Serum Concentrations and Dietary Intake of Vitamin B₁₂ in Children and Adolescents on Metformin: A Case–Control Study

Abstract

The International Society of Pediatric and Adolescent Diabetes (ISPAD) recommends metformin (MET) use for metabolic disturbances and hyperglycemia, either in combination with insulin therapy or alone. A caveat of MET therapy has been suggested to be biochemical vitamin B12 deficiency, as seen mainly in studies conducted in adults. In the present case–control study, children and adolescents of different weight status tiers on MET therapy for a median of 17 months formed the cases group (n = 23) and were compared with their peers not taking MET (n = 46). Anthropometry, dietary intake, and blood assays were recorded for both groups. MET group members were older, heavier, and taller compared with the controls, although BMI z-scores did not differ. In parallel, blood phosphorus and alkaline phosphatase (ALP) concentrations were lower in the MET group, whereas MCV, Δ4-androstenedione, and DHEA-S were higher. No differences were observed in the HOMA-IR, SHBG, hemoglobin, HbA1c, vitamin B12, or serum 25(OH)D3 concentrations between groups. Among those on MET, 17.4% exhibited vitamin B12 deficiency, whereas none of the controls had low vitamin B12 concentrations. Participants on MET therapy consumed less energy concerning their requirements, less vitamin B12, more carbohydrates (as a percentage of the energy intake), and fewer fats (including saturated and trans fats) compared with their peers not on MET. None of the children received oral nutrient supplements with vitamin B12. The results suggest that, in children and adolescents on MET therapy, the dietary intake of vitamin B12 is suboptimal, with the median coverage reaching 54% of the age- and sex-specific recommended daily allowance. This low dietary intake, paired with MET, may act synergistically in reducing the circulating vitamin B12 concentrations. Thus, caution is required when prescribing MET in children and adolescents, and replacement is warranted.

Keywords

• one-carbon metabolism
• childhood obesity
• sulfonylurea
• polycystic ovary syndrome
• insulin resistance
• Glucophage