Endocrine Abstracts

Introduction: Metformin is a cornerstone in the treatment of type 2 diabetes, but in recent years several studies have shown that metformin use is associated with a 4-24% decrease in vitamin B12 levels. It is estimated that this problem occurs in approximately 10-30% of patients using metformin and may contribute to distal symmetrical polyneuropathy (DSPN), a very common and clinically relevant diabetic complication.

Objective: To study vitamin B12 concentrations in type 2 diabetic patients receiving metformin and presenting with DSPN.

Patients and methods: A cross-sectional study was conducted over a period of 19 months, from 1 February 2021 to 30 September 2022, including 123 type 2 diabetic patients treated with metformin consulting at the National Institute Zouhaier Kallel Tunisia. The presence of DSPN was determined by the “douleur neuropathique” DN4 test and its severity was assessed by the Toronto Clinical Neuropathy Score(TCSS). Vitamin B12 and folate levels were determinated for all participants.

Results: The mean age of our population was 60.99 ± 6.85 years (81 females and 42 males). The mean average DN 4 score and TCSS score were 5.31 ± 1.21 and 9.5 ± 3.36, respectively. The mean duration of metformin use was 14.6±7.27 years with a mean dose of 1923±575.4 mg/day. Fifty seven percent of patients had mild neuropathy, 23.5% moderate neuropathy and 19.5% severe neuropathy. The mean serum Vitamin B12 level was 353.77 ± 178.22 pg/ml with extremes ranging from 64.47 to 918.4 pg/ml. Eighteen and a half percent of the population had a vitamin B12 deficiency (level <200 pg/ml) and 29.8% had a borderline level (level between 200 and 300 pg/ml). The Mean average of vitamin B12 level was 387,73 ± 190.97 in mild neuropathy, 319,04 ± 151,54 in moderate neuropathy and et 296,72 ±178,22 in severe neuropathy. There was correlation between TCSS and vitamin B12 levels (P=0.016). Daily metformin dose and duration did not correlate with TCSS (P=0.8 and 0.45 respectively) or vitamin B12 levels.

Conclusion: Our study shows a positive association between vitamin B12 deficiency and the severity of neuropathy in type 2 diabetic patients on metformin. Therefore, We recommand a regular screening for vitamin B12 deficiency. Deficient patients were supplemented with parenteral vitamin B12. We consider a control of TCSS and DN 4 score 6 months later.