Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank.
Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank.
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DOI：
10.1016/s2213-8587(17)30362-5
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Hattersley AT
中科院分区：
文献类型：
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作者：
Thomas NJ;Jones SE;Weedon MN;Shields BM;Oram RA;Hattersley AT
1型糖尿病通常被认为是儿童和年轻人的疾病。1型糖尿病的遗传易感性是明确定义的，不会导致2型糖尿病。目前尚不清楚1型糖尿病的遗传易感性导致30岁后糖尿病诊断的频率。我们的目的是调查1型糖尿病的频率和表型，在生命的前60年中由于高遗传易感性而导致。在这项横断面分析中，我们使用了基于29种常见变异的1型糖尿病遗传风险评分，以确定英国生物库中一半人群中具有1型糖尿病高或低遗传易感性的白色欧洲血统个体。我们使用Kaplan-Meier分析来评估两组在生命的前60年中糖尿病的病例数。我们将1型糖尿病的遗传学定义为与低遗传易感性组相比，高遗传易感性组中发生的额外糖尿病病例。所有其余病例均被定义为2型糖尿病。我们评估了遗传学定义的1型或2型糖尿病患者的临床特征。 英国生物库中的379511名白色欧洲人中有13250人（3.5%）在生命的前60年内患上了糖尿病。在1型糖尿病高遗传易感性人群中，比在低遗传易感性人群中多1286例糖尿病。这些遗传学定义的1型糖尿病病例分布在所有诊断年龄段; 537例（42%）在31-60岁时被诊断，占30岁后诊断的所有糖尿病病例的4%（537/12233）。 31-60岁时诊断为1型糖尿病的组的临床特征与30岁或更年轻时诊断为1型糖尿病的组的临床特征相似。对于31-60岁的糖尿病患者，1型糖尿病的临床特征与2型糖尿病不同：他们的BMI较低（27·4 kg/m2 [95% CI 26·7-28·0] vs 32·4 kg/m2 [32·2-32·5]; p<0.0001），在诊断后第一年更可能使用胰岛素（89% [476/537] vs 6% [648/11696 ]; p<0.0001），更可能患有糖尿病酮症酸中毒（11% [61/537] vs 0.3%[30/ 11696]; p<0.0001）。对1型糖尿病的遗传易感性导致非肥胖相关的胰岛素依赖型糖尿病，其在生命的前六十年中出现。我们的研究结果强调了由于2型糖尿病的背景患病率增加，30岁后识别1型糖尿病的难度。未能诊断迟发性1型糖尿病可能会产生严重后果，因为这些患者会迅速发展为胰岛素依赖。Wellcome Trust和Diabetes UK。
Type 1 diabetes is typically considered a disease of children and young adults. Genetic susceptibility to young-onset type 1 diabetes is well defined and does not predispose to type 2 diabetes. It is not known how frequently genetic susceptibility to type 1 diabetes leads to a diagnosis of diabetes after age 30 years. We aimed to investigate the frequency and phenotype of type 1 diabetes resulting from high genetic susceptibility in the first six decades of life. In this cross-sectional analysis, we used a type 1 diabetes genetic risk score based on 29 common variants to identify individuals of white European descent in UK Biobank in the half of the population with high or low genetic susceptibility to type 1 diabetes. We used Kaplan-Meier analysis to evaluate the number of cases of diabetes in both groups in the first six decades of life. We genetically defined type 1 diabetes as the additional cases of diabetes that occurred in the high genetic susceptibility group compared with the low genetic susceptibility group. All remaining cases were defined as type 2 diabetes. We assessed the clinical characteristics of the groups with genetically defined type 1 or type 2 diabetes. 13 250 (3·5%) of 379 511 white European individuals in UK Biobank had developed diabetes in the first six decades of life. 1286 more cases of diabetes were in the half of the population with high genetic susceptibility to type 1 diabetes than in the half of the population with low genetic susceptibility. These genetically defined cases of type 1 diabetes were distributed across all ages of diagnosis; 537 (42%) were in individuals diagnosed when aged 31–60 years, representing 4% (537/12 233) of all diabetes cases diagnosed after age 30 years. The clinical characteristics of the group diagnosed with type 1 diabetes when aged 31–60 years were similar to the clinical characteristics of the group diagnosed with type 1 diabetes when aged 30 years or younger. For individuals diagnosed with diabetes when aged 31–60 years, the clinical characteristics of type 1 diabetes differed from those of type 2 diabetes: they had a lower BMI (27·4 kg/m2 [95% CI 26·7–28·0] vs 32·4 kg/m2 [32·2–32·5]; p<0·0001), were more likely to use insulin in the first year after diagnosis (89% [476/537] vs 6% [648/11 696]; p<0·0001), and were more likely to have diabetic ketoacidosis (11% [61/537] vs 0·3% [30/11 696]; p<0·0001). Genetic susceptibility to type 1 diabetes results in non-obesity-related, insulin-dependent diabetes, which presents throughout the first six decades of life. Our results highlight the difficulty of identifying type 1 diabetes after age 30 years because of the increasing background prevalence of type 2 diabetes. Failure to diagnose late-onset type 1 diabetes can have serious consequences because these patients rapidly develop insulin dependency. Wellcome Trust and Diabetes UK.