Effects of brief perturbations in energy balance on indices of glucose homeostasis in healthy lean men

Abstract

BACKGROUND:Little is known about the effects of short-term caloric restriction (CR) and overfeeding (OF) on glucose homeostasis in healthy lean individuals. In addition, it remains unclear whether the effects of CR and OF are reversed by a complementary feeding period. METHODS: Ten healthy men participated in two cycles of controlled 7-day periods of CR and refeeding (RF; protocol A), and OF and CR (protocol B) at ±60% energy requirement. At baseline, insulin sensitivity (IS) was assessed by euglycemic clamp (M). Before and during each feeding cycle, fasting and oral glucose tolerance test-derived indices were used to estimate glucose tolerance, IS and glucose-stimulated insulin secretion. RESULTS: Clamp tests revealed normal IS at baseline (M-values 9.4 ± 2.1 mg kg À1 min À1 , coefficient of variation (CV) inter 22%). M-values were significantly correlated with indices of IS. In protocol A, CR-induced weight loss (À3.0±0.4 kg) was associated with an increase in fasting IS. Postprandial IS and glucose-stimulated insulin secretion remained unchanged, but glucose tolerance decreased. RF decreased fasting and postprandial IS at increased glucose-stimulated insulin secretion. In protocol B, OF significantly increased the body weight ( þ 1.6±0.9 kg). Concomitantly, fasting and postprandial IS decreased at increased glucose-stimulated insulin secretion. Subsequent CR reversed these effects. Inter-individual variability in indices of glucose metabolism was high with coefficients of variation ranging from 9 to 59%. CONCLUSION: Significant changes in glucose metabolism are evident within 7-day periods of controlled OF and underfeeding. Although IS was impaired at the end of the CR --RF cycle, IS was normalized after the OF --CR cycle. At different feeding regimens, homeostatic responses of glucose metabolism were highly variable. Keywords: insulin secretion; insulin sensitivity; glucose homeostasis; weight gain; energy balance INTRODUCTION Long-term perturbations in energy balance, either by overfeeding (OF) or underfeeding, are known to modulate insulin sensitivity (IS). Chronic OF and obesity are commonly characterized by insulin resistance, 1 which has been shown to be completely 2 or partially reversed by acute caloric restriction (CR), as well as by moderate weight loss. 3 --5 On the other hand, IS is preserved or even improved with chronic CR in patients with anorexia nervosa and returned to normal values at the end of refeeding (RF). 6 Although considerable research has been devoted to individuals outside the normal range of body weight, there are only few studies examining the effects of short-term controlled perturbations in energy balance on IS in lean subjects without confounding metabolic abnormalities. 7 --17 Moreover, these studies provide discordant findings that may depend on duration and degree of energy imbalance and macronutrient composition of the diets. Fasting (1 --3 days) consistently caused a decline in IS assessed by clamp-and intravenous glucose tolerance test. 7,8,17 Studies with less severe ...

Carbohydrate Quality and Quantity Affect Glucose and Lipid Metabolism during Weight Regain in Healthy Men

“…During the preintervention periods and at the end of refeeding, IS was assessed by the hyperinsulinemiceuglycemic clamp technique according to deFronzo et al (40) as previously described (32,41). Whole-body IS was determined during the last 20 min of the hyperinsulinemic glucose clamp as steady-state glucose disposal rate calculated from the mean rate of exogenous glucose infusion corrected for glucose space [M-value, mg/(kg 3 min)].…”

“…Fat mass and fat-free mass were assessed by airdisplacement plethysmography (BOD POD, Cosmed) as described in detail elsewhere (37). Liver fat was determined by MRI (Magnetom Avanto 1.5-T Siemens) along with the 2-point Dixon method with a volume interpolated breathhold examination as previously described (32). Briefly, a T1-weighted gradient-echo sequence with in-phase and out-of-phase imaging was performed using the following variables: repetition time, 10.4 ms; echo time, 4.76 (in-phase) and 7.14 (opposedphase) ms; flip angle, 10°; matrix, 80 3 128; and field of view, 440 mm.…”

“…Energy intake (EI) was increased by 50% of energy requirements during overfeeding and refeeding (mean EI = 17.0 6 1.9 MJ/d) and was reduced by 50% during CR (mean EI = 5.7 6 0.6 MJ/d). Individual caloric requirements were calculated as resting energy expenditure (REE) multiplied by a sedentary physical activity level of 1.4 as previously described (32,33). The dietary intervention has been described in detail elsewhere (33).…”

“…We recently showed that refeeding a moderate-CHO diet following caloric restriction (CR) decreased IS in healthy young men (32) and that refeeding a diet with a high GI (HGI) resulted in a greater impairment in IS compared with a high-fiber, low-GI diet (33). The aim of the present study was to examine the effect of a moderate-compared with a high-CHO intake with different GIs on IS and liver fat during the refeeding phase of a weight cycle.…”

Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding

“…Furthermore, consistent with our hypothesis, we show that an increase in lipid metabolites are associated with defects in tissue insulin action, suggesting that lipotoxicity is a generalised mechanism associated with the induction of insulin resistance in individual tissues of mice. Studies in rodents [7,[19][20][21]23], dogs [24] and humans [25][26][27], have shown that short-term exposure to HFD/overfeeding (3-28 days) results in the rapid development of insulin resistance and glucose intolerance. Often these changes occur with only modest increases in fat mass, highlighting that metabolic defects occur prior to the onset of obesity and do not require extensive periods of fat feeding.…”