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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 8  |  Issue : 2  |  Page : 120-124

Association of mild cognitive impairment with serum Vitamin D level in type 2 diabetes mellitus


Department of Medicine, Sardar Patel Medical College and P.B.M. Hospital and Associated Group of Hospitals, Bikaner, Rajasthan, India

Date of Web Publication17-Jan-2016

Correspondence Address:
Kulvinder Singh
Plot No. 49, Near Ram Mandir, Industrial Area, Rani Bazar, Bikaner - 334 001, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2349-5006.174240

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  Abstract 

Background: Diabetes is one of the most common diseases around the world and its prevalence is continuously increasing. It is seen that many patients of diabetes with mild cognitive impairment (MCI) have low serum level of Vitamin D. The aim of the study is to identify the correlation between serum levels of 25-hydroxyvitamin D (25(OH)D) and MCI in patients with type 2 diabetes mellitus. This cross-sectional study was conducted at P.B.M. Hospital, Bikaner, Rajasthan, India.
Method: In this study, 100 type 2 diabetic patients were enrolled in which 47 were male and 53 were female. For measuring the cognitive impairment in patients, we used montreal cognitive assessment (MoCA) test. After evaluating all the patients with MoCA test, 43 patients were found to have MCI with MoCA score <26 and 57 patients were considered as no MCI (MoCA score ΃26). Data obtained were analyzed using student t-test, Chi-square test, and Pearson's correlation coefficient.
Results: After analyzing all the patients clinically, it was found that diabetic patients with MCI had low level of serum Vitamin D (21.97 ± 7.063 ng/ml vs. 41.17 ± 11.544 ng/ml, P value 0.0001). It was also found that diabetic patients with MCI had longer duration of diabetes (156.42 ± 58.950 months vs. 40.11 ± 36.198 months, P value 0.0001), poor blood sugar control (glycated hemoglobin [HbA1C] level 9.18 ± 1.137% vs. 7.93 ± 0.462%, P value 0.0001).
Conclusion: The MoCA score was positively correlated with log 10 [25(OH) D] with correlation coefficient r = +0.512 (P = 0.001). The association of MoCA score was found negative with duration of diabetes (r = 0.103), and positive with HbA1C (r = +0.003), and P values were 0.444 and 0.984, respectively.

Keywords: 25-hydroxyvitamin D, mild cognitive impairment, serum 25-hydroxyvitamin D, serum Vitamin D, type 2 diabetes mellitus


How to cite this article:
Singh K, Singh VB, Meena BL, Beniwal S, Gaur S, Ujwal V, Kumar H. Association of mild cognitive impairment with serum Vitamin D level in type 2 diabetes mellitus. Indian J Health Sci Biomed Res 2015;8:120-4

How to cite this URL:
Singh K, Singh VB, Meena BL, Beniwal S, Gaur S, Ujwal V, Kumar H. Association of mild cognitive impairment with serum Vitamin D level in type 2 diabetes mellitus. Indian J Health Sci Biomed Res [serial online] 2015 [cited 2019 Dec 5];8:120-4. Available from: http://www.ijournalhs.org/text.asp?2015/8/2/120/174240


  Introduction Top


Diabetes is characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with long-term dysfunction and failure of different organs, especially the eyes, kidneys, nerves, heart, and blood vessels. Recent studies have shown that diabetic patients are having low level of cognitive function in the form of mild cognitive impairment (MCI) which can lead to dementia and Alzheimer's disease. Cukierman et al. [1] found that the risk of cognitive impairment and future dementia in the patients with diabetes was 1.2 and 1.6-folds, respectively.

MCI is diagnosed when there is: [2] (1) Evidence of memory impairment. (2) Preservation of general cognitive and functional abilities. (3) Absence of diagnosed dementia. The criteria for diagnosing MCI require both subjective and objective memory impairment in the presence of normal general cognitive functioning. Overall, deficits on the measures of verbal episodic memory and new learning are reported in patients with MCI, whereas other cognitive functions, including language and executive functioning, are largely intact.

It is seen that patients with type 2 diabetes mellitus (DM) have low serum 25-hydroxyvitamin D (25(OH) D) levels. [3] The hypovitaminosis D is associated with bone disease, cardiovascular diseases, [4] metabolic syndrome, [5] all-cause mortality, and cognitive impairment. [6] The high prevalence of cognitive impairment and hypovitaminosis D in diabetic patients raises the need of studies to find out if vitamin D is associated with cognitive functions in these patients. Some of the previous studies have shown that Vitamin D may play a role in cognitive impairment in middle and older aged adults [6],[7] but it is not clear yet if hypovitaminosis D causes cognitive impairment or progression of cognitive impairment in diabetic patients. In one of the previous study, it was found that hypovitaminosis D may be associated with the cognitive impairment in type 2 diabetic patients. [8] In that study, Montreal Cognitive Assessment (MoCA) score was positively correlated with log 10 [25(OH) D] and education year, and inversely correlated with duration of DM, history of hypertension, sleepless, fasting blood glucose (FBG), and intima media thickness (IMT). In the present study, we aim to find out the association of serum Vitamin D level with cognitive impairment (i.e., MCI) in type 2 diabetic patients.


  Subjects and Methods Top


The study started from May 2014 to December 2014 in Sardar Patel Medical College and A.G. of Hospitals, Bikaner. The study included 100 patients with type 2 DM attending medical outdoor and those admitted in the hospital. The exclusion criteria were as follows: (1) Patients with age more than 65 years. (2) All patients with the history of dementia. (3) All patients with the history of cerebrovascular accident or head trauma or CNS infection. (4) Patients with thyroid hormone dysfunction. (5) Patients on drugs such as benzodiazepines, opiates, tricyclic antidepressants, corticosteroids, and anticonvulsants in previous 6 months. (6) Patients with chronic diseases such as chronic liver disease and chronic kidney disease. (7) History of auditory disorders and psychological disturbances, which might interfere with the MoCA test. (8) History of alcohol or any drug abuse.

For patient selection, every 10 th patient presenting to our medical open patient department (OPD), diabetic care center OPD and geriatric care center OPD (associated departments of P.B.M. Hospital), was taken for screening. In this way, 565 patients were chosen and after screening for inclusion and exclusion criteria, 104 patients were finalized. Out of these 104 patients, 4 patients did not give consent for the study and thus dropped. In the 100 patients, 47 were male and 53 were female. The patients were diagnosed as diabetes according to American Diabetes Association 2013 criteria. All the patients were interviewed about age, gender, previous disease history, duration of diabetes, education level, or any drug or abuse history. For each patient, following data were collected: Complete blood count, liver function test, renal function test, thyroid profile, chest X-ray, glycated hemoglobin (HbA 1C ), serum 25(OH) D level, and MoCA test score. Serum Vitamin D level was measured by Epi Gold test by Tandem Mass Spectrometry (liquid chromatography [LC]) on Siemens ADVIA Centaur. T3, T4, and thyroid-stimulating hormone levels were measured by chemiluminescent immunoassay. The HbA 1C level was measured in a random blood sample preserved in EDTA and by LC method. For the diagnosis of MCI, we used MoCA test (version 7.1) which is superior to MMSE. The MoCA can detect MCI with 90-96% range of sensitivity and specificity of 87% with 95% confidence interval. [9] The patients with MoCA score <26 were diagnosed as having MCI and patients with MoCA score ≥26 as without MCI. Out of total patients, 57 patients were having MCI and 43 were diagnosed as no MCI.

Because of the skewness of the distribution, serum 25(OH) D concentrations were log transformed. Differences between two groups were examined by unpaired Student's t-test. Associations of MoCA score and 25(OH) D were analyzed using Pearson correlation analysis. Results are expressed as mean ± standard deviation. A P < 0.05 was considered to be significant.


  Result Top


Among 100 patients enrolled in the study, 56 were having serum Vitamin D level <30 ng/ml which is labeled as hypovitaminosis D. [10] Average MoCA score of the patients with hypovitaminosis D was 21.17 ± 3.738 while for patients with serum Vitamin D level above 30 ng/ml, it was 27.38 ± 2.470. P value for both the groups were < 0.05. Out of total patients, 57 were diagnosed as MCI with average Vitamin D level 21.97 ± 7.063 ng/ml and average MoCA score of 20.70 ± 2.456 [Table 1].
Table 1: Demographic and clinical characteristics of total type two diabetic patients with and without MCI

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A comparison was done between male and female diabetic patients with MCI [Table 2]. Out of total 100 patients, 19 male (40.42%) and 38 female (71.69%) patients were diagnosed as having MCI. Average serum Vitamin D level in female diabetics with MCI was 19.68 ± 6.592 ng/ml and in male diabetics with MCI, it was 26.57 ± 5.695 ng/ml. In total female diabetic patients (with and without MCI), average serum Vitamin D level was a bit lower than the total male diabetic patients (with and without MCI) (37.33 ± 13.246 ng/ml in male and 23.93 ± 9.687 ng/ml in female).
Table 2: Comparison of male and female diabetic patients with MCI

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Correlation analysis showed that MoCA score was positively correlated with log 10 [25(OH) D] (r = +0.512, P = 0.001) [Table 3] and [Figure 1]. The MoCA score was negatively correlated with duration of diabetes and RBS level while positively correlated with HbA 1C . In the previous study by Chen et al., [8] the MoCA score was found positively correlated with log 10 [25(OH) D] and education year, and inversely correlated with duration of DM, history of hypertension, sleepless, and FBG.
Figure 1: Scatter diagram showing relationship between Montreal Cognitive Assessment score and log10[25(OH) D] in total patients with mild cognitive impairment

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Table 3: Correlations of MoCA score with other parameters in total patients with MCI (n=57)

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It was also found that in profound Vitamin D deficiency, MoCA score was also lower than the less severe Vitamin D deficiency [Table 4].
Table 4: Average MoCA score in all the patients according to different serum Vitamin D level group

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Association of serum Vitamin D level and MoCA score was also studied in two age groups (≤50 years and >50 years, [Table 5]).
Table 5: Association of serum Vitamin D level and MoCA score in patients with MCI in two age groups

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Vitamin D deficiency in patients with age more than 50 years was more strongly associated with low MoCA score.


  Discussion Top


Our study showed that MCI in type 2 DM was correlated with serum Vitamin D level and MoCA score was positively correlated with serum Vitamin D levels. Female patients had a low average serum Vitamin D level than male patients which may be due to less sun exposure and nutritional factors in Indian context. We were not able to establish a correlation between MoCA score (and thus MCI) with duration of diabetes, blood sugar control status (i.e., HbA 1C ) which may be small group size, widely distributed data, and noncomparable group size. For the same reason, a further study with more number of patients and comparable group formation is advised.

In some previous studies, it was suggestive that low serum Vitamin D level is associated with cognitive impairment in older adults [11] and in diabetic patients. [8] Annweiler et al. [12] reviewed the association between serum 25(OH) D concentrations and cognitive performance in adults over the past 30 years, and revealed positive associations between serum 25(OH) D concentrations and global cognitive functions. Chen et al. [8] found that a lower level of serum 25(OH) D in patients with type 2 diabetes is associated with MCI. It also suggests that reduction of serum 25(OH) D concentrations in type 2 diabetic adults may predict MCI, independent of age, sex, years of education, glucose control, and carotid IMT. A study by Gill et al. [13] found that average of serum Vitamin D level was lower in female population than the male.

There is a strong evidence that 1,25(OH) 2D contributes to neuroprotection by modulating the production of nerve growth, [14] decreasing L-type calcium channel expression, [15] regulating the toxicity of reactive oxygen species, [16] and neurotrophic factors such as nerve growth factor, [17] glial cell-derived neurotrophic factor, [18] and nitric oxide synthase. Furthermore, Vitamin D and its metabolites are involved in other neuroprotective mechanisms, including amyloid phagocytosis and clearance [19] and vasoprotection. [20] 25(OH) D levels are inversely associated with one's risk for developing vascular calcification, [21] which is known as a marker of atherosclerotic burden and a risk factor for dementia.


  Conclusion Top


This study indicates that a lower level of serum 25(OH) D in patients with type 2 diabetes is strongly associated with MCI. It also suggests that early detection of low serum 25(OH) D concentrations in type 2 diabetic adults may predict MCI. This study did not found any significant correlation in cognitive impairment or occurrence of MCI in type 2 diabetic patients with increasing duration of diabetes and long-time blood sugar control status. The findings also suggest the need for ongoing study for the evaluation if serum Vitamin D level is affected by duration of diabetes, long-term blood sugar control, gender, and other medical conditions, and also the possible protective role of Vitamin D in causation and progression of cognitive impairment in type 2 diabetic patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Cukierman T, Gerstein HC, Williamson JD. Cognitive decline and dementia in diabetes - Systematic overview of prospective observational studies. Diabetologia 2005;48:2460-9.  Back to cited text no. 1
    
2.
Morris JC, Storandt M, Miller JP, McKeel DW, Price JL, Rubin EH, et al. Mild cognitive impairment represents early-stage Alzheimer disease. Arch Neurol 2001;58:397-405.  Back to cited text no. 2
    
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Tahrani AA, Ball A, Shepherd L, Rahim A, Jones AF, Bates A. The prevalence of vitamin D abnormalities in South Asians with type 2 diabetes mellitus in the UK. Int J Clin Pract 2010;64:351-5.  Back to cited text no. 3
    
4.
Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J. Harrison′s Principles of Internal Medicine. 18 th ed.  New York: McGraw Hill; 2012. p. 3092.  Back to cited text no. 4
    
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Li LH, Yin XY, Yao CY, Zhu XC, Wu XH. Serum 25-hydroxyvitamin D, parathyroid hormone, and their association with metabolic syndrome in Chinese. Endocrine 2013;44:465-72.  Back to cited text no. 5
    
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Etgen T, Sander D, Bickel H, Sander K, Förstl H. Vitamin D deficiency, cognitive impairment and dementia: A systematic review and meta-analysis. Dement Geriatr Cogn Disord 2012;33:297-305.  Back to cited text no. 6
    
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Llewellyn DJ, Lang IA, Langa KM, Melzer D. Vitamin D and cognitive impairment in the elderly U.S. population. J Gerontol A Biol Sci Med Sci 2011;66:59-65.  Back to cited text no. 7
    
8.
Chen RH, Zhao XH, Gu Z, Gu PL, Zhou B, Zhu ZH, et al. Serum levels of 25-hydroxyvitamin D are associated with cognitive impairment in type 2 diabetic adults. Endocrine 2014;45:319-24.  Back to cited text no. 8
    
9.
Alagiakrishnan K, Zhao N, Mereu L, Senior P, Senthilselvan A. Montreal Cognitive Assessment is superior to standardized mini-mental status exam in detecting mild cognitive impairment in the middle-aged and elderly patients with type 2 diabetes mellitus. Biomed Res Int 2013;2013:186106.  Back to cited text no. 9
    
10.
Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J. Harrison′s Principles of Internal Medicine. 18 th ed. New York: McGraw Hill; 2012. p. 3599.  Back to cited text no. 10
    
11.
Balion C, Griffith LE, Strifler L, Henderson M, Patterson C, Heckman G, et al. Vitamin D, cognition, and dementia: A systematic review and meta-analysis. Neurology 2012;79:1397-405.  Back to cited text no. 11
    
12.
Annweiler C, Allali G, Allain P, Bridenbaugh S, Schott AM, Kressig RW, et al. Vitamin D and cognitive performance in adults: A systematic review. Eur J Neurol 2009;16:1083-9.  Back to cited text no. 12
    
13.
Gill TK, Hill CL, Shanahan EM, Taylor AW, Appleton SL, Grant JF, et al. Vitamin D levels in an Australian population. BMC Public Health 2014;14:1001.  Back to cited text no. 13
    
14.
Chabas JF, Alluin O, Rao G, Garcia S, Lavaut MN, Risso JJ, et al. Vitamin D2 potentiates axon regeneration. J Neurotrauma 2008;25:1247-56.  Back to cited text no. 14
    
15.
Brewer LD, Thibault V, Chen KC, Langub MC, Landfield PW, Porter NM. Vitamin D hormone confers neuroprotection in parallel with downregulation of L-type calcium channel expression in hippocampal neurons. J Neurosci 2001;21:98-108.  Back to cited text no. 15
    
16.
Ibi M, Sawada H, Nakanishi M, Kume T, Katsuki H, Kaneko S, et al. Protective effects of 1 alpha, 25-(OH)(2) D (3) against the neurotoxicity of glutamate and reactive oxygen species in mesencephalic culture. Neuropharmacology 2001;40:761-71.  Back to cited text no. 16
    
17.
Wion D, MacGrogan D, Neveu I, Jehan F, Houlgatte R, Brachet P. 1,25-dihydroxyvitamin D3 is a potent inducer of nerve growth factor synthesis. J Neurosci Res 1991;28:110-4.  Back to cited text no. 17
    
18.
Naveilhan P, Neveu I, Wion D, Brachet P. 1,25-Dihydroxyvitamin D3, an inducer of glial cell line-derived neurotrophic factor. Neuroreport 1996;7:2171-5.  Back to cited text no. 18
    
19.
Masoumi A, Goldenson B, Ghirmai S, Avagyan H, Zaghi J, Abel K, et al. 1alpha, 25-dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-beta clearance by macrophages of Alzheimer′s disease patients. J Alzheimers Dis 2009;17:703-17.  Back to cited text no. 19
    
20.
Pludowski P, Holick MF, Pilz S, Wagner CL, Hollis BW, Grant WB, et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. Autoimmun Rev 2013;12:976-89.  Back to cited text no. 20
    
21.
Watson KE, Abrolat ML, Malone LL, Hoeg JM, Doherty T, Detrano R, et al. Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation 1997;96:1755-60.  Back to cited text no. 21
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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