Abstract

Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients.Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed.Results: The serum level and activity of ACE in diabetic MCI patients (p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) (p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score (p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups (p < 0.05).Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration.

Highlights

  • Several epidemiological studies have shown that type 2 diabetes mellitus (T2DM) may exert influence on the prevalence of mild cognitive impairment (MCI) (Luchsinger et al, 2007), which is a transitional stage between normal aging and dementia

  • The MCI group and the control group were well matched in terms of age, gender distribution, educational level, smoking history, drinking history, Body mass index (BMI), hypertension prevalence, diabetes duration, insulin use, and Angiotensin Converting Enzyme Inhibitors (ACEI) or Angiotensin Receptor Blockers (ARB) use (p > 0.05)

  • No significant difference was found in TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), ApoA1, and ApoB levels between the two groups

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Summary

Introduction

Several epidemiological studies have shown that type 2 diabetes mellitus (T2DM) may exert influence on the prevalence of mild cognitive impairment (MCI) (Luchsinger et al, 2007), which is a transitional stage between normal aging and dementia. The level and activity of ACE within the cerebral cortex are generally elevated in AD patients (Arregui et al, 1982; Barnes et al, 1991; He et al, 2006; Miners et al, 2008). Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer’s disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients

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