Disertasi

Pengaruh Kolekalsiferol pada Gejala Depresi Penyandang Diabetes Melitus Tipe 2 Kajian terhadap Neurotrofin-3, Serotonin, C-peptide, dan Reseptor Vitamin D. = The Effect of Cholecalciferol on Depression in Patients with Type 2 Diabetes Mellitus: A study on Neurotrophin-3, Serotonin, CPeptide, and Vitamin D Receptor.

Kejadian depresi pada penyandang diabetes melitus (DM) tipe 2 dua kali lebih besar dibandingkan populasi umum dan depresi dapat ditemukan pada satu dari empat penyandang DM tipe 2. Depresi dan DM secara bersamaan dapat memperburuk prognosis dan meningkatkan mortalitas. Kolekalsiferol, suatu suplemen vitamin D3, berpotensi memperbaiki depresi penyandang DM tipe 2 melalui modifikasi berbagai proses patogenesis depresi seperti respons perbaikan neuroplastisitas dan neurotransmiter, namun hasilnya masih kontroversial. Penelitian ini bertujuan mengkaji peran kolekalsiferol dalam memengaruhi gejala depresi (skor Beck Depression Inventory-II) melalui respons neuroplastisitas (neurotrophin-3/NT-3), neurotransmiter (serotonin), sekresi insulin (C-peptide), dan reseptor vitamin D (VDR) pada penyandang DM tipe 2. Uji klinis acak tersamar ganda dilakukan di RSCM pada bulan Maret 2021 – September 2022. Sebanyak 77 subjek DM yang mengalami gejala depresi dirandomisasi menjadi kelompok yang mendapat kolekalsiferol 4000 IU/hari (40 subjek) serta kelompok yang mendapat plasebo/hari (37 subjek)kemudian diamati selama 12 minggu. Seluruh subjek pada tiap kelompok menjalani penelitian hingga selesai. Analisis generalized linear model digunakan untuk membandingkan skor BDI-II setiap bulan dan independent t-test untuk membandingkan skor BDI-II antara baseline dan akhir intervensi. Analisis regresi linear digunakan untuk membandingkan konsentrasi NT-3, serotonin, dan C-peptide baseline dan setelah 4 minggu. Pada akhir minggu ke-12, terdapat penurunan skor BDI-II berbeda secara bermakna antara kelompok yang menerima kolekalsiferol dan plasebo (p = 0,001). Terdapat peningkatan konsentrasi C-peptide yang berbeda bermakna pada kelompok intervensi setelah 4 minggu (p = 0,006), sedangkan NT-3, Serotonin dan reseptor vitamin D tidak berbeda bermakna. Terdapat korelasi positif skor depresi dengan serotonin, korelasi negatif serotonin dan C-peptide, dan korelasi positif serotonin dan HbA1c. Pemberian kolekalsiferol selama 12 minggu terbukti efektif dalam memperbaiki gejala depresi pada penyandang DM tipe 2 dengan defisiensi atau insufisiensi vitamin D, meningkatkan C-peptide. Terdapat korelasi positif serotonin dan skor BDI-II.
Kata kunci: C-peptide, depresi, diabetes melitus tipe 2, kolekalsiferol, neurotrofin- 3, reseptor vitamin D, serotonin.


Depression is twice as likely to occur in people with type 2 diabetes (T2DM). One in four T2DM patients may experience depression. Depression in T2DM may worsen the prognosis and increase the mortality. Cholecalciferol has been found to be able to improve depression in T2DM patients through a variety of process that modify the pathogenesis of depression, such as improving neuroplasticity and neurotransmitter. This study aimed to determine the effect of cholecaliferol on depressive symptoms (BDI-II score) through neuroplasticity (neurotrophin-3/NT- 3), neurotransmitter (serotonin), its effect on insulin secretion (C-peptide), and VDR in T2DM patients. A randomized double-blind controlled trial was conducted at the Endocrinology Policlinic at RSCM from March 2021 to September 2022. A total of 77 subjects were randomized into two groups receiving 4000 IU cholecalciferol each day (40 subjects) and groups receiving placebo each day (37 subjects). Observations were made for 12 weeks. Each subjects in both groups completed the study and were included in the analysis. Generalized linear model was used to compare BDI-II score from each month and independent t-test was used to compare changes of BDIII score from baseline to end of intervention. Linear regression was used to compare NT-3, serotonin, and C-peptide between baseline and after four weeks. There was a significant difference in changes of BDI-II score from baseline and after 12 weeks between groups (p = 0.001). Changes in C-peptide also showed a significant difference between the two groups (p = 0.006) while NT-3, serotonin, and vitamin D receptors were not significantly different. There is a positive correlation between depression scores and serotonin, a negative correlation between serotonin and Cpeptide, and a positive correlation between serotonin and HbA1c. Cholecalciferol 4000 IU supplementation daily for 12 weeks was effective in improving depression symptoms in T2DM patients with vitamin D deficiency or insufficiency. There was a positive correlation between serotonin and BDI-II scores
Keywords: cholecalciferol, c-peptide, depression, neurotrophin-3, vitamin D receptor, serotonin, type 2 diabetes mellitus.