Brain-derived neurotrophic factor in diabetes mellitus: A systematic review and meta-analysis.

Fatemeh Moosaie, Soheil Mohammadi, Amene Saghazadeh, Fatemeh Dehghani Firouzabadi, Nima Rezaei

Journal: PloS one 2023;18(2):e0268816

PMID: 36787304

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Plain Language Summary

Brain-derived neurotrophic factor (BDNF) is a key molecule mainly involved in brain cell growth. It is also responsible for the survival of beta cells of the pancreas, which produce a hormone known as insulin, which is responsible for balancing blood sugar. Poor functioning beta cells can result in the development of diabetes. It is unclear as to whether high or low BDNF is present in individuals with diabetes. This meta-analysis and systematic review of 2734 individuals aimed to determine BDNF levels in individuals with diabetes, depression, and diabetic retinopathy. The results showed that serum BDNF levels were low in individuals with diabetes, however plasma levels remained unchanged. BDNF was lower in individuals with type 2 diabetes, diabetes mellitus, depression, and diabetic retinopathy. It was concluded that decreased BDNF may contribute to the development of diabetes and associated complications. This study could be used by healthcare professionals to understand the close links between diabetes and brain disorders such as dementia and Alzheimer’s disease.

Abstract

BACKGROUND

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor expressed in several tissues, including the brain, gut, and pancreas. Activation of the BDNF/TrkB/CREB reduces hepatic gluconeogenesis, induces hepatic insulin signal transduction, and protects against pancreatic beta-cell loss in diabetes mellitus (DM). Several studies have investigated the possible association between BDNF and DM and its complications, but the results have been conflicting.

AIM

In the present study, we aimed at systematically reviewing the literature on the serum and plasma levels of BDNF in DM and its subgroups such as T2DM, DM patients with depression, and patients with retinopathy.

METHODS

A comprehensive search was conducted in PubMed, Scopus, and Web of Science. We identified 28 eligible studies and calculated the standardized mean difference (SMD) of outcomes as an effect measure.

RESULTS

The meta-analysis included 2734 patients with DM and 6004 controls. Serum BDNF levels were significantly lower in patients with DM vs. controls (SMD = -1.00, P<0.001). Plasma BDNF levels were not different in patients with DM compared with controls. When conducting subgroup analysis, serum BDNF levels were lower among patients with T2DM (SMD = -1.26, P<0.001), DM and depression (SMD = -1.69, P<0.001), and patients with diabetic retinopathy (DR) vs. controls (SMD = -1.03, P = 0.01).

CONCLUSIONS

Serum BDNF levels were lower in patients with DM, T2DM, DM with depression, and DM and DR than the controls. Our findings are in line with the hypothesis that decreased BDNF levels might impair glucose metabolism and contribute to the pathogenesis of DM and its complications.

Copyright: © 2023 Moosaie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Address: School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.; Systematic Review and Meta-Analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.; NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences, Tehran, Iran.; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.; NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences, Tehran, Iran.; Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.; MetaCognition Interest Group (MCIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.; Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran.; Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.; MetaCognition Interest Group (MCIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

DOI: 10.1371/journal.pone.0268816