Progression to Diabetes in Relatives of Type 1 Diabetic Patients: Mechanisms and Mode of Onset
Progression to Diabetes in Relatives of Type 1 Diabetic Patients: Mechanisms and Mode of Onset
复制标题
DOI：
10.2337/db09-1378
复制
发表时间：
2010-03-01
期刊：
影响因子：
7.7
通讯作者：
Skyler, Jay S.
中科院分区：
文献类型：
--
作者：
Ferrannini, Ele;Mari, Andrea;Skyler, Jay S.
1型糖尿病患者的亲属患糖尿病的风险增加。我们调查了高血糖症的发病模式以及胰岛素敏感性和β细胞功能如何促进疾病的进展。研究设计和方法-在328名胰岛细胞自身抗体阳性的非糖尿病亲属中进行糖尿病预防试验-1研究（中位年龄11岁[四分位距81]，在基线、每6个月和2.7年后[2.7]，当115名受试者成为糖尿病患者时，进行连续OGTT（共2，143例）。P细胞葡萄糖敏感性通过OGTT葡萄糖/C肽反应的数学建模获得胰岛素敏感性（胰岛素分泌/血浆葡萄糖剂量反应函数的斜率）和胰岛素敏感性。在进展者中，基线胰岛素敏感性、空腹胰岛素分泌和总葡萄糖后胰岛素输出与非进展者相似，而β细胞葡萄糖敏感性受损（中位数48 pmol/min/m2/mmol/l [四分位距36] vs. 87 pmol/min/m2/mmol/l [67]; P < 0.0001）和独立于性别、年龄、BMI和临床风险的预测糖尿病发病率（P < 0.0001）。在进展者中，2小时葡萄糖水平变化不大，直到诊断前0.78年，当他们开始迅速上升（类似于13 mmol . l（-1）.葡萄糖敏感性开始下降的时间（确诊前1.45年）早于血糖峰期（P < 0.0001）。在这一预期阶段，胰岛素分泌和胰岛素敏感性基本上是stabilis. CONCLUSIONS-在高风险的亲属，β细胞葡萄糖敏感性受损，是一个强有力的预测糖尿病进展。血浆葡萄糖的时间轨迹通常是双相的，缓慢线性增加，随后快速激增，并且预期β细胞葡萄糖敏感性进一步恶化。糖尿病59：679-685，2010
OBJECTIVE-Relatives of type I diabetic patients are at enhanced risk of developing diabetes. We investigated the mode of onset of hyperglycemia and how insulin sensitivity and beta-cell function contribute to the progression to the disease.RESEARCH DESIGN AND METHODS-In 328 islet cell autoantibody-positive, nondiabetic relatives from the observational arms of the Diabetes Prevention Trial-1 Study (median age 11 years [interquartile range 81, sequential OGTTs (2,143 in total) were performed at baseline, every 6 months, and 2.7 years [2.7] later, when 115 subjects became diabetic. P-Cell glucose sensitivity (slope of the insulin-secretion/plasma glucose dose-response function) and insulin sensitivity were obtained by mathematical modeling of the OGTT glucose/C-peptide responses.RESULTS-In progressors, baseline insulin sensitivity, fasting insulin secretion, and total postglucose insulin output were similar to those of nonprogressors, whereas beta-cell glucose sensitivity was impaired (median 48 pmol/min per m(2) per mmol/l [interquartile range 36] vs. 87 pmol/min per m 2 per nimol/l [67]; P < 0.0001) and predicted incident diabetes (P < 0.0001) independently of sex, age, BMI, and clinical risk. In progressors, 2-h glucose levels changed little until 0.78 years before diagnosis, when they started to rise rapidly (similar to 13 mmol . l(-1) . year(-1)); glucose sensitivity began to decline significantly (P < 0.0001) earlier (1.45 years before diagnosis) than the plasma glucose surge. During this anticipation phase, both insulin secretion and insulin sensitivity were essentially stable.CONCLUSIONS-In high-risk relatives, beta-cell glucose sensitivity is impaired and is a strong predictor of diabetes progression. The time trajectories of plasma glucose are frequently biphasic, with a slow linear increase followed by a rapid surge, and are anticipated by a further deterioration of beta-cell glucose sensitivity. Diabetes 59:679-685, 2010