The Association of Decreased Serum Gdnf Level with Hyperglycemia and Depression in Type 2 Diabetes Mellitus |
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| Institution: | 1. From Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of medicine, Southeast University, Nanjing, China;2. Department of Psychosomatics and Psychiatry, Zhongda Hospital, Institute of Psychosomatics, School of medicine, Southeast University, Nanjing, China.;1. From the Faculty of Medicine, Hadassah Hebrew University Hospital, Mount Scopus, Jerusalem, Israel.;2. Department of Radiology, Hadassah Hebrew University Hospital, Mount Scopus, Jerusalem, Israel.;3. Department of Internal Medicine, Osteoporosis Center, Hadassah Hebrew University Hospital, Mount Scopus, Jerusalem, Israel.;4. Department of Hematology, Hadassah Hebrew University Hospital, Mount Scopus, Jerusalem, Israel.;1. From the Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois;2. Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center/Bellevue Hospital Center, New York, New York;3. Department of Public Health Sciences, Loyola University, Maywood, Illinois.;1. Division of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan, China;2. Division of Nephrology, Mianyang Central Hospital, Mianyang, China;3. Division of Pathology, West China Hospital of Sichuan University, Chengdu, Sichuan, China. |
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| Abstract: | 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 EuroQol-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.Abbreviations: BP = blood pressure; CHO = cholesterol; DDS = diabetes distress scale; DM = diabetes mellitus; EQ-5D = the health-related dimensions of the EuroQol-5 scale; FPG = fasting plasma glucose; GDNF = glial-derived neurotrophic factor; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; NGT = normal glucose tolerance; PHQ-9 = Patient Health Questionnaire; p-DM = prediabetes; PPG = postprandial plasma glucose; SNP = single-nucleotide polymorphism; T2DM = type 2 diabetes mellitus; TG = triglyceride |
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