Effects of exercise training alone vs a combined exercise and nutritional lifestyle intervention on glucose homeostasis in prediabetic individuals: a randomised controlled trial

Abstract

Aims/hypothesis: Although the Diabetes Prevention Program (DPP) established lifestyle changes (diet, exercise and weight loss) as the 'gold standard' preventive therapy for diabetes, the relative contribution of exercise alone to the overall utility of the combined diet and exercise effect of DPP is unknown; furthermore, the optimal intensity of exercise for preventing progression to diabetes remains very controversial. To establish clinical efficacy, we undertook a study (2009 to 2013) to determine: how much of the effect on measures of glucose homeostasis of a 6 month programme modelled after the first 6 months of the DPP is due to exercise alone; whether moderate- or vigorous-intensity exercise is better for improving glucose homeostasis; and to what extent amount of exercise is a contributor to improving glucose control. The primary outcome was improvement in fasting plasma glucose, with improvement in plasma glucose AUC response to an OGTT as the major secondary outcome.

Methods: The trial was a parallel clinical trial. Sedentary, non-smokers who were 45-75 year old adults (n = 237) with elevated fasting glucose (5.28-6.94 mmol/l) but without cardiovascular disease, uncontrolled hypertension, or diabetes, from the Durham area, were studied at Duke University. They were randomised into one of four 6 month interventions: (1) low amount (42 kJ kg body weight(-1) week(-1) [KKW])/moderate intensity: equivalent of expending 42 KKW (e.g. walking ∼16 km [8.6 miles] per week) with moderate-intensity (50% [Formula: see text]) exercise; (2) high amount (67 KKW)/moderate intensity: equivalent of expending 67 KKW (∼22.3 km [13.8 miles] per week) with moderate-intensity exercise; (3) high amount (67 KKW)/vigorous intensity: equivalent to group 2, but with vigorous-intensity exercise (75% [Formula: see text]); and (4) diet + 42 KKW moderate intensity: same as group 1 but with diet and weight loss (7%) to mimic the first 6 months of the DPP. Computer-generated randomisation lists were provided by our statistician (G. P. Samsa). The randomisation list was maintained by L. H. Willis and C. A. Slentz with no knowledge of or input into the scheduling, whereas all scheduling was done by L. A. Bateman, with no knowledge of the randomisation list. Subjects were automatically assigned to the next group listed on the randomisation sheet (with no ability to manipulate the list order) on the day that they came in for the OGTT, by L. H. Willis. All plasma analysis was done blinded by the individuals doing the measurements (i.e. lipids, glucose, insulin). Subjects and research staff (other than individuals analysing the blood) were not blinded to the group assignments.

Results: Number randomised, completers and number analysed with complete OGTT data for each group were: low-amount/moderate-intensity (61, 43, 35); high-amount/moderate-intensity (61, 44, 40); high-amount/vigorous-intensity (61, 43, 38); diet/exercise (54, 45, 37), respectively. Only the diet and exercise group experienced a decrease in fasting glucose (p < 0.001). The means and 95% CIs for changes in fasting glucose (mmol/l) for each group were: high-amount/moderate-intensity -0.07 (-0.20, 0.06); high-amount/vigorous 0.06 (-0.07, 0.19); low-amount/moderate 0.05 (-0.05, 0.15); and diet/exercise -0.32 (-0.46, -0.18). The effects sizes for each group (in the same order) were: 0.17, 0.15, 0.18 and 0.71, respecively. For glucose tolerance (glucose AUC of OGTT), similar improvements were observed for the diet and exercise (8.2% improvement, effect size 0.73) and the 67 KKW moderate-intensity exercise (6.4% improvement, effect size 0.60) groups; moderate-intensity exercise was significantly more effective than the same amount of vigorous-intensity exercise (p < 0.0207). The equivalent amount of vigorous-intensity exercise alone did not significantly improve glucose tolerance (1.2% improvement, effect size 0.21). Changes in insulin AUC, fasting plasma glucose and insulin did not differ among the exercise groups and were numerically inferior to the diet and exercise group.

Conclusions/interpretation: In the present clinical efficacy trial we found that a high amount of moderate-intensity exercise alone was very effective at improving oral glucose tolerance despite a relatively modest 2 kg change in body fat mass. These data, combined with numerous published observations of the strong independent relation between postprandial glucose concentrations and prediction of future diabetes, suggest that walking ∼18.2 km (22.3 km prescribed with 81.6% adherence in the 67 KKW moderate-intensity group) per week may be nearly as effective as a more intensive multicomponent approach involving diet, exercise and weight loss for preventing the progression to diabetes in prediabetic individuals. These findings have important implications for the choice of clinical intervention to prevent progression to type 2 diabetes for those at high risk.

Trial registration: ClinicalTrials.gov NCT00962962 FUNDING: The study was funded by National Institutes for Health National Institute of Diabetes and Digestive and Kidney Diseases (NIH-NDDK) (R01DK081559).

Keywords: Diabetes Prevention Program; Exercise intensity; Glucose tolerance; Impaired fasting glucose; Insulin sensitivity; Weight-loss diet.

Conflict of interest statement

Duality of interest The authors declare that there is no duality of interest associated with this manuscript.

Figures

Fig. 1

Screening flowchart

Fig. 2

Changes in glucose AUC (a), insulin AUC (b), fasting glucose (c) and fasting insulin (d) for each intervention group. The percentages inside each bar represent the percentage of the diet, exercise and intentional weight loss group (lifestyle) that was obtained for that variable, with lifestyle represented as 100%. ANCOVA with baseline values as a covariate, with post hoc testing between the two groups differing in exercise intensity and between the two groups differing in amount (controlling for baseline values) revealed a statistically significant difference (*p<0.05 [p=0.0207]) between the high amount/moderate intensity and the high amount/vigorous intensity groups for glucose AUC. The improvement in the high amount/moderate intensity group was superior to, but not statistically different from, the low amount group. Mod, moderate; vig, vigorous

Fig. 3

OGTT glucose curves. The pre- and post-training glucose means and standard error bars are plotted for each time point of the OGTT for each group: high amount/moderate intensity (a); high amount/vigorous intensity (b); low amount/moderate intensity (c); and clinical lifestyle (d). Pre-training data are shown with solid lines, post-training data are shown with dashed lines. Significant differences for each within-group time point (pre- vs post-training value) were determined by a two-tailed paired t test: *p<0.05; **p<0.01; ***p<0.001

Fig. 4

OGTT insulin curves. The pre-training and post-training insulin means and standard error bars are plotted for each time point of the OGTT, for each intervention group: high amount/moderate intensity (a); high amount/vigorous intensity (b); low amount/moderate intensity (c); and clinical lifestyle (d). Pre-training data are shown with solid lines, post-training data are shown with dashed lines. Significant differences for each within-group time point (pre- vs post-training value) were determined by a two-tailed paired t test: †p<0.10; *p<0.05; **p<0.01; ***p<0.001