Sains Malaysiana 51(1)(2022): 209-215

http://doi.org/10.17576/jsm-2022-5101-17

Effect of Vitamin D on Aldose Reductase in Indonesian Diabetic Polyneuropathy Patients: A Randomized Clinical Trial

(Kesan Vitamin D kepada Aldosa Reduktase dalam Kalangan Pesakit Polineuropati Diabetes Indonesia: Suatu Ujian Klinikal Rambang)

AIDA FITRI¹*, HASAN SJAHRIR¹, ADANG BACHTIAR² & MUHAMMAD ICHWAN³

¹Department of Neurology, Faculty of Medicine, Universitas Sumatera Utara, No. 5 Dr. Mansyur Road Medan, 20155 North Sumatera, Indonesia

²Faculty of Public Health, University of Indonesia, Lingkar Kampus Raya, Universitas Indonesia, Road Depok 16424, Indonesia

³Department of Pharmacology and Therapeutic, Faculty of Medicine, Universitas Sumatera Utara, No. 5 Dr. Mansyur Road Medan, 20155 North Sumatera, Indonesia

Diserahkan: 17 September 2019/Diterima: 19 April 2021

ABSTRACT

Aldose Reductase (AR) is an important factor in the pathogenesis of several Diabetes Mellitus (DM) complications, including diabetic neuropathy (DN). Vitamin D has a direct effect on the pathogenesis of DN. Aldose reductase inhibition is an important element in the prevention of DM complications. The objective of this paper was to assess the effect of vitamin D on AR in Indonesian diabetic polyneuropathy (DPN) patients. This cohort study was undertaken at Haji Adam Malik General Hospital Medan, North Sumatera, Indonesia. In a double-blind, placebo-controlled, clinical trial, eligible patients were randomized to receive vitamin D 50,000 IU/week or placebo for 10 weeks. The primary end-point was mean changes of nerve conduction velocity (NCV) from baseline and after 10 weeks of supplementation. There was no significant correlation between mean changes of vitamin D and AR levels. There was significant correlation with negative direction and weak strength between mean changes of AR level and NCV of motor Tibial nerve (p<0.05; r=-0.337). There was significant correlation with positive direction and moderate strength between mean changes of vitamin D level and NCV of motor Median and Peroneal nerves, and motor and sensory Ulnar nerves (p<0.001; r=0.438 – 0.527). In conclusion, vitamin D supplementation had no effect on AR level in Indonesian DPN patients. Higher AR level was correlated with decreased NCV of motor Tibial nerve. Vitamin D supplementation improved NCV in DPN.

Keywords: Aldose reductase; diabetic polyneuropathy; nerve conduction velocity; vitamin D

ABSTRAK

Aldosa Reduktase (AR) merupakan faktor penting dalam patogenesis beberapa komplikasi Diabetes Mellitus (DM), termasuk neuropati diabetes (ND). Vitamin D mempunyai kesan langsung kepada patogenesis ND. Perencatan AR merupakan unsur penting dalam pencegahan komplikasi DM. Tujuan kajian ini dijalankan adalah untuk menilai kesan vitamin D pada AR dalam pesakit polineuropati diabetes (PND) Indonesia. Kajian kohort ini dilakukan di Hospital Umum Haji Adam Malik Medan, Sumatera Utara, Indonesia. Dalam percubaan klinikal gelap ganda, plasebo terkawal, pesakit yang layak menerima vitamin D 50.000 IU/minggu atau plasebo selama 10 minggu secara rambang. Titik akhir utama adalah perubahan purata laju konduksi saraf daripada garis dasar dan selepas 10 minggu penambahan. Tiada korelasi yang signifikan antara perubahan purata tahap vitamin D dengan AR. Terdapat korelasi yang signifikan dengan arah negatif dan kekuatan lemah antara perubahan purata tahap AR dengan laju konduksi saraf motor Tibial (p<0,05; r=-0,337). Terdapat korelasi yang signifikan dengan arah positif dan kekuatan sederhana antara perubahan purata tahap vitamin D dengan laju konduksi saraf motor Median dan Peroneal, dan saraf motor dan sensori Ulnar (p<0,001; r=0.438 – 0.527). Secara kesimpulannya, penambahan vitamin D tidak mempunyai kesan pada tahap AR dalam kalangan pesakit PND Indonesia. Tahap AR yang tinggi dikaitkan dengan penurunan laju konduksi saraf motor Tibial. Penambahan vitamin D menambah baik laju konduksi saraf pada PND.

Kata kunci: Aldosa reduktase; laju konduksi saraf; polineuropati diabetes; vitamin D

RUJUKAN

Agarwal, S., Lukhmana, S., Kahlon, N., Malik, P. & Nandini, H. 2018. Nerve conduction study in neurologically asymptomatic diabetic patients and correlation with glycosylated hemoglobin and duration of diabetes. National Journal of Physiology, Pharmacy and Pharmacology 8(11): 1533-1538.

Ariza, L., Pagès, G., Garcia-Lareu, B., Cobianchi, S., Otaegui, P.J., Ruberte, J., Chillón, M., Navarro, X. & Bosch, A. 2014. Experimental diabetes in neonatal mice induces early peripheral sensorimotor neuropathy. Neuroscience 274: 250-259.

Badria, F.A., Elimam, D.M., Elabshihy, M.S. & Ibrahim, A.S. 2017. Aldose reductase inhibitors from nature: A new hope for treatment of cataract. JOJ Ophthal. 5(1): 555655.

Basit, A., Basit, K.A., Fawwad, A., Shaheen, F., Fatima, N., Petropoulos, I.N., Alam, U. & Malik, R.A. 2016. Vitamin D for the treatment of painful diabetic neuropathy. BMJ Open Diabetes Research and Care 4(1): e000148.

Christie-David, D.J., Girgis, C.M. & Gunton, J.E. 2015. Effects of vitamin C and D in type 2 diabetes mellitus. Nutrition and Dietary Supplements 7: 21-28.

Demiryurek, B.E. & Gundogdu, A.A. 2017. The effect of vitamin D levels on pain in carpal tunnel syndrome. Orthopaedics & Traumatology: Surgery & Research 103(6): 919-922.

Derakhshanian, H., Djazayery, A., Javanbakht, M.H., Eshraghian, M.R., Mirshafiey, A., Zarei, M., Alvandi, E., Djalali, E. & Djalali, M. 2019. The effect of vitamin D on cellular pathways of diabetic nephropathy. Reports of  Biochemistry & Molecular Biology 7(2): 217-222.

Gupta, S., Maratha, A., Siednienko, J., Natarajan, A., Gajanayake, T., Hoashi, S. & Miggin, S. 2017. Analysis of inflammatory cytokine and TLR expression levels in type 2 diabetes with complications. Scientific Reports 7: 7633.

Hao, W., Tashiro, S., Hasegawa, T., Sato, Y., Kobayashi, T., Tando, T., Katsuyama, E., Fujie, A., Watanabe, R., Morita, M. & Miyamoto, K. 2015. Hyperglycaemia promotes Schwann cell de-differentiation and de-myelination via sorbitol accumulation and Igf1 downregulation. The Journal of Biological Chemistry 290(28): 17106-17115.

Kakrani, A.L., Gokhale, V.S., Vohra, K.V. & Chaudhary, N. 2014. Clinical and nerve conduction study correlation in patients of diabetic neuropathy. The Journal of the Association of Physicians of India 62(1): 24-27.

Kawano, T. 2014. A current overview of diabetic neuropathy-mechanisms, symptoms, diagnosis, and treatment. Peripheral Neuropathy 10: 89-105.

Kumar, B.J.P., Itaggappa, M. & Thimmaraju, K.V. 2017. Association of vitamin D deficiency with oxidative stress in newly diagnosed type 2 diabetes. International Journal of Research in Medical Sciences 5(12): 5221-5226.

Mitri, J. & Pittas, A.G. 2014. Vitamin D and diabetes. Endocrinology and Metabolism Clinics of North America 43(1): 205-232.

Nisar, M.U., Asad, A., Waqas, A., Ali, N., Nisar, A., Qayyum, M.A., Maryam, H., Javaid, M. & Jamil, M. 2015. Association of diabetic neuropathy with duration of type 2 diabetes and glycemic control. Cureus 7(8): e302.

Oyenihi, A.B., Ayeleso, A.O., Mukwevho, E. & Masola, B. 2015. Antioxidant strategies in the management of diabetic neuropathy. BioMed Research International 2015: 515042.

Pop-Busui, R., Boulton, A.J., Feldman, E.L., Bril, V., Freeman, R., Malik, R.A., Sosenko, J.M. & Ziegler, D. 2017. Diabetic neuropathy: A position statement by the American Diabetes Association. Diabetes Care 40(1): 136-154.

Ramana, K.V. 2011. Aldose reductase: New insights for an old enzyme. Biomolecular Concepts 2(1-2): 103-114.

Santos, G.C., Zeidler, J.D., Pérez-Valencia, J.A., Sant’Anna-Silva, A.C.B., Da Poian, A.T., El-Bacha, T. & Almeida, F.C.L. 2017. Metabolomic analysis reveals vitamin D-induced decrease in polyol pathway and subtle modulation of glycolisis in HEK293T cells. Scientific Reports 7(1): 9510.

Shekharappa, K.R., Srinivas, A.K., Vedavathi, K.J. & Venkatesh, G.A. 2011. A study on the utility of nerve conduction studies in type 2 diabetes mellitus. Journal of Clinical and Diagnostic Research 5(3): 529-531.

Tang, W.H., Martin, K.A. & Hwa, J. 2012. Aldose reductase, oxidative stress, and diabetic mellitus. Frontiers in Pharmacology 3: 87.

Toth, B.E., Takacs, I., Szekeres, L., Szabo, B., Bakos, B. & Lakatos, P. 2017. Safety and efficacy of weekly 30,000 iu vitamin D supplementation as a slower loading dose administration compared to a daily maintenance schedule in deficient patients: A randomized, controlled clinical trial. Journal of Pharmacovigilance 5: 4.

Yagihashi, S., Yamagishi, S.I., Wada Ri, R., Baba, M., Hohman, T.C., Yabe-Nishimura, C. & Kokai, Y. 2001. Neuropathy in diabetic mice overexpressing human aldose reductase and effects of aldose reductase inhibitor. Brain 124(Pt 12): 2448-2458.

Yan, M.K.W. & Khalil, H. 2017. Vitamin supplements in type 2 diabetes mellitus management: A review. Diabetes & Metabolic Syndrome 11(Suppl 2): S589-S595.

Zhu, C. 2013. Aldose reductase inhibitors as potential therapeutic drugs of diabetic complications. In Diabetes Mellitus-Insights and Perspectives, edited by Oguntibeju, O.O. Rijeka, Croatia: IntechOpen. pp. 17-46.

*Pengarang untuk surat-menyurat; email: aida.fithrie@gmail.com