Aldafas Rami, Vinogradova Yana, Crabtree Thomas S J, Gordon Jason, Idris Iskandar
School of Medicine, University of Nottingham, Nottingham, UK.
College of Health Science, Saudi Electronic University, Riyadh, Saudi Arabia.
Ther Adv Endocrinol Metab. 2025 Jun 20;16:20420188251350897. doi: 10.1177/20420188251350897. eCollection 2025.
There is conflicting evidence regarding optimal glycaemic targets to reflect the legacy effect of hyperglycaemia in people with type 2 diabetes (T2D). We examined the risks of microvascular complications and hospital admission with glycated haemoglobin (HbA1c) levels from the diagnosis of T2D.
We identified individuals with incident T2D from 1998 to 2007 from the Clinical Practice Research Datalink and Hospital Episode Statistics. A composite microvascular outcome was defined as a new diagnosis of neuropathy, nephropathy or retinopathy. A multivariate time-varying Cox regression analysis was performed to assess the risk of microvascular disease associated with HbA1c at five different levels (1.0% (11 mmol/mol) intervals). HbA1c 6.5%-7.5% (48.0-58.9 mmol/mol) was defined as the reference.
= 172,869 (mean age 62.6 ± 14.0 years, 54.6% female) were analysed. Average follow-up was 11.2 years. The risk of microvascular disease increased with higher HbA1c levels, the highest risk in the ⩾9.6% (⩾81 mmol/mol; hazard ratio (HR): 1.29, 95% confidence interval (CI): 1.11-1.51) and the lowest in the <6.5% (<48.0 mmol/mol; HR: 0.94, 95% CI: 0.83-1.08). The risk of hospital admission suggested a U-shaped association with HbA1c, highest risk in the lowest (<6.5% (<48.0 mmol/mol); HR: 1.04, 95% CI: 1.01-1.07) followed by HbA1c groups (8.6%-9.6% (70.0-81.0 mmol/mol); HR: 1.02, 95% CI: 0.97-1.08) while the lowest risk for hospital admission was observed for targets with the reference group (target between 6.5% and 7.5%, (48.0-58.9 mmol/mol)).
The risk of microvascular complications was lowest when HbA1c levels were within the non-diabetic range and increased with higher HbA1c levels. The risk of hospital admission was significantly elevated in individuals with HbA1c levels below 6.5%, suggesting a potential U-shaped association, although the increased risk at higher HbA1c levels did not reach statistical significance. This highlights the importance of maintaining individualised HbA1c targets in the management of T2D from diagnosis to prevent these complications.
关于反映2型糖尿病（T2D）患者高血糖遗留效应的最佳血糖目标，现有证据相互矛盾。我们研究了自T2D诊断起糖化血红蛋白（HbA1c）水平与微血管并发症及住院风险之间的关系。
我们从临床实践研究数据链和医院病历统计数据中识别出1998年至2007年期间新诊断为T2D的个体。复合微血管结局定义为新发神经病变、肾病或视网膜病变。进行多变量时变Cox回归分析，以评估五个不同HbA1c水平（间隔1.0%（11 mmol/mol））与微血管疾病风险的相关性。将HbA1c 6.5%-7.5%（48.0-58.9 mmol/mol）定义为参照组。
共分析了172,869例患者（平均年龄62.6±14.0岁，54.6%为女性）。平均随访时间为11.2年。微血管疾病风险随HbA1c水平升高而增加，HbA1c≥9.6%（≥81 mmol/mol）时风险最高（风险比（HR）：1.29，95%置信区间（CI）：1.11-1.51），HbA1c<6.5%（<48.0 mmol/mol）时风险最低（HR：0.94，95%CI：0.83-1.08）。住院风险与HbA1c呈U型关联，HbA1c最低水平组（<6.5%（<48.0 mmol/mol））风险最高（HR：1.04，95%CI：1.01-1.07），其次是HbA1c 8.6%-9.6%（70.0-81.0 mmol/mol）组（HR：1.02，95%CI：0.97-1.08），而参照组目标范围（6.5%至7.5%，（48.0-58.9 mmol/mol））的住院风险最低。
当HbA1c水平处于非糖尿病范围时，微血管并发症风险最低，且随HbA1c水平升高而增加。HbA1c水平低于6.5%的个体住院风险显著升高，提示可能存在U型关联，尽管HbA1c较高水平时增加的风险未达到统计学显著性。这凸显了在T2D管理中从诊断起维持个体化HbA1c目标以预防这些并发症的重要性。
