Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.
Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.
Horm Metab Res. 2014 Jan;46(1):65-72. doi: 10.1055/s-0033-1357193. Epub 2013 Oct 23.
Diabetes mellitus is thought to be progressive. Insufficient insulin secretion in compensation for insulin resistance leads to glucose intolerance. A previously reported proband with type A insulin resistance syndrome and her younger twin brothers with and without the R1174W missense mutation in the insulin receptor gene were followed for 9 years to study the progression of glucose metabolism, insulin sensitivity, and β-cell function around puberty. Five-hour OGTT was performed in them at each visit. Areas under the curves of glucose, insulin and C-peptides, insulinogenic index, AIR, and Homa indices were assessed. Intramyocellular lipids (IMCLs) were quantified in the proband and compared to those of 12 nondiabetic subjects, 118 newly diagnosed type 2 diabetic patients. The proband maintained normal HbA1c (27-37 mmol/mol) and fasting plasma glucose (3.7-4.5 mmol/l), and her glucose tolerance ameliorated over years. The proband's Homa-IR decreased into adulthood, while her Homa-B, insulinogenic index, AIR, AUCs of insulin, and C-peptide decreased accordingly. Homa-B to Homa-IR ratios stayed significantly higher than normal. Homa-B, AUCs of insulin, and C-peptide of the twin brothers increased in response to the increment of Homa-IR as they entered middle and late puberty. The changes were more dramatic in the twin brothers carrying the mutation. IMCLs of the proband were lower than those of the nondiabetic counterparts and were disproportional for the degree of insulin resistance. Our longitudinal data of type A insulin resistance syndrome around puberty provide significant information for the study of insulin secretion in compensation for insulin resistance.
糖尿病被认为是进行性的。胰岛素抵抗补偿不足导致葡萄糖耐量受损。先前报道的一例 A 型胰岛素抵抗综合征患者及其携带胰岛素受体基因突变（R1174W）的年轻双胞胎兄弟（有和无该突变），在青春期前后进行了 9 年的随访，以研究葡萄糖代谢、胰岛素敏感性和β细胞功能的进展。在每次就诊时，对他们进行了 5 小时 OGTT。评估了葡萄糖、胰岛素和 C 肽、胰岛素生成指数、AIR 和 Homa 指数的曲线下面积。在患者和 12 名非糖尿病受试者、118 名新诊断的 2 型糖尿病患者中定量了肌内甘油三酯（IMCLs）。将患者的 IMCLs 与非糖尿病对照组和新诊断的 2 型糖尿病患者的 IMCLs 进行了比较。患者的 HbA1c（27-37mmol/mol）和空腹血糖（3.7-4.5mmol/l）保持正常，且多年来糖耐量逐渐改善。患者的 Homa-IR 在成年后下降，而她的 Homa-B、胰岛素生成指数、AIR、胰岛素和 C 肽的 AUC 也相应下降。Homa-B 与 Homa-IR 的比值仍明显高于正常。随着双胞胎兄弟进入中晚期青春期，Homa-IR 增加，Homa-B、胰岛素和 C 肽的 AUC 也随之增加。携带突变的双胞胎兄弟的变化更为明显。患者的 IMCLs 低于非糖尿病对照组，且与胰岛素抵抗程度不成比例。我们在青春期前后对 A 型胰岛素抵抗综合征的纵向数据提供了关于胰岛素抵抗补偿性胰岛素分泌的重要信息。
