Weight change and sulfonylurea therapy are related to 3 year change in microvascular function in people with type 2 diabetes

Abstract

Aims: Although cardiovascular disease is the biggest cause of mortality in people with diabetes, microvascular complications have a significant impact on quality of life and financial burden of the disease. Little is known about the progression of microvascular dysfunction in the early stages of type 2 diabetes mellitus before the occurrence of clinically apparent complications. We aimed to explore this in a population with diabetes and general population sample. Methods: Demographics were collected in 154 participants with type 2 diabetes and in a further 99 participants without type 2 diabetes. Skin microvascular endothelium dependent response to iontophoresis of acetylcholine (ACh) and endothelium independent responses to sodium nitroprusside (SNP) were measured using laser Doppler fluximetry. All assessments were repeated 3 years later. Results: People with type 2 diabetes had impaired endothelial dependent microvascular response compared to those without (Area under the curve 93.8(95% CI 88.1 -99.4) vs 112(102 -121) arbitrary units per minute(au/min), p <0.001 for those with vs without diabetes respectively). Similarly endothelial independent responses were attenuated in those with diabetes (63.2(59.2 – 67.2) vs. 75.1(67.8 – 82.4)au/min respectively, p = 0.002). Mean microvascular function declined over 3 years in both groups to a similar degree (p for interaction 0.74 for response to ACh and 0.69 for response to SNP). In those with diabetes, use of sulphonylurea was associated with greater decline (p=0.022 after adjustment for co-prescriptions, change in HbA1c and weight), whereas improving glycaemic control was associated with less decline of endothelial dependent microvascular function (p=0.03). Otherwise, the determinants of microvascular decline were similar in those with and without diabetes. The principal determinant of change in microvascular function in the whole population was weight change over 3 years, such that those that lost ≥5% weight had very little decline in either endothelial dependent and independent function compared to those that were weight stable, whereas those who gained weight had a greater decline in function (change in endothelial dependent function was 1.2 (95% CI -13.2 – 15.7) au/min in those who lost weight; -15.8 (-10.5 – -21.0) au/min in those with stable weight and -37.8 (-19.4 – -56.2) au/min in those with weight gain (p trend <0.001). This association of weight change and change in endothelial function was driven by people with diabetes; in people without diabetes, the relationship was non-significant. Conclusion: Over three years, physiological change in weight was the greatest predictor of change in microvascular function.