Skin microvascular function in type 2 diabetes and related aspects of the metabolic syndrome

Microangiopathy is a major cause of morbidity and mortality in type 2 diabetes. This thesis investigates the factors that may influence the microcirculation in type 2 diabetes and related aspects of the metabolic syndrome, using techniques that interrogate the skin microvascular function.;The first study explores the concept of intrinsic microvascular dysfunction. Low birth weight has been linked with the increased risk of developing type 2 diabetes and cardiovascular disease in adult life. Impaired maximum hyperaemic response to local heating was demonstrated in the lowest-quartile birth weight infants compared to the highest-quartile birth weight group. Skin endothelium-dependent vasodilatory function and capillary density were not different between the two groups. In a separate study involving prepubertal and postpubertal subjects, both skin maximum hyperaemic response and postural vasoconstriction response were not related to birth weight. It is possible that extrinsic factors or perhaps the rapid phase of growth and sexual maturation during childhood may have modified the relationship between birth weight and microvascular function.;There has been much interest in the role of postprandial dyslipidaemia in macrovascular disease but its effect on the microcirculation is not known. In a group of healthy volunteers, skin microvascular response was not significantly attenuated after a high-fat meal. However, the change in vasodilatory response correlated strongly with the postprandial rise in triglycerides. In a corresponding study in type 2 diabetic subjects, skin microvascular function was significantly reduced after a high-fat meal.;Thus it would appear that both intrinsic and extrinsic influences are important factors in determining skin microvascular function and the interplay between the elements that are present at birth and subsequent exposures is one of the essential challenges for future research.