HDL-C and HDL-C/ApoA-I Predict Long-Term Progression of Glycemia in Established Type 2 Diabetes

Abstract

OBJECTIVELow 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, HbA 1c , and long-term glycemic deterioration, reflected by initiation of pharmacologic glucose control. RESEARCH DESIGN AND METHODSThe 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 HbA 1c and, in those not taking exogenous insulin (n = 8,271), with estimated b-cell function (homeostasis model assessment of b-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. RESULTSAdjusted for age and sex, baseline HDL-C, apoA-I, and HDL-C/apoA-I were inversely associated with HOMA-IR (r = 20.233, 20.134, and 20.230; all P < 0.001; n = 8,271) but not related to HbA 1c (all P > 0.05; n = 9,795). ApoA-I was also inversely associated with HOMA-B (r = 20.063; 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 HbA 1c 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. CONCLUSIONSHDL-C, apoA-I, and HDL-C/apoA-I were associated with concurrent insulin resistance but not HbA 1c . However, lower HDL-C and HDL-C/apoA-I predicted greater and earlier need for pharmacologic glucose control.

Effectiveness of a Lifestyle Intervention in Patients with Type 2 Diabetes: The Physical Activity and Nutrition for Diabetes in Alberta (PANDA) Trial

“…We also observed significant changes in fat mass and waist circumference similar in magnitude to those observed in the Look AHEAD trial [43]. The inverse relationship between changes in A1c and serum HDL-C shown in the PANDA intervention has been reported by others [44,45] but is not as well established as that between A1c and BMI and is not seen in all studies [46,47]. However, a prospective trial demonstrated that low baseline HDL-C predicted more rapid long-term progression of T2D [46].…”

“…The inverse relationship between changes in A1c and serum HDL-C shown in the PANDA intervention has been reported by others [44,45] but is not as well established as that between A1c and BMI and is not seen in all studies [46,47]. However, a prospective trial demonstrated that low baseline HDL-C predicted more rapid long-term progression of T2D [46]. HDL-C promotes insulin secretion and protection from apoptosis of beta-cells [48], which may be related to HDL-C-mediated anti-oxidative and cellular cholesterol efflux activities [49].…”

LDL-C/apoB and HDL-C/apoA-1 ratios predict incident chronic kidney disease in a large apparently healthy cohort

“…The HDL-C/apoA-I ratio has been suggested to be a useful biomarker to estimate HDL particle size [26]. Smaller cholesterol-poor HDL particles are reflected by lower HDL-C levels and HDL-C/apoA-1 ratios [26,27]. Alterations in HDL size and cholesterol content may reflect reduced efficacy of reverse cholesterol transport [28].…”

Rates of glycaemic deterioration in a real-world population with type 2 diabetes

“…However, these studies have only reported an outcome based on progression to glucoselowering medications (i.e. time to initiation of non-insulin glucose-lowering medication, failure of monotherapy or time to insulin therapy) [1,[3][4][5][6][7][8][9]. In these studies, younger age at diagnosis and insufficient beta cell function were consistently associated with faster progression of diabetes.…”