Metabolic and cardiovascular response to exercise in patients with type 1 diabetes

Physical activity is an effective therapeutic tool for cardiovascular risk prevention. However, exercise aerobic capacity of patients with type 1 diabetes (T1DM) has not been thoroughly investigated. Aim of the present study is to evaluate exercise aerobic capacity in patients with T1DM compared to a normal control population

High serum osteopontin levels are associated with prevalent fractures and worse lipid profile in post-menopausal women with type 2 diabetes

Purpose: Patients with type 2 diabetes (T2DM) have increased fracture risk. Osteopontin (OPN) is a protein involved in bone remodeling and inflammation. The aim of this study was to evaluate the association of OPN with fracture prevalence and with metabolic parameters in post-menopausal women with T2DM. Methods: Sixty-four post-menopausal women with T2DM (age 67.0 ± 7.8 years, diabetes duration 8.9 ± 6.7 years), enrolled in a previous study, were followed up (3.6 ± 0.9 years). Previous fragility fractures were recorded. The FRAX score (without BMD) was calculated and biochemical parameters (plasma glucose, HbA1c, lipid profile and renal function) were assessed. Serum 25OH-vitamin D, calcium, PTH and OPN were evaluated at baseline. The association between OPN and fracture prevalence at baseline was evaluated by a logistic model. Results: OPN levels were higher in patients with previous fractures (n.25) than in patients without previous fractures at baseline (n.39) (p = 0.006). The odds of having fractures at baseline increased by 6.7 (1.9–31.4, 95% CI, p = 0.007) for each increase of 1 ng/ml in OPN levels, after adjustment for vitamin D and HbA1c levels. Fracture incidence was 4.7%. Higher OPN associated with a decrease in HDL-cholesterol (p = 0.048), after adjustment for age, basal HDL-cholesterol, basal and follow-up HbA1c and follow-up duration. 25OH-vitamin D associated with an increase in FRAX-estimated probability of hip fracture at follow-up (p = 0.029), after adjustment for age, 25OH-vitamin D and time. Conclusions: In post-menopausal women with T2DM, OPN might be a useful marker of fracture and worse lipid profile

Short-term effects of glucagon-like peptide 1 (GLP-1) receptor agonists on fat distribution in patients with type 2 diabetes mellitus: an ultrasonography study

AIMS:Glucagon-like peptide 1 receptor agonists (GLP-1 RA) induce weight loss and reduction in adipose tissue, but the effects of GLP-1 RA on the distribution of fat deposits have been poorly investigated. METHODS: In 25 patients with type 2 diabetes (16 females and 9 males, mean age 63.5 ± 8.8 years), treated with GLP-1 RA (exenatide, n. 12; liraglutide, n.13), both before and 3 months after starting treatment, an abdominal ultrasonographic scan, with Doppler of renal arteries, and echocardiography were performed. Subcutaneous fat width (peri-umbilical and sub-xiphoid), deep fat deposits (pre-aortic, peri-renal, and epicardial), and renal resistive index (RI) were evaluated. RESULTS: GLP-1 RA induced highly significant (p < 0.001) decrease in BMI and in fat thickness at all the assessed sites, without differences between exenatide and liraglutide treatment. A slight decrease in RI (p = 0.055) was also found. The percent changes of fat thickness was different between sites (p < 0.025), and the changes in subcutaneous deposits showed no significant correlation (p = 0.064) with those of deep fat deposits. CONCLUSIONS: A short course of treatment with GLP-1 RA, besides weight loss, induces a redistribution of adipose tissue deposits, possibly contributing to a better cardiovascular risk profile in patients with type 2 diabetes mellitus

Diagnosing silent cardiac dysautonomia via ambulatory blood pressure monitoring: early diagnosis shown by the lack of heart rate circadian rhythm in type 1 diabetes mellitus

Introduction. Diabetes mellitus (DM) can be complicated by an involvement of Neurovegetative System (NVS), conventionally and non-invasively diagnosed by the means of Ewing's test and Heart Rate Variability (HRV) analysis. It is well known that the NVS is physiologically responsible, via biological clocks, for the regulation of Circadian Rhythms (CR) characterizing the majority of biological functions. Therefore, this study is aimed at investigating the CR of Heart Rate (HR) and Blood Pressure (BP) in DM, postulating that the diagnosis of Silent Cardiac Dysautonomia (SCD) could be facilitated by detecting anomalous rhythmometric changes, including the worse one, i.e., the lose of a CR. Materials and Methods. The study has been performed on 30 clinically healthy subjects (CHS), 10 patients with DM1 and 30 patients with DM2, who underwent an ambulatory BP monitoring (ABPM) collecting data equidistantly every 30 minutes, under standardized conditions of lifestyle. The group specific monitored values of systolic (S), diastolic (D) BP, as well as HR have been analyzed via: 1. a conventional analysis of their intradiem variability; 2. a chronobiometric analysis (Cosinor method) of their CR. Results. The conventional analysis disclosed that in CHS, DM1 and DM2, both the HR and BP show an intradiem variability that is significant (p&lt;0.001). The chronobiological analysis showed that in CHS and DM2, both the HR and BP show a significant CR (p&lt;0.001), viceversa in DM1 HR is characterized by a non significant CR (p=0.124), notwithstanding that the SBP and DBP maintain a significant CR (p&lt;0.001). Conclusions. The disappearance of HR CR in DM1 reveals the involvement of neurovegetative biological clock that selectively controls the HR CR, as it is demonstrated by the pathophysiological finding of an internal desynchronization between the HR and BP CR. The selective lose of HR CR in DM1 leads to conclude that the ABPM, along with its Cosinor analysis, might be a practical, repeatable, low cost, low risk technique for diagnosing the SCD, at least in DM1. Clin Ter 2010; 161(1):e1-e1

The SNP rs9677 of VPAC1 gene is associated with glycolipid control and heart function in female patients with type 2 diabetes: A follow-up study

BACKGROUND AND AIMS: In a previous study, the single-nucleotide polymorphism (SNP) rs9677, mapped in the 3'-UTR of vasoactive intestinal peptide receptor 1 (VPAC1) gene, was found to be associated with type 2 diabetes (T2D) in Caucasian women. Moreover, the CC genotype correlated with a worse glycolipid profile. The objectives of this study were to confirm this correlation and assess the prevalence of coronary artery disease (CAD) in the previously investigated diabetic women after a follow-up of 4.6 years. METHODS AND RESULTS: A total of 143 women with T2D, with 53 carrying the CC genotype (age: 71.7 ± 7.4 years, diabetes duration: 17.2 ± 9.9 years) and 90 carrying the CT + TT genotypes (age: 69.4 ± 8.8 years, diabetes duration: 14.3 ± 8.2 years), were followed up for 4.6 ± 1.8 years. At follow-up, the clinical and haematochemical parameters were analysed. Twelve-lead electrocardiography, Doppler echocardiography and the percentage of patients with acute myocardial infarction (AMI) or of those subjected to coronary angioplasty and coronary artery bypass surgery were evaluated. At follow-up, there was no significant difference in terms of the clinical and haematochemical parameters between the two groups. However, despite a significantly increased use of statin therapy, no significant improvement in the LDL cholesterol levels was observed in CC female patients unlike those with CT + TT (P = 0.02). Moreover, the CC female patients presented a significantly higher percentage of echocardiographic abnormalities (P = 0.035), especially left ventricular (LV) diastolic dysfunction (P = 0.04). CONCLUSIONS: The rs9677 CC genotype could be correlated with a reduced response to statin therapy and seems to be involved in diabetes cardiomyopathy in female patients with T2D

Lack of the QTc physiologic decrease during cardiac stress test in patients with type 2 diabetes treated with secretagogues

Patients with type 2 diabetes are at increased susceptibility to a prolonged QT interval. Furthermore, insulin secretagogues, drugs used to treat diabetes, may prolong QT interval and provoke arrhythmias. We evaluated whether secretagogues can affect QTc interval during cardiac stress test in 20 patients with type 2 diabetes treated with secretagogues. ECG stress test was performed in all patients. QTc interval was calculated both before cardiac stress test (BCST) and at acme of cardiac stress test (ACST). Diabetic patients treated with secretagogues showed longer QTc-ACST values than those treated with metformin only. QTc-ACST values resulted shorter than QTc-BCST values in control group. Diabetic patients treated with secretagogues showed QTc-ACST values significantly longer than QTc-BCST values. In our study, diabetic patients treated with secretagogues did not show the QTc physiologic decrease that is a protective against arrhythmias. These results suggest to evaluate, in these patients, QT length, even during routine cardiac stress test

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease

Background/Aims: Cardiovascular disease is the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients, often before the onset of renal failure, and the pathogenetic mechanism is not yet well elucidated. The aim of the study was to identify early and noninvasive markers of cardiovascular risk in young ADPKD patients, in the early stages of disease. Methods: A total of 26 patients with ADPKD and 24 control group, matched for age and sex, were enrolled, and we have assessed inflammatory indexes, mineral metabolism, metabolic state and markers of atherosclerosis and endothelial dysfunction (carotid intima media thickness (IMT), ankle brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI), left ventricular mass index (LVMI)) and cardiopulmonary exercise testing (CPET), maximal O2 uptake (V’O2max), and O2 uptake at lactic acid threshold (V’O2@LT). Results: The ADPKD patients compared to control group, showed a significant higher mean value of LVMI, RRI, homocysteine (Hcy), Homeostasis Model Assessment-insulin resistance (HOMA-IR), serum uric acid (SUA), Cardiac-troponinT (cTnT) and intact parathyroid hormone (iPTH) (p&#x3c;0.001, p&#x3c;0.001, p&#x3c;0.001, p&#x3c;0.001, p&#x3c;0.001, p=0.007, p=0.019; respectively), and a lower value of FMD and 25-hydroxyvitaminD (25-OH-VitD) (p&#x3c;0.001, p&#x3c;0.001) with reduced parameters of exercise tolerance, as V’O2max, V’O2max/Kg and V’O2max (% predicted) (p&#x3c;0.001, p&#x3c;0.001, p=0.018; respectively), and metabolic response indexes (V’O2@LT, V’O2 @LT%, V’O2@LT/Kg,) (p&#x3c;0.001, p=0.14, p&#x3c;0.001; respectively). Moreover, inflammatory indexes were significantly higher in ADPKD patients, and we found a positive correlation between HOMA-IR and C-reactive protein (CRP) (r=0.507, p=0.008), and a negative correlation between HOMA-IR and 25-OH-VitD (r=-0.585, p=0.002). Conclusion: In our study, ADPKD patients, in the early stages of disease, showed a greater insulin resistance, endothelial dysfunction, inflammation and mineral metabolism disorders, respect to control group. Moreover, these patients presented reduced tolerance to stress, and decreased anaerobic threshold to CPET. Our results indicate a major and early cardiovascular risk in ADPKD patients. Therefore early and noninvasive markers of cardiovascular risk and CPET should be carried out, in ADPKD patients, in the early stages of disease, despite the cost implication