A significant rise in the incidence of metabolic syndrome, i.e. obesity, insulin resistance and dyslipidemia, has amounted to the presumption of epidemic proportions for type 2 or insulin resistant diabetes mellitus.Diabetes mellitus (DM), now emerges as one of the biggest threats in the 21st century affecting approximately 400 million people round the globe [1]. It is the world's most prevalent non-communicable disease and is placed to be the leading cause of death in developed countries [2]. DM is a fragmented cluster of disorder with elevated levels of blood glucose in the body [3]. Type 2 DM is represented by a differential degree of insulin resistance and β-cell dysfunction leading to hyperglycemia [4]. Single gene disorders affecting the capacity of the pancreatic β cell to secrete insulin or the capacity of muscle [5], fat and liver cells to respond to insulin action are identified as the underlying reason for the incidence of the disorder [6]. Insulin binding in the plasma membrane to its receptor sets in motion a sequence of intracellular signaling pathways leading to a multitude of insulin action on proteins, transporters and transcription [7]. DM is associated with both macrovascular and microvascular complications which includes coronary artery disease, myocardial infarction, hypertension, peripheral vascular disease, retinopathy, end-stage renal disease and neuropathy [8].
Cardiovascular disease (CVD) is the most prevailing factor of death and morbidity in people with diabetes, justifying an interconnection between diabetes and CVD [9]. In the United States, CVD mortality rates are reported to be approximately 1.7 times higher among adults with DM than those without DM, predominantly contributing to higher stroke risk and myocardial infarction (MI) [10].
The pathological pathways and co-morbidities identified with CVD starts to appear early in the childhood. Of particular note, obesity coupled with an abnormal lipid profile is strongly correlated with IR in younger subjects. Multiple factors, such as obesity, irregular lipid profiles and IR play prominent roles in CVD development, as illustrated in the publications [11, 12].
Insulin promotes the usage of metabolic substrates in numerous tissues under physiological conditions. It facilitates glucose and fatty acid uptake in the cardiomyocytes, but prevents the use of fatty acids as a source of energy. Because of resistance to insulin, the pancreas overcompensates by secreting rising quantities of insulin leading to hyperinsulinemia [13].
Insulin resistance is characterized as a clinical state in which insulin imposes a lesser biological action as compared to the standard effect. This phenomenon is attributable to obvious irregularities in the insulin-stimulated glucose uptake in glycogen synthesis and, to a lesser degree during glucose oxidation. The implications of insulin resistance in tissue types rely heavily on both the tissue's physiological and metabolic functions. Due to excessive metabolic demand insulin resistance has significant impacts on the skeletal muscle, adipocytes and liver tissue, which impose to be the key targets for intracellular glucose transport as well as glucose and lipid metabolism [14]. Insulin resistance induces compromised glycogen synthesis and protein catabolism in skeletal muscles. It also inhibits lipoprotein lipase activity in adipocytes leading to greater production of free fatty acids and inflammatory cytokines such as IL-6, TNFα and leptin. In addition, the liver contributes for 30% of insulin-stimulated glucose removal and insulin resistance corresponds to reduced glucose production and fatty acid metabolism resulting in higher triglyceride content and hepatic VLDL secretion [15]. Insulin resistance promotes endothelial cell dysfunction by reducing endothelial cell development of nitric oxide and boosting the release of pro-coagulant factors contributing to platelet aggregation. The PI3 K cascade is impaired in an insulin-resistant state while the MAP kinase pathway is preserved, triggering the mitogenic impact of insulin in the endothelial cells progressing to atherosclerosis [16]. The overload of lipids carted through non-oxidant networks in the cardiomyocyte contributes to the accretion of toxic lipid products leading to lipotoxicity, which modifies cellular signaling and cardiac architecture. Interruptions in numerous cellular signaling pathways have been identified with lipotoxicity, mitochondrial dysfunction and endoplasmic reticulum stress being the dominant examples.
Reports have suggested alterations in the left ventricular architecture to increase the risk of CVD furthering to death. With left ventricular hypertrophy (LVH), the risk of acute myocardial infarction, congestive heart failure, sudden death, ventricular ectopy, extreme arrhythmias and other cardiovascular events raises 6 to 8 fold [17].
LVH, which contributes to an improvement in the left ventricular mass (LVM), raises a substantial risk of an upsurge in cardiovascular diseases and deaths caused by them.8 LVH can be minimized by removing the factors contributing to an increase in LVM, but the complexity of the factors causing an increase in LVM still appears to be fully explored among normotensive and even hypertensive people [18]. A previous study indicated that there was no improvement in LVM in 25–30% of people with high blood pressure. These findings advocate the perspective that metabolic and genetic factors play a pivotal role in the increase in heart mass [19].
In vivo studies have showcased that insulin resistance (IR) and hyperinsulinemia have an impact on LVM [20]. However, other publications have established the fact that an independent relationship between insulin level and heart mass existed, it has not been fully demonstrated that IR is an independent predictor of the increase in LVM [21, 22].
Patients with DM show changes in cardiac function and ultrastructure of cardiomyocytes which can be plausibly linked to the precipitation of DM. Echocardiographic studies on the macroscopic level studies suggest the disorder to be associated with localized left ventricular hypertrophy and increased heart mass, with moderately reduced left ventricular systolic output [23].
That insulin resistance is a cause or effect of heart failure, or both, is not currently completely substantiated. Insulin resistance is a important contributing factor linked to heart disease development including hypertension, left ventricular dysfunction and heart failure. In comparison, cardiac failure promotes insulin resistance and is associated with a higher for type 2 DM development [24].
With the progression of CVD due to compromised insulin signaling, the emergence of insulin resistance is presumably multi-pronged in the patients with heart failure. Appropriate pathways by which insulin resistance induces heart failure typically involves sympathetic over activity, depletion of skeletal muscle mass, sedentary lifestyle followed by patients, endothelial dysfunction with decreased skeletal muscle blood flow, and a consequence of increased circulating cytokines, such as TNF, on peripheral insulin sensitivity [25]. There is however a shortfall of research findings supporting the relationship between insulin resistance and cardiac mass in the elderly normotensive community.
The present piece of research work focuses on the assessment of the effect of insulin resistance on cardiac mass in the elderly normotensive people.
