Distribution of Subcutaneous Fat Predicts Insulin Action in Obesity in Sex‐specific Manner

Abstract

The pattern of adipose tissue (AT) distribution is an important predictor of metabolic risk. The aim of this study was to analyze the association of peripheral (insulin‐mediated glucose disposal—M) and hepatic (suppression of endogenous glucose production—EGP) insulin action with abdominal (subcutaneous abdominal AT—SAAT, intraabdominal AT—IAAT) and thigh AT depots in obese individuals. Fifty‐seven Pima Indians with normal glucose tolerance underwent magnetic resonance imaging (MRI) and euglycemic‐hyperinsulinemic clamp. M was negatively related to intraperitoneal IAAT (P = 0.02) and deep SAAT (P = 0.03). Suppression of EGP was negatively related to total (P < 0.05) or deep SAAT (P < 0.05 and P = 0.01, respectively), and total or intraperitoneal IAAT (P = 0.009 and P = 0.002, respectively). A significant interaction with sex was found in the association between superficial SAAT and M, so that in women, but not men, M negatively correlated with superficial SAAT (P = 0.02). In stepwise regression analysis, both M (r² = 0.09) and EGP suppression (r² = 0.17) were associated only with intraperitoneal IAAT in the whole group. In the sex‐specific analysis (because of the significant interaction), lower M was associated with higher deep SAAT (r² = 0.15) in combination with lower superficial SAAT (r² = 0.09) in men, and with higher superficial SAAT (r² = 0.29) in combination with lower thigh subcutaneous AT (r² = 0.16) in women. Although intraperitoneal IAAT and deep SAAT were major predictors of peripheral and hepatic insulin action in obese Pima Indians, the largest variance in M rate was explained in a sex‐specific manner by relative size of subcutaneous AT depots.