Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes.

Abstract

Abnormalities in vascular reactivity in the micro- and macrocirculation are well established in type 2 diabetes. However, little is known about changes in vascular reactivity in those at risk for developing type 2 diabetes. To address this situation, the vascular reactivity in both the micro- and macrocirculation was studied in four age and sex comparable groups: 30 healthy normoglycemic subjects with no history of type 2 diabetes in a first-degree relative (controls), 39 healthy normoglycemic subjects with a history of type 2 diabetes in one or both parents (relatives), 32 subjects with impaired glucose tolerance (IGT), and 42 patients with type 2 diabetes without vascular complications (diabetes). Laser Doppler perfusion imaging was used to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent) and 1% sodium nitroprusside (SNP) (endothelium-independent), whereas high-resolution ultrasound images were used to measure brachial artery diameter changes during reactive hyperemia. Plasma concentrations of endothelin-1 (ET-1), von Willebrand factor (vWF), soluble intercellular adhesion molecule (sICAM), and soluble vascular cell adhesion molecule (sVCAM) were also measured as indicators of endothelial cell activation. The vasodilatory responses to Ach, expressed as percent increase of blood flow over baseline, were reduced in relatives (98 +/- 48, mean +/- SD), IGT (94 +/- 52), and diabetes (74 +/- 45) compared with controls (126 +/- 67) (P < 0.001 controls versus relatives, IGT, and diabetes). The responses to SNP were similarly reduced: controls (123 +/- 46), relatives (85 +/- 46), IGT (83 +/- 48), and diabetes (65 +/- 31) (P < 0.001 controls versus relatives, IGT, and diabetes) as were the responses in the brachial artery diameter during reactive hyperemia: controls (13.7 +/- 6.1), relatives (10.5 +/- 6.7), IGT (9.8 +/- 4.5), and diabetes (8.4 +/- 5.0) (P < 0.01 controls versus relatives, IGT, and diabetes). Women had greater responses than men in both the micro- and macrovascular circulatory tests, but a similar progressive reduction was observed in both sexes with increasing degrees of glucose intolerance. A significant inverse correlation was found between microvascular reactivity and systolic blood pressure, fasting plasma glucose, HDL cholesterol, fasting plasma insulin, and homeostasis model assessment (HOMA) values, an index of insulin resistance. BMI and diastolic blood pressure had a significant inverse correlation only with endothelium-dependent vasodilation. In the macrocirculation, systolic blood pressure, HbA1c, HDL cholesterol, and HOMA had significant correlation with brachial artery diameter changes. Compared with control subjects, ET-1 was significantly higher in all groups, vWF was higher only in the diabetic group, sICAM levels were higher in the IGT and diabetic groups, while sVCAM concentrations were higher in the relatives and those with diabetes (P < 0.05). On stepwise multivariate analysis, age, sex, fasting plasma glu...

The role of total and high-molecular-weight complex of adiponectin in vascular function in offspring whose parents both had type 2 diabetes

“…The endothelium plays a pivotal role in the pathogenesis of atherosclerosis, and impaired endothelial function is considered an early marker for vascular disease [43][44][45][46]. Offspring of diabetic parents are not only at risk for progression to diabetes, they have also previously been suggested to have diminished endothelial function [31,32]. We restricted our analysis to a diabetesprone group as the relatively narrow range of adiponectin and endothelial function in a solely healthy population could miss an important relationship that might be better revealed during progression from normal to the early pathologic state.…”

“…Thus, we sought to evaluate the relationship between total and high-molecular-weight adiponectin and measures of vascular function in offspring whose parents both had type 2 diabetes. This group is at risk of diabetes [29,30] and may have early atherosclerotic disease manifested as abnormal endothelial function [31,32].…”

The pathogenesis of diabetic complications: the role of DNA injury and poly(ADP-ribose) polymerase activation in peroxynitrite-mediated cytotoxicity

“…Endothelial dysfunction is a well documented complication in various forms of diabetes, and even in pre-diabetic individuals (Ruderman et al 1992, Cosentino & Luscher 1998, Caballero et al 1999, Cai & Harrison 2000, Calles-Escandon & Cipolla 2001, Szabó et al 2002b). The pathogenesis of this endothelial dysfunction includes increased polyol pathway flux, altered cellular redox state, increased formation of diacylglycerol, activation of specific protein kinase C isoforms, and accelerated nonenzymatic formation of advanced glycation endproducts.…”

Angiotensin AT 1 receptor antagonism normalizes retinal blood flow and acetylcholine-induced vasodiliation in normotensive diabetic rats

“…Another early diabetic vascular dysfunction, which has been described for a number of vascular tissues [12,13], is the impairment of acetylcholine-induced (endothelium-dependent) vasodilatation and blood flow. A limited number of studies have shown that ACE inhibitors and AT 1 antagonist can improve endothelial-dependent vasodilator function in brachial and femoral arteries in patients with Type 1 or Type 2 diabetes [14,15,16].…”