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.

The relation between glycemic control and HDL-C in type 2 diabetes: a preliminary step forward?

Low high-density lipoprotein cholesterol (HDL-C) levels are associated with cardiovascular (CV) disease in type 2 diabetes (T2D). Unfortunately available drugs to increase HDL-C have failed to demonstrate a reduction in CV risk. We assessed the effect of improving glycemic control on HDL-C levels. A 6-month intervention resulted in significant improvement in HbA1c but not in HDL-C levels. However, when considering the subgroup of subjects with low levels of HDL-C at baseline, we found a significant and inverse relation between improvement in HbA1c and HDL-C levels.

Metabolic syndrome and erectile dysfunction among obese non-diabetic subjects.

OBJECTIVE: To investigate whether MS is associated with erectile dysfunction (ED) among obese non diabetic individuals. METHODS: A cross-sectional study was carried out to examine the association between the cluster of abnormalities related to the MS and ED as evaluated by the International Index of Erectile Function (IIEF). Fifty consecutive obese [i.e. body mass index (BMI) > or =30 kg/m2], nondiabetic whites (age 42.1+/-11.3 yr, BMI 43.3+/-8.7 kg/m2) were recruited. RESULTS: The prevalence of MS as well as that of any MS component were not different between subjects with or without ED. Neither the prevalence of ED (34.3% vs 33.4%, p=0.6), nor IIEF score (21.5+/-3.9 vs 21.7+/-3.7, p=0.8), were different between patients with or without MS. IIEF was similar across subgroups of individuals stratified according to the number of MS components and was not related to HOMAIR index. Hypogonadism was observed in 30.8% and 28.1% individuals with and without MS (p=0.58). Testosterone and BMI levels were inversely related (r=-0.3, p=0.04). CONCLUSION: Among obese non-diabetic individuals the risk of developing ED is independent of the presence of MS factors. Testosterone levels progressively decrease with increasing body weight.

Waist circumference reduction after insulin detemir therapy in type 2 diabetes patients previously treated with NPH.

We studied the weight-sparing effect and treatment satisfaction when switching from NPH to insulin detemir in type 2 diabetes. Mean HbA(1c) (P<0.05) and waist circumference (P<0.05) were reduced while treatment satisfaction improved (P<0.03). No weight gain was observed. Detemir improves glycemic control, treatment satisfaction, and may provide additional weight-sparing benefits.

Angiotensin blockade and matrix synthesis by glomerular epithelial cells in high glucose: a further experimental insight into the pathophysiology of diabetic nephropathy.

AIMS: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor-1 (AT-1) antagonists are used in the treatment of proteinuria of diabetic nephropathy. One of the major pathogenic events in this condition is represented by the alteration of the extracellular matrix protein synthesis by glomerular epithelial cells. MATERIALS AND METHODS: We evaluated the effects of the angiotensin converting enzyme inhibitor, Enalaprilat, and the AT-1 receptor antagonist, Losartan, on mRNA fibronectin and laminin synthesis by glomerular epithelial cells, in conditions mimicking hyperglycemia. RESULTS: In high glucose conditions, Enalaprilat reduced significantly the mRNA expression of fibronectin (p 0.03), but not significantly that of laminin. Losartan addition to high glucose incubated cells reduced (-30%) mRNA expression of fibronectin, and significantly (p 0.05) the mRNA expression of laminin. CONCLUSIONS: In addition to the known hemodynamic effects, the improvement of renal function in diabetic patients treated with these compounds may also be due to a modulator effect on extracellular matrix content and composition.

The impairment of renal function is not associated to altered circulating vascular endothelial growth factor in patients with Type 2 diabetes and hypertension.

BACKGROUND: Metabolic and haemodynamic factors concur in the development of diabetic nephropathy. Moreover, in diabetes, the presence of hypertension may accelerate the development of renal damage. Vascular endothelial growth factor (VEGF) stimulates microvascular permeability, endothelium-dependent vasodilation and angiogenesis and its synthesis is enhanced by hyperglycaemia, advanced glycation end-products (AGEs), tissue hypoxia and hypertension. VEGF appears to play a central role in mediating diabetic vasculopathy, and although VEGF and its receptors are expressed at renal level, its action in renal pathophysiology is unknown. The aim of this study was to elucidate whether presence and/or severity of renal dysfunction is related to circulating VEGF in patients with Type 2 diabetes and hypertension. DESIGN AND METHODS: Fifty hypertensive Type 2 diabetic patients and 20 non-diabetic patients were included in the study. Renal function parameters such as albumin excretion rate (AER), and glomerular filtration rate (GFR), and VEGF plasma levels were analysed in all subjects, whereas %HbA1c and AGEs levels were evaluated in diabetic patients. RESULTS: GFR was significantly decreased in diabetic patients compared with the control subjects (74.36 +/- 15.95 vs 111.5 +/- 17.0 ml/min, p<0.0001). Three diabetic patients showed AER abnormalities (53.8 +/- 2.3 mg/24h). VEGF in diabetic patients was higher than in the control group (77.95 +/- 65.98 vs 49.30 +/- 40.8 pg/ml), but not significantly. %HbA1c and AGE levels were 6.6 +/- 1.5% and 11.59 +/- 8.09 UAGE/ml, respectively. No correlation was found between renal function, circulating VEGF levels and metabolic control. CONCLUSION: Diabetes, in association with hypertension, significantly decreases renal function, but circulating VEGF may not reflect its concentration and action at renal level.