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Review
. 2023 Dec 25:16:11795514231220780.
doi: 10.1177/11795514231220780. eCollection 2023.

Cardiometabolic Risk Factors Associated With Type 2 Diabetes Mellitus: A Mechanistic Insight

Affiliations
Review

Cardiometabolic Risk Factors Associated With Type 2 Diabetes Mellitus: A Mechanistic Insight

Snigdha Chakraborty et al. Clin Med Insights Endocrinol Diabetes. .

Abstract

A complex metabolic condition referred to as Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR) and decreased insulin production. Obesity, dyslipidemia, hypertension, and chronic inflammation are just a few of the cardiometabolic illnesses that people with T2DM are more likely to acquire and results in cardiovascular issues. It is essential to comprehend the mechanistic insights into these risk variables in order to prevent and manage cardiovascular problems in T2DM effectively. Impaired glycemic control leads to upregulation of De novo lipogenesis (DNL), promote hepatic triglyceride (TG) synthesis, worsening dyslipidemia that is accompanied by low levels of high density lipoprotein cholesterol (HDL-C) and high amounts of small, dense low-density lipoprotein cholesterol (LDL-C) further developing atherosclerosis. By causing endothelial dysfunction, oxidative stress, and chronic inflammation, chronic hyperglycemia worsens already existing cardiometabolic risk factors. Vasoconstriction, inflammation, and platelet aggregation are caused by endothelial dysfunction, which is characterized by decreased nitric oxide production, increased release of vasoconstrictors, proinflammatory cytokines, and adhesion molecules. The loop of IR and endothelial dysfunction is sustained by chronic inflammation fueled by inflammatory mediators produced in adipose tissue. Infiltrating inflammatory cells exacerbate inflammation and the development of plaque in the artery wall. In addition, the combination of chronic inflammation, dyslipidemia, and IR contributes to the emergence of hypertension, a prevalent comorbidity in T2DM. The ability to target therapies and management techniques is made possible by improvements in our knowledge of these mechanistic insights. Aim of present review is to enhance our current understanding of the mechanistic insights into the cardiometabolic risk factors related to T2DM provides important details into the interaction of pathophysiological processes resulting in cardiovascular problems. Understanding these pathways will enable us to create efficient plans for the prevention, detection, and treatment of cardiovascular problems in T2DM patients, ultimately leading to better overall health outcomes.

Keywords: Type 2 diabetic mellitus (T2DM); cardiometabolic risk factors; cardiovascular diseases; diabetic nephropathy; dyslipidemia; hypertension; mortality; obesity.

Plain language summary

Understanding the factors that increase the risk of type 2 diabetes: Exploring how the body works Type 2 diabetes mellitus (T2DM) is a complex condition where the body struggles to use insulin properly and doesn’t produce enough of it. This often leads to other health issues like obesity, high cholesterol, high blood pressure, and chronic inflammation. These problems increase the risk of heart and blood vessel diseases in people with T2DM. To tackle these issues effectively, it’s crucial to understand the underlying mechanisms. When blood sugar levels are not controlled, the body starts making more fat and storing it in the liver, leading to high triglycerides and low levels of good cholesterol. This process can block arteries, causing heart problems. High blood sugar also damages blood vessel linings, making them inflamed and less functional. This inflammation, combined with other factors like high cholesterol and insulin resistance, can lead to high blood pressure. Chronic inflammation, where the body’s defense system stays active for too long, worsens these problems. In T2DM, inflammation occurs in fat tissues, making the situation even worse. Inflammatory cells infiltrate blood vessel walls, promoting plaque buildup and further worsening heart issues. Understanding these processes helps us develop better strategies to prevent, detect, and treat heart problems in people with T2DM. By targeting these mechanisms, doctors can create more effective plans to improve the overall health of individuals with diabetes and reduce the risk of cardiovascular diseases.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Summarized pathway representing the manifestation of cardiovascular disorder due to dyslipidemia in patients with T2DM. Abbreviations: FFA, free fatty acid; HDL, high density lipoprotein; HL, hepatic lipoprotein; IL, interleukin; LDL, low density lipoprotein; LDL-C, low density lipoprotein cholesterol; NO, nitric oxide; Sd-LDL, small dense low density lipoprotein; TG/TGA, triglyceride; TNF-α, tumor necrosis factor-α; VLDL, very-low density lipoprotein.
Figure 2.
Figure 2.
Crossover pathways in hypertension and IR that lead to the development of CVD. Abbreviations: ANG-I, Angiotensin-I; ANG-II, Angiotensin-II; H2O, water; IR, insulin resistance; Na+, sodium ion; NO, nitric oxide; T2DM, Type 2 diabetes mellitus.
Figure 3.
Figure 3.
Pathophysiology involved in the rise of CVD in obese diabetic individual. Abbreviations: AGE, advanced glycation end product; ANG-II, Angiotensin-II; FFA-Free fatty acid; IL6, interleukin6; ROS, Reactive Oxygen Species; TNF-α, tumor necrosis factor-α.
Figure 4.
Figure 4.
Physiological pathway that lead to development of CVD in diabetic nephropathy patients. Abbreviations: ANG II- Angiotensin II; JG cells, Juxtaglomerular cells; Na+, sodium ion; T2DM, Type 2 diabetes mellitus.
Figure 5.
Figure 5.
Interconnection between different cardiometabolic complications that results in development of CVD in T2DM. Abbreviations: FFA, free fatty acid; HDL-C, high density lipoprotein cholesterol; NO, nitric oxide; Sd-LDL, small dense low density lipoprotein; T2DM, Type 2 diabetes mellitus.
Figure 6.
Figure 6.
Major therapeutic targets for the management of cardiovascular disorder in T2DM patient. Abbreviations: ANG II, Angiotensin II; FFA, free fatty acid; HDL, high density lipoprotein; LDL, low density lipoprotein; NO, nitric oxide; T2DM, Type 2 diabetes mellitus.

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