Comparison of insulin sensitivity assessment indices with euglycemic-hyperinsulinemic clamp data after a dietary and exercise intervention in older adults.

Multiple indices to assess insulin sensitivity calculated from mathematical equations based on fasting blood parameters or oral glucose tolerance data have been developed. Although these indices have frequently been validated using euglycemic-hyperinsulinemic clamp data, the utility of each equation in measuring change in insulin sensitivity over time remains uncertain. We examined change in insulin sensitivity in response to a 12-week diet and exercise intervention in 31 older men and women with impaired glucose tolerance using a euglycemic-hyperinsulinemic clamp and 10 commonly used insulin sensitivity equations. Mean glucose disposal as calculated from clamp data was significantly higher after the intervention compared with baseline (5.92 +/- 0.38 vs 5.18 +/- 0.30 mg . kg fat free mass(-1) . min(-1), P = .013). In contrast, none of the examined indices indicated a significant change in insulin sensitivity over time (all P > .3). A limits of agreement approach to compare insulin sensitivity calculated from each equation with the measure of glucose disposal from the clamp indicated overall imperfect agreement between measures (agreement limits ranged from +/-2.48 to +/-4.23 mg . kg fat free mass(-1) . min(-1)) despite significant bivariate correlations between indices and clamp data. The wide variability in the 95% prediction limits of agreement among equations suggests that these equations vary substantially from a euglycemic-hyperinsulinemic clamp in their ability to assess insulin sensitivity. Despite the observed limited agreement using this statistical approach, changes in several calculated indices were significantly correlated with changes in clamp data, suggesting that these indices may have some utility in tracking improvements in insulin sensitivity. Further research is necessary to examine agreement between indices and clamp data in larger, more heterogeneous populations and in response to other interventions where the magnitude of change in insulin sensitivity may be larger.

Exercise-induced changes in insulin action and glycogen metabolism in elderly adults.

PURPOSE: Although data suggest that physical activity is associated with decreased insulin resistance, recommendations for exercise training are not specific for age or level of obesity. Therefore, we examined the influence of moderate-intensity (50% of VO2max) exercise training (MI) versus high-intensity (75% of VO2max) exercise training (HI) on insulin-stimulated glucose disposal (ISGD) in elderly individuals. METHODS: Following medical examinations, 21 overweight (body mass index = 29 +/- 1 kg x m(-2)) elderly (74 +/- 1 yr) subjects were randomized to 1) HI, 2) MI, or a 3) nonexercising control group. Subjects enrolled in HI or MI completed a 12-wk exercise training regimen designed to expend 1000 kcal x wk. ISGD was assessed using a hyperinsulinemic, euglycemic clamp pre- and postintervention. ISGD was corrected for hepatic glucose production (glucose Ra) using a constant rate infusion of [6,6-H2]glucose and determined during the last 30 min of the clamp by subtracting glucose Ra from the exogenous glucose infusion rate. Nonoxidative glucose disposal was calculated using indirect calorimetry. Body composition testing was completed using dual energy x-ray absorptiometry. RESULTS: ISGD increased by approximately 20% with HI (Delta of 1.4 +/- 0.5 mg x kg(-1) FFM.min(-1)). However, ISGD did not change (Delta of -0.4 +/- 0.1 mg x kg(-1) FFM.min(-1)) with MI and was not different (Delta of -0.2 +/- 0.1 mg x kg(-1) FFM.min(-1)) in the control group. Nonoxidative glucose disposal increased with HI (Delta of 1.4 +/- 0.5 mg x kg(-1) FFM.min(-1)), but there was no change in nonoxidative glucose disposal with MI or in the control group. No change in body weight or percentage of body fat was observed in any group. CONCLUSION: In weight-stable subjects, MI resulted in no change in ISGD, and the improvement in ISGD with HI was completely reliant on improvements in nonoxidative glucose disposal.

Effects of an ad libitum, high carbohydrate diet and aerobic exercise training on insulin action and muscle metabolism in older men and women.

BACKGROUND: Previous studies have demonstrated that aerobic exercise training and weight loss have independent effects on insulin-stimulated glucose disposal (ISGD). We hypothesized that ad libitum consumption of a high-carbohydrate diet would result in weight loss and improved ISGD, and that aerobic exercise training would facilitate greater improvements in ISGD compared with diet alone. METHODS: Older participants (13 women, 9 men; age = 66 +/- 1 year) with impaired glucose tolerance were randomly assigned to an ad libitum diet alone (18% fat, 19% protein, 63% carbohydrate) or this diet plus aerobic exercise training (4 d/wk, 45 min/d, 80% VO(2peak)) for 12 weeks. ISGD, abdominal fat distribution, muscle glycogen, and glycogen synthase activity were assessed pre- and postintervention. RESULTS: Consumption of the diet resulted in significant weight loss and an improvement in ISGD. Consumption of the diet plus exercise training also resulted in weight loss and increased ISGD, but results were not significantly different from those in the diet-alone group. Mean abdominal visceral and subcutaneous adipose tissue cross-sectional areas were smaller postintervention compared to baseline with no difference between groups. Exercise training and consumption of the diet increased muscle glycogen content (344.7 +/- 21.3 to 616.7 +/- 34.4 micromol.g(-1)) and decreased glycogen synthase activity (0.21 +/- 0.02 to 0.13 +/- 0.01) compared to the diet alone. CONCLUSIONS: These results demonstrate that consumption of an ad libitum, high-carbohydrate diet alone or in combination with aerobic exercise training results in weight loss and improved insulin sensitivity. Furthermore, exercise combined with this diet appears to limit additional increases in insulin sensitivity due to muscle glycogen supercompensation with a concomitant adaptive response of glycogen synthase.

Effects of an ad libitum low-fat, high-carbohydrate diet on body weight, body composition, and fat distribution in older men and women: a randomized controlled trial.

BACKGROUND: The efficacy of ad libitum low-fat diets in reducing body weight and fat in overweight and obese adults remains controversial. METHODS: We examined the effect of a 12-week low-fat, high-complex carbohydrate diet alone (HI-CHO) and in combination with aerobic exercise training (HI-CHO + EX) on body weight and composition in 34 individuals with impaired glucose tolerance (20 women and 14 men; mean +/- SEM age, 66 +/- 1 years). Participants were randomly assigned to a control diet (41% fat, 14% protein, 45% carbohydrates, and 7 g of fiber per 1000 kcal), a HI-CHO diet (18% fat, 19% protein, 63% carbohydrates, and 26 g of fiber per 1000 kcal), or a HI-CHO diet plus endurance exercise 4 d/wk, 45 min/d, at 80% peak oxygen consumption (HI-CHO + EX). Participants were provided 150% of estimated energy needs and were instructed to consume food ad libitum. Total food intake, body composition, resting metabolic rate, and substrate oxidation were measured. RESULTS: There was no significant difference in total food intake among the 3 groups and no change in energy intake over time. The HI-CHO + EX and HI-CHO groups lost more body weight (-4.8 +/- 0.9 kg [P=.003] and -3.2 +/- 1.2 kg [P=.02]) and a higher percentage of body fat (-3.5% +/- 0.7% [P=.01] and -2.2% +/- 1.2% [P=.049]) than controls (-0.1 +/- 0.6 kg and 0.2% +/- 0.6%). In addition, thigh fat area decreased in the HI-CHO (P=.003) and HI-CHO + EX (P<.001) groups compared with controls. High carbohydrate intake and weight loss did not result in a decreased resting metabolic rate or reduced fat oxidation. CONCLUSION: A high-carbohydrate diet consumed ad libitum, with no attempt at energy restriction or change in energy intake, results in losses of body weight and body fat in older men and women.