Hyperglycemia and metformin use are associated with B-vitamin deficiency and cognitive dysfunction in older adults

Kirsty Porter, M Ward, Catherine Hughes, Maurice O'Kane, L. Hoey, Adrian McCann, Anne M Molloy, Conal Cunningham, Miriam Casey, Fergal Tracey, Sean Strain, Kevin McCarroll, Eamon Laird, Alison M Gallagher, H McNulty

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 <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.

LanguageEnglish
Pages4837-4847
Number of pages11
JournalThe Journal of Clinical Endocrinology & Metabolism
Volume104
Issue number10
Early online date28 Mar 2019
DOIs
Publication statusPublished - 1 Oct 2019

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Vitamin B Deficiency
Vitamin B Complex
Metformin
Hyperglycemia
Biomarkers
Fortified Food
Vitamin B 6
Vitamin B 12
Medical problems
Folic Acid
Independent Living
Vitamin B 12 Deficiency
Pyridoxal Phosphate
Riboflavin
Agriculture
Dementia
Cognitive Dysfunction
Comorbidity
Cohort Studies
Health

Keywords

  • hyperglycaemia
  • metformin
  • B-vitamins
  • cognitive dysfunction
  • fortified food

Cite this

Porter, Kirsty ; Ward, M ; Hughes, Catherine ; O'Kane, Maurice ; Hoey, L. ; McCann, Adrian ; Molloy, Anne M ; Cunningham, Conal ; Casey, Miriam ; Tracey, Fergal ; Strain, Sean ; McCarroll, Kevin ; Laird, Eamon ; Gallagher, Alison M ; McNulty, H. / Hyperglycemia and metformin use are associated with B-vitamin deficiency and cognitive dysfunction in older adults. In: The Journal of Clinical Endocrinology & Metabolism. 2019 ; Vol. 104, No. 10. pp. 4837-4847.
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Hyperglycemia and metformin use are associated with B-vitamin deficiency and cognitive dysfunction in older adults. / Porter, Kirsty; Ward, M; Hughes, Catherine; O'Kane, Maurice; Hoey, L.; McCann, Adrian; Molloy, Anne M; Cunningham, Conal; Casey, Miriam; Tracey, Fergal; Strain, Sean; McCarroll, Kevin; Laird, Eamon; Gallagher, Alison M; McNulty, H.

In: The Journal of Clinical Endocrinology & Metabolism, Vol. 104, No. 10, 01.10.2019, p. 4837-4847.

Research output: Contribution to journalArticle

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T1 - Hyperglycemia and metformin use are associated with B-vitamin deficiency and cognitive dysfunction in older adults

AU - Porter, Kirsty

AU - Ward, M

AU - Hughes, Catherine

AU - O'Kane, Maurice

AU - Hoey, L.

AU - McCann, Adrian

AU - Molloy, Anne M

AU - Cunningham, Conal

AU - Casey, Miriam

AU - Tracey, Fergal

AU - Strain, Sean

AU - McCarroll, Kevin

AU - Laird, Eamon

AU - Gallagher, Alison M

AU - McNulty, H

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

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KW - metformin

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