HDL-C and HDL-C/ApoA-I predict long-term progression of glycemia in established type 2 diabetes

Boris Waldman, Alicia J Jenkins, Timothy M E Davis, Marja-Riitta Taskinen, Russell Scott, Rachel L O'Connell, Val J Gebski, Martin K C Ng, Anthony C Keech, FIELD Study Investigators

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


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.

RESEARCH DESIGN AND 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.

Original languageEnglish
Pages (from-to)2351-8
Number of pages8
JournalDiabetes Care
Issue number8
Publication statusPublished - Aug 2014


  • Aged
  • Apolipoprotein A-I
  • Blood Glucose
  • Cholesterol, HDL
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2
  • Disease Progression
  • Female
  • Fenofibrate
  • Follow-Up Studies
  • Humans
  • Hypoglycemic Agents
  • Insulin
  • Insulin Resistance
  • Insulin-Secreting Cells
  • Male
  • Middle Aged
  • Prognosis
  • Treatment Outcome


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