Type 2 diabetes (T2D) is common and increasing in prevalence. It is possible to prevent or delay T2D using lifestyle intervention programmes. Entry to these programmes is usually determined by a measure of glycaemia in the ‘intermediate’ range. This paper investigated the relationship between HbA1c and future diabetes risk and determined the impact of varying thresholds to identify those at high risk of developing T2D. We studied 4227 participants without diabetes aged ≥ 40 years recruited to the Exeter 10,000 population cohort in South West England. HbA1c was measured at study recruitment with repeat HbA1c available as part of usual care. Absolute risk of developing diabetes within 5 years, defined by HbA1c ≥ 48 mmol/mol (6.5%), according to baseline HbA1c, was assessed by a flexible parametric survival model. The overall absolute 5-year risk (95% CI) of developing T2D in the cohort was 4.2% (3.6, 4.8%). This rose to 7.1% (6.1, 8.2%) in the 56% (n = 2358/4224) of participants classified ‘high-risk’ with HbA1c ≥ 39 mmol/mol (5.7%; ADA criteria). Under IEC criteria, HbA1c ≥ 42 mmol/mol (6.0%), 22% (n = 929/4277) of the cohort was classified high-risk with 5-year risk 14.9% (12.6, 17.2%). Those with the highest HbA1c values (44–47 mmol/mol [6.2–6.4%]) had much higher 5-year risk, 26.4% (22.0, 30.5%) compared with 2.1% (1.5, 2.6%) for 39–41 mmol/mol (5.7–5.9%) and 7.0% (5.4, 8.6%) for 42–43 mmol/mol (6.0–6.1%). Changing the entry criterion to prevention programmes from 39 to 42 mmol/mol (5.7–6.0%) reduced the proportion classified high-risk by 61%, and increased the positive predictive value (PPV) from 5.8 to 12.4% with negligible impact on the negative predictive value (NPV), 99.6% to 99.1%. Increasing the threshold further, to 44 mmol/mol (6.2%), reduced those classified high-risk by 59%, and markedly increased the PPV from 12.4 to 23.2% and had little impact on the NPV (99.1% to 98.5%). A large proportion of people are identified as high-risk using current thresholds. Increasing the risk threshold markedly reduces the number of people that would be classified as high-risk and entered into prevention programmes, although this must be balanced against cases missed. Raising the entry threshold would allow limited intervention opportunities to be focused on those most likely to develop T2D.

中文翻译：

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选择 HbA1c 阈值以识别 2 型糖尿病高风险个体及其对糖尿病预防计划的影响：一项队列研究

2 型糖尿病 (T2D) 很常见，并且患病率不断上升。使用生活方式干预计划可以预防或延缓 T2D。进入这些项目通常由“中间”范围内的血糖测量决定。本文调查了 HbA1c 与未来糖尿病风险之间的关系，并确定了不同阈值的影响，以识别那些患 T2D 的高风险人群。我们研究了 4227 名年龄 ≥ 40 岁的无糖尿病参与者，这些参与者被招募到英格兰西南部的埃克塞特 10,000 人口队列中。HbA1c 在研究招募时测量，重复 HbA1c 可作为常规护理的一部分。根据基线 HbA1c，5 年内发生糖尿病的绝对风险定义为 HbA1c ≥ 48 mmol/mol (6.5%)，通过灵活的参数生存模型进行评估。该队列中发生 T2D 的总体 5 年绝对风险 (95% CI) 为 4.2% (3.6, 4.8%)。在 HbA1c ≥ 39 mmol/mol 的 56% (n = 2358/4224) 被归类为“高风险”的参与者中，这一比例上升至 7.1% (6.1, 8.2%)（5.7%；ADA 标准）。根据 IEC 标准，HbA1c ≥ 42 mmol/mol (6.0%)、22% (n = 929/4277) 的队列被归类为高风险，5 年风险为 14.9% (12.6, 17.2%)。HbA1c 值最高的人（44–47 mmol/mol [6.2–6.4%]）的 5 年风险要高得多，为 26.4%（22.0, 30.5%），而 39–41 为 2.1%（1.5, 2.6%） mmol/mol (5.7–5.9%) 和 7.0% (5.4, 8.6%) 为 42–43 mmol/mol (6.0–6.1%)。将预防计划的进入标准从 39 更改为 42 mmol/mol (5.7-6.0%)，将高风险分类的比例降低了 61%，并将阳性预测值 (PPV) 从 5.8 提高到 12。4% 对阴性预测值 (NPV) 的影响可忽略不计，为 99.6% 至 99.1%。将阈值进一步提高至 44 mmol/mol (6.2%)，将高危人群降低 59%，PPV 从 12.4% 显着提高至 23.2%，对 NPV 影响不大（99.1% 至 98.5%）。使用当前阈值，很大一部分人被确定为高风险人群。提高风险阈值会显着减少被归类为高风险并进入预防计划的人数，尽管这必须与漏诊病例相平衡。提高进入门槛将使有限的干预机会集中在最有可能发展为 T2D 的人群上。PPV 从 12.4% 显着提高到 23.2%，对 NPV 影响不大（99.1% 到 98.5%）。使用当前阈值，很大一部分人被确定为高风险人群。提高风险阈值会显着减少被归类为高风险并进入预防计划的人数，尽管这必须与漏诊病例相平衡。提高进入门槛将使有限的干预机会集中在最有可能发展为 T2D 的人群上。PPV 从 12.4% 显着提高到 23.2%，对 NPV 影响不大（99.1% 到 98.5%）。使用当前阈值，很大一部分人被确定为高风险人群。提高风险阈值会显着减少被归类为高风险并进入预防计划的人数，尽管这必须与漏诊病例相平衡。提高进入门槛将使有限的干预机会集中在最有可能发展为 T2D 的人群上。