TY - JOUR T1 - HDL-C and HDL-C/ApoA-I Predict Long-Term Progression of Glycemia in Established Type 2 Diabetes JF - Diabetes Care JO - Diabetes Care SP - 2351 LP - 2358 DO - 10.2337/dc13-2738 VL - 37 IS - 8 AU - Waldman, Boris AU - Jenkins, Alicia J. AU - Davis, Timothy M.E. AU - Taskinen, Marja-Riitta AU - Scott, Russell AU - O’Connell, Rachel L. AU - Gebski, Val J. AU - Ng, Martin K.C. AU - Keech, Anthony C. Y1 - 2014/08/01 UR - http://care.diabetesjournals.org/content/37/8/2351.abstract N2 - 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 &lt; 0.001; n = 8,271) but not related to HbA1c (all P &gt; 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 &lt; 0.001; and HR 1.16 [CI 1.10–1.23], P &lt; 0.001, respectively) and earlier uptake (median 12.9 and 24.0 months, respectively, for quartile 1 vs. quartile 4; both P &lt; 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. ER -