Liu Xiaonan, Collister Jennifer A, Clifton Lei, Hunter David J, Littlejohns Thomas J
Nuffield Department of Population Health, University of Oxford, Oxford, Oxfordshire OX3 7LF, UK.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
J Endocr Soc. 2023 Jan 30;7(4):bvad020. doi: 10.1210/jendso/bvad020. eCollection 2023 Feb 9.
Early diagnosis of type 2 diabetes is crucial to reduce severe comorbidities and complications. Current screening recommendations for type 2 diabetes include traditional risk factors, primarily body mass index (BMI) and family history, however genetics also plays a key role in type 2 diabetes risk. It is important to understand whether genetic predisposition to type 2 diabetes modifies the effect of these traditional factors on type 2 diabetes risk.
This work aimed to investigate whether genetic risk of type 2 diabetes modifies associations between BMI and first-degree family history of diabetes with 1) prevalent prediabetes or undiagnosed diabetes; and 2) incident confirmed type 2 diabetes.
We included 431 658 individuals aged 40 to 69 years at baseline of multiethnic ancestry from the UK Biobank. We used a multiethnic polygenic risk score for type 2 diabetes (PRS) developed by Genomics PLC. Prediabetes or undiagnosed diabetes was defined as baseline glycated hemoglobin greater than or equal to 42 mmol/mol (6.0%), and incident type 2 diabetes was derived from medical records.
At baseline, 43 472 participants had prediabetes or undiagnosed diabetes, and 17 259 developed type 2 diabetes over 15 years follow-up. Dose-response associations were observed for PRS with each outcome in each category of BMI or first-degree family history of diabetes. Those in the highest quintile of PRS with a normal BMI were at a similar risk as those in the middle quintile who were overweight. Participants who were in the highest quintile of PRS and did not have a first-degree family history of diabetes were at a similar risk as those with a family history who were in the middle category of PRS.
Genetic risk of type 2 diabetes remains strongly associated with risk of prediabetes, undiagnosed diabetes, and future type 2 diabetes within categories of nongenetic risk factors. This could have important implications for identifying individuals at risk of type 2 diabetes for prevention and early diagnosis programs.
2型糖尿病的早期诊断对于降低严重合并症和并发症至关重要。当前2型糖尿病的筛查建议包括传统风险因素，主要是体重指数（BMI）和家族史，然而遗传学在2型糖尿病风险中也起着关键作用。了解2型糖尿病的遗传易感性是否会改变这些传统因素对2型糖尿病风险的影响很重要。
这项研究旨在调查2型糖尿病的遗传风险是否会改变BMI与糖尿病一级家族史之间与1） 糖尿病前期或未诊断糖尿病的患病率；以及2） 确诊的2型糖尿病发病率之间的关联。
我们纳入了英国生物银行中431658名基线年龄在40至69岁之间的多民族血统个体。我们使用了由Genomics PLC开发的2型糖尿病多民族多基因风险评分（PRS）。糖尿病前期或未诊断糖尿病定义为基线糖化血红蛋白大于或等于42 mmol/mol（6.0%），2型糖尿病发病率来自医疗记录。
在基线时，43472名参与者患有糖尿病前期或未诊断糖尿病，17259名在15年随访期间患2型糖尿病。在BMI或糖尿病一级家族史的每一类中，观察到PRS与每种结果之间的剂量反应关联。PRS处于最高五分位数且BMI正常的人与超重的中间五分位数的人风险相似。PRS处于最高五分位数且没有糖尿病一级家族史的参与者与有家族史且处于PRS中间类别的参与者风险相似。
在非遗传风险因素类别中，2型糖尿病的遗传风险仍然与糖尿病前期、未诊断糖尿病和未来2型糖尿病的风险密切相关。这对于识别有2型糖尿病风险的个体以进行预防和早期诊断计划可能具有重要意义。
