Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands.
Cardiometabolic Clinical Development, Nestlé Health Science, Vevey, Switzerland.
Nutr Metab Cardiovasc Dis. 2022 Feb;32(2):355-364. doi: 10.1016/j.numecd.2021.10.013. Epub 2021 Oct 27.
Cognitive dysfunction is increasingly recognized as an important comorbidity of type 2 diabetes (T2D). We aimed to establish if the risk of accelerated cognitive decline (ACD) is higher in females with T2D than males.
3163 participants (38% female) with T2D from the cognition substudy of CAROLINA® (NCT01243424) were included (mean age 64.4 ± 9.2 years; T2D duration 7.6 ± 6.1 years). The cognitive outcome was occurrence of ACD at end of follow-up, defined as a regression based index score ≤16th percentile on either the Mini-Mental State Examination (MMSE) or a composite measure of attention and executive functioning (Trail Making and Verbal Fluency Test). Potential confounders, were taken into account at an individual patient level. Logistic regression analysis was used to investigate ACD risk by sex. We assessed potential mediators for sex differences in ACD using Causal Mediation Analysis (CMA). After a median follow-up duration of 6.1 ± 0.7 years, 361 (30.0%) females compared to 494 (25.2%) males exhibited ACD (OR 1.27 [95%CI 1.08-1.49], p = .003). Depressive symptoms, which were more common in females (24.3% vs 12.5%), mediated between sex and ACD (mediation effect 20.3%, p = 0.03). There were no other significant mediators.
Females with T2D had a higher risk of ACD compared to males. This was partly explained by depressive symptoms. After evaluation of vascular and diabetes-related risk factors, complications and treatment, a major share of the higher risk of ACD in females remained unexplained. Our results highlight the need for further research on causes of sex-specific ACD in T2D.
认知功能障碍日益被认为是 2 型糖尿病（T2D）的一种重要合并症。我们旨在确定 T2D 女性发生认知功能加速下降（ACD）的风险是否高于男性。
纳入了来自 CAROLINA®认知子研究（NCT01243424）的 3163 名 T2D 患者（38%为女性）（平均年龄 64.4±9.2 岁；T2D 病程 7.6±6.1 年）。认知结局为随访结束时发生 ACD，定义为基于 Mini-Mental State Examination（MMSE）或注意力和执行功能综合测量（Trail Making 和言语流畅性测试）的指数评分≤第 16 百分位数。在个体患者水平上考虑了潜在的混杂因素。使用逻辑回归分析调查性别对 ACD 风险的影响。我们使用因果中介分析（CMA）评估 ACD 性别差异的潜在中介因素。中位随访时间为 6.1±0.7 年后，361 名（30.0%）女性与 494 名（25.2%）男性出现 ACD（OR 1.27 [95%CI 1.08-1.49]，p=0.003）。女性更常见的抑郁症状（24.3% vs. 12.5%）在性别与 ACD 之间起中介作用（中介效应 20.3%，p=0.03）。没有其他显著的中介因素。
与男性相比，T2D 女性发生 ACD 的风险更高。这在一定程度上可以用抑郁症状来解释。在评估血管和糖尿病相关的危险因素、并发症和治疗后，女性发生 ACD 的高风险仍有很大一部分无法解释。我们的研究结果强调了需要进一步研究 T2D 中性别特异性 ACD 的原因。
