Fifty-two patients with type I diabetes mellitus were examined. The patients were divided into 4 groups with various duration of the disease: group 1 included patients with the newly diagnosed disease, group 2 those with disease standing of 1 to 5 years, group 3 were patients suffering from diabetes for 6 to 10 years, and group 4 were diabetics for 10 years and more. The parameters examined were antibodies to surface antigens of islet cells, absolute and relative counts of T and В lymphocytes in the peripheral blood, counts of T-helpers and T-suppressors and cytotoxic cells and their ratios, counts of natural killers, DR (+) and IgG (+) cells, and basal C- peptide level. The results showed a correlation between autoantibodies to surface antigens of islet cells and the count of В lymphocytes, an inversion of T lymphocyte subpopulations, with the helper/sup- pressor index increased at the initial stages of the disease and decreasing with the disease progress.

The levels of glucose, insulin, and C-peptide in the blood scrum were measured in 38 subjects with normal and impaired glucose tolerance whose parents suffered from insulin-dependent and noninsulin-dependent diabetes mellitus (IDDM and NID- DM, respectively) and in 12 normal subjects without hereditary aggravation for diabetes mellitus in order to specify the pecualiaritics of development of diabetes mellitus of various types. Reliably increased levels of glucose, insulin, and C-peptide on an empty stomach and absence of adequate secretion of insulin and C-peptide in response to stimulation with 5 mg of minidiab, expressed by a later and less manifest release of insulin and C-peptide, were observed in the test group, in contrast to healthy controls. The detected changes augment with the progress of carbohydrate metabolism disorders, being more marked in the subjects whose parents suffered from IDDM. The findings permit a conclusion that function of the insular system is changed during early disorders of carbohydrate metabolism in subjects whose parents suffered from both forms of diabetes mellitus. Minidiab test is recommended to specify the function of the pancreatic insular system.

Physical development of 710 children and adolescents with insulin-dependent diabetes mellitus (IDDM) was studied over time. The patients were divided into 3 groups: with growth rate above the 25th percentile of the age norm, with growth rate below the 10th percentile of the norm, and with growth rales between the 10th and 25th percentiles of age norm. Analysis showed that (a) the presence of manifest decompensation higher than 12 %, frequent ketoacidosis episodes is a factor of high risk of reduction of physical development rate in children and adolescents with IDDM; (b) the mean statistical rates of diabetic adolescents growth are characterized by delayed (by 1 to 2 years vs. the norm) pubertal growth “skip”, and this growth skip in the patients is more levelled and stretched in time, and in some cases is virtually nor manifest; (c) if good compensation is attained and maintained after previous prolonged decompensation, compensating growth rates may develop in patients of both sexes both in childhood and adolescence.

Blood plasma concentrations of noradrenaline, dopamine, serotonin and their metabolites (DOPAC, HVA) were measured in 28 patients with insulin-dependent and 32 with noninsulin-dependent diabetes mellitus (IDDM and NIDDM, respectively). The patients were divided into 4 groups. Group 1 were 15 patients without late diabetic complications, group 2 were 15 subjects with diabetic neuropathy, group 3 were patients with neuropathy and retinopathy (n=16), and group 4 were 14 patients with neuropathy, retinopathy, and nephropathy. The results showed an increase of serotonin levels in IDDM patients w. those with NIDDM, a positive correlation between serotonin and blood glucose levels in IDDM, increased concentration of dopamine and reduced plasma level of noradrenaline in patients with diabetic neuropathy vs. those without late diabetic complications. Plasma levels of dopamine were decreased in all the patients microvascular involvement. The findings indicate the development of changes in the sympathoadrenal system of patients with late diabetic vascular complications.

Gustatory perception was studied in 10 children aged 8 to 15 suffering from medium-severe diabetes mellitus by the functional mobility method. Glycemia values and the level of mobilization of gustatory lingual papillae were high when the patients were admitted; the characteristic reverse proportinal relationship between these values, observed in healthy children, was absent. A course of therapy resulted in reduction of glycemia level, but the level of mobilization of gustatory papillae on an empty stomach was unchanged, the gastrolingual reflex did not recover. The detected dissociation between glycemia values and the level of mobilization of the gustatory receptor system may be an extra for the diagnosis of diabetes severity and treatment efficacy.

Blood serum fructosamine level were measured on an empty stomach in 97 normal subjects and subjects with various disorders of carbohydrate metabolism (the so-called “prediabetes” and changed glucose tolerance) in order to elucidate the significance of this factor as a marker of such disorders. Fructosamine concentrations were for the first time measured in children whose parents suffered from insulin-dependent or noninsulin-dependent diabetes mellitus. The content of fructosamine on an empty stomach was found to depend on the degree of carbohydrate metabolism disorders, increasing with the progress of these disorders. The findings permit a conclusion on the possibility of using fructosamine as a marker for the diagnosis of “prediabetes” in subjects with its levels of 2.5 to 2.99 mmol/1 and of disordered glucose tolerance in those with its levels over 3 mmol/1 and glucose level on an empty stomach no more than 6 mmol/l.

Use of laser doppler flowmeter helped reveal in patients with diabetes mellitus a decrease of volumetric bloodstream in the capillaries of skin in the absence of clinical and biochemical evidence of microcirculatory disorders. Bloodstream parameters were correlated to the findings of objective methods of diagnosis at the stage of manifest clinical signs of vascular involvement of various localizations. Laser doppler flowmeter may be used for preclinical diagnosis of renal and ophthalmic involvement in diabetics with types 1 and II conditions as a method to monitor the therapy efficacy in patients with apparent clinical signs of microangiopathies. We should like to emphasize the possibility of mass screenings of patients and the simple technique of using the device, as well as the possibility of assessing the bloodstream not only in the skin, but in the organs and retina as well.

The type and degree of changes in the lipid transporting system of blood plasma and levels of hormonal provision of the regulatory processes in juvenile obesity of different degrees were under study. A single fat food loading was used to detect the precursors or latent forms of disorders in lipoprotein spectrum and their hormone regulators. A total of 35 obese patients aged 16 to 18 and 30 age-matched healthy youths were examined. Analysis of the baseline values showed increased levels of apolipoprotein B, cholesterol, triglycerides, insulin, and reduced levels of apolipoprotein Al, high-density lipoprotein cholesterol in obese youths vs. controls. A atherogenic pattern of changes in the lipoprotein and apolipoprotein spectra of the plasma of obese youths was clearly seen under conditions of fat food loading, these changes being associated with disordered insulin reaction to intake if exogenous fat. The examinees suffering from obesity a varying degree, mainly from the ab- dominant variant, presented with a complex of interrelated metabolic disorders (hyperinsulinemia, insulin resistance, dyslipoproteinemias), — the metabolic X syndrome, this referring them to a group at risk of developing atherosclerosis, essential hypertension, diabetes mellitus irrespective of the degree of general obesity.

Clinical efficacy of enalapril, a drug belonging to a group of angiotensin-converting enzyme inhibitors, was studied in patients with pubertal juvenile dyspituitarism (juvenile obesity) coursing with arterial hypertension. A reactive increase of plasma renin activity and reduced concentration of plasma aldosterone were revealed. The drug was characterized by a pronounced hypotensive effect. No negative effects on the blood lipid spectrum or carbohydrate metabolism were observed. The study showed that enalapril may be a drug of choice in the treatment of the hypertensive syndrome in patients with juvenile obesity.

Ten patients with diffuse toxic goiter, 1—2 nd degree, ten ones with hypothyrosis of medium severity, and a group of healthy controls were examined. Manifest emotional, personality, and vegetative disorders were revealed in patients of both groups, as well as changes in the electrical activity of the brain and in status of the afferent systems of the brain, this being indicative of marked dysfunction of nonspecific cerebral systems in patients with thyroid diseases. Anxiety depressive emotional disorders and activation of the in-depth compartments of the membranous reticular complex were revealed in both groups of patients. These changes are nonspecific and appear to represent a common neurogenic mechanism of thyroid dysfunctiion.General activation of the brain and peripheral cerebral activation detected in patients with hyperthyrosis are secondary and result from effects of thyroid hormones on the nervous system.

The efficacy and safety of SAISEN, a recombinant human growtn hormone obtained from mammalian cells, was tested in children with hypophyseal nanism. The treatment duration was 1 year. The results indicate that SAISEN (ARES-SERONO) is a highly effective and safe preparation of growth hormone, noticeblly stimulating the growth rate both in previously untreated children with somatotropic insufficiency, and in those previously treated with STII preparations. Therapy with SAISEN was not associated with any side effects, as shown by both clinical and laboratory data.

Combined staged ultrasonic examination of 53 patients with surgical diseases of the adrenals (Icenko — Cushing’s disease and hormonally active tumors) included preoperative transcutaneous ultrasonic examination, ultrasound-monitored spot fine needle aspiration biopsy, intraoperative and postoperative ultrasonic examinations. Transcutaneous ultrasonic examination was found to be little informative in Icenko —Cushing’s disease, whereas in adrenal tumors it was virtually as sensitive as computer-aided tomography. Ultrasound-monitored spot fine needle aspiration biopsy proved to be a highly informative safe method, which helps morphologically diagnose the disease before surgery. Intraoperative ultrasonic examination helped reduce the surgical trauma in all the cases, and in patients with Icenko — Cushing’s disease it gave an idea of the type of morphologic changes in the removed adrenal. Ultrasonic monitoring of tissue status at the site of intervention helped timely detect the postoperative complications.

In one of the previous publications, the main indicators of the quality of diabetes care in our country have already been analyzed. One of the main (if not the main) reasons for its unsatisfactory quality, in our opinion, is inconsistency of theory and practice with the modern world scientific and clinical level of diabetology. A number of provisions of domestic diabetology are still based on the approaches of the 50-70s. For some recommendations, it is generally impossible to find scientific justifications in either foreign or domestic literature. They are transmitted orally from endocrinologists of the older generation to the young, like legends, without being scientifically proven. The only justification for them is the statement “this is our school” or “this is how practice shows”.

Any approaches are really tested by practice. That is why unsatisfactory indicators of compensation and acute complications and disability for diabetes mellitus indicate significant shortcomings in domestic diabetology. When an endocrinologist says that he repeatedly had to note, for example, the appearance of acetonuria in patients with insulin-dependent diabetes mellitus after a fatty meal, or the ophthalmologist discovers a positive dynamics of the state of the retina while taking “angioprotectors”, these facts in themselves, observations, even numerous ones, do not prove the existence of a causal relationship between the two phenomena. Even the ancients said: "After this - does not mean therefore." Due to the selectivity of attention and memory, the opposite cases, which are no less (in our example, the absence of acetonuria after a fatty meal or the preservation of hemorrhages, despite the many months of taking angioprotectors), prefer to “not notice”.

That is why it seems appropriate to discuss strictly defined principles and rules of evidence-based scientific and clinical research existing in the world practice. The main objective of this article is to help scientists avoid methodological errors in research, learn how to plan them correctly, and practical doctors to critically and thoughtfully understand the publications of medical journals. Programs of medical faculties of many countries include special courses on the formation of a critical type of medical thinking and the ability to reasoned analysis (the course “medical logic”, “decision analysis”, “critical analysis of the postulates of medicine”, etc.), which also address research planning problems. For clarity, this publication will focus on clinical trials conducted with the participation of patients and with the goal, as a rule, of studying the effectiveness of a treatment method or an individual drug, the characteristics of the course of the disease under certain conditions, etc.

We continue to discuss problems regarding patients with thyroid disease. Hypothyroidism is a disease that develops due to a decrease in the function of the thyroid gland, which cannot produce the amount of hormones necessary for the body. If little hormone enters the bloodstream, the saturation of the body with thyroid hormones is significantly reduced and, accordingly, all metabolic processes slow down. Screening for newborns for hypothyroidism means that every newborn is screened for his disease. In the past, treatment of newborns with hypothyroidism only began a few months after birth. Many of these children later had problems with studying at school or they were a little awkward, which could have been prevented if treatment had been started at an earlier time. Unfortunately, in our country there is no such system for screening newborns with all the ensuing consequences.
To screen hypothyroidism in all newborns, a drop of blood is taken on filter paper. Subsequently, the level of TSH is determined in this blood sample. If it is elevated (and this is the main laboratory symptom of hypothyroidism), then the children are examined again more carefully, and with the confirmation of the diagnosis, they are prescribed treatment with thyroxine.

A radioimmunoassay test system has been designed for measurements of free a-subunit (AS) of glycoprotein hormones in human blood serum with a sensitivity of 0.15 ng/ml. This test system revealed the absence of a direct correlation between the levels of free AS and levels of glycoprotein hormones in the blood sera of women with various endocrine profile, this being indicative of the specificity of this test system, on the one hand, and, on the other, confirming the possibility of independent secretion by the pituitary of free AS into the blood. Basal blood serum level of free AS in normal subjects is low: 0,9 ng/ml in women aged 17 to 30. The level of free AS secretion in the blood of many patients with nonfunctioning tumors of the pituitary was found increased, this demonstrating the diagnostic significance of measuring free AS as a marker of such tumors.

Analysis of pancreatic beta-cell receptors binding the sulfanilamide drugs widely used in therapy of type II diabetes, such as glybenclamide, glypizide, and glyclazide, showed that these drugs are characterized by excellent parameters of specific binding to these receptors. The receptors were tested for two parameters: number of binding sites and dissociation constant. Glybenclamide was the most active of the drugs we tested, the other two agents being less active. Binding of these agents was reversible. The problem of identification of the examined receptors of sulfanilamides with K⁺-ATP-sensitive channels, similarly active conductors of the information transported by the sulfanilamide drugs in the mechanism of insulin secretion, is discussed.

Thyroid and adrenocortical function was examined in rats fed increasing quantities of iodine with drinking water. No noticeable deviations in thyroid hormone levels were found in the blood of experimental animals. Thyroid hormone levels in thyroid tissue were changing in the same direction in the animals kept on various iodine diets, these changes depending on experiment duration: an increase of thyroxine and more so, of triiodothyronine was observed in 50 days, and reduction thereof in 90 days. In rats fed the maximal iodine dose, 8000 mcg daily, the level of thyroglobulin in thyroid tissue decreased. Increased iodine consumption reduced the glucocorticoid function of the adrenals in experimental animals, this manifesting by reduction of corticosterone level in the adrenals, blood plasma, and reduction of non-metabolized hormone excretion with the urine.

Changes in the blood hormonal levels were studied In 36 rabbits with electrodes implanted to the area of the dorsomedial nuclei of the hypothalamus in the course of a 5-cycle electrostimulation experiment. After each period blood hormonal levels were correlated to the activities of the hypothalamic catecholamino-, GABA-, and serotoninergic systems. The first two cycles of the experiment were associated with a high activity of the hypothalamic mediator systems and with increased levels of all hormones in the blood. The functional activity of the hypothalamus was reduced due to the predominance of stress-limiting systems. The initial reduction of GABA, and then of serotonin in the hypothalamus caused be the end of experiment a reduction of the blood levels of the tested hormones, except the Ca-regulating ones and active renin. Disturbances in the regulatory mechanisms of hypothalamic mediator systems leads to an increase in its excitability and to transformation of the adaptive pattern of hormonal changes into pathological mechanisms of prolonged emotional stress.

Steroid and thyroid hormones exert a regulatory effect on a whole range of physiological processes that form the basis of the normal development and functioning of the body. In the channel of human blood, from 96 to 99.9% of the total masses of cortisol, progesterone, thyroxine and triiodothyronine circulate in the form of complexes with hormone-binding transport proteins. The “free hormone" hypothesis assigns to these transport proteins the passive function of maintaining a stationary pool of biologically active unbound hormones due to the rapid dissociation of complexes in response to the needs of target tissues. Recent studies have revealed the active role of transport proteins and their receptors on the surface of cell membranes in the interaction of steroid and thyroid hormones with competent tissues.

The structural aspects of the biological activity of complexes of corticosteroid-binding and sex steroid-binding globulins with natural ligands are described in detail in a review article. This literature review is devoted to the description of the physicochemical properties and biomedical characteristics of a multicomponent system of proteins that bind thyroid hormones in human blood plasma. Particular attention is paid to the physiological significance of these proteins in the framework of the hypothesis of free hormones and in the light of their recently discovered specific transport functions.