Hyperglycemia and Metformin Use Are Associated With B Vitamin Deficiency and Cognitive Dysfunction in Older Adults

Abstract:

Context: Emerging evidence suggests that deficiencies of folate-related B vitamins can arise with metformin treatment and are independently linked with cognitive dysfunction, a comorbidity of diabetes.

Objective: To determine the impact of hyperglycemia and metformin use on relevant B vitamin biomarkers and cognitive outcomes in older adults.

Setting and participants: Community-dwelling older adults (74.1 ± 8.3 years, n = 4160) without dementia, recruited to the Trinity, Ulster and Department of Agriculture cohort study in 2008 to 2012, were classified as normoglycemic (n = 1856) or hyperglycemic, based on HbA1c ≥5.7% (39 mmol/mol), either with (n = 318) or without (n = 1986) metformin treatment.

Main outcome measures: Biomarkers of folate, vitamin B12, vitamin B6, and riboflavin were measured. Cognitive assessments included the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) and the Frontal Assessment Battery (FAB).

Results: Metformin use was associated with higher risk of deficiency of vitamin B12 (combined B12 index ≤-1; OR 1.45; 95% CI, 1.03 to 2.02) and vitamin B6 (plasma pyridoxal 5-phosphate

Conclusions: Use of metformin by older adults is associated with poorer cognitive performance; B vitamin deficiency may be implicated. Fortified foods can optimize B vitamin status and may be beneficial for maintaining better cognitive health in older people with or at risk for diabetes.