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MUTUAL INFLUENCE OF HEART FAILURE ON THE COURSE OF TYPE 2
DIABETES MELLITUS
Sotimova Shohida Mansurbek kizi
Student of Tashkent Kimyo International University
Abstract:
Chronic heart failure (CHF) is one of the most significant medical and social
pathologies characterized by a high prevalence and mortality. According to experts, CHF in
Western countries occurs in 1-2% of the general population, reaching 10% in people over 70
years of age. In the Russian Federation, CHF is diagnosed in 7-10% of cases, while more than
65% of Russian patients are people over 60 years old. In the structure of mortality from
diseases of the circulatory system, CHF occupies one of the leading positions 19, 13, 15,
16].Among the reasons leading to the development of CHF, arterial is traditionally considered -
hypertension (AH) and coronary heart disease (CHD), which occupy the largest share in the
structure of nosologies that cause the formation of heart failure (95.5% and 69.7%,
respectively). The classical causes of CHF (heart defects, cardiomyopathies, myocarditis, etc.)
are less common. At the same time, one of the frequent and significant diseases characterized
by the early development of heart failure is type 2 diabetes mellitus (DM), which has been
shown in a number of studies. In the Russian Federation, DM ranks third (15.9%) among the
causes of CHF [9, 13, 14]. In addition, the occurrence and progression of heart failure in
patients with DM is one of the main causes of death in this cohort of patients.
Key words:
diabetes mellitus, pharmacotherapy, ischemic cardiomyopathy, hypoglycemia,
multidisciplinary approach.
Pathogenetic relationships between CHF and type 2 diabetes
The above relationships between CHF and DM, in terms of increasing severity and accelerating
the progression of pathological manifestations, are explained by pathophysiological
relationships that have recently been intensively studied, supplemented by new facts and
theories. Previously The negative impact. Of DM on the development of CHF was considered
from the standpoint of the atherosclerotic concept, according to which heart failure develops as
a result of a multifactorial pathological process associated with changes in lipid metabolism,
hyperglycemia, insulin resistance, hypertension, which create conditions for the formation of
coronary artery disease, and later CHF. An undoubted contribution to the formation of CHF Is
made by developing diabetic cardiomyopathy. In recent years, the above concept has been
supplemented by a cardioreno-metabolic approach that considers the pathogenetic links
between DM and CHF from the point of view of mechanisms not related to the atherosclerotic
process. These include: impaired renal function, systemic inflammation, endothelial
dysfunction, activation of the sympathetic nervous system, renin-angiotensin-aldosterone
system, etc.. leading to an increase in myocardial stiffness, its hypertrophy, interstitial fibrosis,
and ultimately to heart failure [4]. The variety of pathogenetic bases for the development of
CHF in patients with DM determines the importance of adequate and justified, from the
standpoint of evidence-based medicine, pharmacotherapy. The latter should be considered
differentiated depending on the form of heart failure, namely the presence of systolic or
diastolic dysfunction of the left ventricle (LV), which are characterized by reduced or preserved
(respectively) ejection fraction (EF). In patients with DM, the development of the diastolic form
of CHF Predominates [4, 23).
Influence of type 2 diabetes on prognosis in CHF
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DM 2 has a significant adverse effect on the prognosis in individuals with various types of CHF.
According to major meta-analyses, it is considered in CHF with low LV ejection fraction (EF)
as a significant independent risk factor for death. Among in persons with CHF with low LV EF
and DM 2, the risk of decompensated heart failure (HF) is approximately 2 times higher than in
patients with CHF without diabetes. Individuals with a combination of these two conditions
also show a higher rate of repeated admissions to the hospital for CHF, and a lower quality life.
SD 2 negatively also affects course of CHF with preserved LV EF, increasing risk development
decompensation and mortality. Randomized controlled trials (RCTs) CHARM I and I-
PRESERVE [9, 10] have shown that these adverse effects of DM 2 in this variant of CHF may
be even more pronounced than in individuals with CHF with low LV EF.
Pathophysiological aspects of the development of CHF in patients with type 2 diabetes
In the development of CHF in type 2 diabetes, a key stimulating role is assigned to the changes
inherent in diabetes, including insulin resistance, hyperinsulinemia, hyperglycemia, and
accumulation of glycosylation end products (AGES) - advanced glycation end - products -
AGES [2, 11]. The impact of these factors determines the formation of three main
pathophysiological mechanisms: (1) accelerated atherosclerotic lesions of the coronary arteries
(due to increased proliferation of smooth muscle cells of the vascular wall, stimulation of
inflammation processes, thrombosis, endothelial dysfunction, creation of a highly atherogenic
variant of dyslipidemia) with an increased risk of myocardial ischemia (due to increased
vulnerability of atherosclerotic plaques), development of a heart attack, post- infarction LV
remodeling followed by a cascade of disorders leading to systolic and diastolic LV dysfunction
(the complex of these disorders is the so-called "ischemic cardiomyopathy"); (2) an increased
predisposition to the development of LV hypertrophy and increased fibrosis of its myocardium,
which leads to an increase in myocardial stiffness, impaired relaxation processes and an
increase in LV diastolic disorders; in the development of LV diastolic dysfunction, an important
role is played by disturbances in calcium homeostasis and dysfunction of the sarcoplasmic
reticulum inside myocardiocytes (MCC), as well as activation under the action of
hyperglycemia of the local renin- angiotensin-aldosterone system (RAAS) with
hyperproduction angiotensin II and aldosterone, which in turn further stimulates the
development of myocardial hypertrophy and fibrosis; (3) creation of conditions for an
imbalance in the energy balance of the MCC due to defects in the utilization of glucose and free
fatty acids, with the accumulation of lipids in the MCC, the formation of lipotoxicity, increased
apoptosis of the MCC and, ultimately, the development of impaired LV systolic function.
Among the important factors contributing to the formation of LV systolic disorders in DM 2 are
also an increase in the formation of active oxygen radicals in the mitochondria of the MCC
(mitochondrial dysfunction), a violation of the intracellular calcium balance, an increase in the
processes of inflammation and apoptosis of the MCC. Note that the complex of changes listed
above in paragraphs 2 and 3 constitutes the processes united by the general term " diabetic
cardiomyopathy." This designation was proposed back in 1972 [12]; it now means the presence
in a patient with type 2 diabetes diastolic and/or systolic LV dysfunction in the absence of other
than diabetes, clear reasons for the development of these disorders, including coronary heart
disease, arterial hypertension and valvular defects. The terms "ischemic cardiomyopathy" and
"diabetic cardiomyopathy" in the literature are more often used as pathophysiological rather
than clinical concepts; they are recognized as useful for a clearer understanding of the
mechanisms of CHF development in type 2 diabetes [13]. It is quite clear that in practice it is
difficult to distinguish between them; in each individual patient with DM 2 and CHF, they are
more likely to coexist, while the relative importance of each of them varies widely.
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Target levels of glycemia in people with DM 2 and CHF
The question of the optimal levels of HbAIC in individuals both with DM 2 in general and
when it is combined with CHF continues to be discussed. Although a more intense decrease in
glycemia with the achievement of relatively low (6.5-7.0%) levels of HhAIC is associated with
a decrease in the risk of microvascular complications of type 2 diabetes (retinopathy.
nephropathy, peripheral neuropathy ), and possibly the risk of developing myocardial infarction,
there is no decrease in the overall mortality. cardiovascular mortality and the frequency of
cerebral strokes while maintaining the indicated values of HbA1C. The largest RCTS UKPDS,
ADVANCE, ACCORD, VADT [14] showed no significant differences in the incidence of
cardiovascular complications, including those associated with CHF, between groups. with more
intensive glycemic control (mean HbA1C values 6.4-7.0%) and its less intensive control
(HbA1C levels 7.3-8.4%). Epidemiological studies and registries also indicate that the
relationship between HbAIC levels and mortality in individuals with type 2 diabetes and CHF is
U-shaped, with the lowest mortality rates correspond to HbA1C values in the range of 7.0-8.0%.
These data are reflected in the modern recommendations of the world's leading
endocrinological and cardiological associations [2], which indicate that: (1) HbA1C levels of
6.5-7.0% are suitable as targets mainly for those patients with DM 2 who have a sufficiently
long life expectancy and do not have significant comorbidities, complications of diabetes and
severe episodes of hypoglycemia; T2DM, who have a moderate and life expectancy, with the
presence of micro- and macro-vascular complications of diabetes, episodes of severe
hypoglycemia, significant comorbidities; it is these HbAIC values that experts recommend
using as targets for most patients with DM2 and CHF: (3) levels can be recognized as targets
for a limited category of the most severe patients with DM 2 with limited life expectancy,
pronounced micro and macrovascular complications of diabetes, severe concomitant diseases
(final stages of renal, respiratory failure or CHF, severe dementia, uncurable oncological
lesions).
The complexity of the treatment regimen
Persons with a combination of CHF and DM 2 usually require the appointment of a treatment
program consisting of many components, the implementation of which in many cases is
difficult for the patient. So, in order to achieve adequate glycemic control, the patient receives
recommendations from the doctor, including the choice of diet, level of physical activity,
control of div weight and emotional stress, monitoring the level of glycemia, taking
hypoglycemic drugs; particular attention will be drawn to the need to remain committed to all
these advice. In addition, the presence of CHF will entail recommendations to limit salt and
fluid intake, as well as the use of several necessary drugs. The complexity of prescriptions often
leads even motivated and careful patients to emphasize some of them as leaders at the expense
of others (for example, carefully control glycemic levels, ignoring div weight, etc. ), which
reduces the effectiveness of treatment. As the severity of CHF increases, it is the approaches to
its treatment that gain dominance in the eyes of the patient, and the diabetic component of the
treatment regimen goes to the second plan. This requires the attending physicians to
competently create an individual feasible treatment program that takes into account all the
necessary priorities; constant benevolent explanation and control [1-3].
Prospects:
The problem of the combination of CHF and DM 2 is extensive and requires further study.
Unresolved issues include (1) the reversibility of diabetic cardiomyopathy: (2) the optimal
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HbA1C target for individuals with different stages CHF: (3) the safety of hypoglycemic agents
in individuals with type 2 diabetes and high cardiovascular risk, including sulfonylurea drugs
(an ongoing RCT CAROLINA [20]) and DPP-4 (RCT MEASUREHF); (4) the possibility of
improving the prognosis against the background of the use of hypoglycemic drugs in CHF with
low and intact LV EF (RCT EMPEROR, DAPA HF, SOLOIST WHF); (5) the choice of
hypoglycemic agents for individuals with CHF and severe DNP (RCT DAPA-CKD, EMPA-
KIDNEY]); (6) choice of preferred B-AB and AMP in CHF and T2DM; (7) features of
treatment tactics for decompensated heart failure in patients with diabetes. Since both CHF and
DM 2 are chronic progressive diseases, their optimal control requires the combined efforts of
not only doctors of various specialties (a multidisciplinary approach - endocrinologists,
cardiologists, nephrologists, etc.), but also, which is especially important, of the patients and
their family members (which is referred to as an integrative approach).
Conclusion:
At the present stage of development of diabetology, the priorities in planning and
conducting large- scale randomized trials have changed. The results of historical studies of
UKPDS, ACCORD, ADVANCE. VADT, etc. have shown the important role of achieving
glycemic control in preventing the development and progression of chronic complications of
type 2 diabetes. At the same time, hypoglycemia and weight gain, as well as complex
pathophysiological mechanisms for the development and progression of DM 2, which limit the
possibility of optimal long-term treatment, have led to the creation of new pathogenetic
antidiabetic drugs. The question arose about the safety, and above all cardiovascular safety, of
new antidiabetic drugs. The American Agency for the Safety of Medicines and Foods FDA
defined requirements for pharmaceutical manufacturers, according to which an anti-diabetic
drug can be registered for use in real clinical practice based on data not only on sufficient
hypoglycemic potential (HbA1c dynamics of at least 0.6%) but also subject to cardiovascular
and general safety. The main endpoints associated with cardiovascular outcomes, the so-called
MACE ( major cardiovascular events); is the frequency of deaths associated with
cardiovascular events, non-fatal MI, and non-fatal stroke. Unfortunately, HF endpoints were not
included in the MACE list, which led most large randomized clinical trials to include HF as a
secondary endpoint or combined secondary endpoint. Thus, on the basis of the data obtained in
the course of these studies, it is not possible to obtain complete information, and therefore, there
are no grounds for formulating unambiguous conclusions. The data obtained only indicate the
high relevance of research in the field of studying the relationship between the course of DM 2
and HF, as well as a differentiated approach in the choice of antidiabetic therapy, taking into
account the presence of a high risk of developing HF in patients with DM2.
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