Clinical Course and Pathogenetic Therapy of Microangiopathic Complications of Type 2 Diabetes Mellitus in Arterial Hypertension

The dissertation is devoted to the study of the pathogenetic features of the development and clinical course of microangiopathic complications in patients with type 2 diabetes mellitus combined with arterial hypertension. It examines the mechanisms of formation of diabetic retinopathy, nephropathy, and neuropathy under conditions of chronic hyperglycemia and elevated blood pressure, as well as the influence of metabolic, hormonal, and inflammatory factors on the progression of microvascular lesions. Particular attention is given to the role of stress-induced sympathetic and glucocorticoid activity, the state of the renin-angiotensin-aldosterone system, and the psycho-emotional status of patients. Based on the data obtained, optimized therapeutic approaches are formulated, aimed at preventing the progression of microvascular complications and improving the management of patients with combined pathology.

Relevance of the Research Topic:

Diabetes mellitus (DM), according to the WHO definition (1999), is a group of metabolic diseases characterized by the development of persistent hyperglycemia resulting from a defect in insulin secretion, insulin action, or both factors.

DM is one of the most pressing problems of modern public health. At present, DM ranks third among the causes of high disability and mortality of patients after cardiovascular and oncological diseases. The incidence of DM, mainly due to type 2 diabetes mellitus (DM-2), is continuously growing, and every 12-15 years the number of patients on average doubles. In Russia, according to the State Registry, by 2000, 8 million patients with DM-2 had been registered, and by 2025 their number is expected to increase to 12 million people. According to a WHO estimate (1999), the number of patients with DM-2 worldwide will reach more than 300 million by 2025 [17].

DM-2, earlier than other chronic non-infectious diseases, causes generalized damage to the vascular bed, leading to the development of microvascular complications: diabetic retinopathy (DR), nephropathy (DN), and neuropathy (DNP).

In 60-80% of patients with DM-2, arterial hypertension (AH) is observed, which aggravates the course of diabetes [33, 42]. Under conditions of elevated blood pressure (BP), shear stress is exerted on the arterioles and capillaries of the renal glomeruli and the retina, which, in combination with the cascade of reactions initiated by chronic hyperglycemia, determines an increase in the rate and severity of microvascular complications.

In modern society, the problem of diabetes mellitus and late complications is to a greater extent non-endocrinological, since the vast majority of patients are in closer contact with general practitioners (therapists) than with endocrinologists. The general practitioner does not pay sufficient attention to the significance of metabolic parameters for the course of the disease and cannot identify early disturbances caused by pathology of carbohydrate and lipid metabolism, nor record the onset of late complications. In turn, endocrinologists do not interact with this group of patients because therapists do not consider it necessary to refer for consultation patients with subcompensation of carbohydrate metabolism. The need to consult an endocrinologist is dictated by decompensation of the disease and the development of pronounced complications of diabetes.

In light of the above issues, the question of forming a unified therapeutic approach to the management of patients with combined pathology with mild and/or moderate disorders appears to be most relevant. The insufficient attention paid to this group of patients is also not justified from an economic perspective, since the treatment of developed complications is tens of times more expensive than their prevention and prophylaxis [17, 151, 194]. Given the exponential growth in the number of patients with DM-2, the only possible solution for the adequate management of this group of patients is not the total control of an endocrinologist, but ensuring that therapists have a sufficient level of knowledge in the field of hormonal metabolism and metabolism. In addition, this direction seems more promising due to the professionally broader scope of general therapeutic observation, whereas the narrow specialization of the endocrinologist does not allow covering the entire spectrum of ophthalmological, neurological, nephrological, and other diseases of the patient and potentially leads to polypharmacy and/or the formation of unacceptable drug interactions.

At present, the main therapeutic goals for patients combining DM-2 and AH are: strict correction of BP values, correction of glycemic values, weight reduction, elimination of other risk factors for the development of cardiovascular complications, and management of existing complications.

At the same time, the role of inflammatory factors and stress-induced metabolic-hormonal activity in the development and formation of the cascade of reactions leading to a vicious circle of vascular and neurogenic instability, as well as the role of the metabolic activity of antihypertensive and hypoglycemic therapy, remain not fully understood.

The relevance of assessing the possibility of influencing these parameters is dictated by the need to preserve the working capacity of patients for a longer period and to stabilize their psycho-emotional activity.

These questions determined the aim and objectives of the present study.

Aim of the Study:

To investigate the pathogenetic features of the development and course of microvascular complications under various therapeutic interventions in patients with type 2 diabetes mellitus and arterial hypertension.

Objectives of the Study:

1. To assess the influence of metabolic factors on the prevalence and progression of microvascular complications in patients with DM-2 and AH under different antidiabetic therapy regimens.

2. To assess the influence of insulin levels, glucocorticoid hormones, sympathetic activity factors, and the activity of the renin-angiotensin-aldosterone system (RAAS) on the course of microvascular complications in patients with combined pathology.

3. To determine the role of inflammatory factors in the development of microvascular lesions and the level of their activity depending on the therapy administered.

4. To investigate the influence of psycho-emotional activity factors on the stress-induced sympathetic response and the development of microvascular complications in patients with DM-2 and AH.

Scientific Novelty:

Data have been obtained on the influence of metabolic activity factors under different antidiabetic therapy regimens on the development and course of microvascular complications in patients with AH and DM-2. The role of stress in the development of an inadequate sympathetic response in this group of patients and its influence on the mechanisms of formation of microangiopathies has been shown. The role of glucocorticoid activity in patients with combined pathology has been demonstrated. Approaches to the metabolically grounded formation of an optimized management strategy for this group of patients are presented.

Practical Significance:

New therapeutic approaches to the management of patients with DM-2 and AH have been developed in order to prevent the progression of microvascular complications. The significance of conducting a fixed scope and frequency of clinical and laboratory-instrumental assessment of patient status for the earlier detection of metabolic disorders as a predictor of microvascular complications of DM-2 has been evaluated. The role of correction of anxiety disorders in the context of metabolic disorders has been demonstrated.

Statements Defended:

1. Adequate hormonal-metabolic correction is of the greatest significance in preventing the development and progression of microvascular complications of DM-2 in AH.

2. Patients receiving incorrect insulin doses during combination therapy are characterized by higher degrees of risk of progression of microvascular complications of DM-2.

3. The hormonal status of patients with DM-2 and AH is characterized by the absence of an adequate response to stress, which leads to pathological stimulation of glucocorticoid activity and deterioration of metabolic control.

Implementation into Practice:

The results of the study have been implemented into the practice of the endocrinology and therapeutic departments of the 2nd Central Military Clinical Hospital named after P.V. Mandryka.

Approval of the Work:

The materials of the work were reported at a joint meeting of the staff of the Department of Advanced Medical Training Therapy (with a course in naval medicine) of the State Institute for Advanced Medical Training of the Ministry of Defense of the Russian Federation, Moscow, and the Department of Faculty Therapy and Occupational Diseases of the Moscow State University of Medicine and Dentistry.