Middle-aged overweight South Asian men exhibit a different metabolic adaptation to short-term energy restriction compared with Europeans

• Published in: Diabetologia Vol. 58; no. 1; pp. 165 - 177
• Main Authors: Bakker, Leontine E. H., Guigas, Bruno, van Schinkel, Linda D., van der Zon, Gerard C. M., Streefland, Trea C. M., van Klinken, Jan B., Jonker, Jacqueline T., Lamb, Hildo J., Smit, Johannes W. A., Pijl, Hanno, Meinders, A. Edo, Jazet, Ingrid M.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 2015; Springer Nature B.V
• Subjects: Adaptation, Physiological - physiology; Adult; AMP-Activated Protein Kinases - metabolism; Asia - ethnology; Asian Continental Ancestry Group; Asian people; Caloric Restriction - ethnology; Calories; Cell growth; Diabetes; Energy; European Continental Ancestry Group; Glucose; Human Physiology; Humans; Insulin; Internal Medicine; Kinases; Lipid Metabolism; Male; Medical screening; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Middle age; Middle Aged; Muscle, Skeletal - metabolism; Musculoskeletal system; Netherlands; Overweight; Overweight - diet therapy; Overweight - ethnology; Overweight - metabolism; Proteins; Signal Transduction; Netherlands; Energy restriction; Mammalian target of rapamycin; mTOR; South Asian; European; Metabolic flexibility; Skeletal muscle; Very low calorie diet; Caloric restriction; Hyperinsulinaemic–euglycaemic clamp
• DOI: 10.1007/s00125-014-3408-4
• ISSN: 0012-186X

Aims/hypothesis South Asians have a higher risk of developing type 2 diabetes than Europeans. The underlying cause of this excess risk is still poorly understood but might be related to differences in the regulation of energy/nutrient-sensing pathways in metabolic tissues and subsequent changes in whole-body substrate metabolism. In this study, we investigated the whole-body and skeletal muscle metabolic adaptations to short-term energy restriction in South Asian and European volunteers. Methods Twenty-four middle-aged overweight South Asian and European men underwent a two-step hyperinsulinaemic–euglycaemic clamp, with skeletal muscle biopsies and indirect calorimetry before and after an 8 day diet very low in energy (very low calorie diet [VLCD]). Abdominal fat distribution and hepatic triacylglycerol content were assessed using MRI and MR spectroscopy. Results South Asian men had higher hepatic triacylglycerol content than European men, and exhibited elevated clamp insulin levels that probably reflect a lower insulin clearance rate. Despite higher insulin levels, endogenous glucose production rate was similar and glucose disposal rate (R d ) and nonoxidative glucose disposal rate (NOGD) were significantly lower in South Asian than European men, indicating impaired whole-body insulin sensitivity. Energy restriction decreased abdominal fat mass and hepatic triacylglycerol content in both groups. However, the shift induced by energy restriction from glucose towards lipid oxidation observed in European men was impaired in South Asian men, indicating whole-body metabolic inflexibility. Remarkably, although energy restriction improved hepatic insulin sensitivity in both groups, R d improved only in South Asian men owing to higher NOGD. At the molecular level, an increase in insulin-induced activation of the skeletal muscle mTOR pathway was found in South Asian men, showing that skeletal muscle energy/nutrient-sensing pathways were differentially affected by energy restriction. Conclusions/interpretation We conclude that South Asian men exhibit a different metabolic adaptation to short-term energy restriction than European men. Trial registration: Dutch trial registry ( www.trialregister.nl ), trial number NTR 2473.