• Zhiling Chan, Cherlyn Ding, Yu Chung Chooi, John Choo, Suresh Anand Sadananthan, S Sasikala, Amanda Chang, Navin Michael, Sambasivam Sendhil Velan, Melvin K-S Leow, and Faidon Magkos.
• Clinical Nutrition Research Centre (CNRC), Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), National University Health System, Singapore, Singapore.
• Eur. J. Clin. Invest. 2019 May 1; 49 (5): e13079.

BackgroundThe importance of ectopic fat deposition and physical fitness in the pathogenesis of insulin resistance and beta cell dysfunction in subjects from the nonobese Asians is not known.Materials And MethodsWe conducted a cross-sectional study and measured insulin sensitivity (M value; 4-hour hyperinsulinaemic-euglycaemic clamp), insulin secretion rate (3-hour mixed meal tolerance test with oral minimal modelling), percent body fat, visceral adipose tissue, intramyocellular and intrahepatic lipid contents (magnetic resonance imaging and spectroscopy), cardiorespiratory fitness (VO2 max; graded exercise test) and habitual physical activity (short International Physical Activity Questionnaire) in 60 healthy nonobese Asian subjects (BMI = 21.9 ± 1.7 kg/m2 , age = 41.8 ± 13.4 years).ResultsM was inversely associated with percent body fat (r = -0.460, P < 0.001), visceral fat (r = -0.623, P < 0.001) and liver fat (r = -0.601, P < 0.001), whereas insulin secretion correlated positively with these adiposity indices (percent body fat: r = 0.303, P = 0.018; visceral fat: r = 0.409, P = 0.010; hepatic fat: r = 0.393, P = 0.002). VO2 max correlated negatively with insulin secretion rate (r = -0.420, P < 0.001) and positively with M (r = 0.658, P < 0.001). The amount of vigorous physical activity was positively associated with VO2 max (r = 0.682, P < 0.001). Multiple stepwise linear regression analyses indicated that VO2 max, age, and IHTG or VAT were independent determinants of insulin sensitivity and secretion (adjusted R2  = 69% and 33%, respectively, P < 0.001).ConclusionsIncreased ectopic fat deposition is associated with reduced insulin sensitivity and increased insulin secretion in healthy nonobese Asians. Poor cardiorespiratory fitness, likely due to inadequate participation in vigorous exercise, is strongly related to suboptimal metabolic function. Interventions to encourage engagement in physical activity may thus be important for improving metabolic health in nonobese Asians.© 2019 Stichting European Society for Clinical Investigation Journal Foundation.

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