Aims/hypothesis

Prediabetes (HbA_1c 39–47 mmol/mol [5.7–6.4%] or fasting glucose 5.6–6.9 mmol/l) is associated with elevated risks of microvascular and macrovascular complications. It is unknown to what extent these risks in prediabetes remain after accounting for progression to diabetes.

Methods

In 10,310 participants from the Atherosclerosis Risk in Communities (ARIC) Study (aged 46–70 years, ~55% women, ~20% Black adults) without diabetes at baseline (1990–1992), we used Cox regression to characterise age- and sex-adjusted associations of prediabetes with ~30 year incidence of complications (composite and separately), including atherosclerotic CVD (ASCVD), heart failure, chronic kidney disease (CKD) and all-cause mortality before and after accounting for intervening incidence of diabetes, modelled as a time-varying variable. We calculated the excess risk of complications in prediabetes remaining after accounting for progression to diabetes.

Results

Of the 60% of adults with prediabetes at baseline, ~30% progressed to diabetes (median time to diabetes, 7 years). Over the maximum follow-up of ~30 years, there were 7069 events (1937 ASCVD, 2109 heart failure, 3288 CKD and 4785 deaths). Prediabetes was modestly associated with risk of any complication (HR 1.21 [95% CI 1.15, 1.27]) vs normoglycaemia. This association remained significant after accounting for progression to diabetes (HR 1.18 [95% CI 1.12, 1.24]) with 85% (95% CI 75, 94%) of the excess risk of any complication in prediabetes remaining. Results were similar for the individual complications.

Conclusions/interpretation

Progression to diabetes explained less than one-quarter of the risks of clinical outcomes associated with prediabetes. Prediabetes contributes to the risk of clinical outcomes even without progression to diabetes.

Graphical Abstract

中文翻译：

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糖尿病前期与临床结局风险升高相关，即使没有进展为糖尿病

 目标/假设

糖尿病前期（HbA_1c 39-47 mmol/mol [5.7-6.4%] 或空腹血糖 5.6-6.9 mmol/l）与微血管和大血管并发症的风险升高有关。目前尚不清楚在考虑进展为糖尿病后，糖尿病前期的这些风险在多大程度上仍然存在。

 方法

在基线（1990-1992 年）无糖尿病的社区动脉粥样硬化风险 （ARIC） 研究的 10,310 名参与者（年龄 46-70 岁，~55% 女性，~20% 黑人成年人）中，我们使用 Cox 回归来表征糖尿病前期与 ~30 年并发症发生率（复合和单独）的年龄和性别调整关联，包括动脉粥样硬化性 CVD （ASCVD）、心力衰竭、慢性肾病 （CKD） 和前后全因死亡率糖尿病，建模为时变变量。我们计算了在考虑进展为糖尿病后剩余的糖尿病前期并发症的超额风险。

 结果

在基线时 60% 的糖尿病前期成人中，~30% 进展为糖尿病（中位糖尿病时间为 7 年）。在 ~30 年的最长随访中，有 7069 例事件 （1937 例 ASCVD、2109 例心力衰竭、3288 例 CKD 和 4785 例死亡）。与正常血糖相比，糖尿病前期与任何并发症的风险 （HR 1.21 [95% CI 1.15， 1.27] ] 呈中度相关性。在考虑了进展为糖尿病 （HR 1.18 [95% CI 1.12， 1.24]） 和 85% （95% CI 75， 94%） 的糖尿病前期并发症的超额风险后，这种关联仍然显著。个体并发症的结果相似。

结论/解释

进展为糖尿病解释了不到四分之一的糖尿病前期相关临床结局风险。即使没有进展为糖尿病，糖尿病前期也会增加临床结局的风险。

 图形摘要