Association of Vitamin D Level and Nerve Conduction Study Parameters with Cognitive Function in Diabetic Neuropathy Patients

Aida Fithrie; Fasihah Irfani Fitri; Muhammad Reza Putra

doi:10.3889/oamjms.2021.5938

Authors

Aida Fithrie Department of Neurology, Division of Clinical Neurophysiology, Faculty of Medicine, Universitas Sumatera Utara, Adam Malik General Hospital, Medan, Indonesia https://orcid.org/0000-0001-7936-9553
Fasihah Irfani Fitri Department of Neurology, Division of Behavioural and Geriatric Neurology, Faculty of Medicine, Universitas Sumatera Utara, Adam Malik General Hospital, Medan, Indonesia https://orcid.org/0000-0002-0883-3029
Muhammad Reza Putra Resident of Neurology, Faculty of Medicine, Universitas Sumatera Utara, Adam Malik General Hospital, Medan, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.5938

Keywords:

cognitive function, nerve conduction studies, diabetic neuropathy, vitamin D level

Abstract

BACKGROUND: Type 2 diabetes mellitus (T2DM) and its major long-term complication, diabetic polyneuropathy (DPN), continue to be a major global health problem and are important contributors of significant disability worldwide. Vitamin D plays a significant role in their pathogenesis as well as in the development of dementia in non-diabetic patients. Nevertheless, the role of Vitamin D in the development of cognitive impairment in DPN patients has not yet been extensively studied.

AIM: We aimed to investigate the association between Vitamin D level and cognitive function in DPN patients and to evaluate several potential contributor factors to cognition, including demographic factors, glycemic control, and nerve conduction study (NCS) parameters.

METHODS: Thirty-one DPN patients were included in this cross-sectional study. Patients were recruited from the outpatient endocrinology and neurology clinic of Haji Adam Malik General Hospital Medan Indonesia. We used the diabetic neuropathy examination (DNE) scale, diabetic neuropathy symptom (DNS) scale, and NCS to determine the presence and severity of the neuropathy. We measured the levels of Vitamin D, random blood sugar, and glycated hemoglobin (HbA1c). Cognitive function was assessed using the Indonesian version of Montreal Cognitive Assessment (MoCA-INA), trail making test A and B (TMT A and TMT B), and verbal fluency test.

RESULTS: Most of the patients were female (80.6%), with a mean age of 55.71 ± 8.34 years. The proportion of patients with abnormal cognitive function was higher than cognitively unimpaired patients. The mean of MoCA-INA score and level of Vitamin D was lower than normal, 23.32 ± 3.00 and 24.91 ± 13.59 ng/ml, respectively. Using the Pearson correlation test, we did not find any significant association of Vitamin D level, NCS parameters, and other clinical characteristics with global cognitive function. Age and level of education were significantly associated with MoCA-INA score. Blood sugar level was significantly higher in patients with normal TMT-A and TMT-B tests compared to patients with abnormal results.

CONCLUSION: Vitamin D and NCS parameters are not associated with cognitive function. Of the demographic and clinical characteristics, a significant association exists between age, level of education, and blood sugar level and cognition. This might suggest the complexity underlying cognitive impairment in T2DM patients.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of Type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88-98. https://doi.org/10.1038/nrendo.2017.151 PMid:29219149 DOI: https://doi.org/10.1038/nrendo.2017.151

GBD 2013 Mortality and Causes of Death Collaborators. Global, Regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: A systematic analysis for the global burden of disease study 2013. Lancet. 2015;385(9963):117- 71. https://doi.org/10.1016/s0140-6736(14)61682-2 PMid:25530442 DOI: https://doi.org/10.1016/S0140-6736(14)61682-2

Thakur S, Rachana SS. Diabetic neuropathy: Its pathogenesis and therapeutic drug targets. J Cell Sci Mol Biol. 2014;1(1):102.

Kakrani AL, Gokhale VS, Vohra KV, Chaudhary N. Clinical and nerve conduction study correlation in patients of diabetic neuropathy. J Assoc Physicians India. 2014;62(1):24-7. PMid:25327088

Lee JH, Choi Y, Jun C, Hong YS, Cho HB, Kim JE, et al. Neurocognitive changes and their neural correlates in patients with Type 2 diabetes mellitus. Endocrinol Metab. 2014;29(2):112-21. https://doi.org/10.3803/enm.2014.29.2.112 PMid:25031883 DOI: https://doi.org/10.3803/EnM.2014.29.2.112

Kawamura T, Umemura T, and Hotta N. Cognitive impairment in diabetic patients: Can diabetic control prevent cognitive decline? J Diabetes Investig. 2012;3(5):413-23. https://doi.org/10.1111/j.2040-1124.2012.00234.xPMid:24843599 DOI: https://doi.org/10.1111/j.2040-1124.2012.00234.x

Asegaonkar SB. Vitamin D and Type 2 diabetes mellitus: Indian perspectives. J Diabetic Complications Med. 2016;1(3):110. https://doi.org/10.4172/2475-3211.1000110 DOI: https://doi.org/10.4172/2475-3211.1000110

Christie-David DJ, Girgis CM, Guntin JE. Effects of Vitamins C and D in Type 2 diabetes mellitus. Nutr Dietary Suppl 2015;7:21-8. 9. Palomer X, Gonzalez-Clemente M, Blanco-Vaca F, Mauricio D. Role of Vitamin D in the pathogenesis of Type 2 diabetes mellitus. Diabetes Obes Metab 2008;10(3):185- 97. https://doi.org/10.1111/j.1463-1326.2007.00710.x PMid:18269634 DOI: https://doi.org/10.1111/j.1463-1326.2007.00710.x

Bailo B, Sohemy A, Haddad P, Arora P, Benzaied F, Karmali M, et al. Vitamins D, C, and E in the prevention of Type 2 diabetes mellitus: Modulation of inflammation and oxidative stress. Biol Targets Ther. 2011;5:7-19. PMid:21383912 DOI: https://doi.org/10.2147/BTT.S14417

Salum E, Kals J, Kampus P, Salum T, Zilmer K, Aunapuu M, et al. Vitamin D reduces deposition of advanced glycation end-products in the aortic wall and systemic oxidative stress in diabetic rats. Diabetes Res Clin Pract. 2013;100(2):243- 9. https://doi.org/10.1016/j.diabres.2013.03.008 PMid:23522919 DOI: https://doi.org/10.1016/j.diabres.2013.03.008

Sebekova K, Sturmer M, Fazeli G, Bahner U, Stab F, Heidland A. Is Vitamin D deficiency related to accumulation of advanced glycation end products, markers of inflammation, and oxidative stress in diabetic subjects? Biomed Res Int. 2015;2015:958097. https://doi.org/10.1155/2015/958097 DOI: https://doi.org/10.1155/2015/958097

Saif-Elnasr M, Ibrahim IM, Alkady MM. Role of Vitamin D on glycemic control and oxidative stress in Type 2 diabetes mellitus. J Res Med Sci. 2017;22:22. https://doi.org/10.4103/1735-1995.200278 PMid:28413419 DOI: https://doi.org/10.4103/1735-1995.200278

Song Y, Wang L, Pittas AG, Del Gobbo LC, Zhang C, Manson JE, et al. Blood 25-hydroxy Vitamin D levels and incident Type 2 diabetes: A meta-analysis of prospective studies. Diabetes Care. 2013;36(5):1422-8. https://doi.org/10.2337/dc12-0962 PMid:23613602 DOI: https://doi.org/10.2337/dc12-0962

Mezza T, Muscogiuri G, Sorice GP, Prioletta S, Salomone E, Pontecorvi A, et al. Vitamin D deficiency: A new risk factor for Type 2 diabetes. Ann Nutr Metab. 2012;61:337-48. https://doi.org/10.1159/000342771 DOI: https://doi.org/10.1159/000342771

Pilz S, Kienreich K, Rutters F, de Jongh R, van Ballegooijen AJ, Grubler M, et al. Role of Vitamin D in the development of insulin resistance and Type 2 diabetes. Curr Diab Rep. 2013;13(2):261-70. https://doi.org/10.1007/s11892-012-0358-4 PMid:23264189 DOI: https://doi.org/10.1007/s11892-012-0358-4

Talaei A, Mohamad M, Adgi Z. The effect of Vitamin D on insulin resistance in patients with Type 2 diabetes. Diabetol Metab Syndr. 2013;5:8. https://doi.org/10.1186/1758-5996-5-8 DOI: https://doi.org/10.1186/1758-5996-5-8

Alam U, Arul-Devah V, Javed S, Malik RA. Vitamin D and diabetic complications: True or false prophet? Diabetes Ther. 2016;7(1):11-26. https://doi.org/10.1007/s13300-016-0159-x PMid:26971351 DOI: https://doi.org/10.1007/s13300-016-0159-x

Soderstrom LH, Johnson SP, Diaz VA, Mainous AG. Association between Vitamin D and diabetic neuropathy in a nationally representative sample: Results from 2001-2004 NHANES. Diabet Med. 2012;29(1):50- 5. https://doi.org/10.1111/j.1464-5491.2011.03379.x PMid:21726279 DOI: https://doi.org/10.1111/j.1464-5491.2011.03379.x

Qu GB, Wang LL, Tang X, Wu W, Sun YH. The association between Vitamin D level and diabetic peripheral neuropathy in patients with Type 2 diabetes mellitus: An update systematic review and meta-analysis. J Clin Transl Endocrinol. 2017;9:25-31. https://doi.org/10.1016/j.jcte.2017.04.001 PMid:29067266 DOI: https://doi.org/10.1016/j.jcte.2017.04.001

Nadi M, Marandi M, Esfarjani F, Saleki M, Mohammadi M. The comparison between effects of 12 weeks combined training and Vitamin D supplement on improvement of sensory-motor neuropathy in Type 2 diabetic women. Adv Biomed Res. 2017;6:55. PMid:28553628

Papandreou D, Hamid Z. The role of Vitamin D in diabetes and cardiovascular disease: An updated review of the literature. Dis Markers. 2015;2015:580474. https://doi.org/10.1155/2015/580474 PMid:26576069 DOI: https://doi.org/10.1155/2015/580474

Shehab D, Al-Jarallah K, Abdella N, Mojiminiyi OA, Al Mohamedy H. Prospective evaluation of the effect of short-term oral Vitamin D supplementation on peripheral neuropathy in Type 2 diabetes mellitus. Med Princ Pract. 2015;24(3):250-6. https://doi.org/10.1159/000375304 PMid:25720672 DOI: https://doi.org/10.1159/000375304

Schlogl M, Holick MF. Vitamin D and neurocognitive function. Clin Interv Aging. 2014;9:559-68. PMid:24729696 DOI: https://doi.org/10.2147/CIA.S51785

McCann JC, Ames BN. Is there convincing biological or behavioral evidence linking Vitamin D deficiency to brain dysfunction? FASEB J. 2008;22(4):982-1001. https://doi.org/10.1096/fj.07-9326rev PMid:18056830 DOI: https://doi.org/10.1096/fj.07-9326rev

Balion C, Griffith L, Strifler L, Henderson M, Pattersin C, Heckman G, et al. Vitamin D, cognition, and dementia: A systematic review and meta-analysis. Neurology. 2012;79(13):1397- 405. https://doi.org/10.1212/wnl.0b013e31826c197f PMid:23008220 DOI: https://doi.org/10.1212/WNL.0b013e31826c197f

Littlejohns TJ, Henley WE, Lang IA, Annweiler C, Beauchet O, Chaves PH, et al. Vitamin D and the risk of dementia and alzheimer disease. Neurology. 2014;83(10):920- 8. https://doi.org/10.1212/wnl.0000000000000755 PMid:25098535 DOI: https://doi.org/10.1212/WNL.0000000000000755

Sommer I, Griebler U, Kien C, Auer S, Klerings I, Hammer R, et al. Vitamin D deficiency as a risk factor for dementia: A systematic review and meta-analysis. BMC Geriatr. 2017;17:16. https://doi.org/10.1186/s12877-016-0405-0 PMid:28086755 DOI: https://doi.org/10.1186/s12877-016-0405-0

Balbaloglu O, Tanik N. The effect of Vitamin D on cognitive functions in young female patients: A prospective controlled study using the Montreal cognitive assessment. Arq Neuropsiquiatr. 2019;77(1):19-24. https://doi.org/10.1590/0004-282x20180159 PMid:30758438 DOI: https://doi.org/10.1590/0004-282x20180159

Lee DH, Chon J, Kim Y, Seo YK, Park EJ, Won CW, et al. Association between Vitamin D deficiency and cognitive function in the elderly Korean population: A Korean frailty and aging cohort study. Medicine. 2020;99(8):e19293. h t t p s : / / d o i . o r g / 1 0 . 1 0 9 7 / m d . 0 0 0 0 0 0 0 0 0 0 0 1 9 2 9 3 PMid:32080146

Byrn MA, Adams W, Penckofer S, Emanuele MA. Vitamin D supplementation and cognition in people with Type 2 diabetes: A randomized control trial. J Diabetes Res. 2019;2019:5696391. https://doi.org/10.1155/2019/5696391 DOI: https://doi.org/10.1155/2019/5696391

Jayaprakash P, Bhansali A, Bhansali S, Dutta P, Anantharaman R, Shanmugasundar G, et al. Validation of bedside methods in evaluation of diabetic peripheral neuropathy. Indian J Med Res. 2011;133(6):645-9. PMid:21727664

Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal cognitive assessment, MoCA: A brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695- 9. https://doi.org/10.1111/j.1532-5415.2005.53221.x PMid:15817019 DOI: https://doi.org/10.1111/j.1532-5415.2005.53221.x

Husein N, Silvia L, Yetty R. Validity and reliability test Indonesian version of Montreal cognitive assessment (MoCA-INA) for cognitive impairment screening. Neurona. 2010;27(4):15-22. https://doi.org/10.26891/jik.v11i1.2017.12-18. DOI: https://doi.org/10.26891/JIK.v11i1.2017.12-18

Lezak MD, Howieson DB, Bigler ED, Tranel D. Neuropsychological Assessment. 5th ed. Oxford: Oxford University Press; 2012.

Gaudino EA, Geisler MW, Squires NK. Construct validity in the trail making test: What makes part b harder? J Clin Exp Neuropsychol. 1995;17(4):529- 35. https://doi.org/10.1080/01688639508405143 PMid:7593473 DOI: https://doi.org/10.1080/01688639508405143

Strub RL, Black FW. The Mental Status Examination in Neurology. Philadelphia, PA: FA Davis Co.; 2000.

Soelistijo, S, Novida, H, Rudijanto, A, Soewondo, P, Suastika, K, Manaf, A, et al. Consensus of Management and Prevention of Type 2 Diabetes Mellitus in Indonesia. 1st ed. Jakarta, Indonesia: PB PERKENI; 2015. p. 11-2.

Papanas N, Ziegler D. Risk factors and comorbidities in diabetic neuropathy: An update 2015. Rev Diabet Stud. 2015;12(1-2):48-62. https://doi.org/10.1900/rds.2015.12.48 PMid:26676661 DOI: https://doi.org/10.1900/RDS.2015.12.48

Rawlings AM, Sharrett AR, Schneider AL, Coresh J, Albert M, Couper D, et al. Diabetes in midlife and cognitive change over 20 years: A cohort study. Ann Intern Med. 2014;161(11):785-93. https://doi.org/10.7326/m14-0737 PMid:25437406 DOI: https://doi.org/10.7326/M14-0737

Moreira RO, Soldera AL, Cury B, Meireles C, Kupfer R. Is cognitive impairment associated with the presence and severity of peripheral neuropathy in patients with Type 2 diabetes mellitus? Diabetol Metab Syndr. 2015;7:51. https://doi.org/10.1186/s13098-015-0045-0 PMid:26075029 DOI: https://doi.org/10.1186/s13098-015-0045-0

Zilliox LA, Chadrasekaran K, Kwan JY, Russell JW. Diabetes and cognitive impairment. Curr Diab Rep. 2016;16(9):87. https://doi.org/10.1007/s11892-016-0775-x PMid:27491830 DOI: https://doi.org/10.1007/s11892-016-0775-x

Kanaya AM, Barrett-Connor E, Gildengorin G, Yaffe K. Change in cognitive function by glucose tolerance status in older adults: A 4-year prospective study of the rancho Bernardo study cohort. Arch Intern Med. 2004;164(12):1327- 33. https://doi.org/10.1001/archinte.164.12.1327 PMid:15226167 DOI: https://doi.org/10.1001/archinte.164.12.1327

Gregg EW, Yaffe K, Cauley JA, Rolka DB, Blackwell TL, Narayan KM, et al. Is diabetes associated with cognitive impairment and cognitive decline among older women? Study of osteoporotic fractures research group. Arch Intern Med. 2000;160(2):174-80. https://doi.org/10.1001/archinte.160.2.174 PMid:10647755 DOI: https://doi.org/10.1001/archinte.160.2.174

Van den Berg E, Reijmer YD, de Bresser J, Kessels RP, Kappelle LJ, Biessels GJ. A 4 year follow-up study of cognitive functioning in patients with Type 2 diabetes mellitus. Diabetologia. 2010;53(1):58-65. https://doi.org/10.1007/s00125-009-1571-9 PMid:19882137 DOI: https://doi.org/10.1007/s00125-009-1571-9