Renal Function but Not Asymmetric Dimethylarginine Is Independently Associated with Retinopathy in Type 2 Diabetes

Background. Asymmetric dimethylarginine (ADMA) is associated with macrovascular disease and possibly with microangiopathy in type 2 diabetes (T2DM). We tested the hypothesis that ADMA is related to diabetic retinopathy (DR) independently of macrovascular disease. Methods. This cross-sectional study included 127 T2DM patients selected to achieve equal distributions of patients with and without macrovascular disease in the groups with and without DR. Results. Patients with DR had increased ADMA, longer diabetes duration, and reduced glomerular filtration rate (GFR). ADMA correlated with GFR (ρ = -0.35; P < .001), diabetes duration (ρ = 0.19; P = .048), and age (ρ = 0.19; P = .033). Logistic regression analysis revealed an association of ADMA with DR. After adjustment for macrovascular disease, this association remained significant (OR 1.48; 95% CI: 1.02–2.15; P = .039). Inclusion of GFR and T2DM duration into the model abolished this significant relationship. GFR remained the only independent predictor for DR. A 10 mL/min/1.73 m2 GFR decrease was associated with DR in a multivariate model (OR 1.30; 95% CI: 1.08–1.56; P = .006). Conclusions. These findings indicate an association between ADMA and DR in T2DM independent of macrovascular disease. This relationship is modified by GFR, the only parameter significantly related to DR in multivariate analysis

Short-Term Exercise Training Does Not Stimulate Skeletal Muscle ATP Synthesis in Relatives of Humans With Type 2 Diabetes

OBJECTIVE-We tested the hypothesis that short-term exercise training improves hereditary insulin resistance by stimulating ATP synthesis and investigated associations With gene polymorphisms. RESEARCH DESIGN AND METHODS-We studied 24 nono-bese first-degree relatives of type 2 diabetic patients and 12 control subjects at rest, and 48 h after three bouts of exercise. In addition to measurements of oxygen uptake and insulin sensitivity (oral glucose tolerance test), ectopic lipids and mitochondrial ATP synthesis were assessed using H-1 and P-31 magnetic resonance spectroscopy, respectively. They were genotyped for polymorphisms in genes regulating mitochondrial function, PPARGC1A (rs8192678) and NDUFB6 (rs540467). RESULTS-Relatives had slightly lower (P = 0.012) insulin sensitivity than control subjects. In control subjects, ATP synthase flux rose by 18% (P = 0.0001), being 23% higher (P = 0.002) than that in relatives after exercise training. Relatives responding to exercise training with increased ATP synthesis (+19%, P = 0.009) showed improved insulin sensitivity (P = 0.009) compared with those whose insulin sensitivity did not improve. A polymorphism in the NDUFB6 gene from respiratory chain complex I related to ATP synthesis (P = 0.02) and insulin Sensitivity response to exercise training (P = 0.05). ATP synthase flux correlated with O-2 uptake and insulin sensitivity. CONCLUSIONS-The ability of short-term exercise to stimulate ATP production distinguished individuals with improved insulin sensitivity from those whose insulin sensitivity did not improve. lit addition, the NDUFB6 gene polymorphism appeared to modulate this adaptation. This finding suggests that genes involved in mitochondrial function contribute to the response of ATP synthesis to exercise training. Diabetes 58:1333-1341, 200

Cholinergic Regulation of Ghrelin and Peptide YY Release May Be Impaired in Obesity

OBJECTIVE—Ghrelin and peptide YY (PYY) are both hormones derived from the gastrointestinal tract involved in appetite regulation. The cholinergic part of the vagal nerve is involved in the regulation of glucose and insulin. The aim of this study was to examine the effects of the cholinergic antagonist atropine on ghrelin, PYY, glucose, and insulin under basal conditions and after meal ingestion in lean and obese subjects