Low Fasting Insulin Associated With Long-Term Dementia Risk

Having high insulin at baseline was associated with a greater risk for incident diabetes mellitus compared with low insulin values.

Middle-aged women without diabetes and with low fasting serum insulin levels have an increased risk for dementia compared with women with medium insulin levels, according to a study published in Neurology.

A total of 1212 women between the ages of 38 and 60 years who did not have diabetes and had fasting values for serum insulin and blood glucose at year 1968 (baseline) were included. The investigators analyzed the association between baseline serum insulin and glucose levels and the risk for dementia over a 34-year period. Analyses were adjusted for tertiles of insulin and glucose and other covariates. A third end point for comparison with dementia was incident diabetes mellitus. The researchers also included body mass index, hypertension status, total cholesterol level, triglyceride level, leptin levels, parental history of diabetes mellitus, education, physical activity, and smoking in the analysis.

During the 34-year follow-up, incident dementia occurred in 142 women. Compared with the medium insulin tertile, those in the low tertile of insulin exhibited significantly higher rates of dementia (hazard ratio [HR] 2.34; 95% CI, 1.52-3.58). Conversely, those in the highest insulin tertile did not display an increased risk for dementia compared with those in the other 2 tertiles (HR 1.28; 95% CI, 0.81-2.03). Additionally, having high insulin at baseline (HR 1.70; 95% CI, 1.08-2.68) was associated with a greater risk for incident diabetes mellitus compared with low insulin values (HR 0.76; 95% CI, 0.43-1.37) during long-term follow-up.

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Limitations of the analysis include the relatively small number of end points as well as the evaluation of serum samples stored for 45 years.

The findings from the analysis offer “epidemiologic evidence for a new pathway to dementia that is characterized by low fasting serum insulin and differs from the metabolic pathway via hyperinsulinemia or diabetes mellitus,” the researchers concluded.


Mehlig K, Lapidus L, Thelle DS, et al. Low fasting serum insulin and dementia in nondiabetic women followed for 34 years. Neurology. 2018;91:e427-e435.