Background

It has been suggested that long-term glycemic load as reflected in plasma levels of Glycosylated Hemoglobin, Type A1C (HbA1c) is associated with higher risk of depression, however results have been conflicting. We examined the potential association between HbA1c and risk of depression in a large population-based cohort without baseline diabetes (the Glostrup cohort) defined by either self-reported diabetes, registry diagnosis of diabetes or use of antidiabetic medication at baseline and in a national diabetes cohort (the Danish Adult Diabetes Database).

Methods

A total of 16,124 middle-aged individuals from the Glostrup cohort and 93,544 patients registered in the Danish Adult Diabetes Database were followed from the first registered HbA1c measurement (1999–2014) for subsequent diagnosis of depression or use of antidepressant medication in nation-wide Danish registers. The association was analyzed using a Cox proportional hazards regression model with HbA1c on both a continuous scale using restricted cubic splines and categorized based on the groups found in the spline model. We adjusted for relevant sociodemographic and clinical variables including previous depression and tested for interaction of both gender, insulin use and diabetes type.

Results

During follow-up, 2694 (17%) in the Glostrup cohort and 29,234 (31%) in the diabetes cohort developed depression. In the Glostrup cohort, we found an indication of a positive linear association between HbA1c and depression in women, while no clear association was found in men. In patients with diabetes, we found a U-shaped association between HbA1c and depression in both men and women with the lowest risk estimates for HbA1c levels of 58 mmol/mol (7.5%) in men and of 60 mmol/mol (7.6%) in women. When HbA1c was categorized, men with the highest HbA1c-levels had significantly elevated risk of depression (HR_HbA1c>9.4 1.16 (95%CI 1.10–1.23)) after multifactorial adjustment compared to the reference group with HbA1c of 42.1–56.2 mmol/mol (6.0–7.3%). Women in the lowest and highest category of HbA1c had significantly higher risk of depression HR_HbA1c<6.0 1.15 (95% CI 1.09–1.22) and HR_HbA1c>9.3 1.10 (95% CI 1.04–1.16), respectively, compared to the reference group with HbA1c 42.1–55.0 mmol/mol (7.2–9.3%). There was a significant interaction with gender, but no interaction for insulin use or diabetes type.

Conclusions

In a population without baseline diabetes, higher HbA1c levels seemed associated with higher depression risk in women, whereas a U-shaped association was found in patients with known diabetes.

中文翻译：

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糖尿病患者和非糖尿病患者的血红蛋白 A1c 水平和随后的抑郁风险

背景

有人提出，反映在血浆糖基化血红蛋白 A1C 型 (HbA1c) 水平上的长期血糖负荷与更高的抑郁风险相关，但结果相互矛盾。我们在没有基线糖尿病的大型人群队列（Glostrup 队列）中检查了 HbA1c 与抑郁风险之间的潜在关联，该队列由自我报告的糖尿病、糖尿病的登记诊断或在基线和全国糖尿病中使用抗糖尿病药物定义队列（丹麦成人糖尿病数据库）。

方法

来自 Glostrup 队列的 16,124 名中年个体和丹麦成人糖尿病数据库中登记的 93,544 名患者从首次登记的 HbA1c 测量（1999 年至 2014 年）进行随访，以便随后在全国范围内诊断抑郁症或使用抗抑郁药物寄存器。使用 Cox 比例风险回归模型和 HbA1c 在连续尺度上使用受限三次样条和基于样条模型中发现的组进行分类来分析该关联。我们调整了相关的社会人口学和临床变量，包括以前的抑郁症，并测试了性别、胰岛素使用和糖尿病类型的相互作用。

结果

在随访期间，Glostrup 队列中的 2694 人（17%）和糖尿病队列中的 29,234 人（31%）出现了抑郁症。在 Glostrup 队列中，我们发现 HbA1c 与女性抑郁症之间呈正线性关联，而男性未发现明显关联。在糖尿病患者中，我们发现男性和女性的 HbA1c 与抑郁之间存在 U 型关联，男性 HbA1c 水平的风险估计最低，分别为 58 mmol/mol (7.5%) 和 60 mmol/mol (7.6%)在女性中。对 HbA1c 进行分类时，HbA1c 水平最高的男性患抑郁症的风险显着升高（HR _HbA1c>9.41.16 (95%CI 1.10–1.23)) 与 HbA1c 为 42.1–56.2 mmol/mol (6.0–7.3%) 的参考组相比。与参考组相比，HbA1c 最低和最高类别的女性患抑郁症的风险分别显着更高 HR _HbA1c<6.0 1.15 (95% CI 1.09–1.22) 和 HR _HbA1c>9.3 1.10 (95% CI 1.04–1.16) HbA1c 42.1–55.0 mmol/mol (7.2–9.3%)。与性别有显着的交互作用，但与胰岛素使用或糖尿病类型没有交互作用。

结论

在没有基线糖尿病的人群中，较高的 HbA1c 水平似乎与女性较高的抑郁风险相关，而在已知糖尿病患者中发现了 U 型关联。