The Role of Somatotropic Deficiency in the Genesis of Coronary Heart Disease in Patients with Type 2 Diabetes Mellitus

The dissertation is devoted to the study of the role of acquired somatotropic deficiency (growth hormone deficiency) in the pathogenesis of coronary heart disease in patients with type 2 diabetes mellitus. The research examines the hormonal and metabolic mechanisms underlying the formation of macro- and microvascular complications of diabetes, including coronary atherosclerosis, with emphasis on the interrelationship between disorders of carbohydrate and lipid metabolism and growth hormone secretion.

The work analyzes clinical and biochemical parallels between somatotropic deficiency, dyslipoproteinemia, hyperglycemia, and hyperinsulinemia, as well as their influence on physical working capacity and intracardiac hemodynamics. The obtained results may be used for the diagnosis and complex correction of "late" vascular complications and coronary pathology in patients with type 2 diabetes mellitus.

Relevance of the problem.

At present, complications of coronary atherosclerosis and coronary heart disease (CHD) occupy a leading place in the structure of disability and mortality of patients with type 2 diabetes mellitus (DM). [3, 12]. DM is an acute medical and social problem belonging to the priority national health programs of virtually all countries of the world, protected by normative documents (acts) of the WHO. [8]. According to the WHO Expert Committee, more than 100 million people in the world suffer from diabetes mellitus; a tendency toward an increase in morbidity has been noted [6, 40]. The prevalence of DM is so great that further growth of the chronic hyperglycemia syndrome must be taken into account. The frequency of DM in Western countries составляет 2-5% of the population, while in developing countries it reaches 15%. Every 15 years the number of DM patients doubles. If in 1994 there were 120.4 million DM patients in the world, then by 2010 their number, according to forecasts of specialists, will amount to 239.3 million. [8, 76]. Vascular complications of diabetes mellitus (macro- and microangiopathies) significantly hinder the achievement of satisfactory glycemic compensation of diabetes, reduce the quality of life of patients, and require the development and adequate application of contemporary special therapeutic and preventive measures [6, 14].

In recent years, in countries that have achieved significant success in combating ischemic (coronary) heart disease, DM patients are the only population group in which mortality from this disease is slightly increasing [12]. The high risk of vascular complications in type 2 DM gave the American Diabetes Association (ADA) grounds to classify diabetes as a predictor of cardiovascular diseases [86].

It is known that in more than 60% of patients with type 2 DM, life expectancy is reduced due to the early development of CHD [72]. With the development of coronary pathology, atherosclerosis of the coronary arteries, angina pectoris and/or myocardial infarction, mortality of patients with type 2 DM is 2-4 times higher than the corresponding figure in the general population [128].

The rapid growth in the number of DM patients, the predominance among them of patients with type 2 DM, most of whom die from cardiovascular complications, turns the problem of coronary atherosclerosis into one of the most pressing problems of public health and health care. [6, 35].

Despite the fact that the general issues of development and progression of macro- and microvascular complications of DM have been studied sufficiently well, the metabolic component of the pathogenesis of this pathology requires clarification. The effect of postprandial hyperglycemia, oxidative stress, and changes in the concentration of counter-insular hormones on the clinical course of angiopathies has not been fully studied [3, 27]. In this regard, the study of the role of growth hormone deficiency, as the main "fat-mobilizing" hormone, in the genesis of macroangiopathies and other "late" complications of diabetes is of great interest.

Aim of the study.

To study the role of growth hormone deficiency (somatotropic deficiency) in the pathogenesis of coronary heart disease in patients suffering from type 2 diabetes mellitus.

Objectives of the study:

1. To study the influence of somatotropic deficiency on the course and progression of coronary atherosclerosis and CHD in patients with type 2 DM;

2. To carry out clinical and biochemical comparisons of somatotropic deficiency with other hormonal and metabolic disorders in the development and progression of type 2 DM;

3. To determine the role and place of growth hormone deficiency in the genesis of atherosclerosis and other lipid disorders;

4. To characterize the features of physical working capacity and intracardiac hemodynamics in patients with type 2 diabetes mellitus with "late" vascular complications and CHD with reduced basal and/or stimulated growth hormone secretion;

5. To provide recommendations to clinicians on the correction of somatotropic deficiency and the treatment of CHD in patients with type 2 DM with varying severity of coronary pathology.

Novelty of the study.

For the first time, the clinical and functional features of the course of CHD and coronary atherosclerosis in patients with type 2 DM in the presence of acquired somatotropic deficiency have been clarified.

A characterization of "lipid disorders" is given; parameters of insulin secretion, basal and prandial glycemia at varying degrees of severity of the deficiency of "fasting" and stimulated growth hormone secretion are indicated.

The genesis of the development of myocardial dysfunction in the process of formation of the "diabetic heart" in various courses of diabetes with varying degrees of severity of STH deficiency has been detailed. For the first time, the role of the metabolic component (using the example of studying clinical and biochemical parallels of deficiency of basal and/or stimulated growth hormone secretion) in the pathogenesis of myocardial remodeling in patients with type 2 DM has been shown.

Individual aspects of the adverse effect of hormonal and metabolic disorders (hyperglycemia, hyperinsulinemia, and somatotropic deficiency) on the state of the cardiovascular system, the degree of severity and character of progression of vascular complications, microangiopathy, and coronary atherosclerosis in patients with type 2 DM have been characterized.

Practical significance of the study.

The work presents new data on the influence of acquired somatotropic deficiency on the development and progression of "late" vascular complications of type 2 DM and the character of "lipid" disorders. The obtained results of the study of "fasting" and stimulated secretion of STH, IRI, and blood glucose in patients with type 2 DM with CHD and coronary atherosclerosis can be used in the future when choosing methods for the diagnosis and комплексного (complex) treatment of "late" vascular complications and coronary pathology in patients with type 2 DM.

Main propositions for defense.

1. In patients with type 2 DM with and without "late" vascular complications, there is a clear dependence of metabolic disorders on somatotropic deficiency.

2. The revealed interrelationship of acquired somatotropic deficiency and other hormonal and metabolic disorders in patients with type 2 DM indicates a significant role of these components in the development of cardiovascular pathology.

3. The character of the course of CHD and its progression in patients with type 2 DM are associated with insufficient growth hormone secretion.

4. Acquired adult STH deficiency plays a leading role in the development of dyslipoproteinemia, which underlies atherosclerosis, the development and progression of "late" micro- and macrovascular complications of diabetes, a decrease in physical working capacity, and changes in intracardiac hemodynamics.

5. Patients suffering from type 2 DM combined with coronary pathology need complex correction of somatotropic deficiency, which should include methods of medicinal and non-medicinal influence aimed at reducing the frequency and prevalence of "late" micro- and macrovascular complications of diabetes and improving the clinical and occupational prognosis in these patients.

Approval of the work

The main propositions of the work were reported at the Department of Endocrinology and Diabetology of the Medical Faculty of MGMSU and the Department of Hospital Therapy No. 1 of the Medical Faculty of MGMSU, and discussed at: a joint conference of the Department of Endocrinology and Diabetology of the Medical Faculty of MGMSU and staff of Hospital VV No. 2 in Moscow in 2006, at the "26th Final Scientific and Practical Conference of Young Scientists of MGMSU", Moscow, 2005.

Publications

Five scientific works have been published on the topic of the dissertation.

Structure and scope of the dissertation

The dissertation is set out on 146 pages of typewritten text and consists of an introduction, 5 chapters, a conclusion, conclusions, and practical recommendations. The work contains 21 graphs and diagrams, and 16 tables. The bibliography includes 201 sources, of which 49 are domestic and 152 are foreign authors.