Fasting Hyperglycemia Predicts Lower Rates of Weight Gain by Increased Energy Expenditure and Fat Oxidation Rate

Context: Increased adiposity and insulin resistance are associated with hyperglycemia and previous studies have reported that higher glucoses are associated with lower rates of weight gain. One possible mechanism is via increased energy expenditure (EE). Objective: To assess the relationships between changes in EE during spontaneous weight gain and concomitant changes in glucose levels. Design and Participants: Body composition, metabolic, and glycemic data were available from nondiabetic Native Americans who underwent two measurements of 24-h EE during eucaloric feeding in a metabolic chamber (N = 144; time between measurements: 5.0 +/- 3.3 years) or resting EE by ventilated hood system during the euglycemic-hyperinsulinemic clamp (N = 261; 4.5 +/- 3.2 years). Long-term follow-up data (8.3 +/- 4.3 years) for weight and body composition were available in 131 and 122 subjects, respectively. Main Outcome Measures: Twenty four hour EE and respiratory quotient (RQ), resting (RMR), and sleeping (SMR) metabolic rates, glucose, and insulin levels, basal glucose output (BGO). Results: Weight gain-associated increase in fasting plasma glucose (FPG) levels was accompanied with decreased 24-h RQ (partial R = -0.24, P = .002) and increased 24-h EE, RMR, SMR, and fat oxidation after accounting for changes in body composition (partial R: 0.12 to 0.19, all P <= .05). Upon weight gain, BGO tended to increase (P = .07), while insulin infusion induced a decrease in EE (P = .04). Higher baseline FPG predicted lower rates of future weight gain (partial R = -0.18, P = .04). Conclusions: Higher FPG after weight gain was associated with greater-than-expected increase in EE. The rise in BGO and the insulin-induced EE suppression at follow-up indicate that increased hepatic gluconeogenesismaybeanimportant mediator of EE changes associated with weight gain.