Clinical Update: Cardiovascular Disease in Diabetes Mellitus

Wang, Cecilia C. Low; Hess, Connie N.; Hiatt, William R.; Goldfine, Allison B.

doi:10.1161/circulationaha.116.022194

Cited by 837 publications

(383 citation statements)

References 521 publications

(629 reference statements)

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“…In the setting of multifactorial risk reduction with statins and other lipid-lowering agents, antihypertensive therapies, and antihyperglycemic treatment strategies, cardiovascular disease rates are falling, yet remain higher for patients with diabetes mellitus than for those without [50•]. Most guidelines have recognized the significantly increased risk of ASCVD in people with diabetes mellitus, although not necessarily considering them to have CHD equivalence.…”

Section: Current Treatment Guidelinesmentioning

confidence: 99%

Treatment of Dyslipidemias to Prevent Cardiovascular Disease in Patients with Type 2 Diabetes

et al. 2017

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Purpose of Review Current preventive and treatment guidelines for type 2 diabetes have failed to decrease the incidence of comorbidities, such as dyslipidemia and ultimately heart disease. The goal of this review is to describe the physiological and metabolic lipid alterations that develop in patients with type 2 diabetes mellitus. Questions addressed include the differences in lipid and lipoprotein metabolism that characterize the dyslipidemia of insulin resistance and type 2 diabetes mellitus. We also examine the relevance of the new AHA/ADA treatment guidelines to dyslipidemic individuals. Recent Findings In this review, we provide an update on the pathophysiology of diabetic dyslipidemia, including the role of several apolipoproteins such as apoC-III. We also point to new studies and new agents for the treatment of individuals with type 2 diabetes mellitus who need lipid therapies. Summary Type 2 diabetes mellitus causes cardiovascular disease via several pathways, including dyslipidemia characterized by increased plasma levels of apoB-lipoproteins and triglycerides, and low plasma concentrations of HDL cholesterol. Treatments to normalize the dyslipidemia and reduce the risk for cardiovascular events include the following: lifestyle and medication, particularly statins, and if necessary, ezetimibe, to significantly lower LDL cholesterol. Other treatments, more focused on triglycerides and HDL cholesterol, are less well supported by randomized clinical trials and should be used on an individual basis. Newer agents, particularly the PCSK9 inhibitors, show a great promise for even greater lowering of LDL cholesterol, but we await the results of ongoing clinical trials.

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Section: Current Treatment Guidelinesmentioning

confidence: 99%

Treatment of Dyslipidemias to Prevent Cardiovascular Disease in Patients with Type 2 Diabetes

et al. 2017

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“…Diabetes mellitus (DM) is associated with a high prevalence of atherosclerotic cardiovascular disease (ASCVD), including coronary heart disease, ischaemic stroke and peripheral arterial disease, and ASCVD is the main cause of mortality and morbidity among those with DM 1, 2, 3. Furthermore, individuals with both DM and ASCVD represent a particularly high‐risk group, with a higher risk of further ASCVD events compared with individuals with ASCVD but without DM 4, 5, 6…”

Section: Introductionmentioning

confidence: 99%

“…This is supported by data from randomized clinical trials and meta‐analyses showing that treatment with statins reduces LDL‐C levels and ASCVD risk in individuals with DM 11, 12, 13. DM is commonly associated with diabetic dyslipidaemia, including elevated triglycerides and reduced levels of high‐density lipoprotein cholesterol (HDL‐C), and with an increased number of small dense LDL particles and apolipoprotein (apo) B‐containing particles, which is thought to contribute to the increased risk level associated with DM 3, 14. Because of this, some guidelines have suggested using non‐HDL‐C, representative of the sum total of all atherogenic cholesterol‐containing particles, as an alternative or secondary treatment target for LDL‐C 8, 9, 15.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of alirocumab among individuals with diabetes mellitus and atherosclerotic cardiovascular disease in the ODYSSEY phase 3 trials

Ganda

Plutzky

Sanganalmath

et al. 2018

Diabetes Obesity Metabolism

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AimsIndividuals with both diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD) are at very high risk of cardiovascular events. This post‐hoc analysis evaluated efficacy and safety of the PCSK9 inhibitor alirocumab among 984 individuals with DM and ASCVD pooled from 9 ODYSSEY Phase 3 trials.Materials and methodsChanges in low‐density lipoprotein cholesterol (LDL‐C) and other lipids from baseline to Week 24 were analysed (intention‐to‐treat) in four pools by alirocumab dosage (150 mg every 2 weeks [150] or 75 mg with possible increase to 150 mg every 2 weeks [75/150]), control (placebo/ezetimibe) and background statin usage (yes/no).ResultsAt Week 24, LDL‐C changes from baseline in pools with background statins were −61.5% with alirocumab 150 (vs −1.0% with placebo), −46.4% with alirocumab 75/150 (vs +6.3% with placebo) and −48.7% with alirocumab 75/150 (vs −20.6% with ezetimibe), and −54.9% with alirocumab 75/150 (vs +4.0% with ezetimibe) without background statins. A greater proportion of alirocumab recipients achieved LDL‐C < 70 and < 55 mg/dL at Week 24 vs controls. Alirocumab also resulted in significant reductions in non‐high‐density lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) vs controls. Alirocumab did not appear to affect glycaemia over 78‐104 weeks. Overall safety was similar between treatment groups, with a higher injection‐site reaction frequency (mostly mild) with alirocumab.ConclusionAlirocumab significantly reduced LDL‐C and other atherogenic lipid parameters, and was generally well tolerated in individuals with DM and ASCVD.

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“…This distinct process, termed diabetic cardiomyopathy, was first described over four decades ago. Diabetic cardiomyopathy is characterised by the initial impairment of left ventricular (LV) relaxation, with later impairment of LV contractile function 101. The pathophysiological mechanisms underlying diabetic cardiomyopathy are multifactorial and complex, and include an increase in oxidative stress, inflammation, myocardial fibrosis, cardiomyocyte hypertrophy and diastolic dysfunction, as recently reviewed in detail102 (Figure 1).…”

Section: Diabetic Cardiomyopathy Antioxidant Defences and Immunothermentioning

confidence: 99%

Recent novel approaches to limit oxidative stress and inflammation in diabetic complications

et al. 2018

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Diabetes is considered a major burden on the healthcare system of Western and non‐Western societies with the disease reaching epidemic proportions globally. Diabetic patients are highly susceptible to developing micro‐ and macrovascular complications, which contribute significantly to morbidity and mortality rates. Over the past decade, a plethora of research has demonstrated that oxidative stress and inflammation are intricately linked and significant drivers of these diabetic complications. Thus, the focus now has been towards specific mechanism‐based strategies that can target both oxidative stress and inflammatory pathways to improve the outcome of disease burden. This review will focus on the mechanisms that drive these diabetic complications and the feasibility of emerging new therapies to combat oxidative stress and inflammation in the diabetic milieu.

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Clinical Update: Cardiovascular Disease in Diabetes Mellitus

Cited by 837 publications

References 521 publications

Treatment of Dyslipidemias to Prevent Cardiovascular Disease in Patients with Type 2 Diabetes

Treatment of Dyslipidemias to Prevent Cardiovascular Disease in Patients with Type 2 Diabetes

Efficacy and safety of alirocumab among individuals with diabetes mellitus and atherosclerotic cardiovascular disease in the ODYSSEY phase 3 trials

Recent novel approaches to limit oxidative stress and inflammation in diabetic complications

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