Regulation of glucose metabolism in nondiabetic, metabolically obese normal-weight Asians

Research output: Contribution to journalJournal articleResearchpeer-review

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

Type 2 diabetes in Asia occurs largely in the absence of obesity. The metabolically obese normal-weight (MONW) phenotype refers to lean subjects with metabolic dysfunction that is typically observed in people with obesity and is associated with increased risk for diabetes. Previous studies evaluated MONW subjects who had greater body mass index (BMI) or total body fat than respective control groups, making interpretation of the results difficult. We evaluated insulin sensitivity (hyperinsulinemic-euglycemic clamp); insulin secretion (mixed meal with oral minimal modeling); intra-abdominal, muscle, and liver fat contents (magnetic resonance); and fasting and postprandial glucose and insulin concentrations in 18 MONW subjects and 18 metabolically healthy controls matched for age (43 ± 3 and 40 ± 3 yr; P = 0.52), BMI (both 22 ± 1 kg/m2; P = 0.69), total body fat (17 ± 1 and 16 ± 1 kg; P = 0.33), and sex (9 men and 9 women in each group). Compared with controls, MONW subjects had an approximately twofold greater visceral adipose tissue volume and an approximately fourfold greater intrahepatic fat content (but similar muscle fat), 20-30% lower glucose disposal rates and insulin sensitivity, and 30-40% greater insulin secretion rates (all P < 0.05). The disposition index, fasting glucose, and HbA1c concentrations were not different between groups, whereas postprandial glucose and insulin concentrations were ~15% and ~65% greater, respectively, in MONW than control subjects (both P < 0.05). We conclude that the MONW phenotype is associated with accumulation of fat in the intra-abdominal area and the liver, profound insulin resistance, but also a robust β-cell insulin secretion response that compensates for insulin resistance and helps maintain glucose homeostasis.

Original languageEnglish
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Volume314
Issue number5
Pages (from-to)E494-E502
Number of pages9
ISSN0193-1849
DOIs
Publication statusPublished - 2018
Externally publishedYes

    Research areas

  • The Faculty of Science - Asian population, [Beta]-cell function, Glucose metabolism, Insulin sensitivity, Metabolically obese normal weight

ID: 210873896