title: HDL-C and HDL-C/ApoA-I predict long-term progression of glycemia in established type 2 diabetes.
abstract: OBJECTIVE
  Low HDL cholesterol (HDL-C) and small HDL particle size may directly promote hyperglycemia. We evaluated associations of HDL-C, apolipoprotein A-I (apoA-I), and HDL-C/apoA-I with insulin secretion, insulin resistance, HbA1c, and long-term glycemic deterioration, reflected by initiation of pharmacologic glucose control.
  
  
  METHODS
  The 5-year Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study followed 9,795 type 2 diabetic subjects. We calculated baseline associations of fasting HDL-C, apoA-I, and HDL-C/apoA-I with HbA1c and, in those not taking exogenous insulin (n = 8,271), with estimated β-cell function (homeostasis model assessment of β-cell function [HOMA-B]) and insulin resistance (HOMA-IR). Among the 2,608 subjects prescribed lifestyle only, Cox proportional hazards analysis evaluated associations of HDL-C, apoA-I, and HDL-C/apoA-I with subsequent initiation of oral hypoglycemic agents (OHAs) or insulin.
  
  
  RESULTS
  Adjusted for age and sex, baseline HDL-C, apoA-I, and HDL-C/apoA-I were inversely associated with HOMA-IR (r = -0.233, -0.134, and -0.230; all P < 0.001; n = 8,271) but not related to HbA1c (all P > 0.05; n = 9,795). ApoA-I was also inversely associated with HOMA-B (r = -0.063; P = 0.002; n = 8,271) adjusted for age, sex, and HOMA-IR. Prospectively, lower baseline HDL-C and HDL-C/apoA-I levels predicted greater uptake (per 1-SD lower: hazard ratio [HR] 1.13 [CI 1.07-1.19], P < 0.001; and HR 1.16 [CI 1.10-1.23], P < 0.001, respectively) and earlier uptake (median 12.9 and 24.0 months, respectively, for quartile 1 vs. quartile 4; both P < 0.01) of OHAs and insulin, with no difference in HbA1c thresholds for initiation (P = 0.87 and P = 0.81). Controlling for HOMA-IR and triglycerides lessened both associations, but HDL-C/apoA-I remained significant.
  
  
  CONCLUSIONS
  HDL-C, apoA-I, and HDL-C/apoA-I were associated with concurrent insulin resistance but not HbA1c. However, lower HDL-C and HDL-C/apoA-I predicted greater and earlier need for pharmacologic glucose control.
authors.affiliation: NHMRC Clinical Trials Centre, Sydney Medical School, University of Sydney, Sydney, Australia boris.waldman@ctc.usyd.edu.au tony@ctc.usyd.edu.au.
authors.forename: Boris
authors.initials: B
authors.lastname: Waldman
authors.affiliation: NHMRC Clinical Trials Centre, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Jenkins
authors.affiliation: School of Medicine, University of Western Australia, Fremantle, Australia.
authors.forename: Timothy M E
authors.initials: TM
authors.lastname: Davis
authors.affiliation: HUCH Heart and Lung Center, Research Programs Unit Diabetes and Obesity, Cardiovascular Research Group, University of Helsinki, Helsinki, Finland.
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.affiliation: Lipid and Diabetes Research Group, Christchurch Hospital, Christchurch, New Zealand.
authors.forename: Russell
authors.initials: R
authors.lastname: Scott
authors.affiliation: NHMRC Clinical Trials Centre, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: O'Connell
authors.affiliation: NHMRC Clinical Trials Centre, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Val J
authors.initials: VJ
authors.lastname: Gebski
authors.affiliation: Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Martin K C
authors.initials: MK
authors.lastname: Ng
authors.affiliation: NHMRC Clinical Trials Centre, Sydney Medical School, University of Sydney, Sydney, AustraliaDepartment of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Keech
mesh_terms: D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D018450:Disease Progression; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D016632:Apolipoprotein A-I; D001786:Blood Glucose; D008076:Cholesterol, HDL; D007004:Hypoglycemic Agents; D007328:Insulin; D011345:Fenofibrate