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Title: Microvascular function in non-insulin-dependent diabetes mellitus
Author: Jaap, Alan James
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1994
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Epidemiological studies suggest differences in the prevalence and natural history of microvascular complications between subjects with insulin dependent (IDDM) and non-insulin dependent (NIDDM) diabetes. The haemodynamic hypothesis proposes that early functional changes in the microcirculation result in the eventual development of diabetic microangiopathy. There is now a large body of experimental evidence in support of this hypothesis in patients with IDDM, with abnormalities in blood flow, capillary pressure and permeability having been demonstrated. In contrast, there have been few studies investigating microvascular function in NIDDM; however, preliminary work has identified a profound limitation in microvascular vasodilation at an early stage, while capillary pressure does not appear to be elevated. The aim of this thesis was to further investigate functional changes in the skin microcirculation in patients with NIDDM and impaired glucose tolerance (IGT). 1. Using a sensitive plethysmographic system, no difference was found in microvascular fluid permeability between patients with NIDDM and control subjects (5.3 (3.2-9.1) x 10-3 ml.min-1.100g tissue-1.mmHg-1 vs 5.4 (3.5-8.0) x 10-3 ml.min-1. 100g tissue-1 .mmHg-1 median and range; p = 0.98, Mann-Whitney). 2. In confirmation of previous studies, reduced microvascular hyperaemia in response to local heating of the skin was found (using laser Doppler fluximetry) in NIDDM patients with large vessel disease excluded (0.82 (0.42-1.41) V vs 1.40 (0.89-2.13) V control subjects; p < 0.005). Limited vasodilation correlated with fasting plasma insulin (Rg =-0.63, p < 0.04) but not glycaemic control. Microvascular hyperaemia increased after one year of improved glycaemic control in recently diagnosed patients (1.20 (0.51-3.93) V vs 0.97 (0.22-2.17) V at baseline; p < 0.05). In hypertensive NIDDM patients, there was no further reduction in microvascular vasodilation (1.05 (0.70-1.42) V vs 1.04 (0.79-1.63) V normotensive NIDDM, p = 0.82), although there was an increase in calculated resistance to blood flow (127.2 (87.5-181.3) mmHg.V-1 vs 84.7 (61.9-123.0) mmHg.V-1 normotensive patients, p < 0.02). 3. Reduced microvascular hyperaemia was found in subjects with IGT (1.01 (0.71-1.57) V vs 1.41 (1.32-2.13) V control subjects, p < 0.001), and also insulin resistant patients with acromegaly (0.96 (0.56-1.70) V vs 1.46 (1.24-2.13) V control subjects, p < 0,05). In subjects with IGT, limited vasodilation was found to correlate with fasting plasma insulin (Rg = -0.7; p < 0.001) and insulin sensitivity (Rs = 0.52; p < 0.02), but not with β-cell function, plasma glucose or serum lipid concentrations. 4. Using iontophoresis and laser Doppler fluximetry, defective endothelium-dependent vasodilation was found in subjects with IGT (518 (410-905) AU-min-l vs 1236 (875-1588) AU.min-1 control subjects, median and range; p < 0.003). In contrast there was no significant difference in myogenic (683 (301-1175) AU.min-1 vs 898 (303-998) AU.min-1 control subjects; p = 0.5) or neurogenic vasodilation ( 61 (31-109) AU vs 46 (37-146) control subjects; p = 0.8). 5. No differences in skin capillary density were found between patients with NIDDM, subjects with IGT and control subjects under basal conditions (112 (71-144) vs 107 (76-140) vs 112 (76-138) respectively; p= 0.9, Kruskal Wallis), or after venous occlusion (122 (87-157) vs 121 (90-143) IGT vs 123 (81-147); p= 0.9). In light of the above results, a unifying hypothesis has been proposed to explain the differences in epidemiology and pathophysiology of microvascular disease between IDDM and NIDDM.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
Keywords: R Medicine (General)