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年随访研究报道了空腹胰岛素与痴呆之间存在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，重新探讨这一关联，并纳入糖尿病发病情况进行分析。
研究方法：本研究纳入1968年基线时年龄为38~60岁的1212名非糖尿病女性，通过血清样本获取其空腹胰岛素与空腹血糖水平。采用Cox比例风险回归（Cox proportional hazard regression）模型评估痴呆发生风险，模型1校正了胰岛素、血糖及其他协变量；模型2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个结局指标，用于与痴呆的关联分析作对照。
研究结果：在34年的随访期间，共观察到142例新发痴呆病例。与胰岛素三分位中组相比，胰岛素低三分位组的痴呆发生风险显著升高，风险比（HR）=2.34，95%置信区间（95%CI）为(1.52, 3.58)；而胰岛素高三分位组未观察到此类风险升高（HR=1.28，95%CI=0.81, 2.03）。这一关联在无糖尿病共病的痴呆人群中同样存在。与之相反，胰岛素高水平可预测新发糖尿病（共115例），HR=1.70（95%CI=1.08, 2.68），而胰岛素低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与痴呆之间存在非线性关联，低水平胰岛素对应较高的痴呆发生风险，且该关联并非源于临床前痴呆或胰岛素分泌受损。这一发现提示了一条不同于糖尿病相关代谢通路的痴呆发病新机制。