Enhanced insulin sensitivity in successful, long-term weight loss maintainers compared with matched controls with no weight loss history.

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.

Coronary blood flow after the regression of pressure-overload left ventricular hypertrophy.

Abnormal coronary blood flow (CBF) in long-standing left ventricular (LV) pressure-overload hypertrophy has been associated with ischemia and LV dysfunction. Thus, goals of therapy in pressure overload are not only the relief of the overload itself but also regression in hypertrophy and subsequent improvement in CBF. However, little is known about CBF in humans or in large mammals after the relief of pressure overload, when the hypertrophy has regressed. This study was performed to test the hypothesis that, even 6 months after the relief of pressure overload in the dog, CBF would still be abnormal. Three groups of dogs were studied: 1) normal control dogs (NL group), 2) dogs with LV pressure-overload hypertrophy (LVH group), and 3) dogs that had developed LV pressure-overload hypertrophy but in whom the pressure overload was relieved 6 months before the final study (LVH Reg group). CBF was studied in conscious dogs by use of the radiolabeled microsphere technique at rest, during rapid atrial pacing, and during maximum coronary vasodilation produced by adenosine infusion. The ratio of LV weight (g) to body weight (kg) (LVBW) was 4.2 +/- 0.3 in the NL group, 7.1 +/- 0.6 in the LVH group, and 7.7 +/- 0.5 in the LVH Reg group before pressure-overload relief (p = NS, LVH versus LVH Reg). Six months after removal of the pressure overload, the LVBW in the LVH Reg group had fallen to 5.5 +/- 0.3 (p < 0.05), but this LVBW was still greater than that in the NL group (p < 0.05). During rapid atrial pacing, endocardial and epicardial CBF rose significantly in NL dogs. However, during rapid atrial pacing, endocardial CBF fell from 1.18 +/- 0.22 to 0.7 +/- 0.20 ml/min per gram in the LVH group (p < 0.05) and did not rise in the LVH Reg group. During adenosine infusion, endocardial blood flow increased in NL dogs from 1.63 +/- 0.13 to 4.0 +/- 0.3 ml/min per gram and increased to a similar level in the LVH Reg group. Although CBF increased during adenosine infusion in the LVH group, the increase was less than that in the NL or LVH Reg group (p < 0.05). Minimum coronary vascular resistance was similar in NL dogs (14 +/- 2 units) and LVH Reg dogs (18 +/- 3 units, p = NS) but was significantly elevated (32 +/- 10 units) in LVH dogs (p < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Depressed contractile function due to canine mitral regurgitation improves after correction of the volume overload.

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 +/- 12.1 ml (P less than 0.05). All five indices of contractile function which we examined were depressed. For instance, maximum fiber elastance (EmaxF) obtained by assessment of time-varying elastance decreased from 5.95 +/- 0.71 to 2.25 +/- 0.18 (P less than 0.05). The end-systolic stiffness constant (k) was also depressed from 4.2 +/- 0.4 to 2.1 +/- 0.3. 3 mo after mitral valve replacement all indexes of contractile function had returned to or toward normal (e.g., EmaxF 3.65 +/- 0.21 and k 4.2 +/- 0.3). We conclude that previously depressed contractile function due to volume overload can improve after correction of the overload.