RESOLUTION OF NATIONAL ADVISORY BOARD.

On October 2, 2020, by Novo Nordisk initiative, an expert council was held in Tbilisi, Georgia, dedicated to the problems of introducing innovative insulin therapy on the example of insulin degludek into the clinical practice. The council chaired by prof. R. Kurashvili included seven leading endocrinology experts in Georgia and a specialist in the field of pharmaco-economics from Russian Federation Prof. A. Kulikov. During the expert council, important scientific, clinical and economic emphases were made on the benefits of using insulin degludec associated with its unique structure and mechanism of action. Special emphasis was placed on the difficulty in managing children and adolescents with type 1 diabetes. The meeting provided compelling evidence that insulin degludec reduces the incidence of hypoglycemia and diabetic ketoacidosis, thereby contributing to overall health and the prevention of vascular complications in children and adolescents with diabetes. The members of the council resolved to petition the Georgian Ministry of Health to include insulin degludek in the state program for children and adolescents with diabetes.

CONNECTION BETWEEN SERUM VASCULAR ENDOTHELIAL GROWTH FACTOR LEVELS AND SEVERITY OF MICROANGIOPATHY IN PATIENTS WITH TYPE 2 DIABETES AND OBSTRUCTIVE SLEEP APNEA.

Our aim was to evaluate the serum vascular endothelial growth factor (VEGF) level in type 2 diabetes patients with comorbid obstructive sleep apnea (OSA) and to compare it in connection with diabetic retinopathy and chronic kidney disease severity. In the prospective cohort study following data were collected: medical anamnesis; demographic and anthropometric data; laboratory (serum VEGF, complete blood count, biochemistry, immunology, complete urine test, including microalbuminuria) and instrumental investigation data (fundoscophy, laboratory polysomnography). From 232 analyzed patients 54 (23.27%) were placed in OSA+ group, 178-OSA- group Mean VEGF value in OSA+ group was significantly higher, than in OSA- group. Serum VEGF level in patients with diabetic retinopathy was signifcantly higher with OSA comorbidity. Pearson correlation coefficient between VEGF and diabetic retinopathy stages, VEGF and CKD stages was significant in both groups. Our study suggests, that the blood VEGF play an important role in microangiopathy severity in patients with T2DM, especially with OSA comorbily.

SERUM VASCULAR ENDOTHELIAL GROWTH FACTOR CONCENTRATION DECREASES IN CORRELATION WITH GLYCATED HEMOGLOBIN LEVELS IN PATIENTS WITH TYPE 2 DIABETES.

Our aim was to compare serum vascular endothelial growth factor (VEGF) level in type 2 diabetes mellitus (T2DM) patients with comorbid OSA at screening and 6 month follow up visits. In the prospective cohort study following data were collected at screening visit: medical anamnesis; demographic and anthropometric data; Epworth sleepiness score data; laboratory (serum VEGF, complete blood count, biochemistry, immunology, complete urine test, including microalbuminuria) and instrumental investigation data (fundoscophy, laboratory polysomnography). At 6 months follow up visit we evaluated anthropometric data; Epworth sleepiness score; serum VEGF. Comparing VEGF level at screening and 6 month follow up visits showed significant decrease in VEGF level in both groups (P=0.0281 OSA+ and P=0.0278 OSA-). It was established direct correlation between decreased VEGF level and decreased HbA1c level (P=0.04696) and between decreased VEGF level and Epworth sleepiness score (P=0.0153) at 6 month follow up visit in OSA+ group. Our the study suggests that VEGF level decreases in parallel with diabetes compensation quality. Future researches are necessary to support this research.

HIGH MICROANGIOPATHY PREVALENCE IN OBSTRUCTIVE SLEEP APNEA COMORBID TYPE 2 DIABETES PATIENTS.

Our aim was to study OSA prevalence in patients with T2DM referred to the ,,Diacor'' and to evaluate the microangiopathy rate among this two groups. Data were obtained from T2DM patients enrolled in a prospective, cohort study. The study was being carried out in the clinic ,,Diacor'' Tbilisi, Georgia. Patients were screened for OSA with the Epworth Sleepiness Scale. Patients scoring more than 11 points were invited to do Nocturnal, laboratory-based polysomnography (PSG) for final diagnoses. The following data were collected: medical anamnesis; demographic and anthropometric data; laboratory (complete blood count, biochemistry, immunology, complete urine test, including microalbuminuria) and instrumental investigation (fundoscophy, laboratory polysomnography) data. From the total 232 patients 54 (23.27%) were diagnosed with OSA. From OSA + patients 12 (22.22%) had coexistence of diabetic retinopathy and microalbuminuria, 19 (35.19%)- coexistence of diabetic retinopathy and chronic kidney disease (CKD). Prevalence of coexisted diabetic retinopathy and CKD and CKD independently was significantly higher in patients with severe than in moderate and mild OSA patients. Our results suggest that it is important to screen all type 2 diabetes patients in Georgia for OSA, as the disease is associated with high prevalence of microangiopathy.

[Saturin - effective vegetative remedy in treatment of type 2 diabetes mellitus].

A chemical investigation of plant Satureja hortensis L. - garden savory (GS) has been carried out. It is established that the GS is rich in phenolic compounds. Flavonoids apigenin, luteolin, cinaroside, luteolin-glucuronide, luteolin-rutinoside, isoroifolin and phenylcarbonic acids - chlorogenic acid and rosmarinic acid were isolated from the leaves of the plant. The total content of flavonoids and phenylcarbonic acids in GS is 1,6-1,7%. The leaves of GS contain up to 1% essential oil consisting mainly of thymol and methyl carvacrol. Dry aqueous extract of GS leaves, which retains the full range of substances of raw plant material has been obtained. Pharmacological investigation of the GS extract was carried out on intact animals and animals with experimental alloxan diabetes. Antidiabetic Arfasetine was chosen as a reference drug. The study revealed that the GS extract exhibits hypoglycemic activity significantly reducing blood sugar levels and is safe in the long run. Drug dosage form named saturin - capsules containing 0,33 g of dried aqueous extract of GS leaves, has been developed. Clinical trials of Saturin confirmed its effiacy in diabetes mellitus type 2. The drug is registered by the Ministry of Health, Labour and Social Welfare of Georgia (Registration Certificate №003658) and approved for use in type 2 diabetes either independently or in combination with other hypoglycemic agents. Saturin is manufactured at the Experimental and Production Facility of the Institute of Pharmacochemistry.

[Psychopathologic peculiarities in patients with diabetes mellitus and non-proliferative retinopathy].

The aim of the present work was to study clinical course of depression in patients (pts) with diabetes mellitus (DM) and non-proliferative retinopathy (NPR). In total, 250 pts with DM were included into the study, and more separated into 2 groups (Gr): Gr.1 (n=115)--pts with DMT1 and DMT2 without NPR; mean ABP - SBP < or = 130 mmHg/DBP < or = 85 mmHg. Fundus photography grade 10/10. Gr.2 (n=135)--was subdivided in Gr.2a (n=43), pts with DMT1; fundus photography grade from > or = 20/10 to < or = 47/47; mean ABP - SBP < or = 130 mmHg/DBP < or = 85 mmHg; Gr.2b (n=92) pts with DMT2 fundus photography grade from > or = 20/10 to < or = 47/47, mean ABP - SBP < or = 160 mmHg/DBP < or = 90 mmHg. To assess depression severity a 12-question Screening Questionnaire was used, results were compared to Beck's and Hamilton's Depression and Sheehan's Anxiety Scales. According to Sheehan's Scale pts with DMT1 most often complained of profuse sweating (66+/-16%), while in DMT2 more often itching and numbness in different parts of the body (72+/-11%) were registered. According to the Beck's scale the most frequent and acute symptoms were: depressed mood, sadness (100-10%), disappointment about their future (78+/-14%), inferiority feeling (90+/-10%), irritation (89+/-11%), feeling of being unlucky (75+/-15%), decreased working ability (78+/-14%). DMT1 was characterized by light while DMT2 by moderate depression. Thus, depression is one of the most severe DM complications; it has negative effect both on pts compliance and quality of his/her life. When DM is complicated by NPR depression takes the most sever form (psychopathologic symptoms are observed in 85.9% of cases).

[Positive effects of angiotensin [corrected] receptor blockers on the course of microvascular complications of diabetes mellitus].

The aim of the research was to evaluate some clinical and hemodynamic characteristics in patients with diabetes mellitus type 1 and type 2 (DM type 1 and DM type 2), to diagnose diabetic retinopathy (DR) on early stage of its development for the correction of the disease by treating with angiotensin II type 1 receptor blocker (AT I)--Candesartan. Totally 250 patients (pts) with DM type 1 and DM type 2 were studied; they were divided into 3 groups (Gr.): Gr.1 (n=115)--pts with DM and without DR; Gr. 2 (n=43)--pts with DM type 1 and DR; Gr.3 (n=92)--pts with DM type 2 and DR. A comprehensive physical examination was conducted to obtain baseline information about the patient: clinical status, lipid profile, microalbuminuria and urine creatinine, as well as glycemia levels. Patients were treated with Candesartan (16 or 32 mg) or placebo. When necessary, other antihypertensive agents (except ACE-inhibitors) were initiated. Eye fundus monitoring was performed with evaluation of 7,300 standard zone stereoscopic pictures of the retina according to ETDRS (Early Treatment of Diabetic Retinopathy Study). The results of three year observation revealed no pathologic changes on the retina in normotensive and normoglycemic pts; pts with mild diabetic retinopathy at baseline demonstrated normal levels of ABP and blood glucose which resulted in the regression of the changes. The changes of various severity demonstrated no positive shifts in 96% of cases; DR deterioration (proliferative DR, neovascularisation stage) was observed in 4% of cases. Results of the study showed that Candesartan treatment of pts with DM resulted in positive shifts in the pathologic changes, registered on the retina and decrease in urine albumin excretion rate. Thus, we recommend to include Candesartan in the standard treatment, as the have positive effect on the course microvascular complications of diabetes mellitus both in males and females.

[Characteristic changes of skin and its accessories in type 2 diabetes mellitus].

The different changes are seen on skin and it's accessories in Diabetes Mellitus, some of which represent the prognostic indicator of complicated diabetes and some directly contribute in development of them. Numerous problems concerned with the diabetic foot could be avoided due to early detection and treatment of these changes. The objective data on foot examination of 195 patient with Type 2 Diabetes Mellitus were analyzed considering the grade of severity of Diabetic Peripheral Neuropathy (DPN). It was revealed that the skin humidity is dependent on DPN, particularly, the DPN 2-4 times raises the dryness of the skin on the foot; the risk of callus development is significantly high in case of painless and complicated DPN, accordingly, the possibility of neuropathy ulcer is also high in this group. The high incidence of onychomycosis and Yellow nails syndrome was noted, accordingly in 28.7% and 39.4% of cases; the Melin's shin spots were found in fourth of the patients, mainly in men; a few cases of rubeosis plantarum and bulbosis diabeticorum were revealed; the cases of necrobiosis were not noted. Thus, the prevalence of the characteristic changes of skin and it's accessories in Type 2 Diabetes Mellitus is sufficiently high and it depends on the severity of DPN, using early detection of them may avoid many problems related to diabetic foot and its complications.

Twinning project: Israel and Georgia--the birth of a diabetes-in-pregnancy centre in Georgia.

AIMS: To determine the effectiveness of a joint Israeli-Georgian twinning project aimed at introducing modern methods of perinatal care to Georgian women with pregestational diabetes mellitus. METHODS: A Diabetes-in-Pregnancy Centre was established in Georgia (in the former USSR). Thirty-two women with Type 1 diabetes mellitus participated in the first stage of the study (January 1997-June 1998). All were maintained under strict metabolic surveillance starting at least three months prior to conception and were given organized instruction in methods of self-monitoring of glucose levels, insulin dose adjustment, dietary management and close fetal surveillance throughout pregnancy. A second stage of the project was started in January 1998 and aimed at the diagnosis of gestational diabetes mellitus (GDM). RESULTS: Of the 32 women, 20 had had a total of 44 prior pregnancies without proper perinatal care (1990-96); only five (11.3%) ended in the birth of a healthy infant. On entry to the study, all 32 patients had unsatisfactory metabolic indices. HbA1c levels decreased significantly from the preconception period (P<0.001) and were maintained at the lower level throughout pregnancy; insulin doses decreased significantly until the third trimester (P<0.01) and then increased (P<0.001). Since January 1997, 21 women have become pregnant. Eighteen have given birth, 12 (67%) by Caesarean section and six (33%) by vaginal delivery. Gestational age at birth was 36-39 weeks, and birth weight ranged from 2300 to 4100 g. The only neonatal complications were mild respiratory distress syndrome and hypoglycaemia. There were no significant maternal complications in the 236 women screened, eight were diagnosed as having GDM and 12 impaired glucose tolerance. They were actively managed to a successful outcome. CONCLUSIONS: The establishment of the Diabetes-in-Pregnancy Centre in the Republic of Georgia has significantly reduced the prior high pre-programme perinatal morbidity and mortality as well as the incidence of maternal complications in pre-GDM as well as in GDM.

[Rationale for using kinin system inhibitors in patients with acute ischemia and infarction of the myocardium during the prehospital phase]. / Ob obosnovannosti ispol'zovaniia na dogospital'nom étape ingibitorov kininovoi sistemy u bol'nykh s ostroi ishemiei i infarktom miokarda.

The paper discusses if it is advisable to use kallikrein-kinin system inhibitors earlier. A total of 122 patients with acute ischemia and infarction of the myocardium were studied. Contrykal and heparin infused in the prehospital period, followed by hospital treatment are optimal to prevent vascular wall lesions, maximally retain retrograde blood flow, and substantially reduce the size of myocardial infarction. Therapy with protease inhibitors proved to be most beneficial within the first 2 hours of the disease, as evidenced by a profound improvement in the clinical course of myocardial infarction, a decrease in ECG and precordial mapping signs of ischemia, a positive change in myoglobin and MB creatine phosphokinase levels, and a significant reduction in the rehabilitative period.

[Clinical course and the effectiveness of conservative treatment of prolactin-secreting pituitary adenoma]. / Dinamika klinicheskogo techeniia i éffektivnos't konserrvativnogo lecheniia prolaktinsekretiruiushchikh adenom gipofiza.

Forty-eight women with prolactin-secreting adenomas of the hypophysis and 22 patients with suspected microadenomas, aged 16 to 38, were examined. The highest blood prolactin levels and the most manifest symptoms were revealed in the patients with x-ray evidence of hypophyseal macroadenoma. Prolactin levels were lower, though still elevated, in the cases with small adenomas. In the cases with high prolactin levels but without x-ray signs of hypophyseal adenoma the clinical symptoms were less manifest. LH concentrations were significantly reduced in all the patients. Seven patients in whom parlodel therapy was ineffective were operated on. In the rest parlodel therapy, carried out for 1-2 years, was conducive to stabilization of the tumor process, despite a recurrence of hyperprolactinemia.

[Control and correction of the blood sugar in diabetes with concomitant ischemic heart disease using the artificial beta-cell apparatus employing glucose oxidase as the enzyme]. / Kontrol' i korrektsiia glitsemii pri diabete s soputstvuiushchei ishemicheskoi bolezn'iu serdtsa apparatom "iskusstvennaia beta-kletka" s ispol'zovaniem fermenta gliukozooksidazy.

The apparatus "Artificial Beta-Cell" or "Biostator" was used in treatment of 115 patients with diabetes mellitus and concomitant ischemia of the heart. At the same time 30 patients with diabetes mellitus and ischemia of the heart were treated for diabetes mellitus with the routine methods. Hormones such as ACTH, STH, hydrocortisone, immunoreactive insulin and S-peptide, lipid metabolism and glycosylated hemoglobin were investigated in the time course of the treatment. It was shown that adequate correction of glycemia with the "Biostator" promoted renormalization of the levels of ACTH and hydrocortisone. The results were especially favourable in the group of patients with myocardial infarction and chronic ischemia of the heart with the signs of cardiac insufficiency. Moreover, in the patients of the main group there was a tendency for normalization of lipid metabolism and glycosylated hemoglobin. The results of carbohydrate metabolism compensation in patients of the control group were not always satisfactory and the periods of compensation were longer. The clinico-biochemical indices reflected the favourable effect of the use of the "Biostator" and its advantages over the routine methods in treatment of diabetes mellitus.

[Effect of 24-hour intravenous administration of nitroglycerin on the status of the focus of a lesion in patients with an acute myocardial infarct]. / Vliianie 24-chasovogo vnutrivennogo vvedeniia nitroglitserina na sostoianie ochaga porazheniia u bol'nykh ostrym infarktom miokarda.

Nitroglycerin was drip-infused for 24 hours to 35 patients with acute myocardial infarction. Thirty-three patients were taken as controls. Intergroup comparisons were made of the patterns of precordial cartograms from 35 leads and serial measurements of plasma MB CPK activity. The treatment was shown to reduce significantly the activity of MB CPK and total ST elevation, the effect being particularly pronounced with the drug administered within the first 6 hours of the attack. It was also shown that 24-hour intravenous nitroglycerin infusion produced a significant decrease in the end diastolic pressure of the pulmonary artery that occurred by the 15th minute and persisted till the end of the administration.

[Hypermyoglobinemia and creatine phosphokinase MB activity as signs of combined myocardial lesion and acute cerebral circulatory disorder]. / Gipermioglobinemiia i aktivnost' kreatinfosfokinazy MB kak priznaki sochetaniia porazheniia miokarda i ostrogo narusheniia mozgovogo krovoobrashcheniia.

In order to detect simultaneous damage to the myocardium in cerebral stroke the authors radioimmunoassayed myoglubin and activity of the heart fraction of creatine phosphokinase MB (CP K MB) in the blood serum of 22 patients. Hypermyoglobinemia and elevated activity of CP K MB were revealed in almost all cases of hemorrhagic stroke (15 patients) whereas in patients with ischemic stroke they were identified far less frequently. Thus, hypermyoglobinemia and the activity of CP K MB correlate with the macro- and microscopic picture of myocardial damage and may serve as its diagnostic criteria when both the clinical picture and ECG findings prove uninformative.