Department of Epidemiology and Public Health, University College London, UK (A.G.T., E.J.B., J.V.L., A.S.-M., M.J.S., M.K.).
Department of Internal Medicine and Oncology and Department of Public Health, Semmelweis University Faculty of Medicine, Budapest, Hungary (A.G.T.).
Circulation. 2022 Sep 27;146(13):995-1005. doi: 10.1161/CIRCULATIONAHA.122.059430. Epub 2022 Aug 25.
It is unclear whether replacing oral glucose tolerance test (OGTT) with hemoglobin A1c (HbA1c) measurement for diagnosing diabetes is justified. We aimed to assess the proportion of OGTT-diagnosed diabetes cases that can be confirmed by HbA1c and to examine whether individuals with OGTT diagnosis but nondiagnostic HbA1c are at higher risk of macrovascular and microvascular disease.
Participants were 5773 men and women from the population-based Whitehall II prospective cohort study in the United Kingdom. New OGTT diabetes cases diagnosed in clinical examinations in 2002 to 2004 and 2007 to 2009 were assessed for HbA1c confirmation (≥6.5%) in these and subsequent clinical examinations in 2012 to 2013 and 2015 to 2016. All participants were followed up for major cardiovascular events through linkage to electronic health records until 2017 and for incident chronic kidney disease (estimated glomerular filtration rate <60 mL·min·1.73 m) until the last clinical examination. In analysis of vascular disease risk, new OGTT-diagnosed diabetes cases with and without diagnostic HbA1c and preexisting diabetes cases were compared with diabetes-free participants.
Of the 378 (59.3%) participants with OGTT-diagnosed diabetes, 224 were confirmed by HbA1c during 4.1 years (SD, 4.1 years) of follow-up. We recorded 942 cardiovascular events over 12.1 years. After adjustment for nonmodifiable risk factors and compared with the 4997 diabetes-free participants, 371 participants with new HbA1c-confirmed diabetes and 405 participants with preexisting diabetes had increased risk of cardiovascular disease (hazard ratio, 1.53 [95% CI, 1.12-2.10] and 1.85 [95% CI, 1.50-2.28], respectively). The corresponding hazard ratios in the analysis of incident chronic kidney disease (487 cases; follow-up, 6.6 years) were 1.69 (95% CI, 1.09-2.62) for 282 participants with new HbA1c-confirmed diabetes and 1.67 (95% CI, 1.22-2.28) for 276 participants with preexisting diabetes. In both analyses, OGTT cases with nondiagnostic HbA1c (n=149 and 107) had a risk (hazard ratio, 0.99-1.07) similar to that of the diabetes-free population.
More than 40% of OGTT-diagnosed diabetes cases were not confirmed by HbA1c during an extended follow-up. However, because these individuals have a risk of cardiovascular disease and chronic kidney disease similar to that of the diabetes-free population, replacement of OGTT with HbA1c-based diagnosis appears justified.
目前尚不清楚用糖化血红蛋白（HbA1c）测量替代口服葡萄糖耐量试验（OGTT）来诊断糖尿病是否合理。我们旨在评估可通过 HbA1c 确认的 OGTT 诊断的糖尿病病例比例，并研究 OGTT 诊断但 HbA1c 无诊断意义的个体是否存在更高的大血管和微血管疾病风险。
参与者为来自英国基于人群的 Whitehall II 前瞻性队列研究的 5773 名男性和女性。在 2002 年至 2004 年和 2007 年至 2009 年的临床检查中诊断为新 OGTT 糖尿病的病例，评估其 HbA1c 确认（≥6.5%）情况，这些病例以及随后在 2012 年至 2013 年和 2015 年至 2016 年的后续临床检查中进行了评估。所有参与者均通过电子健康记录进行主要心血管事件的随访，直至 2017 年，并对新发生的慢性肾病（估计肾小球滤过率<60 mL·min·1.73 m）进行随访，直至最后一次临床检查。在血管疾病风险分析中，将新 OGTT 诊断的糖尿病病例和无诊断意义的 HbA1c 病例以及既往糖尿病病例与无糖尿病病例进行比较。
在 378 名（59.3%）OGTT 诊断的糖尿病患者中，有 224 名在 4.1 年（SD，4.1 年）的随访期间通过 HbA1c 得到确认。我们记录了 12.1 年内发生的 942 例心血管事件。在调整不可改变的危险因素后，与 4997 名无糖尿病的参与者相比，371 名新 HbA1c 确诊的糖尿病患者和 405 名既往糖尿病患者发生心血管疾病的风险增加（危险比，1.53[95%CI，1.12-2.10]和 1.85[95%CI，1.50-2.28]）。在对新发慢性肾病的分析中（487 例病例；随访时间为 6.6 年），282 名新 HbA1c 确诊的糖尿病患者和 276 名既往糖尿病患者发生该疾病的风险比分别为 1.69（95%CI，1.09-2.62）和 1.67（95%CI，1.22-2.28）。在这两项分析中，HbA1c 无诊断意义的 OGTT 病例（n=149 和 107）的风险（危险比，0.99-1.07）与无糖尿病的人群相似。
在延长的随访中，超过 40%的 OGTT 诊断的糖尿病病例未通过 HbA1c 得到确认。然而，由于这些个体发生心血管疾病和慢性肾病的风险与无糖尿病的人群相似，因此用基于 HbA1c 的诊断替代 OGTT 似乎是合理的。
