Insulin Resistance Impairs Cognitive Performance Even in Healthy Subjects at Risk for Diabetes Mellitus

Increasing scientific evidences support the hypothesis that type 2 diabetes mellitus (T2D) increases the risk of developing dementia and cognitive impairment. Experimental data, although still conflicting, show that insulin resistance (IR) is able to influence cognitive performance (CP). The objective of our study, therefore, was to verify the relationship between insulin resistance and cognitive performance (PC) in subjects at risk for DM2.

For this reason 134 (111 F) volunteers, healthy at risk for diabetes mellitus (overweight and/or fasting hyperglycemia and/or family history for T2D), 39.0±12.3 year old, BMI 25.2±4.8 kg/m², were enrolled; they underwent to metabolic study (OGTT for glycemia, insulinemia and c-peptide), and neuropsychological tests to evaluate global cognitive function, verbal learning, memory, visual attention and executive functions.

The results of the neuropsychological tests were subsequently normalized by age and education; each test was standardized with a score from 0 (worst) to 4 (best performance). The equivalent scores of each test were summed to obtain a composite endpoint (Cognitive Performance Index), from 0 to 16, with increasing gradient for better CP.By dividing the subjects recruited into quartiles on the basis of PCI, the IR indexes gradually worsened as PCI became worse, particularly HOMA-IR, Matsuda, basal insulin secretion and basal insulin clearance (p <0.04, <0.005, <0.and <0.001, respectively). After multiple regression analysis, basal insulin secretion was more related to CP worsening. No correlation with fasting blood glucose, 1 hour and 2 hours glucose after oral load, was found.

These data seem to reinforce the hypothesis that insulin resistance, independently of glycemia, can worsen performance even in Health subjects, at risk for diabetes mellitus.