OBJECTIVEEvidence favors apolipoprotein B (apoB) over LDL cholesterol as a predictor of cardiovascular events, but data are lacking on coronary artery calcification (CAC), especially in type 2 diabetes, where LDL cholesterol may underestimate atherosclerotic burden. We investigated the hypothesis that apoB is a superior marker of CAC relative to LDL cholesterol.RESEARCH DESIGN AND METHODSWe performed cross-sectional analyses of white subjects in two community-based studies: the Penn Diabetes Heart Study (N = 611 type 2 diabetic subjects, 71.4% men) and the Study of Inherited Risk of Coronary Atherosclerosis (N = 803 nondiabetic subjects, 52.8% men) using multivariate analysis of apoB and LDL cholesterol stratified by diabetes status.RESULTSIn type 2 diabetes, apoB was associated with CAC after adjusting for age, sex, and medications [Tobit regression ratio of increased CAC for 1-SD increase in apoB; 1.36 (95% CI 1.06–1.75), P = 0.016] whereas LDL cholesterol was not [1.09 (0.85–1.41)]. In nondiabetic subjects, both were associated with CAC [apoB 1.65 (1.38–1.96), P < 0.001; LDL cholesterol 1.56 (1.30–1.86), P < 0.001]. In combined analysis of diabetic and nondiabetic subjects, apoB provided value in predicting CAC scores beyond LDL cholesterol, total cholesterol, the total cholesterol/HDL cholesterol and triglyceride/HDL cholesterol ratios, and marginally beyond non-HDL cholesterol.CONCLUSIONSPlasma apoB, but not LDL cholesterol, levels were associated with CAC scores in type 2 diabetic whites. ApoB levels may be particularly useful in assessing atherosclerotic burden and cardiovascular risk in type 2 diabetes.

Fatty acid–binding proteins (FABPs) 4 and 5 play coordinated roles in rodent models of inflammation, insulin resistance, and atherosclerosis, but little is known of their role in human disease. The aim of this study was to examine the hypothesis that plasma adipocyte and macrophage FABP4 and FABP5 levels would provide additive value in the association with metabolic and inflammatory risk factors for cardiovascular disease as well as subclinical atherosclerosis. Using the Penn Diabetes Heart Study (PDHS; n = 806), cross-sectional analysis of FABP4 and FABP5 levels with metabolic and inflammatory parameters and with coronary artery calcium, a measure of subclinical coronary atherosclerosis, was performed. FABP4 and FABP5 levels had strong independent associations with the metabolic syndrome (for a 1-SD change in FABP levels, odds ratio [OR] 1.85, 95% confidence interval [CI] 1.43 to 2.23, and OR 1.66, 95% CI 1.41 to 1.95, respectively) but had differential associations with metabolic syndrome components. FABP4 and FABP5 were also independently associated with C-reactive protein and interleukin-6 levels. FABP4 (OR 1.26, 95% CI 1.05 to 1.52) but not FABP5 (OR 1.13, 95% CI 0.97 to 1.32) was associated with the presence of coronary artery calcium. An integrated score combining FABP4 and FABP5 quartile data had even stronger associations with the metabolic syndrome, C-reactive protein, interleukin-6, and coronary artery calcium compared to either FABP alone. In conclusion, this study provides evidence for an additive relation of FABP4 and FABP5 with the metabolic syndrome, inflammatory cardiovascular disease risk factors, and coronary atherosclerosis in type 2 diabetes mellitus. These findings suggest that FABP4 and FABP5 may represent mediators of and biomarkers for metabolic and cardiovascular disease in type 2 diabetes mellitus.

BackgroundCKD, an independent risk factor for CV disease, increases mortality in T2DM. Treating modifiable CV risk factors decreases mortality in diabetics with microalbuminuria, but the role of early CV prevention in diabetics with mild CKD by GFR criteria alone remains unclear. The purpose of this study was to probe whether T2DM patients with mild GFR impairment have atherogenic lipid profiles compared to diabetic counterparts with normal renal function.MethodsIn the Penn Diabetes Heart Study (PDHS), a single-center observational cohort of T2DM patients without clinical CVD, cross-sectional analyses were performed for directly measured lipid fractions in 1852 subjects with eGFR>60 mL/min/1.73 m2 determined by the CKD-EPI equation (n = 1852). Unadjusted and multivariable analyses of eGFR association with log-transformed lipid parameters in incremental linear and logistic regression models (with eGFR 90 mL/min/1.73 m2 as a cut-point) were performed.ResultsMild GFR impairment (eGFR 60–90 mL/min/1.73 m2, median urinary ACR 5.25 mg/g) was associated with higher log-transformed Lp(a) values (OR 1.17, p = 0.005) and with clinically atherogenic Lp(a) levels above 30 mg/dL (OR 1.35, p = 0.013) even after full adjustment for demographics, medications, metabolic parameters, and albuminuria. Logistic regression demonstrated a trend towards significance between worse kidney function and apoB (p = 0.17) as well as apoC-III (p = 0.067) in the fully adjusted model.ConclusionsElevated Lp(a) levels have a robust association with mild GFR impairment in type 2 diabetics independent of race, insulin resistance, and albuminuria.

Scope Fish oil-derived n-3 PUFA may improve cardiometabolic health through modulation of innate immunity; however, findings in clinical studies are conflicting. We hypothesized that n-3 PUFA supplementation would dose-dependently reduce the systemic inflammatory response to experimental endotoxemia in healthy humans. Methods and Results The Fenofibrate and omega-3 Fatty Acid Modulation of Endotoxemia (FFAME) study was an 8-week randomized double-blind trial of placebo or n-3 PUFA supplementation (Lovaza 465mg EPA + 375mg DHA) at “low” (1/day, 900mg) or “high” (4/day, 3,600mg) dose in healthy individuals (N=60; age 18–45; BMI 18–30; 43% Female; 65% European-, 20% African-, 15% Asian-ancestry) before a low-dose endotoxin challenge (LPS 0.6ng/kg intravenous bolus). The endotoxemia-induced temperature increase was significantly reduced with high-dose (P =0.03) but not low-dose EPA+DHA compared to placebo. Although there was no statistically significant impact of EPA+DHA on individual inflammatory responses (TNFα, IL-6, MCP-1, IL-1RA, IL-10, CRP, SAA), there was a pattern of lower responses across all biomarkers with high-dose (9 of 9 observed), but not low-dose EPA+DHA. Conclusions EPA+DHA at 3,600mg/day, but not 900mg/day, reduced fever and had a pattern of attenuated LPS-induction of plasma inflammatory markers during endotoxemia. Clinically and nutritionally relevant long-chain n-3 PUFA regimens may have specific, dose-dependent, anti-inflammatory actions.