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DIABETES MELLITUS AND CHRONIC HEART FAILURE: CURRENT VIEWS ON THE PROBLEM
Salimova G.
Independent researcher, Tashkent medical academy
Najmutdinova D.
Doctor of Science, professor, Tashkent medical academy
Razakova F.
Independent researcher, National University of Uzbekistan
ABSTRACT
This article presents modern views on type 2 diabetes mellitus with its association with chronic heart failure. Keywords: type 2 diabetes mellitus, chronic heart failure, diabetic cardiomyopathy.
Currently, despite the development of high technologies, problems associated with type 2 diabetes mellitus (DM) remain, since the steady increase in this disease and the frequency of its serious consequences is of great concern to the global medical community. Thus, according to the World Diabetes Federation (IDF), there were more than 150 million patients in the world at the end of the 20th century, and according to WHO forecasts, the number of patients with type 2 diabetes will reach 333 million by 2025. Unfortunately, by the time of diagnosis of type 2 diabetes, half of the patients already have complications leading to a decrease in the quality of life, early disability and premature death [1]. This is due to consequences such as loss of vision, the development of terminal stages of renal failure, non-traumatic amputations, as well as complications associated with cardiovascular disease (CVD). It should be noted, according to numerous data in the literature [2], in diabetes cardiovascular disease occur 2-5 times more often than those without the disease. At the same time, there is a high risk of developing conditions such as coronary heart disease (CHD), myocardial infarction (MI), arterial hypertension (AH), and acute cerebrovascular accident (stroke). So, 69% of patients
with diabetes have dyslipidemia, 80% have hypertension, and 50-75% have diastolic dysfunction. Thus, today type 2 diabetes is regarded as the equivalent of the presence of a clinically pronounced cardiovascular disease in a patient, which indicates the need to pay special attention to this problem. As it is known, the main cause of deaths in 52% of patients with diabetes is chronic heart failure (CHF) [3].
It has now been proven that there is a two-way relationship between heart failure and type 2 diabetes, confirmed by pathogenetic studies, as well as a significantly worsening prognosis for the patient with a combination of these nosologies [4]. The Framingham study proved an increase in the risk of developing heart failure in patients with type 2 diabetes, compared with the general population, 2 times for men and 5 times for women [5]. As a result of epidemiological studies, it was found that the prevalence of heart failure among patients with diabetes is approximately 2.5 times higher than in the general population. It is noteworthy that according to the results of population studies, type 2 diabetes is a risk factor for developing heart failure, since the risk increases with increasing severity of type 2 diabetes [6,7]. Moreover, in diabetes, the predictors of
CHF are: high glycosylated hemoglobin (HbA1c), high body mass index (BMI), insulin therapy, terminal stages of chronic kidney disease (CKD), nephropathy, proteinuria, albuminuria, retinopathy [8, 9]. So, when comparing a group of patients with "isolated CHF" and patients with CHF with concomitant diabetes, it was found that with a combined pathology, the BMI level is much higher [10]. At the same time, an increase in HbA1c by 1% increases the risk of developing heart failure by 16%. In addition, in patients suffering from type 2 diabetes with coronary heart disease, an increase of 1% in HbA1c increased the risk of developing heart failure by 36% within 4 years of follow-up [11]. Also, numerous studies have demonstrated that patients with heart failure suffering from diabetes are much more likely to need hospitalization for heart failure. Thus, according to the studies of SAVE, VALIANT and CHARM program, it is precisely the increased need for hospitalization that became decisive in introducing hos-pitalization for CHF into the combined endpoint along with cardiovascular death in assessing cardiovascular safety of hypoglycemic drugs [12].
Data from various population and clinical studies show an increase in mortality among patients with heart failure with concomitant diabetes. So, the pathomor-phological and pathophysiological basis for the development of CHF in diabetes are: myocardial dystrophy, structural remodeling of the myocardium and heart as a whole, macroangiopathy of the coronary arteries, neu-rocardiopathy [13]. Moreover, left ventricular hypertrophy (LVH) is a strong independent risk factor for sudden death, myocardial infarction, stroke and other cardiovascular complications. An important role in the formation and progression of LVH is given to hemody-namic (overload by pressure of the left ventricle, in some cases by volume, decreased compliance of large arteries) and neurohumoral mechanisms (direct and indirect growth-promoting effects of norepinephrine and angiotensin II on myocardiocytes, increased myocar-dial fibrosis under the influence of angiotensin II and aldosterone) [14]. With LVH, coronary circulation is impaired, which is manifested by a decrease in the coronary vasodilator reserve and insufficient perfusion of the subendocardial layers of the myocardium. All this most often leads to LV systolic dysfunction. Thus, in patients with systolic form of CHF (S-CHF) not receiving hypoglycemic treatment, with HbA1c> 6.7%, the risk of death during the year was about 2 times higher compared to patients with HbA1c <6.7% [15]. This is due to the fact that type 2 diabetes leads to the development of myocardial fibrosis and impaired filling of the left ventricle (LV) with the subsequent formation of S-CHF, characterized by dilatation of the LV cavity and a decrease in its contractile function. It should be especially noted that the severity of the clinical course in S-CHF is determined by transferred MI (85.2%), while in a third of patients it is repeated [14]. In addition, patients with S-CHF are most often patients with coronary heart disease, with a reduced ejection fraction (EF), because according to published data, 2 years after myo-cardial infarction, LV size in patients with type 2 diabetes increases to a lesser extent, and heart failure occurs 2 times more often than in patients without type 2
diabetes [15]. However, in patients with diastolic heart failure, characterized by normal or reduced size of the LV cavity and preserved PV, the severity of the clinical course is determined opposite to AH (76.7%), overweight and obesity (39.5 and 33.7%) [15, 16].
Thus, the study of mechanisms for the implementation of the adverse effects of diabetes on the course of heart failure is an urgent issue in terms of the search for new therapeutic goals. It is clear that diabetes-associated heart damage is multifactorial. With all the evidence of the connection between diabetes, arterial hypertension and the pathology of the coronary arteries, there is epidemiological, clinical and experimental evidence of the presence of additional mechanisms for the development of heart failure in diabetes. The set of cardiac changes in diabetes, independent of IHD and arterial hypertension, is commonly called the term "diabetic cardiomyopathy." Morphological and structural changes typical for this syndrome are described; they include an increase in left ventricular myocardial mass, an increase in wall thickness and chamber volumes, myocardial fibrosis, and intracellular lipid accumulation. Functional changes include impaired left ventricular diastolic function, impaired systolic function, and decreased ventricular elasticity [17]. There is a notion of the staged development of diabetic cardiomyopathy. The concept of diabetic cardiomyopathy is based on the presence of a complex of diabetes-associated factors leading to changes at the molecular and cellular levels. Accumulating, these changes lead to structural and functional disorders of the heart, which ultimately manifest the development of heart failure. In addition to the immediate direct impact of diabetes on cardiac myo-cytes, fibroblasts and endothelial cells, on the course of heart failure may affect specific chronic diabetic complications. So, it was shown that diabetic cardiovascular autonomic neuropathy (DACN) is a factor in the progression of heart failure: the presence of autonomous neuropathy leads to a decrease in exercise tolerance, worsening of the clinical condition of patients and morphofunctional heart parameters [18], i.e. DACN is a factor worsening the quality of life of patients and combined with high mortality [19]. The risk of developing myocardial infarction with a combined course of heart failure and type 2 diabetes increases with ACN, the most dangerous manifestation of which is asymptomatic myocardial ischemia [19]. The relationship between DACN and the severity of LV hypertrophy was also noted. According to research [20], there is a reliable relationship between violations of the autonomic regulation of the heart, the severity of ACN in patients with heart failure and type 2 diabetes and structural and functional parameters of the heart: a statistically significant increase in the LV myocardial mass index and the incidence rate of adverse types of LV remodeling as the manifestations of ACN become more severe.
The main pathogenetic link in the development of type 2 diabetes is insulin resistance (IR), which increases with the progression of heart failure [20]. IR has a significant pathogenetic value in the development of not only diabetes, but also heart failure. Thus, target organ damage in patients in such a frequently encountered comorbid situation as CHF and type 2 diabetes
has its own pathogenetic features mediated by the presence of insulin resistance syndromes, lipo-, glucose toxicity, and cardiac sympathetic dysregulation. It should be noted that the heart, kidneys, liver, vascular bed are not only passive target organs in heart failure and type 2 diabetes, but also active participants in mal-adaptive remodeling: with their defeat, there is a further increase in the risk of cardiovascular complications, and their functional state has a significant impact on the prognosis and outcome of both heart failure and type 2 diabetes [21].
Thus, the association of these two pathologies significantly aggravates the course of each of them, and their combination is a decisive factor in high mortality in patients.
Conclusion. Regarding the etiopathogenesis of the studied comorbidity, it should be noted that the etiological relationship of type 2 diabetes and CHF is mutually directed. In conclusion, it is worth noting that due to the frequently encountered combination of diabetes, hypertension, and coronary artery disease, the question remains: in what cases is diastolic dysfunction directly caused by glycometabolic disorder, as well as in any compatible manifestations of all these diseases. From a clinical point of view, this fact justifies the need to prevent the development of heart failure in patients with diabetes through therapy, including comorbid conditions.
Thus, the conjugate course of type 2 diabetes and CHF largely determines the unfavorable prognosis in patients, creating difficulties in managing the latter for both cardiologists and endocrinologists.
From the present review, it becomes obvious that the frequency of the conjugate course of CHF and diabetes is quite high. At the same time, both the cause and the complication of diabetes can be considered simultaneously chronic heart failure, therefore, therapy in this category of patients should be characterized by an integrated approach, including careful glycemic control, as well as effective blockade of neurohumoral changes. At the same time, questions of cardiac safety and the benefits of certain representatives of the group of sugar-lowering drugs in patients with LV dysfunction remain, which determines the continuation of research in this area.
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