title: Different inverse association of large high-density lipoprotein subclasses with exacerbation of insulin resistance and incidence of type 2 diabetes: The Nagahama study.
abstract: OBJECTIVE
  In addition to its antiatherogenic action, high-density lipoprotein (HDL) may also have an antidiabetes function. Although the biological actions of small HDL (HDL3) and large HDL (HDL2) subclasses may be different, evidence in support of that hypothesis is lacking. The aim of this study was to clarify the difference in prognostic significance of HDL subclasses for exacerbation of insulin resistance and incidence of type 2 diabetes in the general population.
  
  
  METHODS
  Study participants included 8365 community residents 52±13years of age not taking lipid lowering drugs. Serum HDL cholesterol subclasses and low-density lipoprotein subclasses, were measured by a homogeneous assay. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR).
  
  
  RESULTS
  Cross-sectional analysis adjusted for possible covariates found that HDL2 cholesterol (HDL2-C) levels were inversely associated with HOMA-IR (β=-0.169, p<0.001), whereas HDL3-C had the opposite association (β=0.054, p<0.001). Similar results were found in an analysis for type 2 diabetes (HDL2-C, odds ratio=0.96, p=0.001; HDL3-C, odds ratio=1.04, p=0.181). In a longitudinal analysis with 5.0years of follow-up, HDL2-C was inversely associated with exacerbation of insulin resistance (β=-0.163, p<0.001); HDL3-C had the opposite association (β=0.026, p=0.037). During follow-up, 205 individuals were newly diagnosed with diabetes, and HDL2-C level was associated with an inverse risk of type 2 diabetes incidence (odds ratio=0.98, p=0.006).
  
  
  CONCLUSIONS
  HDL may have an antidiabetic function; the prognostic value of HDL2-C for diabetes and insulin resistance might be better than that of HDL3-C.
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: tabara@genome.med.kyoto-u.ac.jp.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.affiliation: National Center for Geriatrics and Gerontology, Obu, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Arai
authors.affiliation: Research and Development Center, Denka Seiken Co., Ltd., Tokyo, Japan.
authors.forename: Yuhko
authors.initials: Y
authors.lastname: Hirao
authors.affiliation: Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan.
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Setoh
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Department of Medical Ethics and Medical Genetics, Kyoto University School of Public Health, Kyoto, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kosugi
authors.affiliation: Research and Development Center, Denka Seiken Co., Ltd., Tokyo, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance / Q000276:immunology*; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D008075:Lipoproteins, HDL
keywords: High-density lipoprotein; Insulin resistance; Lipoprotein subclasses; Mendelian randomization analysis; Type 2 diabetes