Impaired Endothelium-Dependent and Independent Dilatation of Forearm Resistance Arteries in Men with Diet-Treated Non-Insulin-Dependent Diabetes: Role of Dyslipidaemia

Abstract

1. We measured endothelium-dependent and independent dilatation of forearm resistance arteries in 29 men with diet-treated non-insulin-dependent diabetes mellitus and 18 age- and sex-matched control subjects. None of the diabetic patients had hypercholesterolaemia, overt hypertension or microproteinuria. 2. We examined endogenous and exogenous nitric oxide-mediated vasodilatation by measuring forearm blood flow with venous occlusive plethysmography after administration of acetylcholine (7.5 and 15 micrograms/min) and sodium nitroprusside (3 and 10 micrograms/min), respectively, into the brachial artery. NG-monomethyl-L-arginine was also infused to study the inhibition of basal and stimulated release of nitric oxide. 3. The vasodilatory response to acetylcholine, expressed as area under curve, was significantly decreased in the diabetic patients compared with the control subjects (P = 0.019). NG-monomethyl-L-arginine significantly reduced basal (P < 0.001) and acetylcholine-stimulated blood flow (P < 0.02) in both groups. The vasodilatory response (also expressed as area under curve) to sodium nitroprusside was significantly less (P = 0.044) in the diabetic patients than in the control subjects. 4. In the diabetic patients, impaired vasodilatory responses to acetylcholine were significantly correlated with higher serum triacylglycerols (P = 0.048) and lower high-density lipoprotein-cholesterol concentrations (P = 0.007); the association with high-density lipoprotein was independent of age, glycated haemoglobin and blood pressure. Sodium nitroprusside responses were not correlated with lipid and lipoprotein concentrations. 5. We conclude that there is impaired endothelial and smooth muscle cell function in men with diet-treated non-insulin-dependent diabetes mellitus uncomplicated by overt hypertension or microproteinuria. Endothelial dysfunction may be related to diabetic dyslipidaemia and associated metabolic disturbances.

Insulin Therapy Improves Endothelial Function in Type 2 Diabetes

“…We recently performed a comprehensive search for such factors and found LDL size to be weakly correlated with endothelium-dependent vasodilatation. 34 A similar relation was also described by Watts et al 11 within a group of type 2 diabetic patients. In other studies, 8,12,13 no significant correlations between cardiovascular risk factors and endothelium-dependent vasodilatation have been identified.…”

“…The reason for normal endothelial function in the study of Avogaro et al is unclear but could be due to the small number of subjects studied (6 normal subjects and 10 patients with type 2 diabetes). Regarding endothelium-independent but guanylate cyclase-dependent vasodilatation, endothelial function has been found to be either impaired 8,11,12 or normal. 9,13 Multiple causes could contribute to endothelial dysfunction in patients with type 2 diabetes compared with nondiabetic subjects matched for age, body weight, LDL cholesterol levels, and blood pressure, as in the present study (Table 1).…”

“…[5][6][7] In patients with type 2 diabetes, the impaired vasodilator response to endothelium-dependent vasodilators, such as acetylcholine (ACh), has been a rather consistent finding. 8 -12 In addition, responses to endothelium-independent vasodilator agents, such as sodium nitroprusside (SNP), have been found to be impaired in many 8,11 although not all 9,13 studies. These data suggest that the function of endothelial or vascular smooth muscle cells or both may be abnormal in type 2 diabetic patients.…”

Six months of aerobic exercise does not improve microvascular function in type 2 diabetes mellitus

“…Since the mean difference between type 2 diabetes and normal controls is 0.50 and 0.44 V, respectively [36,37], this represents a clinically relevant reversal of the abnormalities described. In terms of SD improvement, these represent 0.8 and 0.74 SD, which are smaller than many changes previously described for exercise-induced changes of the macrocirculation, many of which are multiples of SDs [13,38,39]. A type 2 error is therefore unlikely to explain the lack of an effect of exercise on microvascular function.…”

Diabetes potentiates acetylcholine-induced relaxation in rabbit renal arteries

“…In contrast, some authors have reported attenuated responses to nitrovasodilators in diabetic patients Ž . Watts et al, 1996 . In human aortic endothelial cells, prolonged exposure to elevated concentrations of glucose increases eNOS gene, protein expression and NO release, thus indicating that both basal and stimulated production of NO are enhanced Ž in high glucose-treated cells Cosentino and Luscher, . 1998 .…”