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首页> 外文期刊>PLoS Medicine >Obesity, clinical, and genetic predictors for glycemic progression in Chinese patients with type 2 diabetes: A cohort study using the Hong Kong Diabetes Register and Hong Kong Diabetes Biobank
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Obesity, clinical, and genetic predictors for glycemic progression in Chinese patients with type 2 diabetes: A cohort study using the Hong Kong Diabetes Register and Hong Kong Diabetes Biobank

机译：肥胖，临床和遗传预测因素用于糖尿病患者2型糖尿病患者：使用香港糖尿病寄存器和香港糖尿病BIOBANK的队列研究

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Background Type 2 diabetes (T2D) is a progressive disease whereby there is often deterioration in glucose control despite escalation in treatment. There is significant heterogeneity to this progression of glycemia after onset of diabetes, yet the factors that influence glycemic progression are not well understood. Given the tremendous burden of diabetes in the Chinese population, and limited knowledge on factors that influence glycemia, we aim to identify the clinical and genetic predictors for glycemic progression in Chinese patients with T2D. Methods and findings In 1995–2007, 7,091 insulin-na?ve Chinese patients (mean age 56.8 ± 13.3 [SD] years; mean age of T2D onset 51.1 ± 12.7 years; 47% men; 28.4% current or ex-smokers; median duration of diabetes 4 [IQR: 1–9] years; mean HbA1c 7.4% ± 1.7%; mean body mass index [BMI] 25.3 ± 4.0 kg/m2) were followed prospectively in the Hong Kong Diabetes Register. We examined associations of BMI and other clinical and genetic factors with glycemic progression defined as requirement of continuous insulin treatment, or 2 consecutive HbA1c ≥8.5% while on ≥2 oral glucose-lowering drugs (OGLDs), with validation in another multicenter cohort of Hong Kong Diabetes Biobank. During a median follow-up period of 8.8 (IQR: 4.8–13.3) years, incidence of glycemic progression was 48.0 (95% confidence interval [CI] 46.3–49.8) per 1,000 person-years with 2,519 patients started on insulin. Among the latter, 33.2% had a lag period of 1.3 years before insulin was initiated. Risk of progression was associated with extremes of BMI and high HbA1c. On multivariate Cox analysis, early age at diagnosis, microvascular complications, high triglyceride levels, and tobacco use were additional independent predictors for glycemic progression. A polygenic risk score (PRS) including 123 known risk variants for T2D also predicted rapid progression to insulin therapy (hazard ratio [HR]: 1.07 [95% CI 1.03–1.12] per SD; P = 0.001), with validation in the replication cohort (HR: 1.24 [95% CI 1.06–1.46] per SD; P = 0.008). A PRS using 63 BMI-related variants predicted BMI (beta [SE] = 0.312 [0.057] per SD; P = 5.84 × 10?8) but not glycemic progression (HR: 1.01 [95% CI 0.96–1.05] per SD; P = 0.747). Limitations of this study include potential misdiagnosis of T2D and lack of detailed data of drug use during follow-up in the replication cohort. Conclusions Our results show that approximately 5% of patients with T2D failed OGLDs annually in this clinic-based cohort. The independent associations of modifiable and genetic risk factors allow more precise identification of high-risk patients for early intensive control of multiple risk factors to prevent glycemic progression.
机译：背景技术2型糖尿病（T2D）是渐进疾病，从而尽管治疗升级，但葡萄糖控制通常会劣化。在糖尿病发作后，糖尿病的这种进展具有显着的异质性，但影响血糖进展的因素并不熟知。鉴于中国人口中糖尿病的巨大负担，以及对影响糖血症的因素有限的知识，我们的目标是识别中国T2D患者血糖进展的临床和遗传预测因子。方法和结果1995 - 2007年，7,091次胰岛素-NA？VE中国患者（平均年龄为56.8±13.3 [SD]年龄; T2D发病的平均年龄51.1±12.7岁; 47％的男性; 28.4％的当前或前吸烟者;中位数糖尿病持续时间4 [IQR：1-9]年;平均HBA1C 7.4％±1.7％;平均体重指数[BMI] 25.3±4.0 kg / m2）在香港糖尿病寄存器中展示。我们检查了BMI和其他临床和遗传因素与血糖进展的关联，定义为连续胰岛素治疗的要求，或连续2个连续的HBA1c≥8.5％，同时≥2口服葡萄糖降低药物（OGLD），在另一个多中心队的洪核中验证孔糖尿病生物银行。在8.8（IQR：4.8-13.3）年的中位后续期间，每1000人血糖进展的发病率为48.0（95％的置信区间[CI] 46.3-49.8），胰岛素开始2,519名患者。在后者中，33.2％在启动胰岛素之前的滞后期为1.3岁。进展的风险与BMI和高HBA1C的极端有关。在多元COX分析中，诊断的早期性，微血管并发症，高甘油三酯水平和烟草使用是血糖进展的其他独立预测因子。包括123个已知的T2D的风险变量（PRS）的多基因风险评分还预测了胰岛素治疗的快速进展（危害比[HR]：1.07 [95％CI 1.03-1.12]每个SD; P = 0.001），复制中的验证COHORT（HR：1.24 [95％CI 1.06-1.46]每个SD; P = 0.008）。使用63BMI相关变体的PRS预测BMI（β[SE] = 0.312 [0.057]，P = 5.84×10？8）但不是血糖进展（HR：1.01 [95％CI 0.96-1.05]每SD; p = 0.747）。本研究的局限性包括T2D的潜在误诊，并且在复制队列的随访期间缺乏药物使用的详细数据。结论我们的结果表明，在基于诊所的队列中每年约有5％的T2D患者失败了OGLD。可修饰和遗传危险因素的独立协会允许更精确地鉴定高危患者，以预防血糖进展的早期密集控制。

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