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Researchers identify contrasting associations between major lipid subfractions and risk for CAD, diabetes
A recent study published in JAMA Cardiology found that increased LDL, HDL and triglyceride levels are associated with lower diabetes risk, while increased LDL and triglyceride levels are associated with increased risk for CAD.
“Although further studies are needed to examine whether specific pathways or lipid subtypes are implicated, our findings inform potential expected downstream consequences of interventions affecting lipid traits and provide cautionary evidence that therapeutics that lower LDL and [triglyceride] levels may have dysglycemic effects,” Michael V. Holmes, MD, PhD, of the University of Oxford, England, and colleagues wrote in the study.
Holmes and colleagues used data from multiple cardiometabolic genome-wide association studies and mendelian randomization to evaluate the link between routinely measured lipid fractions and risk for CAD and diabetes. The pooled data set included 188,577 patients with measures of blood lipids, 63,158 CAD cases and 34,840 diabetes cases.
A total of 130 single-nucleotide polymorphisms (SNPs) were used for LDL, which explained 7.9% of its variance; 140 SNPs for HDL, which explained 6.6% of its variance; and 140 SNPs for triglycerides, which explained 5.9% of its variance, according to the researchers.
A genetically instrumented increase of 1 standard deviation (SD) in LDL (equivalent to 38 mg/dL) and triglycerides (equivalent to 89 mg/dL) was linked to a higher risk for CAD (OR for LDL = 1.68; 95% CI, 1.51-1.87; OR for triglycerides = 1.28; 95% CI, 1.13-1.45) The OR for HDL and CAD risk was 0.95 (95% CI, 0.85-1.06).
All three lipid traits were linked with to a lower risk for type 2 diabetes (OR for LDL per 1-SD increase = 0.79; 95% CI, 0.71-0.88; OR for HDL = 0.83; 95% CI, 0.76-0.9; OR for triglycerides = 0.83; 95% CI, 0.72-0.95).
In a related editorial, Danish Saleheen, MBBS, PhD, from the University of Pennsylvania, Philadelphia, and colleagues, noted that the findings from the study “will no doubt fuel the controversy on the causal association of major plasma lipids with type 2 diabetes.
“While [mendelian randomization] studies have been successful in solving the causal relevance of major lipids in CHD (LDL and triglycerides, yes, and HDL, no), it seems that other approaches are required to further evaluate the causal relevance of each of these lipid fractions in association with type 2 diabetes. The importance of this issue is clear: it has potential to provide new insights into the pathogenesis of type-2 diabetes and has implications for the effect of specific lipid-altering therapies in the development of type-e diabetes,” Saleheen and colleagues wrote. – by Dave Quaile
Disclosure: One researcher reports receiving honoraria for advisory boards or lectures for Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Merck, Novo Nordisk and Sanofi.