Alternative measures of hyperglycemia and risk of Alzheimer's disease in the community: The hisayama study

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Abstract

Context and Objective: We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), GA/HbA1c ratio, and 1,5-anhydroglucitol (1,5-AG) with the development of Alzheimer's disease (AD). Design and Participants: A total of 1187 community-dwelling Japanese subjects aged ≥65 years without dementia were followed up for an average of 4.8 years. Results: The age- and sex-adjusted incidence of AD increased significantly with higher quartiles of GA/HbA1c ratio, and a similar tendency was seen for GA, whereas no such association was observed for HbA1c and 1,5-AG. After adjusting for potential confounding factors, positive association of GA/HbA1c ratio with the risk of AD remained significant: the multivariable-adjusted hazard ratio (HR) was significantly higher in the third [HR = 2.11, 95% confidence interval (CI) = 1.16 to 3.82] and fourth (HR = 2.01, 95% CI = 1.09 to 3.68) quartile than in the first quartile. Among subjects with normal glucose tolerance, those with high GA/HbA1c ratio had a higher risk of AD than those with low GA/HbA1c ratio (HR = 1.82, 95% CI = 1.05 to 3.16), and a similar tendency was found in those with glucose intolerance (HR = 1.73, 95% CI = 0.96 to 3.13). No such associations were observed for HbA1c, GA, and 1,5-AG, regardless of glucose tolerance status. Conclusions: Our findings suggest that elevated GA/HbA1c ratio-but not HbA1c, GA, or 1,5-AG level-is significantly associated with the risk of AD in subjects both with and without glucose intolerance. GA/HbA1c ratio may be a useful biomarker for predicting incident AD.

Original languageEnglish
Pages (from-to)3002-3010
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume102
Issue number8
DOIs
Publication statusPublished - Aug 1 2017

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Hyperglycemia
Alzheimer Disease
Hemoglobins
Glycosylated Hemoglobin A
Hazards
Confidence Intervals
Glucose
Glucose Intolerance
glycosylated serum albumin
Association reactions
Independent Living
Biomarkers
Dementia
Odds Ratio
1,5-anhydroglucitol
Incidence

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

@article{ef9491f0a67b4a949abe20be6c445023,
title = "Alternative measures of hyperglycemia and risk of Alzheimer's disease in the community: The hisayama study",
abstract = "Context and Objective: We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), GA/HbA1c ratio, and 1,5-anhydroglucitol (1,5-AG) with the development of Alzheimer's disease (AD). Design and Participants: A total of 1187 community-dwelling Japanese subjects aged ≥65 years without dementia were followed up for an average of 4.8 years. Results: The age- and sex-adjusted incidence of AD increased significantly with higher quartiles of GA/HbA1c ratio, and a similar tendency was seen for GA, whereas no such association was observed for HbA1c and 1,5-AG. After adjusting for potential confounding factors, positive association of GA/HbA1c ratio with the risk of AD remained significant: the multivariable-adjusted hazard ratio (HR) was significantly higher in the third [HR = 2.11, 95{\%} confidence interval (CI) = 1.16 to 3.82] and fourth (HR = 2.01, 95{\%} CI = 1.09 to 3.68) quartile than in the first quartile. Among subjects with normal glucose tolerance, those with high GA/HbA1c ratio had a higher risk of AD than those with low GA/HbA1c ratio (HR = 1.82, 95{\%} CI = 1.05 to 3.16), and a similar tendency was found in those with glucose intolerance (HR = 1.73, 95{\%} CI = 0.96 to 3.13). No such associations were observed for HbA1c, GA, and 1,5-AG, regardless of glucose tolerance status. Conclusions: Our findings suggest that elevated GA/HbA1c ratio-but not HbA1c, GA, or 1,5-AG level-is significantly associated with the risk of AD in subjects both with and without glucose intolerance. GA/HbA1c ratio may be a useful biomarker for predicting incident AD.",
author = "Naoko Mukai and Tomoyuki Ohara and Jun Hata and Yoichiro Hirakawa and Daigo Yoshida and Hiro Kishimoto and Masafumi Koga and Udai Nakamura and Takanari Kitazono and Yutaka Kiyohara and Toshiharu Ninomiya",
year = "2017",
month = "8",
day = "1",
doi = "10.1210/jc.2017-00439",
language = "English",
volume = "102",
pages = "3002--3010",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "8",

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TY - JOUR

T1 - Alternative measures of hyperglycemia and risk of Alzheimer's disease in the community

T2 - The hisayama study

AU - Mukai, Naoko

AU - Ohara, Tomoyuki

AU - Hata, Jun

AU - Hirakawa, Yoichiro

AU - Yoshida, Daigo

AU - Kishimoto, Hiro

AU - Koga, Masafumi

AU - Nakamura, Udai

AU - Kitazono, Takanari

AU - Kiyohara, Yutaka

AU - Ninomiya, Toshiharu

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Context and Objective: We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), GA/HbA1c ratio, and 1,5-anhydroglucitol (1,5-AG) with the development of Alzheimer's disease (AD). Design and Participants: A total of 1187 community-dwelling Japanese subjects aged ≥65 years without dementia were followed up for an average of 4.8 years. Results: The age- and sex-adjusted incidence of AD increased significantly with higher quartiles of GA/HbA1c ratio, and a similar tendency was seen for GA, whereas no such association was observed for HbA1c and 1,5-AG. After adjusting for potential confounding factors, positive association of GA/HbA1c ratio with the risk of AD remained significant: the multivariable-adjusted hazard ratio (HR) was significantly higher in the third [HR = 2.11, 95% confidence interval (CI) = 1.16 to 3.82] and fourth (HR = 2.01, 95% CI = 1.09 to 3.68) quartile than in the first quartile. Among subjects with normal glucose tolerance, those with high GA/HbA1c ratio had a higher risk of AD than those with low GA/HbA1c ratio (HR = 1.82, 95% CI = 1.05 to 3.16), and a similar tendency was found in those with glucose intolerance (HR = 1.73, 95% CI = 0.96 to 3.13). No such associations were observed for HbA1c, GA, and 1,5-AG, regardless of glucose tolerance status. Conclusions: Our findings suggest that elevated GA/HbA1c ratio-but not HbA1c, GA, or 1,5-AG level-is significantly associated with the risk of AD in subjects both with and without glucose intolerance. GA/HbA1c ratio may be a useful biomarker for predicting incident AD.

AB - Context and Objective: We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), GA/HbA1c ratio, and 1,5-anhydroglucitol (1,5-AG) with the development of Alzheimer's disease (AD). Design and Participants: A total of 1187 community-dwelling Japanese subjects aged ≥65 years without dementia were followed up for an average of 4.8 years. Results: The age- and sex-adjusted incidence of AD increased significantly with higher quartiles of GA/HbA1c ratio, and a similar tendency was seen for GA, whereas no such association was observed for HbA1c and 1,5-AG. After adjusting for potential confounding factors, positive association of GA/HbA1c ratio with the risk of AD remained significant: the multivariable-adjusted hazard ratio (HR) was significantly higher in the third [HR = 2.11, 95% confidence interval (CI) = 1.16 to 3.82] and fourth (HR = 2.01, 95% CI = 1.09 to 3.68) quartile than in the first quartile. Among subjects with normal glucose tolerance, those with high GA/HbA1c ratio had a higher risk of AD than those with low GA/HbA1c ratio (HR = 1.82, 95% CI = 1.05 to 3.16), and a similar tendency was found in those with glucose intolerance (HR = 1.73, 95% CI = 0.96 to 3.13). No such associations were observed for HbA1c, GA, and 1,5-AG, regardless of glucose tolerance status. Conclusions: Our findings suggest that elevated GA/HbA1c ratio-but not HbA1c, GA, or 1,5-AG level-is significantly associated with the risk of AD in subjects both with and without glucose intolerance. GA/HbA1c ratio may be a useful biomarker for predicting incident AD.

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U2 - 10.1210/jc.2017-00439

DO - 10.1210/jc.2017-00439

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VL - 102

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