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

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 co-morbidity 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 people (74.1 ± 8.3 years, n = 4160) without dementia, recruited to the TUDA cohort study in 2008-2012, were classified as normoglycemic (n = 1856) or hyperglycemic, based on glycosylated hemoglobin (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; odds ratio (95% CI): 1.45 (1.03-2.02)) and vitamin B6 (plasma pyridoxal 5-phosphate <30.0 nmol/L; 1.48 (1.02-2.15)). Fortified foods when eaten regularly had a positive impact on all relevant B-vitamin biomarkers, even with hyperglycaemia. After adjustment for relevant co-variates, metformin use was associated with an increased risk of cognitive dysfunction as assessed using the RBANS (1.36 (1.03-1.80) and FAB (1.34 (1.03-1.74).

Conclusions: Use of metformin in 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 of diabetes.

LanguageEnglish
Number of pages20
JournalThe Journal of Clinical Endocrinology & Metabolism
Early online date28 Mar 2019
DOIs
Publication statusE-pub ahead of print - 28 Mar 2019

Fingerprint

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
Glycosylated Hemoglobin A
Dementia
Cognitive Dysfunction
Cohort Studies
Odds Ratio
Outcome Assessment (Health Care)

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.
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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, 28.03.2019.

Research output: Contribution to journalArticle

TY - JOUR

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 - 2019/3/28

Y1 - 2019/3/28

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 co-morbidity 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 people (74.1 ± 8.3 years, n = 4160) without dementia, recruited to the TUDA cohort study in 2008-2012, were classified as normoglycemic (n = 1856) or hyperglycemic, based on glycosylated hemoglobin (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; odds ratio (95% CI): 1.45 (1.03-2.02)) and vitamin B6 (plasma pyridoxal 5-phosphate <30.0 nmol/L; 1.48 (1.02-2.15)). Fortified foods when eaten regularly had a positive impact on all relevant B-vitamin biomarkers, even with hyperglycaemia. After adjustment for relevant co-variates, metformin use was associated with an increased risk of cognitive dysfunction as assessed using the RBANS (1.36 (1.03-1.80) and FAB (1.34 (1.03-1.74).Conclusions: Use of metformin in 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 of 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 co-morbidity 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 people (74.1 ± 8.3 years, n = 4160) without dementia, recruited to the TUDA cohort study in 2008-2012, were classified as normoglycemic (n = 1856) or hyperglycemic, based on glycosylated hemoglobin (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; odds ratio (95% CI): 1.45 (1.03-2.02)) and vitamin B6 (plasma pyridoxal 5-phosphate <30.0 nmol/L; 1.48 (1.02-2.15)). Fortified foods when eaten regularly had a positive impact on all relevant B-vitamin biomarkers, even with hyperglycaemia. After adjustment for relevant co-variates, metformin use was associated with an increased risk of cognitive dysfunction as assessed using the RBANS (1.36 (1.03-1.80) and FAB (1.34 (1.03-1.74).Conclusions: Use of metformin in 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 of diabetes.

KW - hyperglycaemia

KW - metformin

KW - B-vitamins

KW - cognitive dysfunction

KW - fortified food

U2 - 10.1210/jc.2018-01791

DO - 10.1210/jc.2018-01791

M3 - Article

JO - Journal of Clinical Endocrinology and Metabolism

T2 - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

ER -