Abstract
apoM is a minor HDL apolipoprotein and carrier for sphingosine-1-phosphate (S1P). HDL apoM and S1P concentrations are inversely associated with atherosclerosis progression in rodents. We evaluated associations between plasma concentrations of S1P, plasma concentrations of apoM, and HDL apoM levels with prevalent subclinical atherosclerosis and mortality in the African American-Diabetes Heart Study participants (N = 545). Associations between plasma S1P, plasma apoM, and HDL apoM with subclinical atherosclerosis and mortality were assessed using multivariate parametric, nonparametric, and Cox proportional hazards models. At baseline, participants' median (25th percentile, 75th percentile) age was 55 (49, 62) years old and their coronary artery calcium (CAC) mass score was 26.5 (0.0, 346.5). Plasma S1P, plasma apoM, and HDL apoM were not associated with CAC. After 64 (57.6, 70.3) months of follow-up, 81 deaths were recorded. Higher concentrations of plasma S1P [odds ratio (OR) = 0.14, P = 0.01] and plasma apoM (OR = 0.10, P = 0.02), but not HDL apoM (P = 0.89), were associated with lower mortality after adjusting for age, sex, statin use, CAC, kidney function, and albuminuria. We conclude that plasma S1P and apoM concentrations are inversely and independently associated with mortality, but not CAC, in African Americans with type 2 diabetes after accounting for conventional risk factors.
Highlights
Abstract apoM is a minor HDL apolipoprotein and carrier for sphingosine-1-phosphate (S1P)
Sex and increasing albuminuria were significantly associated with CAC, we found no significant associations between CAC and plasma S1P (P = 0.76), plasma apoM (P = 0.48), or HDL apoM (P = 0.97)
The present study tested to determine whether plasma S1P, plasma apoM, and HDL apoM concentrations are associated with subclinical atherosclerosis and mortality in African Americans with type 2 diabetes mellitus
Summary
The AA-DHS recruited unrelated African Americans at the Wake Forest School of Medicine from 2007 to 2010. Type 2 diabetes mellitus was clinically diagnosed based on disease onset after the age of 30 years in the absence of diabetic ketoacidosis and with active glucose-lowering treatment (insulin and/or oral agents), a fasting glucose 7.0 mmol/l (126 mg/dl), nonfasting glucose 11.1 mmol/l (200 mg/dl), or glycosylated hemoglobin (GHb) 48 mmol/mol (6.5%). Individuals with prior serum creatinine concentrations 176.8 mol/l (2 mg/dl) were not eligible. The study abides by the Declarations of Helsinki Principles and was approved by the Wake Forest School of Medicine Institutional Review Board and all participants provided written informed consent. Baseline assessments consisted of interviews for medical history, anthropometric measurements, blood pressures, fasting blood (glucose, serum creatinine, GHb, lipid panels), imaging, and a spot urine test for urine albumin:creatinine ratio (UACR). Estimated glomerular filtration rate (eGFR) was computed using the creatinine-based CKD-EPI equation [24]
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