Abstract
ObjectiveChanges in insulin sensitivity (IS) and insulin secretion occur with perturbations in energy balance and glycemic load (GL) of the diet that may precede the development of insulin resistance and hyperinsulinemia. Determinants of changes in IS and insulin secretion with weight cycling in non-obese healthy subjects remain unclear.MethodsIn a 6wk controlled 2-stage randomized dietary intervention 32 healthy men (26±4y, BMI: 24±2kg/m2) followed 1wk of overfeeding (OF), 3wks of caloric restriction (CR) containing either 50% or 65% carbohydrate (CHO) and 2wks of refeeding (RF) with the same amount of CHO but either low or high glycaemic index at ±50% energy requirement. Measures of IS (basal: HOMA-index, postprandial: Matsuda-ISI), insulin secretion (early: Stumvoll-index, total: tAUC-insulin/tAUC-glucose) and potential endocrine determinants (ghrelin, leptin, adiponectin, thyroid hormone levels, 24h-urinary catecholamine excretion) were assessed.ResultsIS improved and insulin secretion decreased due to CR and normalized upon RF. Weight loss-induced improvements in basal and postprandial IS were associated with decreases in leptin and increases in ghrelin levels, respectively (r = 0.36 and r = 0.62, p<0.05). Weight regain-induced decrease in postprandial IS correlated with increases in adiponectin, fT3, TSH, GL of the diet and a decrease in ghrelin levels (r-values between -0.40 and 0.83, p<0.05) whereas increases in early and total insulin secretion were associated with a decrease in leptin/adiponectin-ratio (r = -0.52 and r = -0.46, p<0.05) and a decrease in fT4 (r = -0.38, p<0.05 for total insulin secretion only). After controlling for GL associations between RF-induced decrease in postprandial IS and increases in fT3 and TSH levels were no longer significant.ConclusionWeight cycling induced changes in IS and insulin secretion were associated with changes in all measured hormones, except for catecholamine excretion. While leptin, adiponectin and ghrelin seem to be the major endocrine determinants of IS, leptin/adiponectin-ratio and fT4 levels may impact changes in insulin secretion with weight cycling.Trial RegistrationClinicalTrials.gov NCT01737034
Highlights
Insulin resistance and hyperinsulinemia are early symptoms of metabolic dysfunction that precede the onset of type 2 diabetes
Weight loss-induced improvements in basal and postprandial insulin sensitivity (IS) were associated with decreases in leptin and increases in ghrelin levels, respectively (r = 0.36 and r = 0.62, p
Weight regain-induced decrease in postprandial IS correlated with increases in adiponectin, fT3, TSH, glycemic load (GL) of the diet and a decrease in ghrelin levels (r-values between -0.40 and 0.83, p
Summary
Insulin resistance and hyperinsulinemia are early symptoms of metabolic dysfunction that precede the onset of type 2 diabetes. Because a diet high in rapidly absorbed carbohydrates and low in cereal fiber augments postprandial glycemia and insulin secretion it may contribute to glucotoxicity as well as increased insulin demand and eventually the development of insulin resistance. To understand the etiology of early changes in IS and insulin secretion with perturbations in energy balance it is important to investigate healthy non-obese subjects, because a chronic disturbance in energy balance may increase visceral and liver fat and lead to impaired hepatic insulin clearance [9], chronic low grade inflammation [10] and elevated FFA levels [11] associated with IR and pathological hyperinsulinemia. Determinants of changes in insulin sensitivity and insulin secretion that precede the development of ectopic fat accumulation could facilitate the identification of novel strategies for prevention of type 2 diabetes
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