[Effect of components of the renin-angiotensin system, rs2106809 polymorphism of the ACE2 gene, and therapy with RAS blockers on the severity of COVID-19].

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a key component of the renin-angiotensin system (RAS), providing counter-regulation of its effects and, simultaneously, a receptor for the SARS-CoV-2 entering. It is suggested that factors regulating the balance of the major components of RAS, including ACE2 gene polymorphism, therapy with RAS blockers (ACE inhibitors and angiotensin receptor blockers) - may affect the severity of COVID-19. AIM: The aim of the study was to investigate the effect of RAS components, the relationship of ACE2 gene polymorphism rs2106809 and ACEi/ARBs therapy with the COVID-19 severity. MATERIALS AND METHODS: The study included patients with COVID-19 hospitalized in Endocrinology research centre (n = 173), who were divided into groups of moderate and severe course. Determination of RAS components was performed by ELISA, identification of polymorphism by PCR. Statistical analysis was performed using nonparametric statistical methods; differences in the distribution of genotype frequencies were assessed using Fisher's exact test χ2. RESULTS: The groups differed significantly in age, blood glucose levels, and inflammatory markers: leukocytes, neutrophils, IL-6, D-dimer, C-reactive protein, ferritin and liver enzymes, which correlated with the severity of the disease. When comparing patients in terms of ACE, ACE2, angiotensin II, ADAM17 there were no statistically significant differences between the groups (p=0.544, p=0.054, p=0.836, p=1.0, respectively), including the distribution by gender (in men: p=0.695, p=0.726, p=0.824, p=0.512; in women: p=0.873, p=0.196, p=0.150, p=0.937). Analysis of the distribution of AA, AG, and GG genotypes of the rs2106809 polymorphism of the ACE2 gene also revealed no differences between patients: χ2 1.35, p=0.071 in men, χ2 5.28, p=0.244 in women. There were no significant differences in the use of RAS blockers between groups with different course severity: χ2 0.208, p=0.648 for ACEi, χ2 1.15, p=0.283 for ARBs. CONCLUSION: In our study, the influence of activation of RAS components (ACE, ACE2, AT II, ADAM17) and ACE2 gene polymorphism on the severity of COVID-19 course was not confirmed. The severity of COVID-19 course correlated with the level of standard inflammatory markers, indicating the general principles of the infection as a systemic inflammation, regardless of the genetic and functional status of the RAS.

[Determination of prolactin reference intervals in different age groups].

BACKGROUND: Clinical diagnostic laboratories (CDL) have at their disposal various automated systems for the measurement of biochemical parameters and markers such as prolactin. Each of the test systems manufactures offers its own alternate design of the method, which makes standardization difficult. In endocrinological practice, the problem of result discrepancies often arises. In hormonal assays, the clinical picture of patients sometimes does not correspond to the reference values provided by the manufacturers, which determines the need to develop the method-specific reference values for a specific population. The difficulty in interpreting basal prolactin levels is not only due to a transient increase in the hormone levels caused by stress or excessive physical exertion, but also due to a significant variability of indicators in the same patient, even if all recommendations for blood sampling are followed. AIM: The aim of the study to determine the reference values in serum samples of women, men and children of different age groups for the VITROS Immunodiagnostic Systems and compare the results with the "expected prolactin levels" recommended by the method manufacturerMATERIALS AND METHODS: The monocentric study included 879 serum samples of apparently healthy subjects who were admitted to the Endocrinology Research Center. Measurements were performed using the VITROS ECi 3600 automatic chemiluminescence analyzer (Ortho-Clinical Diagnostics, Great Britain). RESULTS: For adult men and women reference values were 66-436 and 94-500 mIU/l respectively. When comparing the results of prolactin determination in women and men of the studied cohort with the "expected values" of the VITROS ECi 3600 manufacturer a systematic shift towards an increase in lower and upper limits of the reference values was found in both -cohorts. CONCLUSION: The obtained reference values of prolactin can be use in the determination of prolactin in the Russian population for VITROS ECi 3600 Immunodiagnostic Systems.

[Calcitonin measurement in fine-needle washout fluids in detecting medullary thyroid cancer].

BACKGROUND: The diagnostic value of calcitonin measurement in fine-needle aspiration biopsy wash-out fluid is a promising tool in the diagnosis of medullary thyroid cancer. AIMS: We assessed the potential usefulness and the diagnostic significance of Ct-FNAB alone in comparison with cytology in the diagnosis and localization of primary or metastatic MTC. MATERIALS AND METHODS: For this purpose, we retrospectively examined data from 67 patients with suspicious thyroid nodules and/or lymph nodes who ultimately underwent surgical treatment at the Endocrinology Research Centre in 2015-2020. The primary endpoint of the study was to evaluate the diagnostic accuracy of Ct-FNAB when compared to cytological examination. The secondary endpoint was to determine the optimal diagnostic level for use in clinical practice. RESULTS: The obtained results showed that high Ct-FNAB concentrations were present in all histologically proven MTC, either in thyroid gland (sensitivity 92.5%, specificity 100%) or neck masses (sensitivity 88.5%, specificity 100%). The optimal diagnostic threshold for Ct-FNAB values from thyroid nodes was > 122 pg/ml, from lymph nodes >35.8 pg/ml. CONCLUSIONS: Our findings suggest that Ct-FNAB is a highly reliable diagnostic procedure to identify primary and recurrent/metastatic MTC. The actual relevance of this technique in the management of MTC needs further longitudinal studies in a larger number of patients.

[Reference intervals of thyroidstimulating hormone in pregnant women living in the central regions of the Russian Federation].

BACKGROUND: Pregnancy is a condition with important structural and physiological changes in the thyroid gland. In this regard, experts of thyroid associations have recommended developing specific reference intervals taking into account the natural and socio-geographical characteristics of the region under study. AIM: To conduct an epidemiological analysis and evaluate TSH reference intervals in pregnant women living in the central regions of the Russian Federation with mild iodine deficiency. MATERIALS AND METHODS: We have conducted the observational multicenter cross-sectional study included 2008 healthy pregnant women at different trimesters of pregnancy, from three regions of the Russian Federation (Moscow, Ivanovo and Smolensk). We assessed the level of thyroid-stimulating hormone, antibodies to thyroid peroxidase, antibodies to serum thyroglobulin, the level of iodine concentration in the morning portion of urine (cerium arsenic method) and we have conducted a questionnaire (date birth and gestational age). Women with elevated titers of anti-TPO and/or anti-TG antibodies were excluded from the study (245 women). As a result, we assessed high and medium levels of TSH and its overestimation with iodine sufficiency in pregnant women. The results are presented using the calculation of 2.5 and 97.5 percentiles. RESULTS: We confirmed the presence of iodine deficiency in the study areas. The median concentration of iodine in the urine was: in Moscow 106 µg/l, in Ivanovo 119 µg/l, in Smolensk 134 µg/l. Pregnant women were divided into 2 groups according to iodine adequacy. In the group with optimal iodine supply, the level of TSH was 0,006-3,36 in the 1st trimester, 0,20-3,74 in the 2nd trimester, and 0,33-3,68 mIU/L in the 3rd trimester. In the group with mild iodine deficiency - in the 1st trimester it was 0,11-3,00, in the 2nd trimester 0,22-3,78, in the 3rd trimester 0,07-3,04 mIU/l. Statistical analysis of the data revealed that when comparing the level of TSH by trimester, depending on the place of residence, no statistical difference was found (p = 0,239). CONCLUSION: We obtained that the level of TSH in healthy pregnant women living in the central regions of the Russian Federation does not exceed 3.8 mIU/l in all trimesters.

[Iodine Deficiency Disorders: Current State of the Problem in the Bryansk Region].

BACKGROUND: The Bryansk region is one of the regions of the Russian Federation most affected by the accident at the Chernobyl nuclear power plant on April 26, 1986.In the conditions of a chronic uncompensated deficiency of iodine in the diet in the first months after the accident, an active seizure of radioactive iodine by the thyroid tissue took place, which inevitably resulted in an increase in thyroid diseases from the population in the future. The article presents the results of a control and epidemiological study carried out in May 2021 by specialists of the National Medical Research Center of Endocrinology of the Ministry of Health of Russia, aimed at assessing the current state of iodine provision in the population of the Bryansk region. AIM: Assessment of iodine supply of the population of the Bryansk region. MATERIALS AND METHODS: The research was carried out in secondary schools of three districts of the Bryansk region (Bryansk, Novozybkov and Klintsy).The study included 337 schoolchildren of pre-pubertal age (8-10 years), all children underwent: measurement of height and weight immediately before the doctor's examination, which included palpation of the thyroid gland (thyroid gland); Thyroid ultrasound using a portable device LOGIQe (China) with a multi-frequency linear transducer 10-15 MHz; determination of iodine concentration in single portions of urine. A qualitative study for the presence of potassium iodate in samples of table salt (n = 344) obtained from households and school canteens was carried out on the spot using the express method. RESULTS: According to the results of a survey of 337 pre-pubertal children, the median urinary iodine concentration (mCIM) is 98.3 µg / L (range from 91.5 to 111.5 µg / L, the proportion of urine samples with a reduced iodine concentration was 50.1%). According to the ultrasound of the thyroid gland, 17% of the examined children had diffuse goiter, the frequency of which varied from 9.4 to 29% in the areas of study. The share of iodized salt consumed in the families of schoolchildren in the study areas was 17.8% (values range from 15.6 to 19%), which indicates an extremely low level of iodized salt consumption by the population. All salt used for cooking in school canteen areas of the study was iodized, which confirms compliance with the requirements of SanPiN 2.4.5.2409-08. CONCLUSION: Despite the active implementation in the Bryansk region of various preventive programs of IDD and social activities to promote the use of iodized salt, in the absence of mass prevention with the help of iodized salt to date, their unsatisfactory results should be noted.

Analytical platforms Vitros ECi 3600 and Cobas 6000: comparative analysis of prolactin measurement.

Prolactin is a polypeptide hormone secreted by the lactotrophic cells of the anterior pituitary gland and has a wide range of biological effects in the human body. Accurate measurements of prolactin concentration are essential in obtaining biochemical data to support clinical decisions in the diagnosis, treatment and prevention of diseases of the pituitary gland, reproductive, immune and other body systems. The aim of our study is to carry out a comparative analysis of the serum prolactin measurement determined by the two analytical platforms Vitros ECi 3600 (Ortho-Clinical Diagnostics) and Cobas 6000 (Roche). Serum samples from 664 patients undergoing examination at the Endocrinology Research Center were included in the study. Comparative analysis of serum prolactin measurement showed that results obtained by the two analytical systems are consistent with each other (r = 0.89, p<0,05). Clinically accuracy of prolactin measurement and to a large extent using the same method is of particular importance in primary diagnosis, treatment and long-term follow-up of the patient.

[Monitoring of iodine deficiency disorders in the Republic of Tyva].

BACKGROUND: The Republic of Tyva is a region with a proven severe natural iodine deficiency and a high prevalence of IDD (iodine deficiency disorders). However, in the region in certain periods of time, measures were taken to eliminate iodine deficiency in the diet of the population. The article presents the results of the October 2020. by specialists of the Endocrinology Research Centre, a control and epidemiological study aimed at assessing the current state of iodine supply in the population of the Republic of Tyva. The study was carried out on behalf of the Ministry of Health of Russia within the framework of the state task «Scientific assessment of the need to take additional regulatory legal and other measures to eliminate iodine deficiency in pilot regions with severe iodine deficiency¼. AIM: Assessment of iodine supply of the population of the Republic of Tuva. MATERIALS AND METHODS: The research was carried out in three settlements of the republic - years. Kyzyl, Shagonar, Saryg-Sep settlement. A total of 227 pre-pubertal schoolchildren (8-10 years old) were examined with anamnesis collection, examination by an endocrinologist, palpation of the thyroid gland, collection of single urine samples into disposable eppendorfs, followed by freezing to minus 20-25 degrees to further determine the concentration of iodine in urine with using the cerium-arsenitic method in the laboratory (clinical diagnostic laboratory of the Federal State Budgetary Institution «National Medical Research Center of Endocrinology¼ of the Ministry of Health of Russia). In addition, all schoolchildren underwent an ultrasound examination of the thyroid gland (using a portable ultrasound machine LOGIQe (China) with a multifrequency linear transducer 10-15 MHz, in the supine position). The height and weight of children was determined according to the standard method at the time of the examination. A collection of samples of edible salt, which is used in families of schoolchildren, was carried out and the presence of iodine in it was determined by an express method for the qualitative determination of potassium iodate.Parents of schoolchildren signed informed consent for the examination of children. Permission of the local ethical committee of the Endocrinology Research Centre - received, date: March 25, 2020, N 5. RESULTS: 227 schoolchildren of 8-10 years old were examined. The median concentration of iodine in urine was determined, the presence of iodine in food salt was investigated, and an ultrasound examination of the thyroid gland was carried out in order to clarify the iodine supply, the coverage of the use of iodized salt in nutrition and the prevalence of goiter.The median concentration of iodine in urine was 153 µg/l, the frequency of goiter was 7.7%, and the proportion of households using iodized salt was 95.2%. CONCLUSION: Results of assessment (median urinary iodine concentration) confirm that population of Tuva, Russian Federation, has optimum iodine nutrition. The prevalence of goiter in schoolchildren significantly decreased compared to earlier assessments. The proportion of households using iodized salt indicates the effectiveness of preventive measures in the -region.

[Dynamic changes of renin-angiotensin-aldosterone system parameters after surgery of primary hyperparathyroidism].

AIM: To study an activity of the Renin-Angiotensin-Aldosterone System (RAAS) components in patients with primary hyperparathyroidism (PHPT) before and after parathyroidectomy (PTE). MATERIALS AND METHODS: A comparative study of patients with PHPT and control group. The first stage of the study included 56 patients with PHPT (group 1) before and on the third day after PTE. The second stage was carried out in 27 patients with remission of PHPT (group 2). All patients and healthy volunteers were tested for the main parameters of phosphorus-calcium metabolism and the RAAS parameters (plasma renin activity PRA, serum aldosterone, angiotensin II AT II). RESULTS: Patients with active PHPT demonstrated changes in RAAS activity (lower PRA, higher AT II level) comparing to control group, that have statistical significance in group 1 (p0.001 for both parameters). There were no significant differences in aldosterone levels (p1=0.090;p2=0.140). On the third day after PTE (group 1), a decrease in aldosterone level (p=0.009) and a tendency to decrease in PRA (p=0.030) were detected. However, an increase in PRA (p=0.018), a decrease in AT II concentration (p=0.032) comparing to the initial values and their normalization were observed 12 months after surgery when permanent normal serum calcium and PTH levels had been achieved. There were controversial correlations between the parameters of phosphorus-calcium metabolism and RAAS. The influence of angiotensin-converting-enzyme inhibitors and AT II receptor blockers on phosphorus-calcium metabolism in patients with PHPT was not observed. CONCLUSION: In patients with PHPT, there were no сlear correlations of phosphorus-calcium metabolism parameters with RAAS, however an increase of AT II concentration was noted, that can take part in a development of hypertension for this endocrinopathy. PTE can have a positive effect on AT II level.

[Autoantibodies, immunoglobulins and cytokine profile in patients with graves' disease and Graves' orbitopathy].

BACKGROUND: Graves' Orbitopathy (GO) - also known as Thyroid Eye Disease (TED) - is an autoimmune condition in the modern sense. It is closely associated with autoimmune thyroid diseases. Cytokine-mediated mechanisms play a critical part in immunopathogenesis of autoimmune thyroid diseases including GO. Investigating cytokine profiles as well as antibodies to tissue-specific antigens is essential for explaining GO pathogenesis and developing future therapeutic strategies. AIMS: The study examines serum levels of cytokines, autoantibodies and immunoglobulins IgG and IgG4 as mediators of autoimmune inflammation in patients with GO and Graves' Disease (GD). MATERIALS AND METHODS: The study included 52 patients (104 orbits) aged 25-70 years (mean age 48,8±12,3) in the active phase of GO and GD verified with the international diagnostic standards. These patients did not get any treatment for GO before. The control group consisted of 14 individuals (28 orbits) aged 30-68 years without known autoimmune disease.Serum levels of IgG, IgG4,TNFα, IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-13, sIL-6R, sTNFα- RI и TNFα- R2 IL-2R, TGFß1, TGF ß3, antibodies to TSH-receptor, free T4, free T3 and TSH were measured. A diagnostic ultrasound exam of thyroid gland, multislice computed tomography (MSCT) / magnetic resonance imaging (MRI) of orbits were performed. RESULTS: Mean duration of GO prior to being admitted to the centre was 8,8±1,5 months (range: 1 - 48 months). According to the degree of thyrotoxicosis compensation: 24 patients were clinically euthyroid, TSH 3,3±0,7 mU/L, free T4 11,9±0,59 pmol/L, free T3 3,97±0,1 pmol/L; 28 patients were considered to have subclinical thyrotoxicosis: TSH 0,03±0,01 mU/L, free T4 14,2±1,0 pmol/L, free T3 5,77±0,49 pmol/L. Serum levels of sTNFα-R2 (p=0,041, p≤0,05), sIL-2R (p=0,020, p≤0,05), TGFß1 (p=0,000, p≤0,001) were significantly higher in patients with GO compared to the control group. Serum levels of sTNFRα2 (p=0,038, p<0,05) and TGFß1 (P=0,011, p≤0,05) were positively correlated with the duration of GO. The positive correlations between the serum level of sIL-6R (p=0,034, p≤0,05) and the severity of GO as well as between the serum level of sTNFα- R 1 (P=0,012, p≤0,05) and activity of GO were observed. 54% of patients had elevated concentration level of IgG4 in IgG ( >5%). CONCLUSION: High levels of soluble cytokine receptors sTNFα-R2 and sIL-2R and cytokine TGFß1 in patients with long-standing untreated GO and GD being euthyroid or having subclinical thyrotoxicosis indicate activation of regulatory T cells aimed at suppressing autoimmune processes. High concentration level of IgG4 in IgG and cytokine TGFß1 can determine the development of fibrotic changes in the orbital tissues. A decrease in the concentration of cytokine TGFß1 can indicate an unfavorable course of the disease GO.

[Vitamin D and pregnancy: current state of the problem in the central regions of the Russian Federation].

BACKGROUND: It has been proven that vitamin D plays an important role in pregnancy. Deficiency of this element may be associated with the risk of developing gestational diabetes mellitus, preeclampsia, placentar insufficiency, low birth weight and premature birth. AIMS: To conduct an epidemiological analysis of vitamin D supply in women at different stages of pregnancy, living in Russia. MATERIALS AND METHODS: We included 1198 pregnant women living in 3 regions of Russia in the observational, multicenter, cross-sectional, continuous study. All pregnant women were tested for serum 25(OH)D levels. We collected biomaterial from August 2018 to December 2019. The end point of the study was the indicator of vitamin D supply in pregnant women and its level depending on the trimester of pregnancy and region of Russia. Statistical analysis included counting and grouping according to vitamin D levels, and calculating the median vitamin D concentration in each region. RESULTS: We confirmed vitamin D deficiency in all regions. The optimum level of this element is present in less than 7% of women. Insufficiency of this element is present in 20,62% of all women. The largest percentage of them is in a deficit of this element - 46,66%. We found that the lowest rates are in Smolensk, where the median was 12,75 ng/ml. In addition, we found changes in vitamin D concentration: with an increase in gestational age revealed a decrease in its level. CONCLUSIONS: In our study, we confirmed the presence of a 25(OH)D deficiency in most of the examined pregnant women, which is consistent with international epidemiological data. We should remember about these both at the stage of pre-gravid preparation and at the stage of pregnancy itself in order to achieve the optimal level of vitamin D.

[The comparative analysis of the results of detection of testosterone in blood serum applying analyzers Architect and Vitros and tandem mass-spectrometry, a highly efficient fluid chromatography technique.]

The testosterone is a key element of hypothalamus hypophysis gonad system. Its physiological role in males is well known and consists primarily in formation of male phenotype and support of spermatogenesis. The evaluation of androgenic status is necessary in case of such wide specter of clinical symptoms and pathological states as hypogonadism, delayed of premature puberty, polycystic ovary syndrome, particular types of cancer, etc. The precise measurements of testosterone concentrations have a decisive value in case of receiving biochemical data for supporting clinical decisions at diagnostic, treatment and prevention of androgenic diseases. The purpose of the study is to carry out a comparative analysis of the results of detection of testosterone in blood serum using analyzers Architect 2000 and Vitros 3600 and applying technique of highly-effective fluid chromatography - a tandem mass-spectrometry. The analysis was applied to samples of blood serum from 230 patients send to the endocrinological research center of Minzdrav of Russia. The comparative analysis of the results of detection of concentrations of testosterone demonstrated consistent difference in absolute values. However, a statistically significant correlation (р < 0,05) between values of testosterone obtained by different techniques was established. The correlation coefficient in different groups of patients made up to 0,894-0,920 and 0,955--0,965 correspondingly to comparing the results of Architect and Vitros and highly-effective fluid chromatography - a tandem mass-spectrometry. The calculated percentage of distribution of the results of detection of content of testosterone by the ranges of expected values demonstrated an admissible comparativeness of obtained results from point of view of practical diagnostic. The choice of technique of detection of biochemical parameters in case of primary diagnostic is very important. However, even more important is the application of the very same technique in treatment and long-term observation of patient.

[The modification of technique of detection of free cortizol in urine.]

The detection of free cortizol in day urine is an informative marker for diagnosing conditions of hypo- and hypercorticism. Up to 1% of cortizol, in invariable form and with no association with proteins and secreted by adrenal cortex, is excreted with urine during a day. The level of free cortizol in urine has no dependencies from day variation of hormone in blood and hence it reflects total secretion of cortizol by adrenal cortex. Besides, as a rule a direct proportional dependence exists between level of free cortizol in urine and level of biologically active cortizol in blood. The developers of automated systems propose various techniques of detecting cortizol not only in blood but in other biological fluids too. In our laboratory techniques of detection of level of free cortizol in day urine were approved, modified and adapted meant for analyzer Vitros ECi (Ortho Clinical Diagnostics, Great Britain) and analyzer Cobas 6000 (Hoffmann-La Roche, Switzerland). The comparison of results obtained by these techniques was carried out (r = 0,96-1). The reproducibility of detection of cortizol was evaluated by force of analysis of every sample of urine in one and various settings. The spread made up to 1,7-3,7% for one setting and 5,2-6,7% for various settings. The schemes were proposed to detect level of free cortizol in urine for analyzer Vitros ECi (with preliminary extraction by diethyl ether and subsequent removal of water fraction by force of freezing), and also for analyzer Elecsys (with preliminary extraction by dichlormethane and subsequent separation of phases by centrifugation and evaporation of organic phase by force of vacuum concentrator).

[Diagnostic capacities of determination of biologically active free testosterone in blood, by using current ultrafiltration techniques].

In most cases, current methods for immunoassay of blood total testosterone fail to provide a sufficient diagnostic accuracy. The authors measured the concentration of free testosterone in the blood and saliva samples from 189 males aged 19 to 83 years who had come to the clinic to confirm or exclude the diagnosis of various endocrine dysfunctions. Ultrafiltration had been previously carried on Amicon® Ultra membrane 30K filters (MILLIPORE) to determine the serum level of free testosterone. The ultrasensitive enhanced luminescence technique (IBL-Hamburg, Germany) was used to measure its concentration in the ultrafiltrate and saliva. The detection rate of androgen deficiency from the levels of free testosterone in the ultrafiltrate was higher than that from those of total testosterone and calculated free testosterone in blood. The preultrafiltration salivary and serum free testosterone values measured by the ultrasensitive enhanced luminescence technique may complement a sensitive marker of clinical symptoms to detect different forms of androgenic disorders.

[Evaluation of the efficacy of porous alumina ceramic use for defects elimination in maxillofacial region].

To study the biocompatibility of porous glass ceramics, experiments were conducted on: 75 white mice (Vistar); 11 rabbits (Shinshila) and 6 dogs. The porous alumina ceramic implants were embedded subperiostaly without additional fixation to bone surface. The osseointegration of implants, the size and form maintaining, changing of physical properties and long-term results in bone substitution were studied. The handling properties during surgery were also evaluated.

[The angiotensin II inhibition escape phenomenon in patients with type 2 diabetes and diabetic nephropathy].

AIM: To study prevalence and clinical implications of paradoxical rise of angiotensin II (AII) level in blood plasma in long-term therapy with ACE inhibitors in patients with type 2 diabetes mellitus (DM-2) and diabetic nephropathy (DN). MATERIAL AND METHODS: General clinical and hormonal (renin, AII, aldosteron, endothelin-1) examinations were conducted in 62 patients (37 males and 25 females) with DM-2 and DN on long-term ACE inhibitors. Escape of AII inhibition was defined as an increase in plasma AII more than 50 pg/ml corresponding to M+1SD in the control group (normotensive persons free of DM matched by age). Diet salt was controlled in all the patients. RESULTS: The patients received ACE inhibitors for 7.8 +/- 2.6 years. Plasma AII level in the control group was 34.5 +/- 16.1 pg/mL. The patients were divided into two groups according to their levels of AII: more than 50 pg/ml (group 1), less than 50 pg/ml (group 2). AII inhibition escape occurred in 24 patients (39%). No significant difference between the groups was registered by age, diabetes history, albuminuria, blood lipids, glycosylated hemoglobin, mean circadian blood pressure, duration of therapy with ACE inhibitors, intake of diuretics and beta-blockers. Patients of group 1 had a significantly higher cardiac interventricular septum thickness (p = 0.02), were more likely to have akinetic segments of the myocardium (p = 0.05), had lower 24-h urinary potassium (p = 0.03), insignificantly higher renal insufficiency. Plasma renin concentration was higher in group 1 (p = 0.004). AII did not correlate with aldosterone levels in both groups. CONCLUSION: A relatively large percentage of type 2 diabetics with DN is due to AII inhibition escape. It may explain the lack of reno- and cardioprotective effect of rennin-angiotensin-aldosterone system blockade.