Glycaemic variability using continuous glucose monitoring and endothelial function in the metabolic syndrome and in Type 2 diabetes

Abstract

Subjects who are at increased risk of developing diabetes may have increased glycaemic variability associated with endothelial dysfunction and possibly subclinical atherosclerosis, which may lead to increased cardiovascular risk observed at the time of diabetes diagnosis. To investigate this hypothesis, we measured endothelial function, carotid intima-media thickness and glycaemic variability using 48-h continuous subcutaneous glucose monitoring in 3 groups of overweight or obese subjects--those without the metabolic syndrome, and those with the metabolic syndrome with or without newly diagnosed Type 2 diabetes. Consecutive subjects, aged 30-65 years with a body mass index >or= 25 kg/m(2) were recruited. Patients were classified as with or without the metabolic syndrome,or as metabolic syndrome with newly diagnosed Type 2 DM. Glycaemic variability was calculated in terms of the coefficient of variation. Endothelial function was measured using brachial artery flow-mediated dilation. We identified 75 subjects. Mean flow mediated dilation decreased (P < 0.001) and carotid intima-media thickness increased (P < 0.05) across groups. Flow mediated dilation predictors included mean 48-h continuous subcutaneous glucose monitoring values (beta = -0.022; P < 0.005) and the coefficient of variation (beta = -0.10; P = 0.01). Carotid intima-media thickness predictors included age (beta = 0.009; P < 0.001) and flow mediated dilation (beta = -0.014; P = 0.076). Patients re-stratified according to cut-offs for mean 48-h glycaemia and variability demonstrated that subjects with high mean glycaemia but low coefficient of variability had similar flow mediated dilation and carotid intima-media thickness to subjects with low mean glycaemia but high coefficient of variation. This study suggests that glycaemic variability influences endothelial function even in non-diabetic subjects. Such variability may explain the increased cardiovascular risk observed in patients prior to developing overt Type 2 diabetes.