Insulin Sensitivity and Endothelial Function in College-Age Subjects with Family History of Type 2 Diabetes

Abstract

The pre-clinical phase of type 2 diabetes may precede overt diabetes by 10–12 years and includes increasing levels of insulin resistance (IR). Evidence suggests that the progression of insulin resistance to type 2 diabetes parallels the progression of endothelial dysfunction to atherosclerosis but it is not known how early these abnormalities can be detected in the pre-diabetic state. To our knowledge healthy college-age adults are totally unrepresented in this literature especially with control for known independent variables that affect endothelial function (obesity, hypertension, disglycemia, exercise). PURPOSE: To investigate levels of reduced insulin sensitivity concomitant with the level of impairment in macrovascular endothelial function in the brachial artery of healthy, normoglycemic college-age subjects with a family history of Type 2 diabetes. METHODS: Six young (19–26 y), healthy subjects (3M/3F) with a family history of Type 2 diabetes performed an OGTT [1 g/kg body weight]. Venous blood samples were taken at 0, 30, 45, 60, 75, 90 and 120 min. for measurements of plasma glucose (YSI 2300 glucose oxidase analyzer) and insulin (Mercodia Insulin ELISA). Hepatic insulin sensitivity index was calculated by the HOMA (ISIHOMA). Incremental areas under the curve (AUCs-baseline) were used to determined mean OGTT glucose and mean OGTT insulin for a measure of whole-body insulin sensitivity (ISICOMPOSITE). Cuff occlusion proximal to the antecubital fossa induced brachial artery post occlusive reactive hyperemia (PORH). Maximal vasoldilation following cuff release indicated endothelial function. Measures of % change in diameter from post occlusion constriction were standardized by the 55 sec. AUC shear rate (SR) change from resting values and correlated with the measures of insulin sensitivity. RESULTS: There was a wide intersubject range of whole body insulin sensitivity (ISICOMPOSITE = 5.55–18.48) which was highly correlated (P<.025) with ISIHOMA. The measurement usually reported for PORH (% change in diameter from rest) was typical for healthy subjects (6.7% ± 4.4%) but was not correlated with ISICOMPOSITE. Conversely, the measure of vessel dilation capacity (% change in diameter from post occlusion constriction =13.1% ± 6.4%)) when standardized by the 55 sec. AUC shear rate (SR) change from resting values and correlated with the measures of insulin sensitivity. RESULTS: There was a wide intersubject range of whole body insulin sensitivity (ISICOMPOSITE = 5.55–18.48) which was highly correlated (P<.025) with ISIHOMA. The measurement usually reported for PORH (% change in diameter from rest) was typical for healthy subjects (6.7% ± 4.4%) but was not correlated with ISICOMPOSITE. Conversely, the measure of vessel dilation capacity (% change in diameter from post occlusion constriction =13.1% ± 6.4%)) when standardized by the wide range of AUC shear rate (32.4 ± 9.2) was highly correlated (r2 = 0.80, P > .01) with ISICOMPOSITE. CONCLUSIONS: Young college-age adults with a family history of Type 2 diabetes but without clinical symptoms of pre-diabetes or the metabolic syndrome may demonstrate reduced insulin sensitivity that is correlated with markers of macrovascular endothelial dysfunction.