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| Year : 2014 | Volume
: 60
| Issue : 1 | Page : 97 |
Authors' reply
AK Singh, A Kumar, D Karmakar, RK Jha
Department of Medicine, Rajendra Institute of Medical Sciences (RIMS), Ranchi, Jharkhand, India
| Date of Web Publication | 14-Mar-2014 |
Correspondence Address:
A K Singh
Department of Medicine, Rajendra Institute of Medical Sciences (RIMS), Ranchi, Jharkhand
India
 Source of Support: None, Conflict of Interest: None  | Check |
How to cite this article:
Singh A K, Kumar A, Karmakar D, Jha R K. Authors' reply. J Postgrad Med 2014;60:97 |
Sir,
Thank you for the response. [1] A) As has been pointed out in the 'Introduction' section, our study includes a clinically important outcome like neuropathyin addition to B12 deficiency as a response variable. The effect of metformin on the neuropathy scores has been evaluated by only two studies previously to the best of our our knowledge. [2],[3] Furthermore, this is Indian study has evaluated the effect of metformin on neuropathy and B12 scores in a very large cohort. Our aim was to examine the association between metformin use and these outcome variables. The causation has been addressed by two large placebo controlled studies. [4],[5]
B) Both groups were matched for age and duration of diabetes. We also accounted for the potential confounding caused by these variables by conducting multiple linear regression with B12 levels and the Toronto clinical scoring system (TCSS) score as dependent variables, and age, duration of diabetes, HbA1c, and the cumulative metformin dose as independent variables. The multiple linear regression helped us to account for the effect of these potentially confounding variables. In our study, the cumulative metformin dose and HBA1c emerged as independent explanatory variables for neuropathy after controlling for age and duration of diabetes, (refer methods(F ratio = 23.39, R square = 0.45, P < 0.001). This also showed that HbA1c was an independent risk factor for neuropathy and a higher HbA1c (HbA1C 8.2 ± 1.02 vs. 8.4 ± 0.81) in both groups accounted for the 21 extra cases of neuropathy (n = 45) not explained by B12 deficiency alone, (n = 24). We attempted to account for all possible causes of neuropathy like alcohol abuse, hypothyroidism, renal failure, and vitamin B 12 supplementation, in the exclusion criteria. In the study referred to by the reader, there was a change only in the Holo-Tc II levels and no significant alteration in vitamin B 12 levels on calcium supplementation. [6] Although we have also referenced this small study (n = 14 metformin, n = 7 control) in the discussion, we did not find systematic evidence of a larger cohort for prevention and reversal of metformin-induced B12 deficiency by calcium supplementation, hence we did not actively exclude people taking calcium supplements from our study.
C) The unit of the cumulative metformin dose provided in the figure is in grams.
| :: References | |  |
| 1. | Chowta MN, Gaurav. Comment on: Association of B12 deficiency and clinical neuropathy with metformin use in type 2 diabetes patients. Jr Postgrad Med 2014;60:96-7. 
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| 2. | Wile 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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| 3. | Chen S, Lansdown AJ, Moat SJ, Ellis R, Goringe A, Dunstan FD, et al. An observational study of the effect of metformin on B12 status and peripheral neuropathy. Br J Diabetes Vascular Dis 2012;12:189-93.
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| 4. | DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The multicenter metformin study group. N Engl J Med 1995;333:541-9.
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| 5. | de Jager J, Kooy A, Lehert P, Wulffelé MG, van der Kolk J, Bets D, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: Randomized placebo controlled trial. BMJ 2010;340:c2181.
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| 6. | Bauman WA, Shaw S, Jayatilleke E, Spungen AM, Herbert V. Increased in take of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care 2000;23:1227-31.
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