Microvascular Dysfunction Is Associated With a Higher Incidence of Type 2 Diabetes Mellitus

Abstract

Objective-Recent data support the hypothesis that microvascular dysfunction may be a potential mechanism in the development of insulin resistance. We examined the association of microvascular dysfunction with incident type 2 diabetes mellitus (T2DM) and impaired glucose metabolism by reviewing the literature and conducting a meta-analysis of longitudinal studies on this topic. Methods and Results-We searched Medline and Embase for articles published up to October 2011. Prospective cohort studies that focused on microvascular measurements in participants free of T2DM at baseline were included. Pooled relative risks were calculated using random effects models. Thirteen studies met the inclusion criteria for this meta-analysis. These studies focused on T2DM or impaired fasting glucose, not on impaired glucose tolerance. The pooled relative risks for incident T2DM (3846 cases) was 1.25 (95% confidence interval, 1.15; 1.36) per 1 SD greater microvascular dysfunction when all estimates of microvascular dysfunction were combined. In analyses of single estimates of microvascular dysfunction, the pooled relative risks for incident T2DM was 1.49 (1.36; 1.64) per 1 SD higher plasma soluble E-selectin levels; 1.21(1.11; 1.31) per 1 SD higher plasma soluble intercellular adhesion molecule-1 levels; 1.48 (1.03; 2.12) per 1 SD lower response to acetylcholine-mediated peripheral vascular reactivity; 1.18 (1.08; 1.29) per 1 SD lower retinal arteriole-to-venule ratio; and 1.43 (1.33; 1.54) per 1 logarithmically transformed unit higher albumin-to-creatinine ratio. In addition, the pooled relative risks for incident impaired fasting glucose (409 cases) was 1.

Cerebral Perfusion in Insulin Resistance and Type 2 Diabetes

“…Our measurements of the resting cortical CBF in middle-age adults agree well with the cortical CBF distribution previously measured using PET 15 O and other techniques (Table 1). However, the variability of our CBF technique (standard deviation~6 mL/ 100 g per minute) is approximately two times better than the variability for competing methods.…”

“…14 The model suggests alterations in cerebral blood flow (CBF) and its regulation. By examining the literature on several markers of microcirculation, Muris et al 15 proposed that microvascular impairment is part of the etiology of T2DM. However, there are no CBF studies of individuals with IR but with no diabetes and few publications in diabetic patients.…”

Arterial stiffness and endothelial inflammation in prediabetes and newly diagnosed diabetes patients

“…Insomuch that, diabetes has been accepted as a cardiovascular disease equivalent, meaning that these patients should be accepted as having atherosclerotic disease at the time of diagnosis. The blamed underlying factors of these risks are the mentioned endothelial inflammation and microcirculatory dysfunction (4). These patients will benefit much from any intervention in the diagnosis, follow-up, and therapy.…”

Endothelial Dysfunction Plays a Key Role in Increasing Cardiovascular Risk in Type 2 Diabetes

“…7,8 There is abundant evidence that DM2, IGM, and insulin resistance cause endothelial dysfunction, 9 but evidence for the reverse process is relatively recent.…”

“…The mechanism that may underlie this phenomenon is a bidirectional association between endothelial dysfunction and DM2, in which endothelial dysfunction may act as both cause 6,7 and consequence 6,8 of DM2. On the one hand, DM2 leads to endothelial dysfunction via, amongst others, formation of advanced glycation end products, intraendothelial accumulation of glucose, and increased oxidative stress.…”