Serum level of endogenous secretory receptor for advanced glycation end products and other factors in type 2 diabetic patients with mild cognitive impairment

OBJECTIVE

Determine the serum levels of endogenous secretory receptor for advanced glycation end products (esRAGEs) in patients with type 2 diabetes and mild cognitive impairment (MCI) and in control patients with type 2 diabetes but no MCI, and examine the relationship of esRAGE and MCI with other clinical factors.

RESEARCH DESIGN AND METHODS

A total of 101 patients with type 2 diabetes who were hospitalized in the Department of Endocrinology at Fujian Provincial Hospital between January 2010 and January 2011 were enrolled. There were 58 patients with MCI and 43 patients without MCI (control). Serum levels of esRAGE were measured using an enzyme-linked immunosorbent assay (ELISA). Other clinical parameters were also measured.

RESULTS

Type 2 diabetic patients with MCI had a longer duration of diabetes; elevated HbA_1c, total cholesterol (CHOL), LDL cholesterol (LDL-C), triglyceride (TG), intima-media thickness, C-reactive protein (CRP), and brachial-ankle pulse wave velocity (ba-PWV); and lower ankle brachial index (ABI) and esRAGE relative to the control group. Among patients with MCI, the Montreal Cognitive Assessment (MoCA) score was positively correlated with serum esRAGE but negatively correlated with CHOL. Spearman rank correlation analysis indicated that esRAGE was positively correlated with MoCA score and ABI but negatively correlated with ba-PWV, CHOL, TG, and CRP in all subjects.

CONCLUSIONS

Our results suggest that esRAGE may be a potential protective factor for dyslipidemia, atherosclerosis, and MCI in patients with type 2 diabetes.The condition of mild cognitive impairment (MCI) was first described in 1999 as a common disorder of aging adults that increases the risk for dementia and Alzheimer disease (AD) (1). Patients with MCI progress into dementia at an annual rate of 15.0% (1). There are approved treatments for AD, but not for MCI, although numerous clinical trials are investigating treatments for both conditions (2). The high worldwide prevalence of MCI, AD, and dementia points to the need to understand the pathogenesis of these disorders.The elevated serum glucose of patients with diabetes leads to nonenzymatic glycosylation of lipids and proteins and formation of advanced glycation end products (AGEs) (3). The accumulation of AGEs and their binding to receptors for AGE (RAGEs) on the plasma membrane triggers a series of reactions implicated in the development of disorders, such as diabetes complications and AD (4). In recent years, the endogenous soluble receptor for AGE (esRAGE) has been identified as a tissue-specific, soluble, alternative splicing isoform of RAGE that is primarily present in circulation (5). The cell-protecting function of esRAGE is attributed to its ability to capture extracellular AGEs (6).In the current study, we measured serum esRAGE levels in adult patients with type 2 diabetes and MCI and in a control group with type 2 diabetes but no MCI, and examined the association of esRAGE with clinical factors.