Humphriss D B, Stewart M W, Berrish T S, Barriocanal L A, Trajano L R, Ashworth L A, Brown M D, Miller M, Avery P J, Alberti K G, Walker M
Human Diabetes and Metabolism Research Centre and Department of Medicine, University of Newcastle upon Tyne, UK.
Diabetologia. 1997 Oct;40(10):1185-90. doi: 10.1007/s001250050805.
Non-diabetic first degree relatives of non-insulin-dependent diabetic (NIDDM) families are at increased risk of developing diabetes mellitus, and have been studied to identify early metabolic abnormalities. Hormone concentrations measured by specific enzyme immunoassays were assessed in non-diabetic relatives of North European extraction, and control subjects with no family history of diabetes were matched for age, sex and ethnicity. A 75-g oral glucose tolerance test was conducted and those with newly diagnosed NIDDM were excluded. Basal insulin resistance was determined by homeostasis model assessment (HOMA), and hepatic insulin clearance by C-peptide:insulin molar ratio. Relatives (n = 150) were heavier (BMI: p < 0.0001) than the control subjects (n = 152), and had an increased prevalence of impaired glucose tolerance (15 vs 3%, p < 0.01). The relatives had increased fasting proinsulin levels and decreased C-peptide levels following the glucose load, while insulin levels were increased at all time points. To examine whether the differences in hormone levels were secondary to the differences in glucose tolerance and adiposity, we studied 100 normal glucose tolerant relatives and control subjects pair-matched for age, sex, waist-hip ratio and BMI. The differences in proinsulin levels were no longer apparent. However, the relatives remained more insulin resistant, and had decreased C-peptide levels and C-peptide:insulin ratios at all time points. In conclusion, we have identified several metabolic abnormalities in the normal glucose tolerant relatives, and propose that the decreased hepatic insulin clearance helps to maintain normoglycaemia in the face of combined insulin resistance and decreased insulin secretion.
非胰岛素依赖型糖尿病（NIDDM）家族中的非糖尿病一级亲属患糖尿病的风险增加，并且已经对他们进行了研究以确定早期代谢异常情况。通过特定酶免疫测定法测量的激素浓度在北欧血统的非糖尿病亲属中进行了评估，并且将没有糖尿病家族史的对照受试者按年龄、性别和种族进行了匹配。进行了75克口服葡萄糖耐量试验，并排除了新诊断为NIDDM的患者。通过稳态模型评估（HOMA）确定基础胰岛素抵抗，通过C肽：胰岛素摩尔比确定肝脏胰岛素清除率。亲属（n = 150）比对照受试者（n = 152）更重（BMI：p < 0.0001），并且糖耐量受损的患病率增加（15% 对3%，p < 0.01）。亲属在葡萄糖负荷后空腹胰岛素原水平升高而C肽水平降低，而胰岛素水平在所有时间点均升高。为了检查激素水平的差异是否继发于糖耐量和肥胖的差异，我们研究了100名年龄、性别、腰臀比和BMI匹配的糖耐量正常的亲属和对照受试者。胰岛素原水平的差异不再明显。然而，亲属仍然更具胰岛素抵抗性，并且在所有时间点C肽水平和C肽：胰岛素比值均降低。总之，我们在糖耐量正常的亲属中发现了几种代谢异常情况，并提出肝脏胰岛素清除率降低有助于在胰岛素抵抗和胰岛素分泌减少的情况下维持血糖正常。
