Hyperglycemia and Metformin Use Are Associated With B Vitamin Deficiency and Cognitive Dysfunction in Older Adults.
J Clin Endocrinol Metab. 2019 Oct 1 ;104(10):4837-4847. PMID: 30920623
Kirsty M Porter
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<30.0 nmol/L; OR 1.48; 95% CI, 1.02 to 2.15). Fortified foods when eaten regularly had a positive impact on all relevant B vitamin biomarkers, even with hyperglycemia. After adjustment for relevant covariates, metformin use was associated with an increased risk of cognitive dysfunction as assessed with the RBANS (OR 1.36; 95% CI, 1.03 to 1.80) and FAB (OR 1.34; 95% CI, 1.03 to 1.74).
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.