Impaired Delivery of Insulin to Adipose Tissue and Skeletal Muscle in Obese Women with Postprandial Hyperglycemia

Abstract

CONTEXT: An impaired transfer of insulin from the circulation to the interstitial fluid has been suggested to contribute to insulin resistance. OBJECTIVE: The objective of the study was to address whether the delivery of insulin from the circulation to adipose tissue and skeletal muscle is impaired in obese women with postprandial hyperglycemia compared with lean healthy controls. DESIGN, SETTING, AND PARTICIPANTS: Seven obese nondiabetic women with postprandial hyperglycemia and nine lean healthy women were recruited. The interstitial insulin concentration in adipose tissue and muscle tissue was measured by the microdialysis technique during an oral glucose tolerance test (75 g). In parallel, arterial insulin levels were measured. We used ¹³³Xe clearance and plethysmography to monitor blood flow. Subcutaneous needle biopsies were taken to obtain fat cell size. RESULTS: After oral glucose ingestion, mean arterial insulin levels were higher in obese women than in the lean group. However, interstitial insulin levels in sc adipose tissue and forearm muscle were similar in both groups. Accordingly, the proportion of circulating insulin being transported across the vascular endothelium to the interstitial fluid in adipose tissue and in muscle tissue was significantly lower in the obese compared with the lean group. CONCLUSIONS: Obese subjects with postprandial hyperglycemia need higher circulating insulin levels than lean controls to attain similar interstitial insulin levels in adipose tissue and skeletal muscle, indicating an impaired transfer of insulin across the endothelium.