Plasma Nesfatin-1: Potential Predictor and Diagnostic Biomarker for Cognitive Dysfunction in T2DM Patient

Dandan Xu,1– 3,&ast; Yue Yu,1,4,&ast; Yayun Xu,5,&ast; Jinfang Ge1– 3 1School of Pharmacy, Anhui Medical University, Hefei, People’s Republic of China; 2Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Hefei, People’s Republic of China; 3The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, People’s Republic of China; 4Department of Pharmacy, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 5Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinfang GeSchool of Pharmacy, Anhui Medical University, 81 Mei-Shan Road, Hefei, Anhui, 230032, People’s Republic of ChinaTel +86 551 65172131Fax +86 551 65161115Email gejinfang@ahmu.edu.cnPurpose: Nesfatin-1 plays a crucial role in glucose metabolism and cognitive function. This study aimed to investigate the correlation between plasma nesfatin-1 levels and clinical indicators and cognitive function in patients with type 2 diabetes mellitus (T2DM).Methods: Demographic and medical history data, physical examination, and biochemical test results of 132 T2DM patients were collected. The plasma concentrations of nesfatin-1, C-reactive protein (CRP), interleukin-6 (IL-6), soluble triggering receptors expressed on myeloid cells 1 (sTREM1), and sTREM2 in T2DM patients were measured. Cognitive function was evaluated using the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A). The patients were divided into two groups: a low-nesfatin-1 group (n = 75) and a high-nesfatin-1 group (n = 57) based on a plasma nesfatin-1 concentration less than or above the 50th percentile value of all the samples.Results: The results showed that plasma HbA1c levels were positively correlated with CRP, IL-6, sTREM1, and sTREM2 levels in patients with T2DM (P < 0.05). Plasma nesfatin-1 concentrations were positively associated with diabetes-related biochemical indicators including glycated haemoglobin (HbA1c), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), and inflammation-related indicators including CRP, IL-6, sTREM1, and sTREM2 among patients with T2DM (P < 0.05). Moreover, T2DM patients with high nesfatin-1 levels showed higher HbA1c and fasting plasma glucose (FPG) levels (P < 0.05). Furthermore, T2DM patients with high nesfatin-1 levels also showed higher BRIEF-A scores (P = 0.01). Additionally, T2DM patients with high total scores of BRIEF-A (scores > 50th percentile) could be identified with a sensitivity of 59.1% and a specificity of 72.7% by nesfatin-1.Conclusion: These findings indicate that plasma nesfatin-1 might be involved in the T2DM-associated comorbidities and the development of cognitive dysfunction, and the mechanism underlying this involvement is related to the imbalance in the expression of CRP, IL-6, sTREM1, and sTREM2 levels.Keywords: type 2 diabetes mellitus, cognitive dysfunction, nesfatin-1, inflammatoryresponse, sTREM1/2