Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links

Abstract

Type 2 diabetes mellitus (DM) is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD), which could lead to heart failure through a variety of mechanisms, including myocardial infarction and chronic pressure overload. Pathogenetic mechanisms, mainly linked to hyperglycemia and chronic sustained hyperinsulinemia, include changes in metabolic profiles, intracellular signaling pathways, energy production, redox status, increased susceptibility to ischemia, and extracellular matrix remodeling. The close relationship between type 2 DM and CVD has led to the common soil hypothesis, postulating that both conditions share common genetic and environmental factors influencing this association. However, although the common risk factors of both CVD and type 2 DM, such as obesity, insulin resistance, dyslipidemia, inflammation, and thrombophilia, can be identified in the majority of affected patients, less is known about how these factors influence both conditions, so that efforts are still needed for a more comprehensive understanding of this relationship. The genetic, epigenetic, and environmental backgrounds of both type 2 DM and CVD have been more recently studied and updated. However, the underlying pathogenetic mechanisms have seldom been investigated within the broader shared background, but rather studied in the specific context of type 2 DM or CVD, separately. As the precise pathophysiological links between type 2 DM and CVD are not entirely understood and many aspects still require elucidation, an integrated description of the genetic, epigenetic, and environmental influences involved in the concomitant development of both diseases is of paramount importance to shed new light on the interlinks between type 2 DM and CVD. This review addresses the current knowledge of overlapping genetic and epigenetic aspects in type 2 DM and CVD, including microRNAs and long non-coding RNAs, whose abnormal regulation has been implicated in both disease conditions, either etiologically or as cause for their progression. Understanding the links between these disorders may help to drive future research toward an integrated pathophysiological approach and to provide future directions in the field.

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 .…”

Lipid Lowering Oxopropanylindole Hydrazone Derivatives with Anti-oxidant and Anti-hyperglycemic Activity

“…The synthesis of target compounds is outlined in Scheme 1. The starting material DL-tryptophan methyl ester (1) was synthesized by our earlier reported procedure [16] which on reaction with substituted benzoyl chlorides in the presence of triethylamine afforded respective N-benzoyl tryptophan methyl esters (2)(3)(4). These esters on refluxing with hydrazine hydrate in ethanol gave the key intermediates 5-7.…”

“…The involvement of oxidative stress in combination with hyperlipidemia in the pathogenesis and development of atherosclerosis as well as type 2 diabetes has recently been reported [3]. There is growing evidence that hydroxyl free radicals are involved as major factor causing peroxidative damage to lipoproteins present in the blood, which are responsible for the onset and advancement of atherosclerosis [4].…”

Depressive symptoms in asymptomatic stage B heart failure with Type II diabetic mellitus

“…Like HF, Type II diabetic mellitus (T2DM) is a significant health problem, with rates expected to increase an estimated 25% over the next 7 years . T2DM is a significant comorbidity because, along with hypertension and obesity, it represents an independent risk factor for the development of HF . Like HF, T2DM is associated with chronic inflammation .…”

“…3 T2DM is a significant comorbidity because, along with hypertension and obesity, it represents an independent risk factor for the development of HF. 4,5 Like HF, T2DM is associated with chronic inflammation. 6 Among symptomatic HF patients, presence of T2DM predicts morbidity and mortality.…”