Journal of Postgraduate Medicine
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Year : 2014  |  Volume : 60  |  Issue : 1  |  Page : 95-96  

Authors' reply

AK Singh, A Kumar, D Karmakar, RK Jha 
 Department of Medicine, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India

Correspondence Address:
A K Singh
Department of Medicine, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand

How to cite this article:
Singh A K, Kumar A, Karmakar D, Jha R K. Authors' reply.J Postgrad Med 2014;60:95-96

How to cite this URL:
Singh A K, Kumar A, Karmakar D, Jha R K. Authors' reply. J Postgrad Med [serial online] 2014 [cited 2022 Sep 28 ];60:95-96
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We appreciate the rapid response to our article. [1] A point by point response is outlined below.

The power calculation was based on previous studies done by Reinstatler et al., [2] Liu et al., [3] and Wile et al. [4] Our outcome variable for power calculation defined B 12 deficiency as B 12 level < 220 pg/ml, as has been done by most of these studies.. The values are 16.2, [2] 52, [3] and 31% [4] respectively in the metformin arms of these studies. We thus chose a middle value of expected vitamin B 12 level deficiency percentage to be 25%. Even in the study [1] quoted by the reader, 16.2% of the patients using metformin had borderline B 12 deficiency < 220 pg/ml, while 5.8% (quoted in the abstract of the study by the reader [1] had severe B 12 deficiency (B 12 < 148 pg/ml). In our clinical setting and indeed in most of the studies around the world, a B 12 level of between 200 - 220 pg/ml has been used as a marker of B 12 deficiency. In our study, possible B 12 deficiency and severe deficiency were seen in 21.4% and 7.1% of the patients, respectively. This proportion of B 12 deficiency observed in our study was in agreement with studies across the world, including the National Health and Nutrition Examination Survey (NHANES) [2] referenced by the reader [1] and us, where this figure is 16.8 and 5.8%, respectively. Based on the studies [2],[3],[4] referenced above, we believe that valid assumptions for power calculation were made in our study leading to an appropriate sample size. Even in the metformin-taking group in our study, 71.5% patients had normal vitamin B 12 levels. Only 21.4% had possible B 12 deficiency and 5.7% had severe B 12 deficiency. As a majority of this group population had above-normal B 12 levels, the mean B 12 level was normal despite this group having a higher proportion of patients with B 12 deficiency than the non-metformin group. The mean level of B 12 in non-vegetarians was higher than vegetarians. Please refer erratum on page (92). Thus, "Vitamin B 12 levels were significantly higher in the non-vegetarian population than in the vegetarian population (529.7 ± 162.3 versus 450 ± 170, p = 0.048, 95% CI 4.41-164.75)." The chi-square test was used to compare the proportion of -vegetarians and not the absolute numbers, as inferred by the reader. [1] As the metformin group had a higher number of patients (n = 84) than the non-metformin group (n = 52), therefore, despite having a higher number of -vegetarians (12 versus 6), the difference in proportion was statistically insignificant (12/84 versus 6/52, difference = 8.30%, 95% CI = -1.59 to 18.19, chi-square = 1.477, p = 0.2243).Low B 12 levels were observed in all patients with neuropathy. There was negative correlation between the B 12 levels and neuropathy scores. As a majority of the patients in the metformin group had normal B 12 levels, the mean B 12 levels in this group was normal despite having a higher proportion of B 12 deficiency. Thus, a higher proportion of patients with B 12 deficiency in the metformin group accounts for a higher proportion of neuropathy observed in this group, as compared to the non-metformin group.As has rightly been pointed out by the reader, [1] further studies should be done to evaluate which modes of B12 supplements (intramuscular or oral) are suitable to correct this deficiency.


1Shah V. Association of B12 deficiency and clinical neuropathy with metformin use in type 2 diabetes patients. Jr Postgrad Med 2014;60:95.
2Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP Jr. Association of biochemical B12 deficiency with metformin therapy and vitamin B12 supplements: The national health and nutrition examination survey, 1999-2006. Diabetes Care 2012;35:327-33.
3Liu KW, Dai DL, Ho W, Lau E, Woo J. Metformin-associated vitamin B12 deficiency in the elderly. Asian J Gerontol Geriatr 2011;6:82-7.
4Wile DJ, Toth C. Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy. Diabetes Care 2010;33:156-61.

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