Introduction Postprandial glucose (PPG) is an independent predictor of cardiovascular events and death, regardless of diabetes status. While changes in physical activity produce changes in insulin sensitivity, it is not clear whether changes in daily physical activity directly impact PPG in healthy, free-living persons. Methods We utilized continuous glucose monitors to measure PPG and PPG excursions (ΔPPG; post- minus pre-meal blood glucose) at 30-min increments after meals in healthy, habitually active volunteers (n=12, Age 29±1 y, BMI 23.6±0.9 kg•m-2, VO2max 53.6±3.0 mL•kg-1•min-1) during three days of habitual (≥10,000 steps•d-1) and reduced (<5,000 steps•d-1) physical activity. Diets were standardized across monitoring periods, and fasting-state oral glucose tolerance tests (OGTT) were performed on the fourth day of each monitoring period. Results During three days of reduced physical activity (12,956±769 to 4,319±256 steps•d-1), PPG increased at 30 and 60-min post-meal (6.31±0.19 to 6.68±0.23 mmol•L-1 and 5.75±0.16 to 6.26±0.28 mmol•L-1, P<0.05 relative to corresponding ACTIVE time point), and ΔPPG increased by 42%, 97%, and 33% at 30, 60, and 90-min post-meal, respectively (P<0.05). Insulin and C-peptide responses to the OGTT increased after three days of reduced activity (P<0.05), and the glucose response to the OGTT did not change significantly. Conclusions Thus, despite evidence of compensatory increases in plasma insulin during an OGTT, ΔPPG assessed by CGMS increased markedly during three days of reduced physical activity in otherwise healthy, free-living individuals. These data indicate that daily physical activity is an important mediator of glycemic control, even among healthy individuals, and reinforce the utility of physical activity in preventing pathologies associated with elevated PPG.

Insulin-mediated glucose disposal is dependent on the vasodilator effects of insulin. In type 2 diabetes, insulin-stimulated vasodilation is impaired as a result of an imbalance in NO and ET-1 production. We tested the hypothesis that chronic voluntary wheel running (RUN) prevents impairments in insulin-stimulated vasodilation associated with obesity and type 2 diabetes independent of the effects of RUN on adiposity by randomizing Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of hyperphagia-induced obesity and type 2 diabetes, to 1) RUN, 2) caloric restriction (CR; diet adjusted to match body weights of RUN group), or 3) sedentary control (SED) groups (n = 8/group) at 4 wk. At 40 wk, NO- and ET-1-mediated vasoreactivity to insulin (1-1,000 μIU/ml) was assessed in the presence of a nonselective ET-1 receptor blocker (tezosentan) or a NO synthase (NOS) inhibitor [N(G)-nitro-L-arginine methyl ester (L-NAME)], respectively, in second-order arterioles isolated from the white portion of the gastrocnemius muscle. Body weight, fasting plasma glucose, and hemoglobin A1c were lower in RUN and CR than SED (P < 0.05); however, the glucose area under the curve (AUC) following the intraperitoneal glucose tolerance test was lower only in the RUN group (P < 0.05). Vasodilator responses to all doses of insulin were greater in RUN than SED or CR in the presence of a tezosentan (P < 0.05), but group differences in vasoreactivity to insulin with coadministration of L-NAME were not observed. We conclude daily wheel running prevents obesity and type 2 diabetes-associated declines in insulin-stimulated vasodilation in skeletal muscle arterioles through mechanisms that appear to be NO mediated and independent of attenuating excess adiposity in hyperphagic rats.

Aims/hypothesis Cardiovascular events and death are better predicted by postprandial glucose (PPG) than by fasting blood glucose or HbA1c. While chronic exercise reduces HbA1c in patients with type 2 diabetes, short-term exercise improves measures of insulin sensitivity but does not consistently alter responses to the OGTT. The purpose of this study was to determine whether short-term exercise training improves PPG and glycaemic control in free-living patients with type 2 diabetes, independently of the changes in fitness, adiposity and energy balance often associated with chronic exercise training. Methods Using continuous glucose monitors, PPG was quantified in previously sedentary patients with type 2 diabetes not using exogenous insulin (n=13, age 53±2 years, HbA1c 6.6±0.2% (49.1±1.9 mmol/mol)) during 3 days of habitual activity and during the final 3 days of a 7 day aerobic exercise training programme (7D-EX) which does not elicit measurable changes in cardiorespiratory fitness or body composition. Diet was standardised across monitoring periods, with modifications during 7D-EX to offset increases in energy expenditure. OGTTs were performed on the morning following each monitoring period. Results 7D-EX attenuated PPG (p<0.05) as well as the frequency, magnitude and duration of glycaemic excursions (p<0.05). Conversely, average 24 h blood glucose did not change, nor did glucose, insulin or C-peptide responses to the OGTT. Conclusions/interpretation 7D-EX attenuated glycaemic variability and PPG in free-living patients with type 2 diabetes but did not significantly alter responses to the laboratory-based OGTT. These effects appeared to be independent of changes in fitness, body composition or energy balance.

Voluntary wheel running (RUN) prevents declines in insulin-mediated vasodilation, an important component of insulin-mediated glucose disposal, in rats prone to obesity and insulin resistance. Objective Determine whether RUN: 1) improves insulin-stimulated vasodilation after insulin resistance has been established, and 2) differentially affects arterioles from red and white muscle. Methods Insulin signaling and vasoreactivity to insulin (1–1000 μIU/mL), were assessed in second order arterioles (2A) from the white (Gw) and red (Gr) gastrocnemius of sedentary OLETF rats at 12 and 20 weeks of age (SED12; SED20) and those undergoing RUN (RUN20) or caloric restriction (CR20; to match body weight of RUN) from 12–20 weeks. Results Glucose and insulin responses to i.p. glucose were reduced in RUN20, elevated in SED20 (P<0.05 vs. SED12), and maintained in CR20. Insulin-stimulated vasodilation was greater in Gw, but not Gr, 2As of RUN20 (P<0.01 vs. all groups) and was improved by ET-1 receptor inhibition in Gw 2As from SED20 and CR20 (P<0.05). There were no differences in microvascular insulin signaling among groups or muscle beds. Conclusions RUN selectively improved insulin-mediated vasodilation in Gw 2As, in part through attenuated ET-1 sensitivity/production, an adaptation that was independent of changes in adiposity and may contribute to enhanced insulin-stimulated glucose disposal.

The vasodilatory effects of insulin account for up to 40% of insulin-mediated glucose disposal; however, insulin-stimulated vasodilation is impaired in individuals with type 2 diabetes, limiting perfusion and delivery of glucose and insulin to target tissues. To determine whether exercise training improves conduit artery blood flow following glucose ingestion, a stimulus for increasing circulating insulin, we assessed femoral blood flow (FBF; Doppler ultrasound) during an oral glucose tolerance test (OGTT; 75 g glucose) in 11 overweight or obese (body mass index, 34 ± 1 kg/m²), sedentary (peak oxygen consumption, 23 ± 1 ml·kg⁻¹·min⁻¹) individuals (53 ± 2 yr) with non-insulin-dependent type 2 diabetes (HbA1c, 6.63 ± 0.18%) before and after 7 days of supervised treadmill and cycling exercise (60 min/day, 60-75% heart rate reserve). Fasting glucose, insulin, and FBF were not significantly different after 7 days of exercise, nor were glucose or insulin responses to the OGTT. However, estimates of whole body insulin sensitivity (Matsuda insulin sensitivity index) increased (P < 0.05). Before exercise training, FBF did not change significantly during the OGTT (1 ± 7, -7 ± 5, 0 ± 6, and 0 ± 5% of fasting FBF at 75, 90, 105, and 120 min, respectively). In contrast, after exercise training, FBF increased by 33 ± 9, 39 ± 14, 34 ± 7, and 48 ± 18% above fasting levels at 75, 90, 105, and 120 min, respectively (P < 0.05 vs. corresponding preexercise time points). Additionally, postprandial glucose responses to a standardized breakfast meal consumed under "free-living" conditions decreased during the final 3 days of exercise (P < 0.05). In conclusion, 7 days of aerobic exercise training improves conduit artery blood flow during an OGTT in individuals with type 2 diabetes.

Emerging evidence suggests statins, unlike exercise, may cause deleterious effects on skeletal muscle oxidative capacity and insulin sensitivity.Purpose: The purpose of this study was to determine if daily statin therapy altered the ability of exercise to lower fasting plasma insulin and glucose and improve cardiorespiratory fitness.Methods: Fifteen obese, sedentary adults with ≥ 2 MSynd risk factors were recruited and randomized into 1) exercise (Ex; treadmill 45 min ·day -1 , 5 day·week -1 at 65% VO 2 max) or 2) statin plus exercise (St+Ex; 40 mg·day -1 simvastatin plus exercise) therapies for 12 weeks.Results: Baseline age, body weight, and body mass index (BMI) of St+Ex and Ex were as follows: 41±2.5 and 40±4.7 yr, 98.2±7.0 and 84.7±4.0 kg, 33.6±1.6 and 30.3±1.0 kg·m -2 , respectively. Body weight and BMI were unchanged in response to both therapies. Fasting insulin levels decreased significantly with Ex therapy (10.6±5.0 to 8.8±4.8 uIU·ml -1 , p<0.05), while no difference was observed after St+Ex therapy (8.7±3.3 to 9.9±3.9 uIU·ml -1 ). Fasting blood glucose did not change in response to St+Ex (94.4±3.2 to 90.7±3.4 mg·dL -1 ) or Ex (83.7±3.6 to 85.5±3.8 mg·dL -1 ) therapy. Only exercise improved maximal oxygen consumption (fitness) (33.8±2.6 to 36.3±3.4 ml·kg -1 ·min -1 ) while no improvements were observed in response to combined St+Ex therapy (25.7±1.4 to 26.0±1.3 ml·kg -1 ·min -1 ). Conclusion:Preliminary findings suggest St-therapy may have deleterious effects on the capacity for exercise training to lower fasting insulin and improve cardiorespiratory fitness in obese, sedentary subjects. Further investigation utilizing a larger study population is needed to definitively determine the scope of effects that St-therapy may have on insulin sensitivity and cardiorespiratory fitness.

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