Nicole M. Gilbertson

Combining Short-Term Interval Training with Caloric Restriction Improves ß-Cell Function in Obese Adults

Although low-calorie diets (LCD) improve glucose regulation, it is unclear if interval exercise (INT) is additive. We examined the impact of an LCD versus LCD + INT training on ß-cell function in relation to glucose tolerance in obese adults. Twenty-six adults (Age: 46 ± 12 year; BMI 38 ± 6 kg/m2) were randomized to 2-week of LCD (~1200 kcal/day) or energy-matched LCD + INT (60 min/day alternating 3 min at 90 and 50% HRpeak). A 2 h 75 g oral glucose tolerance test (OGTT) was performed. Insulin secretion rates (ISR) were determined by deconvolution modeling to assess glucose-stimulated insulin secretion ([GSIS: ISR/glucose total area under the curve (tAUC)]) and ß-cell function (Disposition Index [DI: GSIS/IR]) relative to skeletal muscle (Matsuda Index), hepatic (HOMA-IR) and adipose (Adipose-IRfasting) insulin resistance (IR). LCD + INT, but not LCD alone, reduced glucose and total-phase ISR tAUC (Interactions: p = 0.04 and p = 0.05, respectively). Both interventions improved skeletal muscle IR by 16% (p = 0.04) and skeletal muscle and hepatic DI (Time: p < 0.05). Improved skeletal muscle DI was associated with lower glucose tAUC (r = −0.57, p < 0.01). Thus, LCD + INT improved glucose tolerance more than LCD in obese adults, and these findings relate to ß-cell function. These data support LCD + INT for preserving pancreatic function for type 2 diabetes prevention.

Bariatric Surgery Resistance: Using Preoperative Lifestyle Medicine and/or Pharmacology for Metabolic Responsiveness.

Bariatric surgery is an effective and durable treatment for individuals with obesity and its associated comorbidities. However, not all patients meet weight loss and/or cardiometabolic goals following bariatric surgery, suggesting that some people are bariatric surgery resistant. The reason for this resistance is unclear, but potential factors, such as adiposity-derived inflammation, insulin resistance, hyperglycemia, and aerobic fitness prior to surgery, have been related to blunted surgery responsiveness. Exercise, diet, and/or pharmacology are effective at reducing inflammation and improving insulin action as well as physical function. Herein, we present data that supports the novel hypothesis that intervening prior to surgery can enhance disease resolution in people who are resistant to bariatric surgery.

Low cardiorespiratory fitness is associated with higher extracellular vesicle counts in obese adults

Low cardiorespiratory fitness (CRF) is associated with cardiovascular disease (CVD) independent of obesity. Extracellular vesicles (EVs) are a novel target of CVD, however, it remains unknown if obese individuals with very poor fitness (VPF) have elevated EVs versus people with poor fitness (PF). Thus, we tested whether VPF was associated with greater EV subtypes in obese adults. Subjects with VPF (n = 13, VO2peak: 15.4 ± 0.6 mL/kg/min, BMI: 34.1 ± 1.7 kg/m2) and PF (n = 13, VO2peak: 25.9 ± 3.0 mL/kg/min, BMI: 32.1 ± 1.2 kg/m2) were compared in this cross‐sectional study. After an overnight fast, AnnexinV (AV) +/− platelet (CD31+/CD41+), leukocyte (CD45+/CD41−), and endothelial EVs (CD105+, CD31+/CD41−) were analyzed from fresh platelet poor plasma via imaging flow cytometry. Body fat, blood pressure (BP), and glucose tolerance (OGTT) were also tested. Body weight, BP, and circulating glucose were similar between groups, although VPF subjects were older than PF (64.0 ± 2.1 vs. 49.8 ± 4.2 year; P < 0.05). People with VPF, compared with PF, had higher total AV− EVs (P = 0.04), AV− platelet EVs (CD31+/CD41+; P = 0.006), and AV− endothelial EVs (CD31+/CD41−; P = 0.005) independent of age and body fat. Higher AV− platelet and endothelial EVs were associated with lower VO2peak (r = −0.56, P = 0.006 and r = −0.55, P = 0.005, respectively). Endothelial‐derived AV−/CD31+/CD41−EVs were also related to pulse pressure (r = 0.45, P = 0.03), whereas AV−/CD105 was linked to postprandial glucose (r = 0.41, P = 0.04). VPF is associated with higher AnnexinV− total, endothelial, and platelet EVs in obese adults, suggesting that subtle differences in fitness may reduce type 2 diabetes and CVD risk through an EV‐related mechanism.

Impact of Short-Term Exercise Training Intensity on β-cell Function in Older Obese Adults with Prediabetes

The effect of work-matched exercise intensity on β-cell function is unknown in people with prediabetes before clinical weight loss. We determined if short-term moderate continuous (CONT) vs. high-intensity interval (INT) exercise increased β-cell function. Thirty-one subjects (age: 61.4 ± 2.5 yr; body mass index: 32.1 ± 1.0 kg/m2) with prediabetes [American Diabetes Association criteria, 75-g oral glucose tolerance test (OGTT)] were randomized to work-matched CONT (70% HRpeak) or INT (3 min 90% HRpeak and 3 min 50% HRpeak) exercise for 60 min/day over 2 wk. A 75-g 2-h OGTT was conducted after an overnight fast, and plasma glucose, insulin, C-peptide, and free fatty acids were determined for calculations of skeletal muscle [oral minimal model (OMM)], hepatic (homeostatic model of insulin resistance), and adipose (Adipose-IR) insulin sensitivity. β-Cell function was defined from glucose-stimulated insulin secretion (GSIS, deconvolution modeling) and the disposition index (DI). Glucagon-like polypeptide-1 [GLP-1(active)] and glucose-dependent insulinotropic polypeptide (GIP) were also measured during the OGTT, along with peak oxygen consumption and body composition. CONT and INT increased skeletal muscle- but not hepatic- or adipose-derived DI ( P < 0.05). Although both treatments tended to reduce fasting GLP-1(active) ( P = 0.08), early phase GLP-1(active) increased post-CONT and INT training ( P < 0.001). Interestingly, CONT exercise increased fasting GIP compared with decreases in INT ( P = 0.02). Early and total-phase skeletal muscle DI correlated with decreased total glucose area under the curve ( r = -0.52, P = 0.002 and r = -0.50, P = 0.003, respectively). Independent of intensity, short-term training increased pancreatic function adjusted to skeletal muscle in relation to improved glucose tolerance in adults with prediabetes. Exercise also uniquely affected GIP and GLP-1(active). Further work is needed to elucidate the dose-dependent mechanism(s) by which exercise impacts glycemia. NEW & NOTEWORTHY Exercise is cornerstone for reducing blood glucose, but whether high-intensity interval training is better than moderate continuous exercise is unclear in people with prediabetes before weight loss. We show that 2 wk of exercise training, independent of intensity, increased pancreatic function in relation to elevated glucagon-like polypeptide-1 secretion. Furthermore, β-cell function, but not insulin sensitivity, was also correlated with improved glucose tolerance. These data suggest that β-cell function is a strong predictor of glycemia regardless of exercise intensity.

Short-Term Interval and Continuous Training Improves Pancreatic ß-Cell Function Adjusted for Skeletal Muscle Insulin Resistance in Adults with Prediabetes

Exercise improves pancreatic function in an energy dose-dependent manner. We previously showed that when calories are matched, an acute exercise bout changes glucose-stimulated insulin secretion (GSIS) relative to multi-organ insulin resistance (IR) in an intensity-based manner during the immediate post-exercise period in people with prediabetes. However, the impact of short-term training intensity on s-cell function is unknown. Thus, we examined the impact of high-intensity interval and moderate-continuous training on GSIS relative to multi-organ IR in adults with prediabetes. Thirty-one adults (Age: 61±8y; BMI: 33±6 kg/m2) with prediabetes according to ADA 75g OGTT and/or HbA1c criteria were randomized to energy-matched interval (INT: 60-min/d alternating 3-min at 90 and 50% HRpeak) or continuous training (CONT: 60-min/d 70% HRpeak) for 2 weeks. Fitness (VO2peak) and body mass were measured before and after, and a 120-min 75g OGTT with blood samples for glucose, insulin, C-peptide and FFA were determined every 30-min. GSIS (C-pep/Glc tAUC0-120min) and s-cell function (Disposition Index [DI: GSIS/IR]) relative to skeletal muscle (InsulintAUC x GlctAUC), hepatic (HOMA-IR) and adipose (Adipose-IRfasting) IR were calculated. Training increased VO2peak (+1.1±2.1 mL/kg/min), and reduced body mass (-0.6±1.1 kg) and IR (-11±31%), independent of intensity (P Disclosure M.E. Francois: None. N. Eichner: None. N.M. Gilbertson: None. E.M. Heiston: None. E. Barrett: None. S.K. Malin: None.