title: Association of hemoglobin A1c and glycated albumin with carotid atherosclerosis in community-dwelling Japanese subjects: the Hisayama Study.
abstract: BACKGROUND
  It is not clear which glucose measure is more useful in the assessment of atherosclerosis. We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), 1,5-anhydroglucitol (1,5-AG), fasting plasma glucose (FPG), and 2-hour postload glucose (PG) with carotid intima-media thickness (IMT) in community-dwelling Japanese subjects.
  
  
  METHODS
  A total of 2702 subjects aged 40-79 years underwent a 75-g oral glucose tolerance test and measurements of HbA1c, GA, 1,5-AG, and carotid IMT by ultrasonography in 2007-2008. Carotid wall thickening was defined as a maximum IMT of >1.0 mm. The crude and multivariable-adjusted linear and logistic regression models were used to analyze cross-sectional associations between levels of glycemic measures and carotid IMT.
  
  
  RESULTS
  The crude average of the maximum IMT increased significantly with rising quartiles of HbA1c, GA, FPG, and 2-hour PG levels in subjects with and without glucose intolerance (GI), while no clear association was observed for 1,5-AG. After adjustment for other confounding factors, positive trends for HbA1c, GA, and FPG (all p for trend < 0.05), but not 2-hour PG (p = 0.07) remained robust in subjects with GI, but no such associations were found in those without GI. When estimating multivariable-adjusted β values for the associations of 1 SD change in glycemic measures with the maximum IMT in subjects with GI, the magnitude of the influence of HbA1c (β = 0.021), GA (β = 0.024), and FPG (β = 0.024) was larger than that of 2-hour PG (β = 0.014) and 1,5-AG (β = 0.003). The multivariable-adjusted odds ratios for the presence of carotid wall thickening increased significantly with elevating HbA1c, GA, and FPG levels only in subjects with GI (all p for trend < 0.001). Among subjects with GI, the area under the receiver operating characteristic curve significantly increased by adding HbA1c (p = 0.04) or GA (p = 0.04), but not 1,5-AG, FPG, or 2-hour PG, to the model including other cardiovascular risk factors.
  
  
  CONCLUSIONS
  In community-dwelling Japanese subjects with GI, elevated HbA1c, GA, and FPG levels were significantly associated with increased carotid IMT, and HbA1c and GA provided superior discrimination for carotid wall thickening compared to 1,5-AG, FPG, and 2-hour PG, suggesting that HbA1c and GA are useful for assessing carotid atherosclerosis.
authors.affiliation: Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. n-mukai@cohort.med.kyushu-u.ac.jp.|Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. n-mukai@cohort.med.kyushu-u.ac.jp.|Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. n-mukai@cohort.med.kyushu-u.ac.jp.
authors.forename: Naoko
authors.initials: N
authors.lastname: Mukai
authors.affiliation: Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. nino@cohort.med.kyushu-u.ac.jp.|Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. nino@cohort.med.kyushu-u.ac.jp.|Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. nino@cohort.med.kyushu-u.ac.jp.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ninomiya
authors.affiliation: Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. junhata@cohort.med.kyushu-u.ac.jp.|Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. junhata@cohort.med.kyushu-u.ac.jp.|Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. junhata@cohort.med.kyushu-u.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Hata
authors.affiliation: Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. you1@envmed.med.kyushu-u.ac.jp.|Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. you1@envmed.med.kyushu-u.ac.jp.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Hirakawa
authors.affiliation: Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. fumikeda@envmed.med.kyushu-u.ac.jp.|Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. fumikeda@envmed.med.kyushu-u.ac.jp.|Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. fumikeda@envmed.med.kyushu-u.ac.jp.
authors.forename: Fumie
authors.initials: F
authors.lastname: Ikeda
authors.affiliation: Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. fukuharm@envmed.med.kyushu-u.ac.jp.|Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. fukuharm@envmed.med.kyushu-u.ac.jp.
authors.forename: Masayo
authors.initials: M
authors.lastname: Fukuhara
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital, Fukuoka, Japan. thotta@med.kyushu-u.ac.jp.
authors.forename: Taeko
authors.initials: T
authors.lastname: Hotta
authors.affiliation: Department of Internal Medicine, Kawanishi City Hospital, Hyogo, Japan. m-koga@kawanishi-city-hospital.com.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Koga
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. uday@intmed2.med.kyushu-u.ac.jp.
authors.forename: Udai
authors.initials: U
authors.lastname: Nakamura
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital, Fukuoka, Japan. kang@cclm.med.kyushu-u.ac.jp.
authors.forename: Dongchon
authors.initials: D
authors.lastname: Kang
authors.affiliation: Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. kitazono@intmed2.med.kyushu-u.ac.jp.|Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kitazono@intmed2.med.kyushu-u.ac.jp.
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
authors.affiliation: Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. kiyohara@envmed.med.kyushu-u.ac.jp.|Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kiyohara@envmed.med.kyushu-u.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kiyohara
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000378:metabolism*; D059168:Carotid Intima-Media Thickness; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003847:Deoxyglucose / Q000378:metabolism*; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism*; D017127:Glycation End Products, Advanced; D006801:Humans; D057187:Independent Living; D007333:Insulin Resistance; D007564:Japan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012709:Serum Albumin / Q000378:metabolism*; D013223:Statistics as Topic; D000093423:Glycated Serum Albumin
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D003847:Deoxyglucose; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D000093423:Glycated Serum Albumin; C517652:hemoglobin A1c protein, human; C006584:1,5-anhydroglucitol