A型胰岛素抵抗综合征胰岛素分泌变化的七年随访

目的 对1例A型胰岛素抵抗综合征患者随访7年,观察血糖及胰岛素分泌变化.方法 患者初诊年龄16岁,分别于基线、第3、6、7年进行临床随访,观察患者延长口服葡萄糖耐量试验(OGTT)及同步胰岛素、C肽的分泌,比较各随访年血糖、胰岛素、C肽曲线下面积(AUC);比较基线与第7年静脉葡萄糖耐量试验急性胰岛素分泌反应(AIR)的变化;将延长OGTT各时间点胰岛素分泌速率用体表面积标化后,与相应血浆葡萄糖作出剂量反应曲线,比较各随访年胰岛β细胞对葡萄糖的分泌反应.结果 患者7年间糖化血红蛋白均维持正常(4.6%～5.5%),葡萄糖AUC无增加,胰岛素及C肽AUC呈下降趋势;第7年胰岛素AIR较基线时减少56%;胰岛β细胞对葡萄糖的分泌反应随时间推移而呈下降趋势.结论 随着青春期结束,该患者总体胰岛素分泌水平呈下降趋势,因不伴血糖的进行性恶化,考虑为青春期过后生理性胰岛素敏感性恢复,而非真正意义的胰岛β细胞分泌功能衰退.

Abstract：

Objective A previously reported female diagnosed with type A insulin resistance syndrome bearing a heterozygous missense mutation of R1174W in the insulin receptor gene was followed for 7 years since the age of 16 years. Methods Five-hour oral glucose tolerance tests (OGTT) were done on baseline, the 3rd, 6th and 7th year respectively, with serum insulin and C-peptide measured at the same time points. Areas under of curve (AUC) of glucose, insulin and C-peptide were compared between the years.Acute insulin response (AIR) was determined at baseline and the 7th year. The dose response were insulin secretion rates at each time point during OGTT being plotted over the corresponding glucose levels, and the slopes of which quantified the insulin secretion responding to glucose. Results The follow up data showed that the glucose metabolism of the subject did not deteriorate over time with yearly glycosylated hemoglobin A1c (HbAlc) being normal (4.6%-5.5%), and hyperinsulinemic hypoglycemia was a persistent phenomenon observed at 4-5 hours post-load. The fasting and AUCs of serum insulin and C-peptide tended to decline without simultaneously increase of those of plasma glucose. The AIR decreased by 56% as compared to baseline. The dose response curves shifted downward as years went by. Conclusions It supports that with the alleviation of physiological insulin resistance after puberty, the gross hyperinsulinemia tends to ameliorate, and β-cell secretion does not deteriorate over time as glucose homeostasis maintains.

The changes of insulin secretion in type A insulin resistance syndrome: a 7-year follow up

Objective A previously reported female diagnosed with type A insulin resistance syndrome bearing a heterozygous missense mutation of R1174W in the insulin receptor gene was followed for 7 years since the age of 16 years. Methods Five-hour oral glucose tolerance tests (OGTT) were done on baseline, the 3rd, 6th and 7th year respectively, with serum insulin and C-peptide measured at the same time points. Areas under of curve (AUC) of glucose, insulin and C-peptide were compared between the years.Acute insulin response (AIR) was determined at baseline and the 7th year. The dose response were insulin secretion rates at each time point during OGTT being plotted over the corresponding glucose levels, and the slopes of which quantified the insulin secretion responding to glucose. Results The follow up data showed that the glucose metabolism of the subject did not deteriorate over time with yearly glycosylated hemoglobin A1c (HbAlc) being normal (4.6%-5.5%), and hyperinsulinemic hypoglycemia was a persistent phenomenon observed at 4-5 hours post-load. The fasting and AUCs of serum insulin and C-peptide tended to decline without simultaneously increase of those of plasma glucose. The AIR decreased by 56% as compared to baseline. The dose response curves shifted downward as years went by. Conclusions It supports that with the alleviation of physiological insulin resistance after puberty, the gross hyperinsulinemia tends to ameliorate, and β-cell secretion does not deteriorate over time as glucose homeostasis maintains.