Fasting proinsulin concentrations predict the development of type 2 diabetes
Fasting proinsulin concentrations predict the development of type 2 diabetes
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DOI：
10.2337/diacare.22.2.262
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发表时间：
1999-02-01
期刊：
影响因子：
16.2
通讯作者：
Hales, CN
中科院分区：
文献类型：
--
作者：
Wareham, NJ;Byrne, CD;Hales, CN
目的：开发特异性检测方法，可以分别测量胰岛素原加工途径中的不同分子。32,33分裂型胰岛素原是胰岛素原的主要形式，是2型糖尿病患者中不成比例的高胰岛素原血症的原因。这项研究是为了检验这种分子的浓度是否能预测糖尿病。研究设计和方法-在剑桥郡进行了一项基于人群的纵向队列研究。在基线时，1122人完成了75克口服葡萄糖耐量试验（OGTT）。在为期4.5年的随访研究中，对1071名基线时非糖尿病患者中的937人进行了重复ogtt。结果：经ogtt检测，共有26人进展为糖尿病。进展风险与空腹血糖浓度（相对风险[RR]比较上、下四分位数为17.6 [95% CI 2.4-130.4]）和空腹32,33分离胰岛素原（RR 16.4[2.2-121.9]）密切相关，但与空腹胰岛素（RR 4.41[1.5-12.9]）或完整胰岛素原（RR 5.2[1.5-17.3]）关系较弱。在多变量分析中，这些关联与年龄、性别、BMI和基线葡萄糖耐量类别无关。空腹血糖和总胰岛素原水平最高的四分之一有糖尿病家族史的受试者是高危亚组（每1000人-年随访中发病率为65.8）；30%的人在随访中发展为糖尿病。结论：空腹32,33分离胰岛素原独立预测糖尿病的发展。这一预测结果优于胰岛素或完整胰岛素原浓度的预测结果。结合家族史、空腹血糖和总胰岛素原确定了一组可能从靶向干预中受益的高风险进展个体。
OBJECTIVE - The development of specific assays allows the different molecules in the proinsulin processing pathway to be measured separately. 32,33 Split proinsulin is the predominant form of proinsulin and accounts for the disproportionate hyperproinsulinemia seen in individuals with prevalent type 2 diabetes. This study was established to examine whether the concentration of this molecule predicts diabetes.RESEARCH DESIGN AND METHODS - A population-based longitudinal cohort study was conducted in fly, Cambridgeshire. At baseline, 1,122 individuals completed a 75-g oral glucose tolerance test (OGTT). At the 4.5-year follow-up study repeat OGTTs were performed on 937 of the cohort of 1,071 individuals who had been nondiabetic at baseline.RESULTS - A total of 26 people progressed to diabetes as determined by the OGTTs. The risk of progression was strongly related to the fasting glucose concentration (relative risk [RR] comparing top with bottom quartile 17.6 [95% CI 2.4-130.4]) and fasting 32,33 split proinsulin (RR 16.4 [2.2-121.9]), but less strongly to the fasting insulin (RR 4.41 [1.5-12.9]) or intact proinsulin (RR 5.2 [1.5-17.3]). In multivariate analyses, these associations were independent of age, sex, BMI, and baseline glucose tolerance category. Subjects in the top quartile for fasting glucose and total proinsulin with a family history of diabetes were a high-risk subgroup (incidence 65.8 per 1,000 person-years of follow-up [pyfu]); 30% of them progressed to diabetes at follow-up.CONCLUSIONS - Fasting 32,33 split proinsulin independently predicts the development of diabetes. This prediction was better than that observed for either the insulin or intact proinsulin concentrations. The combination of family history, fasting glucose, and total proinsulin identified a subgroup of individuals at high risk of progression who might benefit from targeted interventions.