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

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.