Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes

Abstract

Malin SK, Haus JM, Solomon TP, Blaszczak A, Kashyap SR, Kirwan JP. Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes. Am J Physiol Endocrinol Metab 305: E1292-E1298, 2013. First published September 24, 2013; doi:10.1152/ajpendo.00441.2013.-Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG ϩ IGT is unknown. Twenty-four older (66.7 Ϯ 0.8 yr) obese (34.2 Ϯ 0.9 kg/m 2 ) adults were categorized as IFG (n ϭ 8), IGT (n ϭ 8), or IFG ϩ IGT (n ϭ 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at ϳ85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m 2 ·min Ϫ1 ) with [6,6-2 H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG ϩ IGT (P Ͻ 0.05). Exercise reduced glucose iAUCOGTT in IGT only (P Ͻ 0.05), and the decrease in glucose iAUCOGTT was inversely correlated with the increase in peripheral but not hepatic insulin sensitivity (P Ͻ 0.01). Increased clamp-derived peripheral insulin sensitivity was also correlated with enhanced metabolic flexibility, reduced fasting RQ, and higher nonoxidative glucose disposal (P Ͻ 0.05). Adults with IFG ϩ IGT had smaller gains in clamp-derived peripheral insulin sensitivity and metabolic flexibility, which was related to blunted improvements in postprandial glucose. Additional work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training. obesity; prediabetes; insulin resistance; cardiometabolic; exercise APPROXIMATELY 79 MILLION ADULTS in the US have impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both (IFG ϩ IGT) and are collectively referred to as having prediabetes (2). Focusing on adults with IFG, IGT, and IFG ϩ IGT is clinically important since each phenotype has a unique pathology that promotes different degrees of cardiovascular disease risk (8, 31). The exact cause for the difference in disease risk is unclear, but the degree of insulin resistance in skeletal muscle or the liver is a likely candidate. Individuals with IGT [2-h oral glucose tolerance test (OGTT) values between 140 and 199 mg/dl] are typically characterized as having reduced skeletal muscle insulin sensitivity, whereas adults with IFG (fasting glucose 100 -125 mg/dl) generally h...

High-intensity interval training without weight loss improves exercise but not basal or insulin-induced metabolism in overweight/obese African American women

“…For example, given that impaired postabsorptive fat oxidation predicts the severity of insulin resistance (37) and subjects with low rates of postabsorptive fat oxidation improve to a greater extent because of training (26), it is possible that the "window for adaptation" was not sufficiently large for our subjects to benefit from training. Indeed, postabsorptive NPRER for the HIIT group prior to the training intervention in our study (ϳ0.79) was lower than that which was present pretraining for the subjects of Goodpaster et al (26) and that which has been reported for obese metabolically inflexible individuals (37,43). Consequently, it appears as if metabolic flexibility in our at-risk subjects was quite high prior to training (e.g., ⌬NPRER Ϸ 0.14), which means that the present findings cannot be used as conclusive proof that HIIT without bodyweight loss does not improve metabolic flexibility in metabolically inflexible subjects.…”

“…Similarly, endurance training improves fasting fat oxidation in older obese subjects with impaired glucose tolerance (57) and nonobese subjects with Type 2 diabetes (61). However, the ability of endurance training to increase fasting fat utilization might depend upon the intensity/volume of exercise, the severity of pathological progression, and/or whether caloric restriction and weight loss accompany training (26,43).…”

Exercise-Induced Lowering of Fetuin-A May Increase Hepatic Insulin Sensitivity

“…Twenty older obese adults (Table 1) volunteered for this study, and a subgroup had participated in a previous investigation (13). They were nonsmokers, weight stable (<2-kg weight loss during the previous 6 months), and sedentary (exercising <60 min·wk −1 ).…”

“…or took medications known to affect glucose metabolism. Before metabolic testing, subjects were fed isocaloric meals (resting metabolic rate × 1.2 activity factor; 55% CHO, 30% fat, 15% protein) and instructed to refrain from vigorous physical activity for 3 d. Subjects underwent 12 wk of supervised exercise, which consisted mainly of aerobic treadmill walking performed at 85% HR max for 60 min·d −1 , as previously described (13). Postintervention metabolic testing was conducted approximately 16–18 h after the last exercise bout.…”

Metabolic and endocrine response to exercise: sympathoadrenal integration with skeletal muscle

“…Repeated exercise has been shown to improve insulin sensitivity (Borghouts & Keizer 2000, Kirwan et al 2009, Malin et al 2013, Goyaram et al 2014, reduce the catecholamine response to exercise (Kjaer & Galbo 1988), increase lipid catabolism (Phillips et al 1996, Henderson & Alderman 2014, improve arterial compliance and endothelial function (Seals et al 2008, Pierce et al 2011 and maintain both bone density and skeletal muscle mass during ageing (Layne & Nelson 1999) and maintain muscle metabolic capacity with ageing (Olesen et al 2014). Recent work has suggested that both skeletal muscle and adipose tissue function as integrated endocrine organs in response to an exercise stimulus (Pedersen 2013).…”