Assessment of non–insulin-mediated glucose uptake: association with body fat and glycemic status

In the fasting state, approximately 83% of glucose uptake occurs via non–insulin-mediated mechanisms. A widely accepted static rate for NIMGU is 1.62 mg kg−1·min−1. To investigate the variability of NIMGU, we examined differences by glucose tolerance, sex, age, race (American Indian/African American/Caucasian), and adiposity in 616 volunteers (including individuals with normal glucose regulation [NGR] and impaired glucose regulation [IGR] and diabetes mellitus [DM]) using data from euglycemic-hyperinsulinemic clamp experiments. NIMGU was determined by plotting basal glucose output and insulin action against fasting and steady-state clamp insulin. The intercept with the y-axis after extrapolation was interpreted as NIMGU at zero insulin. Body composition was determined by dual-energy x-ray absorptiometry; and glucose regulation, by a 75-g oral glucose tolerance test. Energy expenditure was measured by indirect calorimetry in a metabolic chamber. In individuals with NGR (n = 385), NIMGU was 1.63 mg kgestimated metabolic body size (fat free mass + 17.7 kg)−1 min−1 (95% confidence interval, 1.59-1.66). NIMGU increased with IGR and DM (IGR: n = 189, 1.67 [1.62-1.72]; DM: n = 42, 2.39 [2.29-2.49]; P < .0001 across groups). NIMGU did not differ by sex (P = .13), age (P = .22), or race (P = .06); however, NIMGU was associated with percentage body fat (r2 = 0.04, P < .0001). Furthermore, NIMGU was positively associated with 24-hour and sleep energy expenditure (r2 = 0.002, P = .03; r2 = 0.01, P < .01). Extrapolated NIMGU in individuals with NGR is remarkably consistent with previously published data. Our results indicate that NIMGU is associated with adiposity. NIMGU increases with declining glucose tolerance perhaps to preserve glucose uptake during increased insulin resistance.