Life-style-induced metabolic derangement and epigenetic changes promote diabetes and oxidative stress leading to NASH and atherosclerosis severity

  • Rai Ajit K. SrivastavaEmail author
Review Article


Energy imbalance resulting from high calorie food intake and insufficient metabolic activity leads to increased body mass index (BMI) and sets the stage for metabolic derangement influencing lipid and carbohydrate metabolism and ultimately leading to insulin resistance, dyslipidemia, and type 2 diabetes. 70% of cardiovascular disease (CVD) deaths occur in patients with diabetes. Environment-induced physiological perturbations trigger epigenetic changes through chromatin modification and leads to type 2 diabetes and progression of nonalcoholic fatty liver disease (NAFLD) and CVD. Thus, in terms of disease progression and pathogenesis, energy homeostasis, metabolic dysregulation, diabetes, fatty liver, and CVD are interlinked. Since advanced glycation end products (AGEs) and low-grade inflammation in type 2 diabetes play definitive roles in the pathogenesis of liver and vascular diseases, a natural checkpoint to prevent diabetes and associated complications appears to be the identification and management of prediabetes together with weight management, since 70% of prediabetic individuals develop diabetes during their life time, and every kg of weight increase is associated with up to 9% increase in diabetes risk. A good proportion of diabetes and obesity population have fatty liver that progresses to non-alcoholic steatohepatitis (NASH) and cirrhosis, and increased risk of hepatocellular carcinoma. Diabetes and NASH both have elevated oxidative stress, impaired cholesterol elimination, and increased inflammation that leads to CVD risk. This review addresses life-style-induced metabolic pathway derangement and how it contributes to epigenetic changes, type 2 diabetes and NASH progression, which collectively lead to increased risk of CVD.


Life-style Diabetes Epigenetic Cardiovascular NASH Inflammation Atherosclerosis 



very low-density lipoprotein


low-density lipoprotein


high-density lipoprotein


cardiovascular disease


non-alcoholic fatty liver disease


advanced glycation end-products


non-alcoholic steatohepatitis


metabolic syndrome


apolipoprotein A-I


body mass index


micro RNA


chronic obstructive pulmonary disease


histone deacetylase


histone acetyl transferase


type 2 diabetes mellitus


Vascular smooth muscle cells


monocyte chemoattractant protein 1


lysine-specific demethylase


vascular cell adhesion molecule 1


nuclear factor kappa B


cyclooxygenase 2


tumor necrosis factor-α


farnesoid X receptor


triglyceride-rich lipoproteins


reverse cholesterol transport


scavenger receptor class B type 1


ATP binding cassette transporter 1


hemoglobin A1c


receptor for advanced glycation end-products


Compliance with ethical standards

Conflict of interest

The author declares that there is no conflict of interest.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Integrated Pharma SolutionsPhiladelphiaUSA
  2. 2.Department of NutritionWayne State UniversityDetroitUSA

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