Background:Weight gain is associated with deterioration in metabolic health, whereas weight loss improves insulin sensitivity. This study assesses the impact of long-term, successfully maintained weight loss and weight-loss relapse on measures of insulin sensitivity and identifies factors that explain variability in insulin sensitivity.Methods:Women (20–45 years) were recruited into four groups: reduced-overweight/obese (RED, n=15); body mass index (BMI)-matched controls (stable low-weight, n=19), BMI⩽27 kg m−2; relapsed-overweight/obese subjects (REL, n=11); and BMI-matched controls (obese stable weight, n=11), BMI⩾27 kg m−2. A 75 g oral glucose tolerance test determined fasting and 2 h plasma glucose and insulin. Homeostatic Model Assessment (HOMA-IR) and insulin sensitivity index (ISI(0,120)) assessed insulin sensitivity. Anthropometric measurements, fasting resting metabolic rate (RMR) and respiratory quotient (RQ) were measured. Questionnaires and dietary intake were recorded, and physical activity was measured using accelerometers.Results:RED were more insulin sensitive, characterised by lower fasting (P=0.001) and 2 h insulin (P=0.003) levels compared with all other groups. There were no significant differences in dietary intake, sedentary, light and moderate activity, RMR or RQ in the RED compared with the other three groups. % Body weight (BW) lost (P<0.001), % BW regained (P<0.05), body fat %, light activity (P<0.05, only log HOMA), vigorous activity (P<0.05) and RQ (P<0.01) predicted 61.4% and 59.7% of variability in log HOMA and log ISI(0,120), respectively, in multiple linear regression models.Conclusion:This study showed sustained enhanced insulin sensitivity in successful weight loss maintainers compared with BMI-matched controls with no weight loss history. Weight-loss-relapsed individuals were indistinguishable from controls. Weight loss itself was the strongest predictor of improved insulin sensitivity, whereas weight regain significantly predicted reduced insulin sensitivity. Weight-loss maintenance programs are essential to retaining metabolic benefits acquired through weight loss. Being physically active, reducing sedentary behaviour and, in particular, including small amounts of vigorous physical activity significantly predicted improved insulin sensitivity.

BackgroundThe pathogenesis of type 2 diabetes (T2D) in black African women is complex and differs from that in their white counterparts. However, earlier studies have been cross-sectional and provide little insight into the causal pathways. Exercise training is consistently used as a model to examine the mechanisms underlying insulin resistance and risk for T2D.ObjectiveThe objective of the study was to examine the mechanisms underlying the changes in insulin sensitivity and secretion in response to a 12-week exercise intervention in obese black South African (SA) women.MethodsA total of 45 obese (body mass index, BMI: 30-40 kg/m2) black SA women were randomized into a control (n=22) or experimental (exercise; n=23) group. The exercise group completed 12 weeks of supervised combined aerobic and resistance training (40-60 min, 4 days/week), while the control group maintained their typical physical activity patterns, and both groups were requested not to change their dietary patterns. Before and following the 12-week intervention period, insulin sensitivity and secretion (frequently sampled intravenous glucose tolerance test) and its primary and secondary determinants were measured. Dietary intake, sleep quality and quantity, physical activity, and sedentary behaviors were measured every 4 weeks.ResultsThe final sample included 20 exercise and 15 control participants. Baseline sociodemographics, cardiorespiratory fitness, anthropometry, cardiometabolic risk factors, physical activity, and diet did not differ between the groups (P>.05).ConclusionsThe study describes a research protocol for an exercise intervention to understand the mechanisms underlying insulin sensitivity and secretion in obese black SA women and aims to identify causal pathways underlying the high prevalence of insulin resistance and risk for T2D in black SA women, targeting specific areas for therapeutic intervention.Trial RegistrationPan African Clinical Trial Registry PACTR201711002789113; http://www.pactr.org/ATMWeb/ appmanager/atm/atmregistry?_nfpb=true&_pageLabel=portals_app_atmregistry_portal_page_13 (Archived by WebCite at http://www.webcitation.org/6xLEFqKr0)

It is known that long-standing volume overload on the left ventricle due to mitral regurgitation eventually leads to contractile dysfunction. However, it is unknown whether or not correction of the volume overload can lead to recovery of contractility. In this study we tested the hypothesis that depressed contractile function due to volume overload in mitral regurgitation could return toward normal after mitral valve replacement. Using a canine model of mitral regurgitation which is known to produce contractile dysfunction, we examined contractile function longitudinally in seven dogs at baseline, after 3 mo of mitral regurgitation, 1 mo after mitral valve replacement, and 3 mo after mitral valve replacement.After 3 mo of mitral regurgitation (regurgitant fraction 0.62±0.04), end-diastolic volume had nearly doubled from 68±6.8 to 123±12

Objective We investigated the effects of a 12-week exercise intervention on insulin sensitivity (SI) and hyperinsulinemia and associated changes in regional and ectopic fat. Research design and methods Healthy, black South African women with obesity (mean age 23 ± 3.5 years) and of isiXhosa ancestry were randomised into a 12-week aerobic and resistance exercise training group (n = 23) and a no exercise group (control, n = 22). Pre and post-intervention testing included assessment of SI, insulin response to glucose (AIRg), insulin secretion rate (ISR), hepatic insulin extraction (FEL) and disposition index (DI) (AIRg × SI) (frequently sampled i.v. glucose tolerance test); fat mass and regional adiposity (dual-energy X-ray absorptiometry); hepatic, pancreatic and skeletal muscle fat content and abdominal s.c. and visceral adipose tissue volumes (MRI). Results Exercise training increased VO2peak (mean ± s.d.: 24.9 ± 2.42 to 27.6 ± 3.39 mL/kg/min, P < 0.001), SI (2.0 (1.2–2.8) to 2.2 (1.5–3.7) (mU/l)−1 min−1, P = 0.005) and DI (median (interquartile range): 6.1 (3.6–7.1) to 6.5 (5.6–9.2) × 103 arbitrary units, P = 0.028), and decreased gynoid fat mass (18.5 ± 1.7 to 18.2 ± 1.6%, P < 0.001) and body weight (84.1 ± 8.7 to 83.3 ± .9.7 kg, P = 0.038). None of these changes were observed in the control group, but body weight increased (P = 0.030). AIRg, ISR and FEL, VAT, SAT and ectopic fat were unaltered after exercise training. The increase in SI and DI were not associated with changes in regional or ectopic fat. Conclusion Exercise training increased SI independent from changes in hyperinsulinemia and ectopic fat, suggesting that ectopic fat might not be a principal determinant of insulin resistance in this cohort.

This 12-week exercise intervention study assessed changes in cardiorespiratory fitness (CRF), energy expenditure (EE), and substrate utilisation at rest and during exercise in obese, black South African (SA) women and explored associations with changes in body composition. Black SA women (body mass index: 30–40 kg·m−2, age: 20–35 years) were randomised into control (CTL; n = 15, maintaining usual activity) or exercise (EXE; n = 20; 12 weeks, 4 days·week−1, 40–60 min·day−1 at >70% peak heart rate) groups. Pre- and post-intervention testing included peak oxygen consumption, resting and steady state (50% peak oxygen consumption) EE, respiratory exchange, and body composition (dual-energy X-ray absorptiometry). Dietary intake (4-day) and daily step-count (ActivPAL, activPAL3c; PAL Technologies Ltd, Glasgow, UK) was collected at pre-testing and at 4, 8, and 12 weeks. EXE increased peak oxygen consumption (24.9 ± 2.4 to 27.6 ± 3.4 mL·min−1·kg−1; p < 0.001) and steady state fat oxidation rates (7.5 ± 2.5 to 9.0 ± 2.7 mg·min−1·kg−1 fat-free soft tissue mass; p = 0.003) (same relative exercise intensity). CTL remained unchanged (p > 0.05). EXE reduced proportional gynoid fat mass (percentage total fat mass, p = 0.002). Baseline resting carbohydrate oxidation rates (p = 0.036) and steady state fat oxidation rates (p = 0.021) explained 60.6% of the variability in Δgynoid fat mass (p < 0.001) in EXE. This 12-week exercise intervention improved CRF and steady state fat oxidation rates. Greater reliance on fat oxidation at baseline promoted proportional reductions in gynoid, not visceral, fat mass in response to exercise training. Novelty Combined exercise training in obese black South African women increased cardiorespiratory fitness and rates of fat oxidation during steady state exercise. Exercise training reduced proportional gynoid, not visceral, fat, potentially representing an ethnic/sex-specific response. Baseline substrate utilisation (resting and steady state exercise (50% peak oxygen uptake)) predicted changes in gynoid fat mass.