Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Diabetes. 2024 Jun 1;73(6):953-963. doi: 10.2337/db23-0966.
Normal-weight individuals with usual-onset type 2 diabetes have reduced β-cell function and greater insulin sensitivity compared with their obese counterparts. The relative contribution of β-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 with normal weight and 20 with obesity) and 24 healthy control individuals with normoglycemia (12 with normal weight and 12 with obesity), we conducted 2-h 12 mmol/L hyperglycemic clamps to measure acute (0-10 min) and steady-state (100-120 min) insulin and C-peptide responses, as well as insulin sensitivity index. Normal-weight individuals with YOD had lower acute insulin response, steady-state insulin and C-peptide responses, and a higher insulin sensitivity index compared with their obese counterparts with YOD. Compared with BMI-matched healthy control individuals, normal-weight individuals with YOD had lower acute and steady-state insulin and C-peptide responses but a similar insulin sensitivity index. The impairment of steady-state β-cell response relative to healthy control individuals was more pronounced in normal-weight versus obese individuals with YOD. In conclusion, normal-weight Chinese with YOD exhibited worse β-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.
与肥胖的 2 型糖尿病患者相比，起病年龄正常的 2 型糖尿病患者中体重正常者的胰岛β细胞功能降低，胰岛素敏感性更高。体重正常的起病年龄正常的 2 型糖尿病（YOD）患者中，β细胞功能障碍和胰岛素抵抗对疾病的相对贡献尚未明确。在 44 例 YOD 患者（24 例体重正常，20 例肥胖）和 24 例血糖正常的健康对照者（12 例体重正常，12 例肥胖）中，我们进行了 2 小时 12mmol/L 高血糖钳夹试验，以测量急性（0-10 分钟）和稳态（100-120 分钟）胰岛素和 C 肽反应以及胰岛素敏感性指数。与肥胖的 YOD 患者相比，体重正常的 YOD 患者的急性胰岛素反应、稳态胰岛素和 C 肽反应更低，胰岛素敏感性指数更高。与 BMI 匹配的健康对照者相比，体重正常的 YOD 患者的急性和稳态胰岛素和 C 肽反应更低，但胰岛素敏感性指数相似。与肥胖的 YOD 患者相比，体重正常的 YOD 患者稳态β细胞反应相对于健康对照者的损害更为明显。总之，中国起病年龄正常的体重正常的 2 型糖尿病患者与肥胖的 YOD 患者和 BMI 匹配的血糖正常的健康对照者相比，β细胞功能更差，但胰岛素敏感性保留。降血糖治疗的选择应考虑体重正常和肥胖的 YOD 患者在病理生理学上的差异。
