Ectopic fat and aerobic fitness are key determinants of glucose homeostasis in non-obese Asians

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Zhiling Chan, Cherlyn Ding, Yu Chung Chooi, John Choo, Suresh Anand Sadananthan, S Sasikala, Amanda Chang, Navin Michael, S Sendhil Velan, Melvin K-S Leow, Faidon Magkos

Background: The importance of ectopic fat deposition and physical fitness in the pathogenesis of insulin resistance and beta cell dysfunction in non-obese Asians is not known.

Materials and methods: We conducted a cross-sectional study and measured insulin sensitivity (M value; 4-h hyperinsulinaemic-euglycaemic clamp), insulin secretion rate (3-h 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 (VO2max; graded exercise test) and habitual physical activity (short International Physical Activity Questionnaire) in 60 healthy non-obese Asian subjects (BMI=21.9±1.7 kg/m2 , age=41.8±13.4 years).

Results: M 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). VO2max 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 VO2max (r=0.682, p<0.001). Multiple stepwise linear regression analyses indicated that VO2max, age, and IHTG or VAT were independent determinants of insulin sensitivity and secretion (adjusted R2 =69% and 33%, respectively, p<0.001).

Conclusions: Increased ectopic fat deposition is associated with reduced insulin sensitivity and increased insulin secretion in healthy non-obese 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 non-obese Asians. This article is protected by copyright. All rights reserved.

Trial registration: NCT03239782

Original languageEnglish
Article numbere13079
JournalEuropean Journal of Clinical Investigation
Issue number5
Number of pages9
Publication statusPublished - 2019

ID: 213152207