Experts Discuss Diabetic Dyslipidemia

San Francisco—Diabetic dyslipidemia is a well-recognized factor for atherosclerotic cardiovascular disease. Characteristic dyslipidemia of insulin resistance and type 2 diabetes presents with a triad of lipid abnormalities, including low–high-density lipoprotein cholesterol, hypertriglyceridemia, and qualitative low-density lipoprotein (LDL) particle changes. Hypertriglyceridemia is closely linked to elevated hepatic very-LDL, elevated apolipoprotein B levels, postprandial hyperlipidemia, and elevated remnant particles.

“Collectively, the change in lipid profile from the insulin sensitive state to the insulin resistance state contributes to the elevated risk of coronary heart disease [(CHD)],” said Changting Xiao, PhD, Banting and Best Diabetes Centre, University of Toronto. He was 1 of several expert presenters at a symposium at the ADA meeting.

Incretin-based therapies—glucagon-like peptide-1 (GLP-1) mimetics or the GLP-1 agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors—have demonstrated efficacy in blood glucose lowering. “Recent evidence in clinical trials and some mechanistic studies have also suggested that these incretin-based therapies may improve lipid profiles,” he said. Clinical trials have shown that GLP-1 receptor agonists improved lipid profiles in patients with type 2 diabetes. For example, a study of the GLP-1 agonist, liraglutide, published by Hermansen et al in 2013 in Diabetes, Obesity and Metabolism found that use of liraglutide for 3 weeks suppressed postprandial triglycerides and apolipoprotein B-48.

“Many of these studies, due to their nature on the effects on postprandial lipids, may be attributed to the multiple physiologic actions of the GLP-1, including slow gastric emptying,” he explained.

Similar effects on postprandial lipids were also found with DDP-4 inhibitors. Dr. Xiao referenced a study conducted by Eliasson et al and published in Diabetologia in 2012, which found use of alogliptin at 16 weeks reduced total postprandial triglycerides and apolipoprotein B-48.

Overall, secretion of the hepatic very-LDL is characeteristic of patients with insulin resistance and represents a major factor in high prevalence of premature atherosclerosis, according to Murray W. Huff, PhD, professor, biochemistry and medicine, University of Western Ontario. He continued the symposium with a presentation on emerging nutraceuticals and lipid metabolism.

He noted that the search for therapeutics continues, but it is “abundantly clear that as the incidence of metabolic syndrome and type 2 diabetes increases, conventional therapies for dyslipidemia, diabetes, and their cardiovascular complications are insufficient to meet the rising demand.” As a result, therapeutics derived from functional foods have emerged as promising agents.

To illustrate this point, Dr. Huff discussed flavonoids. They are powerful, biological molecules derived from a variety of foods that show potential therapeutic efficacy. He mentioned 3 flavonoids: (1) epigallocatechin gallate (EGCG), found in green tea; (2) epicatechin gallate (ECG), found in cocoa; and (3) nobiletin, found in citrus fruits. These 3 flavonoids have epidemiological evidence, have the ability to show mechanism both in vitro and in vivo, and have sufficient bioavailibility to show therapeutic benefit. Dr. Huff reviewed the evidence by Munir et al published in American Journal of Physiology-Endocrinology and Metabolism in 2013 on EGCG and ECG.

Data from epidemiological studies of EGCG showed that the consumption of green tea was associated with decreased all-cause mortality, cardiovascular mortality, and type 2 diabetes. Additionally, meta-analyses demonstrated that green tea consumption lowered both total and LDL cholesterol levels and improved endothelial function. Epidemiological studies of ECG revealed an inverse relationship between cocoa consumption and blood pressure, stroke, myocardial infarction, CHD, and cardiovascular mortality, he explained.

While translation to clinical use has started with some flavonoids, Dr. Huff noted, “Attention to dose and pharmacology is particularly important, because as a class, these flavonoids tend to have relatively low bioavilability, so attention to improving bioavailability is going to be important as we move forward.”

Currently, statins remain the first-line therapy in reducing cholesterol. Gary F. Lewis, MD, Toronto General Hospital, discussed statins in diabetic therapy and potential safety concerns. While evidence has shown good outcomes with statins, particularly in type 2 diabetes, safety concerns have been raised with statins and new-onset diabetes, according to Dr. Lewis. He mentioned that diabetes risk is related to the intensity of statin therapy. It is possible that statin therapy can accelerate the onset of diabetes by a few months in susceptible prediabetic patients.

“I do not think we can ignore this relationship between statins and increasing glucose, but it is a small increase in glucose,” he said. “Selecting appropriate patients is very important and so is addressing other risks and factors that cause diabetes, such as healthy body weight.”

Dr. Lewis outlined recommendations for clinicians starting statins in the absence of known diabetes:

     • Assess risk factors for diabetes
     • Use statins in accordance with guidelines to lower cardiovascular risk, unless contraindicated
     • If diabetes develops on statin therapy, it is not necessary to withdraw the statin; however,
       clinicians should continue to emphasize weight maintenance, diet, and activity, and should start
       hypoglycemic therapy as indicated

The recommendations given by Dr. Lewis will help to customize statin therapy for patients by taking the individual’s risk factors into account.—Eileen Koutnik-Fotopoulos