. These results need be replicated to support the concept that in T2DM the CVD genetic risk clock may start ticking long before hyperglycemia appears. ClinicalTrials.gov Identifier: NCT01526720.

American Diabetes Association 75th Scientific Meeting - Epidemiology/Genetics Section; Poster 1563-P: Pancreatic Beta-Cell Function, Insulin Sensitivity, and Metabolic Phenotypes in Type 2 Diabetes at the Time of Diagnosis—The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS)

& 1472-P Disability-Free Life-Years Lost due to Diabetes Mellitus among Older U.S. Adults BARBARA BARDENHEIER, JI LIN, XIAOHUI ZHUO, MOHAMMED K. ALI, TED THOMPSON, EDWARD W. GREGG, Atlanta, GA, North Wales, PA Increases in diabetes incidence and life expectancy among the diabetes population have led to an increase in the number of years spent with diabetes. However, the effect of diabetes on the quality of those extra years is unknown. We analyzed longitudinal data from the Health and Retirement Study and modeled disability-free life-years lost due to diabetes over a lifetime in the United States. We estimated incidence of disability, remission from disability, and mortality by self-reported diabetes status among 11,141 adults aged > 50 years with baseline years of 1998 and 2004, followed to 2010. Three measures of disability were examined: severe functional decline (mobility), some diffi culty with >1 instrumental activities of daily living (IADL), and some diffi culty with >1 activities of daily living (ADL). Using these estimates, we developed a discrete-time fi ve state Markov model to estimate the numbers of years with and without disability by baseline age and diabetes status. From ages 50 and 60 for all 3 disability defi nitions, diabetes was signifi cantly associated (p<0.05) with earlier average age of disability onset, reduced total years of life and reduced disability-free life years. Compared to those without diabetics, from age 50 men have 1.5 to 2.2 more disabled years for all 3 disability measures and women have 3.5 more mobility loss disabled years and 2.6 more ADL disabled years. From age 50, men with diabetes have 6-7 years earlier onset of disability (mobility, IADL, ADL) than non-diabetic men, 2-4 fewer total years of remaining life, and have 6-7 fewer disability-free total years of life. From age 50, women with diabetes have a 7-8 year earlier onset of disability (mobility, IADL, ADL) than non-diabetic women, 2-4.5 fewer total years of remaining life, and have 6-7 fewer disability-free total years of life. This study suggests diabetes reduces the quality of life of adults by exposing them to disability at earlier ages and reducing disability-free years remaining compared to adults without diabetes.

Influence of Ulipristal Acetate Therapy on Uterine Fibroid-Related Symptoms and on Uterine and Fibroid Volumes and Vascularity Indices Assessed by Ultrasound: Influence of Ulipristal Acetate on Uterine Fibroids

To investigate the modifications of uterine and fibroid volume, to study Doppler changes in uterine arteries and fibroid‐supplying vessels, and to assess possible symptomatic relief after 3 months of treatment with ulipristal acetate.

Long-Acting GLP-1 Receptor Agonist Exenatide Influence on the Autonomic Cardiac Sympatho-Vagal Balance

Long-acting glucagon-like peptide 1 receptor agonists are increasingly used to treat type 2 diabetes. An increase of heart rate (HR) has been observed with their use. To elucidate the role of the cardiac sympatho-vagal balance as a possible mediator of the reported increase in HR, we performed power spectral analysis of HR variability (HRV) in patients receiving exenatide extended-release (ER). Twenty-eight ambulatory patients with type 2 diabetes underwent evaluation at initiation of exenatide-ER and thereafter at 3 and at 6 months. To obtain spectral analyses of HRV, a computerized acquisition of 10 minutes of RR electrocardiogram intervals (mean values of ~700 RR intervals) were recorded both in lying and in standing positions. All patients showed a substantial increase of HR both in lying and in standing positions. Systolic blood pressure, body weight, and glycated hemoglobin A1c significantly decreased both at 3 and 6 months compared with basal levels. The low-frequency/high-frequency ratio varied from 3.05 ± 0.4 to 1.64 ± 0.2 (P < 0.001) after 3 months and to 1.57 ± 0.3 (P < 0.001) after 6 months in a lying position and from 4.56 ± 0.8 to 2.24 ± 0.3 (P < 0.001) after 3 months and to 2.38 ± 0.4 (P < 0.001) after 6 months in a standing position compared with basal values, respectively. HR variations, induced by exenatide-ER treatment, do not appear to be related to sympathetic autonomic tone. Of note, we observed a relative increase of vagal influence on the heart.

Sex differences in the association of psychological status with measures of physical activity and sedentary behaviour in adults with type 2 diabetes

AimTo assess the association of psychological variables on leisure-time physical activity and sedentary time in men and women with type 2 diabetes mellitus (T2D).MethodsIn this cross-sectional study, we evaluated 163 patients with T2D, consecutively recruited at the Diabetes Centre of the Verona General Hospital. Scores on depression and anxiety symptoms, psychosocial factors (including self-efficacy, perceived interference, perceived severity, social support, misguided support behaviour, spouse’s positive behaviour), physical activity and time spent sitting were ascertained using questionnaires responses to the Beck Depression Inventory-II, Beck Anxiety Inventory, Multidimensional Diabetes Questionnaire, International Physical Activity Questionnaire.ResultsPhysical activity was significantly associated with higher social support in women and with increased self-efficacy in men. Sedentary time was significantly associated with higher perceived interference, anxiety and depressive symptoms, and with reduced diabetes self-efficacy in women, while it was associated solely with anxiety in men. Depressive symptoms and self-efficacy in women and anxiety symptoms in men were independent predictors of sedentary time when entered in a multivariable regression model also including age, BMI, haemoglobin A1c, diabetes duration, perceived interference and self-efficacy as covariates.ConclusionsLower self-efficacy and higher symptoms of depression were closely associated with increased sedentary time in women, but not in men, with T2D. It is possible that individualized behavioural interventions designed to reduce depressive symptoms and to improve diabetes self-efficacy would ultimately reduce sedentary behaviours, particularly in women with T2D.

Depressione, supporto sociale e stato di salute percepita in soggetti con piede diabetico

Il piede diabetico e una delle complicanze piu invalidanti in soggetti con Diabete Mellito (DM) e si associa a peggior status psicologico e minore qualita della vita. La mancanza di supporto sociale potrebbe inoltre aggravare lo stato psicologico di tali pazienti. Scopo di questo studio e stato indagare la relazione tra depressione, supporto sociale e stato di salute percepita in pazienti con piede diabetico e determinare se all’aumentare della gravita delle lesioni si riduceva il supporto sociale e aumentava lo stato depressivo. Sono stati arruolati 74 pazienti con diabete (52M; 22 F) tra quelli regolarmente afferenti presso l’ambulatorio del piede diabetico del Servizio di Diabetologia dell’AOUI di Verona. A tutti sono stati somministrati 3 questionari: Patient Health Questionnaire-9 (PHQ-9), Questionario sul Supporto Sociale Percepito (MSPSS) e Questionario sullo Stato di Salute (SF-36) per valutare rispettivamente depressione, supporto sociale e stato di salute percepita. Coloro che vivevano con il coniuge presentavano un migliore stato di salute psicologica percepita rispetto a coloro che vivevano da soli. In tutto il campione, all’aumentare del sup-porto sociale proveniente da partner, famiglia e amici, migliorava lo stato di salute percepita. Inoltre, e stata rilevata una correlazione negativa tra sintomi depressivi e tutte le sottoscale dell’SF-36. Non e stata invece rilevata alcuna relazione tra severita dell’ulcera e le variabili esaminate ad eccezione della sottoscala attivita fisica dell’SF-36. I risultati emersi in questo studio sottolineano l’importanza di una valutazione socio-psicologica preliminare in pazienti con diabete complicato da piede diabetico.