Endocrine determinants of changes in insulin sensitivity and insulin secretion during a weight cycle in healthy men

Judith Karschin, Merit Lagerpusch, Janna Enderle, Ben Eggeling, Manfred J Müller, Anja Bosy-Westphal, Judith Karschin, Merit Lagerpusch, Janna Enderle, Ben Eggeling, Manfred J Müller, Anja Bosy-Westphal

Abstract

Objective: Changes 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.

Methods: In 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.

Results: IS 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.

Conclusion: Weight 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 registration: ClinicalTrials.gov NCT01737034.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. CONSORT flow chart, showing the…
Fig 1. CONSORT flow chart, showing the passage of participants through the different stages of the present trial: enrollment, first allocation after OF to the 65%CHO and 50%CHO intervention and second allocation after CR to 65%CHO-HGI, 65%CHO-LGI, 50%CHO-HGI and 50%CHO-LGI intervention, follow-up, and analysis.
OF, overfeeding; CR, caloric restriction; CHO: carbohydrate, HGI, high glyceamic index; LGI, low glyceamic index
Fig 2. Schematic overview of the study…
Fig 2. Schematic overview of the study protocol.
OGTT, oral glucose tolerance test, CHO, carbohydrate; LGI, low glycaemic index; HGI, high glycaemic index
Fig 3. Comparison between fasting insulin level,…
Fig 3. Comparison between fasting insulin level, IS (HOMA-index and Matsuda-ISI) as well as insulin secretion (insulin-iAUC, insulin-tAUC/glucose-tAUC, Stumvoll-index) at baseline (T0), after caloric restriction (CR, T2) and refeeding (RF, T3).
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