Data from: Low fasting serum insulin and dementia in nondiabetic women followed for 34 years

Objective: A previous study reported a U-shaped association between fasting insulin and dementia in a 5-year follow-up of a male cohort, which was now re-investigated in a representative population of women followed over 34 years, and taking into account the incidence of diabetes. Methods: Fasting values for insulin and glucose were obtained from serum samples in 1212 non-diabetic women aged 38-60 at the 1968 baseline. Risk of dementia was assessed by Cox proportional hazard regression adjusting for insulin, glucose, and other covariates, and, in a second model, after censoring for incident cases of diabetes. Incident diabetes was considered as a third endpoint, for comparison with dementia. Results: Over 34 years, we observed 142 incident cases of dementia. The low tertile of insulin displayed excess risk for dementia, hazard ratio (HR) = 2.34, 95% confidence interval = (1.52, 3.58), compared to the medium tertile, but the high tertile of insulin did not, HR = 1.28 (0.81, 2.03). These associations were also seen for dementia without diabetes comorbidity. In contrast, high but not low insulin predicted incident diabetes (115 cases), HR = 1.70 (1.08, 2.68) and HR = 0.76 (0.43, 1.37), respectively. Conclusions: Our results revealed a non-linear association between fasting serum insulin and dementia in a female population, with high risk at low insulin values that was not attributable to preclinical dementia or impaired insulin secretion. This condition suggests a new pathway to dementia, which differs from the metabolic pathway involving diabetes.研究目的：既往一项针对男性队列的5年随访研究显示，空腹胰岛素与痴呆症呈U型关联；本研究针对具有代表性的女性人群开展为期34年的随访，重新探讨该关联，并将糖尿病发病情况纳入考量。 研究方法：本研究纳入1212名1968年基线时年龄为38~60岁的非糖尿病女性，从其血清样本中获取空腹胰岛素及空腹血糖水平。采用Cox比例风险回归（Cox proportional hazard regression）模型评估痴呆症发病风险，模型校正了胰岛素、血糖及其他混杂因素；另一模型则在剔除新发糖尿病病例后进行分析。此外，将新发糖尿病作为第三结局指标，用于与痴呆症进行对比。 研究结果：34年随访期间共观察到142例新发痴呆症病例。以胰岛素中等三分位组为参照，低三分位组人群的痴呆症发病风险显著升高，风险比（hazard ratio, HR）=2.34，95%置信区间（confidence interval, CI）为(1.52, 3.58)；而高三分位组未呈现此关联，HR=1.28（95%CI: 0.81, 2.03）。该关联在无糖尿病共病的痴呆症人群中同样存在。与之相反，高胰岛素水平可预测新发糖尿病（共115例），HR=1.70（95%CI:1.08, 2.68），低胰岛素水平则无此预测效应，HR=0.76（95%CI:0.43, 1.37）。 研究结论：本研究结果显示，女性人群中空腹血清胰岛素水平与痴呆症呈非线性关联：低胰岛素水平组痴呆症发病风险升高，且该效应并非源于临床前期痴呆或胰岛素分泌受损。该发现提示了一条不同于糖尿病相关代谢通路的痴呆症发病新途径。