Skin microvascular vasodilatory capacity in offspring of two parents with Type 2 diabetes

Abstract

Aims Microvascular dysfunction occurs in Type 2 diabetes and in subjects with fasting hyperglycaemia. It is unclear whether this dysfunction relates to dysglycaemia. This study investigated in normogylcaemic individuals whether a genetic predisposition to diabetes, or indices of insulin resistance including endothelial markers, were associated with impaired microvascular function.Methods Maximum microvascular hyperaemia to local heating of the skin was measured using laser Doppler¯owmetry in 21 normoglycaemic subjects with no family history of diabetes (Group 1) and 21 normoglycaemic age, sex and body mass index-matched offspring of two parents with Type 2 diabetes (Group 2).Results Although Group 2 had normal fasting plasma glucose and glucose tolerance tests, the 120-min glucose values were signi®cantly higher at 6.4 (5.3±6.6) mmol/l (median (25th ± 75th centile)) than the control group at 4.9 (4.6±5.9) mmol/l (P = 0.005) and the insulinogenic index was lower at 97.1 (60.9±130.8) vs. 124.0 (97.2±177.7) (P = 0.027). Skin maximum microvascular hyperaemia (Group 1: 1.56 (1.39±1.80) vs. Group 2: 1.53 (1.30±1.98) V, P = 0.99) and minimum microvascular resistance which normalizes the hyperaemia data for blood pressure (Group 1: 52.0 (43.2±67.4) vs. Group 2: 56.0 (43.7±69.6) mmHg/V, P = 0.70) did not differ in the two groups. Signi®cant positive associations occurred between minimum microvascular resistance and indices of the insulin resistance syndrome; plasminogen activator inhibitor type 1 (R s = 0.46, P = 0.003), t-PA (R s = 0.36, P = 0.03), total cholesterol (R s = 0.35, P = 0.02), and triglyceride concentration (R s = 0.35, P = 0.02), and an inverse association with insulin sensitivity (R s = ±0.33, P = 0.03).Conclusions In normoglycaemic adults cutaneous microvascular vasodilatory capacity is associated with features of insulin resistance syndrome, particularly with plasminogen activator inhibitor type 1. A strong family history of Type 2 diabetes alone does not result in impairment in the maximum hyperaemic response.

Endothelial Function in Pre-diabetes, Diabetes and Diabetic Cardiomyopathy: A Review

“…Such result was independent of insulin-resistance conditions of the subjects. Nevertheless, Lee et al's [62] results contrasted all of these. In fact, they measured microvascular hyperemia induced by heat locally applied to skin by means of laser Doppler-flowmetry in 21 patients with family history of T2D.…”

Effect of family history of type-2 diabetes on coronary flow reserve and it’s relationship with insulin resistance: an observational study

“…Several previous investigations also found endothelial dysfunction in relatives of type-2 diabetics (14), though this remains controversial (17). In these studies, offspring cohorts differed from control subjects with respect to post-challenge glucose and insulin, cholesterol, severity of IR, BMI, blood pressure, and other factors (14,17). These confounding differences make it difficult to assess independent effects of family history of diabetes on endothelial function.…”

“…Although the pleiotropic metabolic disturbances of the prediabetic state may contribute to atherosclerosis progression, our findings suggest that a strong family history of diabetes is associated with diminished CFR and may contribute to cardiovascular risk in advance of overt diabetes. Several previous investigations also found endothelial dysfunction in relatives of type-2 diabetics (14), though this remains controversial (17). In these studies, offspring cohorts differed from control subjects with respect to post-challenge glucose and insulin, cholesterol, severity of IR, BMI, blood pressure, and other factors (14,17).…”

Childhood Diabetes Mellitus and the Double Burden of Malnutrition: An Emerging Public Health Challenge in Developing Countries

“…Although this is not supported by strong scientific evidence, many observational studies have revealed its relationship with increased cardiovascular risk [21]. For instance, several workers have confirmed significant endothelial dysfunction in subjects with parental history of type 2 DM [26][27][28][29], although another study has reported a contrasting finding [30]. Nevertheless, an association between carotid intima-media thickness (CIMT) and risk factors for atherosclerosis has been documented by some investigators [31]; underscoring the role of family history of type 2 DM on development of cardiovascular risk.…”