Fasting hyperglycemia predicts lower rates of weight gain by increased energy expenditure and fat oxidation rate

Abstract

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 gluconeogenesis may be an important mediator of EE changes associated with weight gain.

Trial registration: ClinicalTrials.gov NCT00340132.

Figures

Figure 1.

Time course of energy expenditure during 24 h in the respiratory chamber (Panel A), glucose and insulin concentrations during OGTT (Panels B and C), and glucose disposal (Panel D), and metabolic rates (Panel E) during glucose clamp at baseline and follow-up visits. Time courses of energy expenditure inside the respiratory chamber (median time course of 144 subjects, follow-up time: 5.0 ± 3.3 years, weight change: +6.1 ± 11.7 kg, (Panel A), glucose (Panel B), and insulin (Panel C) concentrations during a 3-h OGTT, glucose disposal (Panel D) and metabolic rate (Panel E) during the basal phase and during insulin infusion of the glucose clamp at the baseline and follow-up visits. Error bars represent mean with 95% confidence intervals.

Figure 2.

Relationships between changes (Δ) in fasting glucose concentration and changes in the metabolic parameters at the follow-up visit. Direct associations between changes (Δ, calculated as follow-up minus baseline values) in fasting glucose concentration with changes in 24-h EE (Panel A), sleeping metabolic rate (SMR, Panel B), resting metabolic rate (RMR, Panel C), fat oxidation rate (FATOX, Panel E), and inverse relationship with changes in 24-h respiratory quotient (RQ, Panel D) and carbohydrate oxidation rate (CARBOX, Panel F). Associations were all significant after adjustment for changes in physiological determinants of EE measures (results reported in the main text). The best-fit line is displayed in each panel. Vertical and horizontal lines indicate points with Δ = 0 (ie, no change between baseline and follow-up visits).

Figure 3.

Metabolic characteristics of subjects with NGR and IGR glucose regulation at baseline. Differences between subjects with NGR and IGR glucose regulation in glucose disposal (Panel A) and metabolic (Panel B) rates during clamp, resting, and sleeping EE (Panel C) all measured at the baseline visit and future rates of weight and fat mass changes (Panel D). Normal glucose regulation was defined as FPG

Figure 4.

Relationships between baseline fasting glucose concentration and rates of future body weight and fat mass change. Inverse relationships between baseline fasting glucose concentration and the rate of future body weight change (expressed as percent of initial body weight (Panel A) and the rate of future body fat mass change (Panel B). The median follow-up time is 8.0 years (IQR: 5.2–11.6 years). Rates of weight and fat mass changes are reported on a safe-logarithmic scale. The best-fit line is displayed in each panel. Horizontal lines indicate points with Δ = 0 (ie, no change between baseline and follow-up visits). The association between fasting glucose concentration and the rate of weight change was still significant after adjustment for gender, baseline body weight and age (partial R = −0.18, P = .04) while fasting glucose was not associated with the rate of FM change after adjustment for gender, baseline body weight and age (partial R = −0.09, P = .34).