Diabetes Mellitus and Cardiovascular Disease: Exploring Epidemiology, Pathophysiology, and Treatment Strategies

Abstract

Diabetes mellitus (DM) affects 537 million people as of 2021, and is projected to rise to 783 million by 2045. This positions DM as the ninth leading cause of death globally. Among DM patients, cardiovascular disease (CVD) is the primary cause of morbidity and mortality. Notably, the prevalence rates of CVD is alarmingly high among diabetic individuals, particularly in North America and the Caribbean (46.0%), and Southeast Asia (42.5%). The predominant form of CVD among diabetic patients is coronary artery disease (CAD), accounting for 29.4% of cases. The pathophysiology of DM is complex, involving insulin resistance, β-cell dysfunction, and associated cardiovascular complications including diabetic cardiomyopathy (DCM) and cardiovascular autonomic neuropathy (CAN). These conditions exacerbate CVD risks underscoring the importance of managing key risk factors including hypertension, dyslipidemia, obesity, and genetic predisposition. Understanding the genetic networks and molecular processes that link diabetes and cardiovascular disease can lead to new diagnostics and therapeutic interventions. Imeglimin, a novel mitochondrial bioenergetic enhancer, represents a promising medication for diabetes with the potential to address both insulin resistance and secretion difficulties. Effective diabetes management through oral hypoglycemic agents (OHAs) can protect the cardiovascular system. Additionally, certain antihypertensive medications can significantly reduce the risk of diabetes-related CVD. Additionally, lifestyle changes, including diet and exercise are vital in managing diabesity and reducing CVD risks. These interventions, along with emerging therapeutic agents and ongoing clinical trials, offer hope for improved patient outcomes and long-term DM remission. This study highlights the urgent need for management strategies to address the overlapping epidemics of DM and CVD. By elucidating the underlying mechanisms and risk factors, this study aims to guide future perspectives and enhance understanding of the pathogenesis of CVD complications in patients with DM, thereby guiding more effective treatment strategies.

Keywords: cardiovascular and obesity; cardiovascular drugs; diabetes mellitus; hyperglycemia; hypertension; insulin resistance.

Fig. 1.

Global prevalence of cardiovascular disease among diabetic individuals. This figure illustrates the distribution of CVD in individuals diagnosed with DM in 13 countries. This visualization aims to underscore the global impact of cardiovascular complications among those with DM. CVD, cardiovascular disease; DM, diabetes mellitus; KSA, Kingdom of Saudi Arabia.

Fig. 2.

Geographic variation in CVD prevalence rates among T2DM individuals. This figure illustrates the prevalence rates of CVD among individuals with T2DM across various global regions, according to the International Diabetes Federation’s (IDF) classification system. The chart details prevalence percentages in regions such as Africa, Europe, the Middle East and North Africa, North America and the Caribbean, South and Central America, Southeast Asia, the Western Pacific (including China), and other nations. Notably, the highest CVD prevalence occurs in North America and the Caribbean, Southeast Asia, and the Western Pacific. CVD, cardiovascular disease; T2DM, type 2 diabetes mellitus.

Fig. 3.

Pathophysiology of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). This figure illustrates the distinct pathophysiological mechanisms underlying the development of T1DM and T2DM. Autoimmune processes in T1DM lead to the elimination of pancreatic $\beta$-cells that are responsible for insulin production. This process involves CD4+ and CD8+ T cells, as well as the infiltration of macrophages which damage the pancreatic islets, leading to inadequate secretion of insulin. In T2DM, pancreatic $\beta$-cell dysfunction impairs insulin secretion while IR hinders insulin action. These processes collectively contribute to dysfunction in the maintenance of glucose homeostasis and the onset of metabolic disorders associated with each type of DM. DM, diabetes mellitus.

Fig. 4.

Interactions of risk factor for diabetes mellitus (DM) and cardiovascular disease (CVD). This figure visually represents the complex interplay of modifiable and non-modifiable risk factors that contribute to the development of DM and CVD. This highlights their significance in screening and intervention strategies to mitigate potential CVD risks.

Fig. 5.

Anti-diabetic drug classes and their mechanisms of action. A summary of the various classes of oral antihyperglycemic agents (OHAs), also known as oral antihyperglycemic drugs (OADs), used in the treatment of type 2 diabetes mellitus (T2DM). This illustrates the pharmacotherapy options available for managing T2DM. ATP, adenosine triphosphate.

Fig. 6.

Macro and microvascular complications of DM and the mode of action of anti-diabetic drugs on different organs of the body. Fig. 6 portrays the complications of DM across different organs and tissues, highlighting the associated microvascular and macrovascular complications, as well as the therapeutic actions of anti-diabetic drugs. The left side details how DM impacts the brain, eyes, heart, kidneys, nerves, and extremities, leading to conditions such as retinopathy, CAD, nephropathy, neuropathy, and peripheral vascular diseases. On the right side, the diagram outlines how different classes of anti-diabetic drugs act on various organs of the body to alleviate these complications by modifying appetite, insulin sensitivity, glucose uptake, and other metabolic functions. CAD, coronary artery disease.

Fig. 7.

Overview of cardiovascular drug classes and their mechanism of action. Fig. 7 illustrates the diverse classes of cardiovascular drugs and their specific mechanisms of action within the cardiovascular system. It provides a comprehensive visual representation of the pharmacological strategies used to treat conditions ranging from hypertension to congestive heart failure, highlighting the targeted effects on either the heart or blood vessels [167, 168, 169, 170, 171, 172, 173]. ACE, angiotensin converting enzyme.

Fig. 8.

Comparison of lipid profiles in well-controlled vs. poorly controlled DM. This figure depicts the lipid profiles in well-controlled and poorly controlled cases of type 1 and type 2 diabetes mellitus, illustrating how lipid metabolism differs based on the level of diabetes management. The diagram emphasizes the impact of dyslipidemia on cardiovascular risk associated with diabetes. DM, diabetes mellitus.

Fig. 9.

Overview of anti-hyperlipidemic medications and their mechanism of action. Fig. 9 provides a comprehensive overview of the various classes of anti-hyperlipidemic drugs, detailing their unique mechanisms of action and the specific ways they reduce lipid levels. It serves to illustrate the diversity and specificity of pharmacological approaches to lipid control in the context of diabetes management.