[Russian Eligibility Criteria for Prescribing Menopausal Hormone Therapy to Patients With Cardiovascular and Metabolic Diseases. Consensus Document of RSC, RSOG, RAE, EUAT, RAP].

Menopausal symptoms can impair the life of women at the peak of their career and family life. At the present time, the most effective treatment for these manifestations is menopausal hormone therapy (MHT). The presence of cardiovascular and metabolic diseases in itself does not exclude the possibility of prescribing MHT to relieve menopausal symptoms and improve quality of life. However, often an obstacle to the use of this type of hormone therapy is the fear of physicians to do more harm to patients than good. Caution is especially important when it comes to women with concurrent diseases. Moreover, it should be recognized that there is a shortage of high-quality research on the safety of MHT for underlying chronic non-infectious diseases and common comorbidities. The presented consensus analyzed all currently available data from clinical trials of various designs and created a set of criteria for the appropriateness of prescribing MHT to women with concomitant cardiovascular and metabolic diseases. Based on the presented document, physicians of various specialties who advise menopausal women will receive an accessible algorithm that will allow them to avoid potentially dangerous situations and reasonably prescribe MHT in real-life practice.

[Diabetes mellitus type 2: National Russian guidelines vs real clinical practice].

According to the "Federal Law on the Fundamentals of Protection of the Public Health", medical care for patients should be provided in accordance with National Russian guidelines for the relevant nosology, which are based on the principles of evidence-based medicine. The article presents an analysis of the compliance with the completeness of implementation of National Russian guidelines in the treatment of patients with type 2 diabetes mellitus (DM 2) in real clinical practice. The analysis of the actual state of management of DM 2 patients was carried out from the Federal Register of diabetes as of 01.01.2023. Incomplete compliance with the guidelines on the frequency of measuring glycated hemoglobin, the rate of intensification of hypoglycemic therapy, and the appointment of new classes of hypoglycemic drugs was established. Possible reasons for the identified discrepancies between real practice and guidelines requirements are discussed, as well as possible measures to overcome these discrepancies.

[Adrenal incidentaloma. Part 2. Modern concepts of computed tomography semiotics of adrenal gland incidentalomas: algorithm of differential diagnosis].

While accidentally detecting an adrenal gland lesion (incidentaloma) during a routine computed tomography (CT) scan, the radiologist should correctly interpret revealed changes. The most common lesion is adenoma with high lipid content, but a lipid poor adenoma, pheochromocytoma, adrenocortical cancer, metastasis and other less common adrenal diseases are also worth of attention and require detailed knowledge of their CT semiotics. The article presents criteria of differential diagnosis of the adrenal incidentalomas on the basis of which an algorithm of differential diagnosis was proposed for the most common adrenal lesions.

[Clinical and laboratory characteristics and results of treatment of patients with ACTH-producing neuroendocrine tumors of various localization].

AIM: To study the clinical, biochemical characteristics, treatment results and follow-up of patients with ectopic ACTH syndrome EAS (ACTH adrenocorticotropic hormone ). MATERIALS AND METHODS: A retrospective, observational, single-center study of 130 patients with EAS. Demographic information of patients, medical history, results of laboratory and instrumental investigations at the pre- and postoperative stages and follow-up of EAS were analyzed. RESULTS: The mean age at the diagnosis ranged from 12 to 74 years (Me 40 years [28; 54]). The duration of the disease from the onset of symptoms to the verification of the diagnosis varied from 2 to 168 months (Me 17.5 months [7; 46]). Eighty-one (62,3%) patients had bronchopulmonary NET, 9 thymic carcinoid, 7 pancreatic NET, 5 pheochromocytoma, 1 cecum NET, 1 appendix carcinoid tumor, 1 medullary thyroid cancer and 25 (19.2%) had an occult source of ACTH. The median follow-up period of patients was 27 months [9.75; 61.0] with a maximum follow-up of 372 months. Currently, primary tumor was removed in 82 (63.1%) patients, bilateral adrenalectomy was performed in 23 (18%) patients, in 16 of them there was an occult source of ACTH-producing NET and in 7 patients in order to control hypercortisolism after non-successful surgical treatment. Regional and distant metastases were revealed in 25 (19.2%) patients. At the time of the last observation 59 (72%) patients were exhibited a full recovery, 12 (14.6%) had relapse of the disease and 26 (20%) died from multiple organ failure (n=18), pulmonary embolism (n=4), surgical complications (n=2), disseminated intravascular coagulation syndrome (n=1) or COVID-19 (n=1). CONCLUSION: In our cohort of patients bronchopulmonary NET are the most frequent cause of EAS (62.3%). Surgical treatment leads to remission of hypercortisolism in 72% cases; the proportion of relapse (14.6%) and fatal outcome (20%) remains frequent in EAS.

[Obesity without diabetes: the role of hormonal regulation].

AIM: Obese patients without diabetes present an interesting phenotype to explore protective mechanisms against type 2 diabetes (T2D) development. In our study we looked for specific hormonal features of obese patients without T2D. MATERIALS AND METHODS: We included 6 groups of patients with different metabolic profiles (n=212): controls with BMI25 kg/m2, HbA1c6%, age 30 years; patients with 25BMI30 kg/m2and HbA1c6%; patients with 25BMI30 kg/m2and HbA1c6%; patients with BMI30 kg/m2and HbA1c6% (+ Obesity - T2D) obese patients without T2D or prediabetes; patients with BMI30 kg/m2and newly-diagnosed T2D/prediabetes, HbA1c6%; patients with known history of T2D on glucose-lowering drugs with BMI30 kg/m2. Insulin, GLP-1, GIP were measured during glucose-tolerance test at 0, 30 and 120 minutes; insulin resistance (IR) was assessed by HOMA-IR. RESULTS: Waist circumference was bigger in patients with obesity despite their metabolic profile comparing to patients without obesity (p0.001). Waist-to-hip ratio was similar in patients with different metabolic status. According to IR + Obesity - T2D group had intermediate position: IR was higher in that group comparing to people without obesity, but was less that in patients with obesity and HbA1c6% (p0.001). + Obesity - T2D group had the most potent baseline insulin secretion, assessed by НОМА-%band the highest postprandial secretion, measured by insulinogenic index among all patient groups with obesity (p0.001). There was no significant difference in GLP-1 secretion; GIP secretion was higher in patients with BMI30 kg/m2comparing to people with BMI30 kg/m2(p0.01).

[Adrenal incidentaloma. Part 1. Computed tomography of adrenal incidentaloma: the possibilities and difficulties of differential diagnosis].

The adrenal incidentaloma is a lesion of a different etiology and found incidentally in patients who underwent a diagnostic study not about the disease of this organ. Lesions can be both hormonally inactive and hormonally active, can arise from different zones of the adrenal gland or have non-specific organ affiliation, can be benign or malignant. Computed tomography characterization of these lesions, especially the differential diagnosis of benign and malignant, is extremely important for the correct diagnosis in order to provide adequate management of the patient. The article presents the key computed tomography criteria that allow radiologist to characterize the lesion most accurately and consider appropriate diagnosis.

[Morphofunctional features of non-functioning pituitary adenomas]. / Morfofunktsional'nye osobennosti gormonal'no-neaktivnykh adenom gipofiza.

Non-functioning pituitary adenomas (NFPAs) account for about 30% of all pituitary tumors. NFPAs are characterized by the lack of secretory potential or its weak expression insufficient for determination of the blood level of adenohypophyseal tropic hormones and for development of a specific clinical picture. Morphologically, NFPAs are a heterogeneous group of tumors, the classification of which was previously based only on immunoreactivity for pituitary tropic hormones. The WHO revised its Classification of Tumors of Endocrine Organs (4th edition) in 2017. The main changes relate to adenohypophysial-cell lineage for the designation of adenomas into subtypes. The introduction of transcription factor antibodies has become a fundamentally new approach to the classification of NFPAs, which is necessary to recognize less differentiated tumor types. This paper provides information on the new histopathological classification of pituitary adenomas, on the theories of silent adenomas, and on the proliferative and prognostic markers of NFPAs.

[Diabetes epidemiology in Russia: what has changed over the decade?]

The National diabetes register (NDR) was created as unified dynamic database in online format. It allows providing clinical and epidemiological monitoring of diabetes mellitus (DM) in the whole country. AIM: To analyze the epidemiological characteristics of diabetes over the past decade, to access the dynamics of the prevalence of acute (coma) and chronic (micro - and macrovascular) complications of DM. MATERIALS AND METHODS: The object of the study was the depersonized NDR database of DM patients. It consists of 84 regions of the Russian Federation (RF), included in the online registry system on 01.01.2019. RESULTS AND DISCUSSION: The total number of patients with DM in RF on 01.01.2019 was 4 584 575 (3.12% of the population), comprising 256.2 thousand patients with T1DM, 4.24 million with T2DM, 89.9 thousand other types of DM. Since 2000, the number of DM patients in RF has grown 2.2 times. 34.7% patients with T1DM reached target level of HbA1c.

[Intravascular ultrasound with virtual histology in assessment of atherosclerotic plaque composition in patients with coronary artery disease and type 2 diabetes mellitus].

Type 2 diabetes mellitus (T2DM) is a serious medical and social problem leading to early disability of patients and high mortality from cardiovascular complications. The development of cardiovascular events is associated not only with the degree of coronary artery stenosis, but also with the structure of the atherosclerotic plaque. AIM: This study aimed to characterize structure and composition of coronary artery atherosclerotic plaque in target lesion of T2DM patients and patients without diabetes using intravascular ultrasound (IVUS) and IVUS with virtual histology (IVUS-VH). MATERIALS AND METHODS: We observed 25 patients with coronary artery disease (CAD) with T2DM and without T2DM, which admitted to Endocrinology Research Centre to perform percutaneous coronary intervention (PCI). Patients with CAD and T2DM were included at group 1 and patients with CAD and without T2DM were included at group 2. IVUS and IVUS-VH assessment of target lesion were performed prior to stent implantation. We observed 24 plaques at group 1 and 10 plaques at group 2. RESULTS: In grey - scale IVUS 2D analysis there were no differences in mean cross - sectional area of the vessel (12.5 [10.4; 15.8] mm2 vs. 13.5 [12,7; 16.5] mm2; p=0.223, respectively) and lumen area (3.71 [2.5; 4.5] mm2 vs. 3.2 [2.7; 3.8] mm2; p=0.589, respectively). Plaque burden were higher in patients without T2DM (71.6 [65.5; 75.7] % vs. 77.6 [74.4; 80.4] %; p=0.008, respectively). IVUS-VH analysis showed that percent of necrotic core and dense calcium areas were significantly higher in the T2DM group (31.3 [25.3; 36.5] % vs. 21.65 [14.3; 27.8] %; p=0.01 and 4.7 [2.3; 7.8] % vs. 2.45 [1.2; 4.05] %; p=0.046, respectively). Percent of the fibrotic tissue were higher in non-T2DM group (55.35 [49.7; 63.6] % vs 67.7 [61.8; 76.5] %; p=0.004, respectively). There were no differences in percent of lipidic tissue in both groups. CONCLUSIONS: IVUS-VH assessment of coronary artery atherosclerotic plaques showed greater amount of necrotic core and dense calcium in patients with T2DM compared to patients without diabetes.

[Relationship of the ovarian reserve with autoimmune thyroid diseases in the reproductive period].

AIM: To compare ovarian reserve in healthy women of reproductive age - carriers of antithyroid antibodies (ATA) and in healthy women of reproductive age negative for ATA. MATERIALS AND METHODS: 70 healthy women of young reproductive age in the state of euthyroidism (from 18 to 38 years old) were examined. Participants were divided into equal groups (n=35) depending on the status of the presence of antithyroid antibodies (AT-TPO, AT-TG). On the 2nd-4th days of the menstrual cycle, the following markers of the ovarian reserve were determined: serum levels of anti-Müllerian hormone (AMG), inhibin B, FSH, LH, estradiol, testosterone and progesterone, as well as ultrasound parameters - the number of antral follicles and the volume of the ovaries. In addition, to determine the predisposition to premature ovarian failure, an analysis was performed to the number of CGG repeats in the FMR1 gene. RESULTS AND DISCUSSION: Statistically significantly differs such parameters as the level of estradiol and testosterone, while the differences were not clinically significant. All the parameters evaluated were within the normal range, the main predictors of the ovarian reserve (levels of AMG and inhibin B, the number of antral follicles) remained in the normal range. An increase in the number of repeats of CGG in the FMR1 gene was not detected in any of the participants in the study. CONCLUSION: In healthy young reproductive age women, the status of ATA does not have a direct effect on the ovarian reserve.

Effects of endogenous hypercortisolism on bone mRNA and microRNA expression in humans.

Hypercortisolism in humans suppresses osteoblastogenesis and osteoblast function through the upregulation of Wnt-signaling antagonists (sclerostin, Dkk1) and changes in microRNAs levels (miR-125b-5p, miR-218-5p, miR-34a-5p, miR-188-3p, miR-199a-5p) which are associated with mesenchymal stem-cell commitment to adipocytes or cartilage cells over the osteoblasts. INTRODUCTION: The purpose of this study was to evaluate the responses of bone to chronic glucocorticoid (GC) excess by measuring the levels of selected mRNA and microRNA (miR) in bone samples of patients with Cushing's disease (CD). METHODS: Bone samples were obtained during transsphenoidal adenomectomy from the sphenoid bone (sella turcica) from 16 patients with clinically and biochemically evident CD and 10 patients with clinically non-functioning pituitary adenomas (NFPA) matched by sex, age, and body mass index. Quantitative polymerase chain reactions (qPCR) were used to examine the expression of genes (mRNA and miRs) known to be involved in bone remodeling regulation based on studies in animals and cell culture. RESULTS: Hypercortisolism was associated with the downregulation of genes involved in osteoblast function and maturation (ACP5, ALPL, BGLAP, COL1A1, COL1A2, BMP2, RUNX2, TWIST1). An excess of GC caused increased expression of Wnt-signaling antagonists (Dkk1, SOST) and changes in the levels of miRs that are known to suppress osteoblastogenesis (miR-125b-5p, miR-218-5p, miR-34a-5p, miR-188-3p, miR-199a-5p) p < 0.05, q < 0.1. Interestingly, compensatory mechanisms were found in long-term hypercortisolism: upregulation of Wnt10b, LRP5, and LRP6; downregulation of SFRP4; changes in miRs involved in osteoblastogenesis (miR-210-5p, miR-135a-5p, miR-211, miR-23a-3p, miR-204-5p); and downregulation of genes associated with osteoclastogenesis. None of these changes prevented the suppression of bone formation. CONCLUSIONS: An excess of endogenous GC in humans suppresses bone formation through the upregulation of Wnt-signaling antagonists and dysregulation of miRs involved in mesenchymal stem-cell commitment. Both Wnt-signaling antagonists and miRs seem to be promising targets for further research in therapeutic intervention in glucocorticoid-induced osteoporosis.

[Pituitary lactotroph adenomas resistant to dopamine agonist treatment: histological and immunohistochemical characteristics]. / Laktotrofnye adenomy gipofiza, rezistentnye k lecheniiu agonistami dofamina: gistologicheskaia i immunogistokhimicheskaia kharakteristika.

OBJECTIVE: To present the histological and immunohistochemical characteristics of pituitary lactotroph adenomas (PLAs) resistant to dopamine agonist treatment. SUBJECT AND METHODS: The investigators examined paraffin-embedded blocks and histological sections obtained from 19 patients (13 women, 6 men), whose median age was 29 (19, 38) years, after surgical treatment (adenomectomy) for PLAs resistant to dopamine agonist treatment. Immunohistological examination was performed using antibodies against prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), type 2 dopamine receptors (DR2), estrogen receptors-α (ERα), the proliferation marker Ki-67, and the endothelial cell marker CD34. RESULTS: The expression of PRL by adenoma cells was revealed in all the patients. The coexpression of PRL and GH without clinical and laboratory signs of acromegaly was established in 3 cases. No expression of TSH, ACTH, LH, or FSH was revealed in any cases. Positive immunoreaction using antibodies against DR2 and ERα was detected in 8 and 6 cases, respectively. No expression of any of the studied receptors was found in 6 patients. Ki-67 was more than 3% in 3 patients and higher in patients with supra- or retrosellar growth. There was a positive correlation between the serum level of Ki-67 and that of PRL at the onset of the disease. There were 37 (25, 85) adenoma vessels, as measured by CD34 immunoexpression. It was ascertained that the patients with parasellar adenoma had more tumor vessels than those without parasellar growth of adenoma and that with the latter invading the cavernous vessels, the number of vessels was statistically significantly more. CONCLUSION: PLAs resistant to dopamine agonists in addition to PRL (100%) can express GH in 16% of cases are characterized by the immunoexpression of DR2 (42%) and ERα (32%), a low proliferative activity, increased angiogenesis in the adenomas with parasellar growth and invasion into the cavernous sinus.

Personalized strategies in reproductive medicine for patients with endocrine disorders.

Endocrine Medical Research center (EMRC) of the Ministry of health of Russia is unique clinical center, that have no analogs in the world. All forms of endocrine disorders may be diagnosed and treated here by implication of innovative methods. Institute of reproductive medicine of EMRC was open on 2017, director of this institute - MD, PhD E.N. Andreeva. Staff of this institute include highly experienced investigators and physicians. One of the most ambitious projects of the institute is development of prevention, diagnostic and treatment algorithm for patients with infertility of endocrine origin. For these purposes large prospective clinical trial (5000 patients) will be conducted with implementation of most modern genetic, laboratory and instrumental diagnostic methods. Results of this trial will allow diagnose, treat and prevent reproductive pathology in patients with endocrine diseases.

Comparative analysis of ovarian reserve in women with obesity in reproductive period.

AIM: To evaluate the ovarian reserve function in female patients with obesity in comparison with women without obesity. MATERIALS AND METHODS: This study evaluated 500 caucasian women, age 20-30 years, 250 with obesity (body mass index, BMI ≥30 kg/m2) and 250 without obesity (BMI <30 kg/m2). Anthropometrics, serum concentrations of anti-Mullerian hormone (AMH), inhibin B, follicle stimulating hormone, luteinizing hormone, estradiol, progesterone, and testosterone were compared as ovarian volume (cm3) and antral follicle count (AFC), determined by ovarian transvaginal ultrasonography. RESULTS: We reveal statistically significant difference in following parameters: AMH (2.7±0.47 ng/ml vs. 3.8±0.63 ng/ml; p<0.05), testosterone (1.4±0.3 nmol/l vs. 0.7±0.2 nmol/l; p<0.01), ovarian volume (7.2±1.9 cm3 vs 9.5±1.7 cm3; p<0.05), and AFC (13.3±4.5 vs 20.7±7.2; p<0.01) in obesity group vs. control group respectively. CONCLUSION: Ovarian reserve function is significantly lower in obese patients than in healthy control subjects of young reproductive age, but ovarian reserve parameters are in normal reference range even in obese patients.

Computed tomography diagnosis of primary hyperparathyroidism.

The article presents data on modern approaches to the diagnosis of various manifestations of hyperparathyroidism according to multispiral computed tomography, which do not require morphological verification and ensure the correctness of the diagnostic process. The radiological picture and differential diagnostics of changes from parathyroid glands and bone structures at hyperparathyroidism are described in detail.

Renal effects of glucagon-like peptide receptor agonists in patients with type 1 diabetes mellitus.

AIM: The purpose of our study is to assess the effects of glucagon-like peptide-1 receptor agonists (GLP-1R agonists) on early markers of kidney damage in patients with type 1 diabetes mellitus (DM). MATERIALS AND METHODS: The study included 27 patients with type 1 diabetes with normo- (n=16) and microalbuminuria (n=11) on intensive insulin injection regimen with insulin analogs. Patients were divided into two groups: 15 patients continued insulin therapy throughout the follow-up period, 12 patients were given 1.2 mg GLP-1R agonist (Liraglutide) once a day in addition to the insulin therapy for 6 months. HbA1c, lipid profile, classic markers of kidney damage (albuminuria, creatinine, glomerular filtration rate); plazma (neutrophilic gelatinase-associated lipoxalin - NGAL, molecule renal damage of type 1 - KIM-1, cystatin C, osteopontin) and urinary kidney biomarkers (nephrin, podocyne, uromodulin, NGAL, KIM-1, collagen type IV, cystatin C) were evaluated prior and in dynamics at 6 months. Kidney biomarkers levels were assessed by the enzyme-linked immunosorbent assay (ELISA). RESULTS: We observed a significant decrease in the urinary excretion of type IV collagen, cystatin C, increased uromodulin excretion and decrease in the plasma levels of osteopontin, NGAL and cystatin C in the group of combined insulin and GLP-1R agonist therapy. CONCLUSION: Changes in the level of sensitive kidney biomarkers indicate a possible renoprotective effect of GLP-1R agonist therapy in patients with type 1 diabetes at an early stages of kidney damage.

[Is it possible to achieve sustained remission or cure of type 2 diabetes mellitus in the 21st century?] / Vozmozhna li dlitel'naia remissiia ili izlechenie sakharnogo diabeta 2-go tipa v XXI veke?

A practitioner has a wide range of the hypoglycemic drugs for type 2 diabetes mellitus (T2DM) treatment, which can be used within a normal or near-normal range for long-term glycemic control. However, the question remains whether there are ways to achieve not only satisfactory glycemic control, but also T2DM remission (or even complete cure). The review presents an update on the concept of T2DM remission and describes the ways of its possible achievement with non-drug and drug treatments and surgery. The mechanisms of T2DM remission are given.

[Shereshevsky-Turner syndrome: Estrogen replacement therapy and cardiovascular risk factors]. / Sindrom Shereshevskogo-Ternera: zamestitel'naia terapiia éstrogenami i faktory riska razvitiia serdechno-sosudistykh oslozhnenii.

AIM: To investigate the impact of menopausal hormone therapy (MHT) on the expression of risk factors for cardiovascular events (CVEs) in patients with Shereshevsky-Turner syndrome (STS); to elaborate an algorithm for patient management using MHT. SUBJECTS AND METHODS: From 2010 to 2012, a total of 41 patients aged 14 to 35 years with STS were examined in the framework of a prospective observational study. 100 STS case histories in 2000 to 2009 were retrospectively analyzed. The indicators of the so-called cardiometabolic risk, such as body mass index (BMI), lipidogram readings, venous plasma glucose levels, and blood pressure, were estimated in relation to the type of MHT. In the prospective part of the investigation, an angioscan was used to estimate vessel characteristics (stiffness, wall tone, endothelial function (EF)), by using the examination data. RESULTS: 90% of the patients with STS were found to have risk factors for CVEs: atherogenic dyslipidemia (85%; 51% in the general female population of the same age), diastolic hypertension (36%; no more than 5% that is not typical for age-matched healthy general female population). In addition to increased arterial wall stiffness (AWS), obvious EF disorder is typical for STS patients. MHT was accompanied by a dose-dependent (estradiol, at least 2 mg) reduction in diastolic blood pressure by an average of 13% over 24 months, an increase in high density lipoprotein levels by more than 10% over 24 months and also contributedto a decrease in AWS and an improvement in EF. CONCLUSION: By favorably affecting the EF of vessels and reducing the severity of atherogenic dyslipidemia, MHT potentially enables a reduction in CV risk in patients with STS.

[Long-term consequences of polycystic ovary syndrome]. / Otdalennye posledstviia sindroma polikistoznykh iaichnikov.

Polycystic ovary syndrome (PCOS) is the most common chronic endocrine disease in women. The prevailing complaints at a young age are menstrual irregularities, infertility, and hyperandrogenism-related problems. However, metabolic disorder-induced complications have been in the foreground over years. The review gives the current ideas on a change of clinical manifestations in the natural course of PCOS, as well as the pathogenetically grounded prevention of complications in patients.

[A 20-year prospective follow-up study to evaluate the development of retinopathy and nephropathy after the onset of type 1 diabetes mellitus: Contribution of glycemic control and metabolic memory]. / Prospektivnoe 20-letnee nabliudenie, otsenivaiushchee razvitie retinopatii i nefropatii ot momenta debiuta sakharnogo diabeta 1-go tipa: vklad kontrolia glikemii i 'metabolicheskoi pamiati'.

AIM: To assess the time course of changes in the level of glycated hemoglobin (HbA1c) for 20 years after the onset of type 1 diabetes mellitus (T1DM) and to compare its correlation with the development of microvascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN). SUBJECTS AND METHODS: A total of 187 children with new-onset T1DM were registered in Moscow in 1994. During the 20-year follow-up study, these patients underwent regular check-ups at the Endocrinology Research Center, Ministry of Health of the Russian Federation, which included assessment of physical data, HbA1c 2-4 times a year, biochemical blood and albuminuria tests (once per year), and ophthalmologic examination (twice a year). A total of 155 people fully completed the 20-years follow-up study. RESULTS: During the 20-year follow-up period after the onset of T1DM, 86 of the 155 patients developed microvascular complications: DR and DN in 86 (55.5%) and 24 (15.5%) cases, respectively; while DR concurrent with DN were noted in 20 patients. By the time of their last visit, 69 (44.5%) patients had no evidence suggesting the presence of microvascular complications. The level of HbA1c at the onset of the disease in patients who later developed the complications was higher than in those without complications (10.2±0.6 and 8.5±0.2%, respectively (p = 0.003). The statistically significant differences in HbA1c levels between the groups persisted during subsequent 15 years of follow-up, averaging 9.2±1.5, 9.7±0.9, and 8.1±0.7% after 5, 10, and 15 years, respectively, in the complication group and 7.1±0.3, 8.1±0.4, and 7.2±0.2% in the non-complication group (p < 0.01). Over the last 5 years of the follow-up, the mean HbA1c level between the groups was not significantly different, which at the end of the 20-year follow-up period was 7.8±0.3 and 7.4±0.6%, respectively (p > 0.05). The mean duration of T1DM, in which DR developed, was 9.6±6.2, 11.0±2.0, and 13.6±4.6 years for the non-proliferative, pre-proliferative, and proliferative stages, respectively. That of T1DM, in which DN developed, was 11.8±0.6 years for microalbuminuria and 16.1±1.3 years for macroalbuminuria. CONCLUSION: The 20-year clinical follow-up of patients who had fallen ill with T1DM in childhood showed that diabetic microangiopathies developed with the long-term preservation of poor blood glucose control (BGC) starting at the onset of the disease. At the same time, the complications progressed to more severe stages, despite a clear trend toward better BGC. This may be suggestive of the negative metabolic memory phenomenon, which necessitates stable BGC, starting at the onset of the disease, for the prevention of microvascular complications.