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.
© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.