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

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).

Association of the Composite Inflammatory Biomarker GlycA, with Exercise-Induced Changes in Body Habitus in Men and Women with Prediabetes.

GlycA is a new composite measure of systemic inflammation and a predictor of many inflammatory diseases. GlycA is the nuclear magnetic resonance spectroscopy-derived signal arising from glucosamine residues on acute-phase proteins. This study aimed to evaluate how exercise-based lifestyle interventions modulate GlycA in persons at risk for type 2 diabetes. GlycA, fitness, and body habitus were measured in 169 sedentary adults (45-75 years) with prediabetes randomly assigned to one of four six-month exercise-based lifestyle interventions. Interventions included exercise prescription based on the amount (energy expenditure (kcal/kg weight/week (KKW)) and intensity (%VO2peak). The groups were (1) low-amount/moderate-intensity (10KKW/50%) exercise; (2) high-amount/moderate-intensity (16KKW/50%) exercise; (3) high-amount/vigorous-intensity (16KKW/75%) exercise; and (4) a Clinical Lifestyle (combined diet plus low-amount/moderate-intensity exercise) intervention. Six months of exercise training and/or diet-reduced GlycA (mean Δ: -6.8 ± 29.2 µmol/L; p = 0.006) and increased VO2peak (mean Δ: 1.98 ± 2.6 mL/kg/min; p < 0.001). Further, visceral (mean Δ: -21.1 ± 36.6 cm2) and subcutaneous fat (mean Δ: -24.3 ± 41.0 cm2) were reduced, while liver density (mean Δ: +2.3 ± 6.5HU) increased, all p < 0.001. When including individuals in all four interventions, GlycA reductions were associated with reductions in visceral adiposity (p < 0.03). Exercise-based lifestyle interventions reduced GlycA concentrations through mechanisms related to exercise-induced modulations of visceral adiposity. This trial is registered with Clinical Trial Registration Number NCT00962962.

Aerobic and resistance training effects on energy intake: the STRRIDE-AT/RT study.

PURPOSE: Our study characterizes food and energy intake responses to long-term aerobic training (AT) and resistance training (RT) during a controlled 8-month trial. METHODS: In the STRRIDE-AT/RT trial, overweight/obese sedentary dyslipidemic men and women were randomized to AT (n = 39), RT (n = 38), or a combined treatment (AT/RT, n = 40) without any advice to change their food intakes. Quantitative food intake assessments and food frequency questionnaires were collected at baseline (before training) and after 8 months of training (end of training); body mass (BM) and fat-free mass (FFM) were also assessed. RESULTS: In AT and AT/RT, respectively, meaningful decreases in reported energy intake (REI) (-217 and -202 kcal, P < 0.001) and in intakes of fat (-14.9 and -14.9 g, P < 0.001, P = 0.004), protein (-8.3 and -10.7 g, P = 0.002, P < 0.001), and carbohydrate (-28.1 and -14.7 g, P = 0.001, P = 0.030) were found by food frequency questionnaires. REI relative to FFM decreased (P < 0.001 and P = 0.002), as did intakes of fat (-0.2 and -0.3 g, P = 0.003 and P = 0.014) and protein (-0.1 and -0.2 g, P = 0.005 and P < 0.001) in AT and AT/RT and carbohydrate (-0.5 g, P < 0.003) in AT only. For RT, REI by quantitative daily dietary intake decreased (-3.0 kcal.kg(-1) FFM, P = 0.046), as did fat intake (-0.2 g, P = 0.033). BM decreased in AT (-1.3 kg, P = 0.006) and AT/RT (-1.5 kg, P = 0.001) but was unchanged (0.6 kg, P = 0.176) in RT. CONCLUSIONS: Previously sedentary subjects completing 8 months of AT or AT/RT reduced their intakes of calories and macronutrients and BM. In RT, fat intakes and REI (when expressed per FFM) decreased, BM was unchanged, and FFM increased.