THE ASSOCIATION OF DECREASED SERUM GDNF LEVEL WITH HYPERGLYCEMIA AND DEPRESSION IN TYPE 2 DIABETES MELLITUS

Objective: Comorbidity of diabetes and depression is a critical problem. Decreased glial-derived neurotrophic factor (GDNF) has been demonstrated in depression, but no evidence of a relationship between GDNF and diabetes has been shown. The present studies were designed to investigate the relationship between GDNF and metabolism. Methods: In Study 1, we performed a case-control study in which subjects with type 2 diabetes mellitus (T2DM), prediabetes (p-DM), and normal glucose tolerance (NGT) were included. In Study 2, we performed a cross-sectional study in 296 patients having pre-existing diabetes in whom the levels of serum GDNF, blood glucose, blood lipids, blood pressure, body mass index, scores from the Patient Health Questionnaire (PHQ-9), the EuroQo1-5 scale, and the diabetes distress scale were measured, as well as single-nucleotide polymorphisms of GDNF including rs884344, rs3812047, and rs2075680. Results: In Study 1, serum GDNF concentration was significantly lower in the T2DM group than in the NGT group (NGT: 11.706 +/- 3.918 pg/mL; p-DM: 10.736 +/- 3.722 pg/mL; type 2 diabetes mellitus [T2DM group]: 9.884 +/- 2.804 pg/mL, P = .008). In Study 2, significantly decreased serum GDNF levels were observed in subjects with poor glycemic control or depression (glycated hemoglobin [HbA1c] <7.0% without depression: 11.524 +/- 2.903 pg/mL; HbA1c >= 7.0% without depression: 10.625 +/- 2.577 pg/mL; HbA1c <7.0% with depression: 10.355 +/- 2.432 pg/mL; HbA1c >= 7.0% with depression: 8.824 +/- 2.102 pg/mL, P = .008). Double-factor variance analysis showed that glycemic control and depression were independent factors for the GDNF level. Moreover, the serum GDNF level was significantly inversely associated with the fasting plasma glucose, 2 hours postprandial plasma glucose, HbA1c, and PHQ-9 score. Conclusion: Glycemic dysregulation was an independent factor for the GDNF level. These findings suggest that GDNF level might be involved in the pathophysiology of T2DM and depression through various pathways.