American Diabetes Association
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Comparison of beta-cell function and insulin sensitivity between normal-weight and obese Chinese with young-onset type 2 diabetes

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posted on 2024-03-20, 15:37 authored by Yingnan Fan, Elaine Chow, Cadmon K.P. Lim, Yong Hou, Sandra T.F. Tsoi, Baoqi Fan, Eric S.H. Lau, Alice P.S. Kong, Ronald C.W. Ma, Hongjiang Wu, Juliana C.N. Chan, Andrea O.Y. Luk

Normal-weight individuals with usual-onset type 2 diabetes had reduced beta-cell function and greater insulin sensitivity compared to their obese counterparts. The relative contribution of beta-cell dysfunction and insulin resistance to young-onset type 2 diabetes (YOD) among normal-weight individuals is not well established. In 44 individuals with YOD (24 normal-weight and 20 obese) and 24 healthy controls with normoglycemia (12 normal-weight and 12 obese), we conducted 2-h 12mmol/L hyperglycemic clamps to measure acute (0-10 minute) and steady-state (100-120 minute) insulin and C-peptide responses, and insulin sensitivity index. Normal-weight individuals with YOD had lower acute insulin response, steady-state insulin and C-peptide responses, and higher insulin sensitivity index compared to their obese counterparts with YOD. When compared to BMI-matched healthy controls, normal-weight individuals with YOD had lower acute and steady-state insulin and C-peptide responses but similar insulin sensitivity index. The impairment of steady-state beta-cell response relative to healthy controls was more pronounced in normal-weight versus obese individuals with YOD. In conclusion, normal-weight Chinese with YOD exhibited worse beta-cell function but preserved insulin sensitivity relative to obese individuals with YOD and BMI-matched healthy individuals with normoglycemia. The selection of glucose-lowering therapy should account for pathophysiological differences underlying YOD between normal-weight and obese individuals.


This study was supported by the Hong Kong Research Grants Council (Project Reference Number 2141159, to A.O.Y.L.). The funder had no role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript.


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