Addressing Hypertriglyceridemia and Cardiovascular Risk in Diabetes

atherosclerosis, hyperlipidemia, hypercholesterolemia, dyslipidemia
There is growing evidence that the addition of triglyceride-lowering medication and lifestyle changes may be valuable in diabetes management.

In light of growing evidence that moderate hypertriglyceridemia contributes to cardiovascular risk, there is a need to look at the impact of lowering triglycerides in patients with the diabetic dyslipidemia phenotype.

What Defines Diabetic Dyslipidemia?

Diabetic dyslipidemia is characterized by a pattern of high triglycerides and low high-density lipoprotein (HDL) cholesterol, which is most frequently observed in people with type 2 diabetes.1 It may present several years before the onset of hyperglycemia and could be a treatable risk factor for subsequent cardiovascular disease.2

Triglycerides provide energy storage in adipose cells and transport esterified fatty acids when circulating in chylomicrons, very low-density lipoproteins (VLDL), and lipoprotein remnants.1 Hypertriglyceridemia is defined by excess triglycerides in the blood as a result of metabolic dysfunction, arising from surplus VLDL production or inefficient lipolysis.

Inefficient lipolysis occurs when HDL and low-density lipoprotein (LDL) particles undergo triglyceride enrichment.1 HDL particles lose apolipoproteins that aid in the assembly, transport, and metabolism of lipids, while LDL particles become smaller and more atherogenic.1,3 The classic presentation of diabetic dyslipidemia involves low levels of HDL, which has a protective role against heart disease through antioxidative and anti-inflammatory mechanisms.2 The dynamic interaction of high triglyceride levels and low HDL therefore yields an effect that contributes to cardiovascular risk.

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Are Triglycerides a Risk Factor for Heart Disease?

The relationship between triglycerides and coronary heart disease (CHD) is quite strong. “Raised serum triglycerides herald the development of type 2 diabetes mellitus, particularly when associated with other features of metabolic syndrome or CHD, and once diabetes has developed they continue to predict CHD risk, often independent of other risk factors,” wrote Jonathan D. Schofield, PhD, clinical lead for diabetes, endocrinology, and metabolic at the University of Manchester in the United Kingdom, and colleagues in a 2016 review.2

In multivariate analyses, including individual factors that are associated with hypertriglyceridemia — including obesity, elevated cholesterol levels, and glucose intolerance — somewhat attenuates the cardiovascular risk associated with elevated triglycerides. Still, risk for CHD is substantial in hypertriglyceridemia: fasting triglyceride levels of 230.09 to 398.23 mg/dL are linked to double the risk for CHD and fasting levels of 398.23 to 796.46 mg/dL are linked to a 9-fold increase in CHD risk.2