Metabolic Dyslipidemia and Cardiovascular Outcomes in Type 2 Diabetes Mellitus: Findings From the Look AHEAD Study

Abstract

Background Metabolic dyslipidemia (high triglyceride) and low high‐density lipoprotein cholesterol (HDL‐C) is highly prevalent in type 2 diabetes mellitus (T2DM). The extent to which diabetes mellitus–related abnormalities in the triglyceride–HDL‐C profile associates with cardiovascular disease (CVD) risk is incompletely understood. We evaluated the associations of triglyceride and HDL‐C status with CVD outcomes in individuals with T2DM. Methods and Results We analyzed data from 4199 overweight/obese adults with T2DM free of CVD with available data on triglyceride and HDL‐C at baseline (2001–2004) in the Look AHEAD (Action for Health in Diabetes) study. We used Cox proportional models to estimate hazard ratios (HRs) and 95% CIs of: (1) composite CVD outcome (myocardial infarction, stroke, hospitalization for angina, and/or death from cardiovascular causes); (2) coronary artery disease events; and (3) cerebrovascular accidents (stroke). Of the 4199 participants, 62% (n=2600) were women, with a mean age of 58 years (SD, 7), and 40% (n=1659) had metabolic dyslipidemia at baseline. Over a median follow‐up of 9.5 years (interquartile range, 8.7–10.3), 500 participants experienced the composite CVD outcome, 396 experienced coronary artery disease events, and 100 experienced stroke. Low HDL‐C was associated with higher hazards of the composite CVD outcome (HR, 1.36; 95% CI, 1.12–1.64 [ P =0.002]) and coronary artery disease events (HR, 1.46; 95% CI, 1.18–1.81 [ P =0.001]) but not stroke (HR, 1.38; 95% CI, 0.90–2.11 [ P =0.140]). Compared with patients with normal triglyceride and normal HDL, participants with metabolic dyslipidemia had higher risks of the composite CVD outcome (HR, 1.30; 95% CI, 1.03–1.63 [ P =0.025]) and coronary artery disease events (HR, 1.48; 95% CI, 1.14–1.93 [ P =0.003]) but not stroke (HR, 1.23; 95% CI, 0.74–2.05 [ P =0.420]). Conclusions In a large sample of overweight/obese individuals with T2DM, metabolic dyslipidemia was associated with higher risks of CVD outcomes. Our findings highlight the necessity to account for metabolic dyslipidemia in CVD risk stratification among patients with T2DM. Registration URL: https://www.lookaheadtrial.org ; Unique identifier: NCT00017953 .

Omega-3 fatty acids coordinate glucose and lipid metabolism in diabetic patients

“…These findings are noteworthy inasmuch as the association of diabetes mellitus and dyslipidemia is known to significantly increase the risk of cardiovascular complications [ 1 , 21 , 22 ], particularly coronary artery disease [ 23 , 24 ]. Furthermore, the diverse impact on glucose and lipid homeostasis shown by the different sources of n-3 PUFA might help explain numerous controversial results in studies examining the effects on n-3 PUFA consumption in people with T2DM [ 14 , 15 , 25 – 29 ].…”

“…Type 2 Diabetes Mellitus (T2DM) is commonly associated with dyslipidemia, leading to a higher risk of atherosclerosis and cardiovascular diseases [ 1 , 2 ]. Hypertriglyceridemia represents an important risk factor for atherosclerosis, especially in diabetic patients [ 3 ].…”

Inverse Association between High-Density Lipoprotein Cholesterol and Adverse Outcomes among Acute Ischemic Stroke Patients with Diabetes Mellitus

“…Previous studies have showed inconsistent results regarding the association between HDL-C levels and MACEs [ 8 , 28 , 29 , 30 ]. Our study showed a significantly higher risk of MACEs in lower HDL-C concentration groups than in higher HDL-C concentration groups.…”

Triglyceride-Rich Lipoproteins and Their Remnants as Silent Promoters of Atherosclerotic Cardiovascular Disease and Other Metabolic Disorders: A Review

“…Finally, yet importantly, in diabetic subjects, the increased risk of adverse cardiovascular events seems to be significantly modulated by hypertriglyceridemia. A recent analysis of the Action of Health in Diabetes (Look AHEAD) study comprising 4199 individuals emphasized that in overweight and obese diabetic patients, metabolic dyslipidemia, characterized by increased levels of TGs and decreased plasma concentration of HDL, is associated with a higher risk of atherosclerotic cardiovascular events [ 61 ]. Specifically, in middle-aged, non-insulin-treated diabetic men, lower adiponectin concentrations are connected to increased production of plasma thrombin, and plasma TGs substantially influence this association.…”