Saula de Kreutzenberg | PubMed Health

PubMed2006

Endothelial dysfunction in type 2 diabetes mellitus.

AIMS: Vascular endothelial cells play a major role in maintaining cardiovascular homeostasis in health. Diabetes mellitus (DM) substantially impairs the vasodilating properties of the endothelium and leads to endothelial dysfunction, which can thus be considered the first step in the progression of cardiovascular disease. The aim of the present study is to illustrate possible mechanisms responsible for endothelial dysfunction in DM. DATA SYNTHESIS: We have shown that NADPH oxidase gene expression is increased in circulating lymphomonocytes from patients with DM, and that this increased gene expression is dependent upon metabolic control. Hyperglycemia can mediate its adverse effects through the activation of protein kinase C. We have shown an increase in membrane-associated PKC beta 2 activity in monocytes from patients with DM. This activity was reduced by 40% in the euglycemic condition. Finally, we show a reduction of the circulating endothelial progenitor cells, a subset of bone marrow-derived endothelial-oriented stem cells, which can give rise to mature endothelial cells. CONCLUSION: Endothelial dysfunction, the initial step of the atherosclerotic process, is reversible. Thus, major efforts should be made to control not only hyperglycemia but also the other risk factors for cardiovascular disease, in order to prevent the onset of all these processes that eventually leads the diabetic patient to premature death.

Diabetes Complications↗

PubMed2002

Glucose tolerance during moderate alcohol intake: insights on insulin action from glucose/lactate dynamics.

Moderate alcohol (ETOH) intake has been associated with a significant reduction in risk for infarction among general populations. In this study, we assessed the effects of low-dose ETOH (40 g over 3-h period as vodka) on the interaction between glucose (G), insulin, and lactate (L) during the insulin-modified frequently sampled i.v. glucose tolerance test (FSIGT) (0.3 U/kg body weight between 20-25 min) in eight normal volunteers. In the control (C) study, water was administered. An insulin-independent two-compartment model was used to describe G and L kinetics. Insulin sensitivity (S(I)) was significantly higher in the ETOH study than in the C study (2.49 +/- 0.52 vs. 0.92 +/- 0.20 10(-4) min(-1)microU(-1)ml, C vs. ETOH; P = 0.0391). No significant differences were observed in G effectiveness (0.029 +/- 0.004 vs. 0.033 +/- 0.004 min(-1)). Blood L levels were higher during FSIGT when ETOH was administered [area under the curve (AUC), 201 plus minus 16 vs. 123 +/- 23 mmol/liter in 240 min; P = 0.0001]. The dynamic analysis of blood L concentrations showed that ETOH also significantly decreased L clearance (0.0016 +/- 0.0011 vs. 0.0029 +/- 0.0002 min(-1); P = 0.0156), whereas no difference was observed for the fractional conversion of the rate of G disappearance to L (0.0033 +/- 0.0012 vs. 0.0031 +/- 0.0005 min(-1)). ETOH decreased baseline plasma FFA concentration; AUC of FFA was markedly reduced with ETOH (65 +/- 14 vs. 109 plus minus 17 mmol/liter in 240 min; P = 0.0063) and inversely correlated with S(I) (r = 0.693; P = 0.0029). The amount of C-peptide in 240 min as well as the amounts before and after insulin administration were not different between the two tests. We concluded that G and L kinetics derived from FSIGT shows that moderate ETOH intake: 1) improves insulin action; 2) decreases L clearance; and 3) does not affect beta cell function. Because ETOH at moderate doses has a marked antilipolytic action, it might improve insulin action by improving substrate competition. The present findings suggest that moderate alcohol consumption in the diet should not be discouraged.

Adult↗