1. DIABETES JOURNAL CLUB MARCH 15, 2012 MARGAUX AÑEL-TIANGCO, MD

2. Introduction Prevalence of DM among adults ≥ 65 years = 21.2% Prevalence of B12 deficiency in adults ≥ 60 years = 6% Prevalence of borderline B12 deficiency in adults ≥ 60 years = 20% DeFronzo and Goodman 1995 (First metformin efficacy trial)  Metformin lowered B12 level by 22% vs. placebo, 29% vs. glyburide after 29 wks of treatment

3. Demographic data

4. Definition of Terms B12 deficiency ≤ 148 pmol/L Borderline B12 deficiency 148-221 pmol/L Normal >221 pmol/L B12 intake categories:  0-6 µg – amount typically found in OTC MVI  >6-25 µg – amount typically found in MVI for senior adults

5. Results T2DM on Metformin T2DM not on Metformin No DM

7. Table 2 Interpretation For those without DM, B12 supplements assoc. with  ~66.7% lower prevalence of B12 deficiency and borderline def. For those with DM on Metformin, supplements  not assoc. with decrease in the prevalence of B12 deficiency and borderline def. Among metformin users who used supplements  >0-6 µg B12 had prevalence of deficiency of 14.1%  > 6 µg B12 had prevalence of deficiency of 1.8%*

8. Results Metformin therapy was associated with  B12 deficiency (OR 2.89, 95% CI)  Borderline B12 deficiency (OR 2.32, 95% CI) *even after adjusting for BMI, insulin, and supplement use Among those with T2DM  B12 supplements protective against borderline but not biochemical B12 deficiency Among those without T2DM  B12 supplements were ~70% protective against biochemical B12 deficiency and borderline deficiency

9. Conclusions Metformin use is associated with B12 deficiency B12 supplements in OTC MVI decrease the prevalence of B12 deficiency in those without DM but not in those with T2DM Pts with T2DM not on metformin had the lowest prevalence of B12 deficiency  May seek medical care more frequently so are better treated for B12 deficiency than other groups  Or these pts may have been switched from metformin to other DM therapies that may increase B12 levles

10. Limitations Cross-sectional survey – association only and not causation May have included Type 1 DM patients

11. Take Home Points In the diabetic on metformin who complains of  Neuropathy  Fatigue  Depression  Cognitive impairement Think B12 deficiency.Think B12 deficiency. Screen and treat aggressively!Screen and treat aggressively!

12. Questions?