The last two decades of the outgoing century were marked by the birth and rapid development of a new field of knowledge neuroimmunoendocrinology. Before talking about its problems and development prospects, we will consider the prerequisites for the formation of this branch of endocrinology in our center.
Clinical endocrinology
The main problem in analysis of the register of diabetes mellitus is evaluation of the reliability of data and the probability of extrapolating the results to a population of patients in the studied region. Our task was to assess the efficacy of diagnostic methods used in a region. Study of the prevalence of diabetic retinopathy and neuropathy by referent tests revealed poor sensitivity of methods for diagnosis of these complications in patients with insulin-dependent diabetes mellitus (IDDM) in the Mytischi region; hence, the prevalence of diabetic retinopathy and neuropathy might be higher than recorded in IDDM register.
Analysis confirmed the usefulness of active detection of early stages of complicated IDDM by screening (examination of the fundus oculi, detection of microalbuminuria and vibration sensitivity) for reflecting the true incidence of complications and timely therapy. Detection of numerous patients with IDDM at the phase of diabetes decompensation necessitates revision of preventive and therapeutic measures. High incidence of hypoglycemic reactions among IDDM patients necessitates their more active prevention, specifically, training IDDM patients to practice automonitoring methods.
Polymorphism of dinucleotide microsatellite in the aldose reductase (AR2) gene and two polymorphic microsatellite markers (DI 1S907 and DI IS2008) near catalase (CAT) gene were studied in insulin-dependent diabetics with and without diabetic nephropathy (DN). We formed the groups of patients to compare using the "extremephenotype"approach. Twenty-seven proteinuric patients with relatively short diabetes duration (<15 years) and 41 patients with a longer diabetes duration (>20years) without signs of DNserved as the "case"(DN+) and "control"(DN-) groups, respectively. Seven alleles of the AR2 gene ranging from 132 to 144 base pairs (bp) long were detected. For DI 1S907 and DI 1S2008, seven and eight alleles from 161 to 173 and from 120 to 148 bp long were found, respectively. No significant differences in the distribution of alleles and genotypes of AR2 and DI IS2008 loci in the DN+ and DN— groups were detected by Fisher's test. For D11S907, a significant increase in the frequency of both 15 (16.7% vs. 6.1%), p<0.05) and 18 (29.6%) vs. 15.9%, p<0.05) alleles was revealed in DNpatients in comparison with the controls, while the 17 allele of D11S907 was significantly rarer (9.3% vs. 30.5%, p<0.005) in the "nephropaths" than in diabetics without DN. Hence, the polymorphism of the AR2 gene is not associated with DN in IDDM, while a chromosome region near the CA T gene is likely to be linked with the disorder.
The aim of the study was to investigate the levels of testosterone (T), hydrocortisone (HC), and dihydroepiandrosterone (DEA) in patients with type 2 diabetes immediately after diagnosis of the disease and after 30-day diet and sulfonurea therapy. Three groups of patients were distinguished: A) 6 males aged 62.0+3.03 years, B) 15 females aged 63.5+1.69 years who achieved good metabolic control, and C) 4females aged 51.5+6.42years whose treatment was ineffective. The levels of DEA increased significantly in the A and В groups in comparison with the pre-treatment levels. The T level increased to 9.82+0.91 in group A vs. the initial 5.28+0.79 nmol/liter, p<0.01. By contrast, group В showed a decrease in T level to 0.68+0.15 vs. the initial 1.4+0.21 nmol/liter, p<0.02. A decrease in DHA to 6.23+1.53 vs. the initial 13.25+1.72 nmol/liter was observed in group C, while the decrease in the level of T was negligible. Basal insulinemia decreased over the period of follow-up in all patients. Hence, our findings demonstrate that the achievement of a good metabolic status in newly diagnosed diabetics with type 2 condition is associated with an increase in DHA level both in men and women, while the changes in the level of T are determined by the gender. A poor metabolic status results in a positive relationship between the DHA and insulin levels in male patients with hyperinsulinemia, while in female subjects this relationship depends on the basal insulin level.
Capotene is an effective drug for preventing and treating diabetic myocardiodystrophy. A two-month capotene therapy (12.5 mg daily) was carried out in 20 patients with IDDM aged 12-18 years with disease of different duration without clinical signs of cardiac insufficiency, with echocardiographic changes typical of diabetic myocardiodystrophy. Eight patients were administered 3 similar courses with 6-month intervals. The major hemodynamic parameters were investigated by echolocation, and exercise tolerance was evaluated by bicycle ergometry. The data indicate the efficacy of capotene therapy in patients with diabetic myocardiodystrophy, particularly of repeated courses, carried out under conditions of compensated carbohydrate metabolism. The diastolic parameters improved in comparison with those in patients administered no capotene; myocardial contractility and exercise tolerance increased. Capotene therapy did not involve changes in insulin protocols.
The relationship between the ecological factors in the city of Krasnodar and the incidence of autoimmune thyroiditis (AIT) has been studied. Ecological situation was evaluated on the basis of the data bank of the Municipal Center for State Sanitary and Epidemiological Surveillance for the period 1992-1997. The incidence of AIT was analyzed by the municipal outpatient endocrinological service.
Evaluation of sanitary and hygienic situation in the city showed progressive contamination of water bodies and alteration of microbiocenosis at the expense of predominance of potentially hazardous bacteria (Klebsiella, Cytobacter, and Proteus). The maximum epidemic strain was recorded in 1995, when the incidence of salmonellosis, hepatitis B, diphtheria, and leptospirosis increased. Analysis of correlation between the incidence of enteric infections in 1995 and the quality of drinking water showed a statistically significant direct medium relationship. Complex index of atmospheric air pollution was 6.3 (third-degree pollution). The peak of AIT was recorded in 1995 (90.9 per 100,000 population).
Within the AIT structure, the incidence of the hypothyroid status increased from 26.2%) in 1993 to 34.9%) in 1995 and 41%) in 1997. A direct medium relationship has been detected between the total incidence of AIT and complex indicator of atmospheric air pollution (r—^0.54, p<0.05).
Comparative characterization of clinical patterns of the disease showed a notable increase in the number of cases with manifest hypothyrosis by the end of 1995 (615 cases vs. 171 in 1993). In 1996 and 1997 the number of patients with manifest hypothyrosis remained high (684 and 793, respectively). Hence, our complex medical ecological surveillance showed an increased contribution of unfavorable environmental factors to the increased incidence of AIT; this permits us to consider this condition an ecologically determined nosological entity.
All this necessitates a comprehensive approach to studies of thyroid diseases and the environment, making use of multifactorial analysis. The ecological monitoring system should include evaluation of the thyroid function.
Fat deposition patterns and incidence of the main components of the metabolic syndrome have been studied in the indigenous population of Northern Siberia in the Krasnoyarsk region. The incidence of excessive body weight, insulin resistance (by the levels of insulin and C-peptide), dyslipidemia (HDLP hypocholesterolemia, hypertriglyceridemia, and hypercholesterolemia), disorders of carbohydrate metabolism, and arterial hypertension (AH) were evaluated in the Evenk population (596 subjects, 89.9%) of the population of the Evenk Autonomous Territory). The reference group consisted of 306 newcomers to this region (69.9% of newcomers to the region). Northern residents aged over 18 years were examined in winter. The examinations of 166 aborigines included measurements of fat folds on the arms, back, and abdomen. The anthropometric parameters of fat deposition were compared in indigenous Northerners and in non-aborigines (792 subjects). The thickness of the subcutaneous fat is less in indigenous men and women than in the newcomers, and fat distribution is more even. The thickness of subcutaneous fat in indigenous Northerners was closely related to body weight index. Development of obesity manifested by even thickening of subcutaneous fatty layer. The incidence of hyperinsulinemia, dyslipidemia, carbohydrate metabolism disorders, and AH was lower in the indigenous population than in the newcomers. The incidence of insulin resistance and metabolic disorders in the Evenks with excessive body weight was the same as in subjects with normal body weight, but the incidence of AH was higher in obese Evenks. The incidence of AH in obese Evenks and newcomers was the same, while insulin resistance was 8.6 times rarer among obese aborigines. In indigenous Northerners obesity consists mainly in increase of the subcutaneous but not visceral fat, and therefore involves a lesser number of metabolic disorders.
For practitioners
Morphological methods for studying the thyroid gland (thyroid gland) can clarify its structure and the nature of the pathological changes that developed in it, and thereby verify the diagnosis. There are 2 main methods of morphological diagnostics: microscopic examination of punctate obtained using a fine-needle puncture biopsy (aspiration and non-aspiration), and macro and microscopic examination of removed thyroid tissue.
Experimental endocrinology
The adrenocortical function has been studied in Macaca mulatto of different age: 6-9 years (young adult, n=5) and 20-26 years old, n=5). Corticosteroids (hydrocortisone and dihydroepiandrosterone sulfate DEAS) were measured by radioimmunoassay and enzyme immunoassay under basal conditions, during acute stress (insulin-induced hypoglycemia and 2-hour immobilization), and after dexamethasone injection.
The basal hydrocortisone levels were virtually the same in both groups, while the concentration of DEAS dropped in old animals. The reaction of the adrenal cortex to immobilization was decreased in old monkeys, which manifested by delayed peak values of both hydrocortisone and DEAS and a lesser area of their response for the examined 4-hour period. Dexamethasone test detected in monkeys aged 20-26years the development of relative resistance of the hypothalamo-pituitary-adrenal system to the overwhelming majority of glucocorticoids by the feedback mechanism. The feedback impairment in the regulation of the adrenocortical function may be at least partially mediated by the formation of a steroid imbalance in the peripheral blood during aging, primarily by a decrease in DEA (DEAS).
Reviews
Diabetes mellitus is one of the diseases that, due to the widespread prevalence and the presence of complications, pose a real threat to the economy of many countries of the world. The prevalence of diabetes and impaired glucose tolerance in Europe is 3-10 and 3-15%, respectively [7, 38].
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