Exercise improves metformin 72-h glucose control by reducing the frequency of hyperglycemic peaks.

PURPOSE: To determine the separated and combined effects of metformin and exercise on insulin sensitivity and free-living glycemic control in overweight individuals with prediabetes/type 2 diabetes (T2DM). METHODS: We recruited 16 adults with BMI of 32.7 ± 4.3 kg m-2 and insulin resistance (HOMA-IR 3.2 ± 0.4) under chronic metformin treatment (1234 ± 465 g day-1) enrolled in a high-intensity interval training (HIIT) program. Participants underwent four 72-h experimental trials in a random-counterbalanced order: (1) maintaining their habitual metformin treatment (MET); (2) replacing metformin treatment by placebo (CON); (3) placebo plus two HIIT sessions (EX + CON), and (4) metformin plus two HIIT sessions (MET + EX). We used intermittently scanned continuous glucose monitoring (isCGM) during 72 h in every trial to obtain interstitial fluid glucose area under the curve (IFGAUC) and the percentage of measurements over 180 mg dL-1 (% IFGPEAKS). Insulin sensitivity was assessed on the last day of each trial with HOMA-IR index and calculated insulin sensitivity (CSI) from intravenous glucose tolerance test. RESULTS: IFGAUC was lower in MET + EX and MET than in CON (P = 0.011 and P = 0.025, respectively). In addition, IFGAUC was lower in MET + EX than in EX + CON (P = 0.044). %IFGPEAKS were only lower in MET + EX in relation to CON (P = 0.028). HOMA-IR and CSI were higher in CON in comparison with MET + EX (P = 0.011 and P = 0.022, respectively) and MET (P = 0.006 and P < 0.001, respectively). IFGAUC showed a significant correlation with HOMA-IR. CONCLUSION: Intense aerobic exercise in patients with diabetes and prediabetes under metformin treatment reduces free-living 72-h blood hyperglycemic peaks. This may help to prevent the development of cardiovascular complications associated with diabetes.

Insulin sensitivity improvement with exercise training is mediated by body weight loss in subjects with metabolic syndrome.

AIM: To determine whether exercise training improves insulin actions through concomitant body weight loss (BWL). METHODS: Subjects (aged 55±8 years) with metabolic syndrome (MetS), prediabetes (fasting blood glucose: 111±2mg·dL-1, HbA1c: 5.85±0.05%) and abdominal obesity (waist circumference: 104±7.9cm) were randomly allocated to either a group performing aerobic interval training (EXER; n=76) or a sedentary group receiving lifestyle counselling (CONT; n=20) for 16 weeks. RESULTS: At baseline, insulin sensitivity (according to HOMA2 and intravenous glucose tolerance test; CSI), body composition and VO2max were similar between the groups. After the intervention, both groups had similar BWL (1-2%), but only the EXER group showed decreased [mean (95% CI)] trunk fat mass [from 18.2 (17.4-18.9) to 17.3kg (16.6-17.9); P<0.001] and HOMA2 scores [from 1.6 (1.5-1.7) to 1.4 (1.3-1.5); P=0.001], and increased VO2max [from 2.07 (1.92-2.21) to 2.28 (2.11-2.45) LO2·min-1; P<0.001]. However, CSI did not improve in any group. Within-group subdivision by BWL (≤0%, 0-3%, ≥3%) revealed higher CSI in those with BWL≥3% in both groups. Trunk fat mass reductions were closely associated with CSI and HOMA-IR improvement (r=-0.452-0.349; P<0.001). CONCLUSION: In obese MetS subjects with prediabetes, 3% BWL is required for consistent improvement in insulin sensitivity. Thus, exercise-training programmes should be combined with calorie restriction to achieve BWL levels that prevent the development of diabetes.