Impaired Insulin Sensitivity and Secretion in Patients with Alzheimer's Disease: The Relationship with Other Atherosclerosis Risk Factors

Abstract

Background: The growing body of evidence suggests that atherosclerosis risk factors are important in cognitive decline.

Objective: To analyse insulin sensitivity, insulin secretion capacity, plasma insulin, adiponectin and lipid levels in normoglycaemic, nonobese patients with Alzheimer's disease (AD) (group A, n=62), mild cognitive impairment (MCI) (group B, n=41), and healthy controls (group C, n=25).

Method: Insulin sensitivity was determined by euglycemic hyperinsulinaemic clamp (M value) and homeostasis model assessment (HOMA-IR), insulin secretion capacity by first-phase insulin response (FPIR), plasma insulin by RIA, adiponectin by ELISA, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides by enzymatic method.

Results: Insulin sensitivity was the lowest in group A (M value: A: 6.2±2.5; B:7.7±2.7; C:8.2±1.5 mg/min/kg, p<0.001; HOMA-IR: A: 4.6±2.2; B: 3.3±1.7; C: 1.5±1.0, p<0.001) as well as FPIR (A:68.9±27.8; B:112.5±47.1; C:147.4±56.0 mU/l, p<0.001). Plasma insulin was higher in group A vs B vs C, while adiponectin was lower in group A vs B vs C. Simultaneously, total and LDL-C were higher and HDL-C levels were lower in groups A and B vs C, with no difference between groups A and B. Triglycerides did not differ between the groups. Binary logistic regression analysis identified only M value, FPIR and plasma insulin as independent predictors of AD and MCI.

Conclusion: These results imply that in AD and MCI insulin resistance with increased plasma insulin and decreased FPIR may be associated with the development of AD and MCI, accompanied with milder influence of low adiponectin levels and atherogenic lipid profile.

Keywords: Alzheimer’s disease; cardiovascular risk factors; insulin resistance; mild cognitive impairment.