New treatment options for lipid-lowering therapy in subjects with type 2 diabetes

Abstract

Dyslipidemias represent a variety of quantitative and/or qualitative lipoprotein abnormalities. According to etiology, we distinguish primary dyslipidemias with strictly genetic background and secondary ones with their origin in other disease or pathological states. Diabetic dyslipidemia is a type of secondary dyslipidemia and plays an important role in determining the cardiovascular risk of subjects with type 2 diabetes. In these patients, insulin resistance is responsible for overproduction and secretion of atherogenic very low density lipoprotein. In addition, insulin resistance promotes the production of small dense low-density lipoprotein (LDL) and reduces high-density lipoprotein (HDL) production. Cardiovascular disease remains a leading cause of morbidity and mortality in diabetic patients. Previous results support the role for small, dense LDL particles in the etiology of atherosclerosis and their association with coronary artery disease. Moreover, lowering LDL cholesterol reduces the risk of cardiovascular death. Therefore, the European guidelines for the management of dyslipidemias recommend an LDL cholesterol goal < 100 mg/dL in diabetic subjects without cardiovascular events. Moreover, if triglycerides (TG) are elevated (> 400 mg/dL), they recommend a non-HDL cholesterol goal < 130 mg/dL in diabetic individuals without cardiovascular events. Statins are the first line of LDL-lowering therapy in diabetic patients and combined therapy with ezetimibe and statins could be useful in very high cardiovascular risk diabetic subjects. Furthermore, the effect of a fibrate as an add-on treatment to a statin could improve the lipid profile in diabetic individuals with high TG and low HDL cholesterol. Regarding new therapies, recent data from phase III trials show that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors considerably decrease LDL cholesterol. Thus, they may be useful in diabetic patients with concomitant diseases such as familial dyslipidemia, recurrent cardiovascular events, and elevated LDL cholesterol after second drug administration in addition to maximal statin dose or statin intolerance.

Effect of Resveratrol on Blood Lipid Levels in Patients with Type 2 Diabetes: A Systematic Review and Meta‐Analysis

“…High blood lipid levels affect both the macrovascular system, promoting the occurrence of coronary heart disease and cerebral infarction, and the microvascular system, promoting diabetic microvascular diseases such as diabetic nephropathy and retinopathy. Thus, high blood lipid levels can result in serious damage to systemic blood vessels and organs . Although statins can influence blood lipid levels, the incidence of vascular events remains elevated after statin therapy.…”

HbA1c showed a positive association with carcinoembryonic antigen (CEA) level in only diabetes, not prediabetic or normal individuals

“…The associations among diabetes, metabolic syndrome, dyslipidemia, and cardiovascular disease (CVD) are well known: Diabetes mellitus is associated with an increased risk of CVD, and dyslipidemia is common in diabetes ; additionally, HbA1c was associated with subclinical cardiac alterations . Although tight lipid control in diabetes is recommended to improve the cardiovascular outcomes, interestingly, dyslipidemia treated with lipophilic statin impairing mitochondrial function in pancreatic islets might have caused type 2 diabetes in reverse . On the other hand, CEA levels were reported to be associated with metabolic syndrome and coronary artery disease .…”

“…30 Although tight lipid control in diabetes is recommended to improve the cardiovascular outcomes, interestingly, dyslipidemia treated with lipophilic statin impairing mitochondrial function in pancreatic islets might have caused type 2 diabetes in reverse. 31,32 On the other hand, CEA levels were reported to be associated with metabolic syndrome and coronary artery disease. 33,34 Moreover, the lipid profiles have been reported to be significantly associated with colon cancer.…”

Association of small dense low-density lipoprotein with cardiovascular outcome in patients with coronary artery disease and diabetes: a prospective, observational cohort study

“…In both European Society of Cardiology/European Atherosclerosis Society (ESC/ EAS) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines, patients with DM and ASCVD were defined as very high risk individuals and intensive LDL-C lowering treatment was highly recommended [1,2]. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor considerably decreased LDL-C and could be useful in reducing the risk of events in patients with DM and ASCVD receiving maximally tolerated statin [32,33]. However, routine lipid measures may not well reflect the compositional changes of lipid parameters in DM and Pre-DM patients.…”