[Primary hyperparathyroidism in Russia according to the registry].

BACKGROUND: There are no large-scale epidemiological studies on primary hyperparathyroidism (PHPT) in Russia. The high prevalence of the disease, the high risk of disability and death in this cohort of patients requires the study of the epidemiological and clinical structure of PHPT to determine the extent of medical care. AIM: Evaluate the frequency of PHPT detection and characterize its clinical forms in Russia using an online registry. METHODS: The object of the study is the database of the State Register of Patients with PHPT 1914 patients from 71 regions of the Russian Federation. New cases of the disease, as well as dynamic indicators are recorded when patients visit outpatient clinics or medical institutions. The analysis of data made at the end of December 2017 was carried out. The following parameters were evaluated: demographic and clinical indicators; indicators of phosphorus-calcium metabolism, the main forms of PHPT and its course, the primary characteristic of PHPT in hereditary syndromes and parathyroid carcinoma. Results are presented as mean and standard deviations, or medians and quartiles; descriptive statistics of qualitative attributes absolute and relative frequencies. RESULTS: the total number of patients with PHPT in the registry on 31 of December 2017 was 1914 cases (0.001% of the population of the Russian Federation). Identification of PHPT was 1.3 cases per 100 thousand of the population in Russia, 7.6 cases in Moscow, 6.1 cases per 100 thousand in the Moscow region. The average age of patients at the time of diagnosis was 55.6 10 years. The active phase of the disease was registered in 84.6% of patients (1620/1914), most of whom had a symptomatic PHPT 67.1% (1087/1620), and 32.9% a asymptomatic disease (533/1620). Symptomatic disease with visceral complications was detected in 15.8% cases (172/1087), with bone complications in 48.4% (526/1087). The mixed form of the disease was detected in 35.8% of patients with manifest form (389/1087). Normocalcemic variant PHPT (nPHPT) was registered in 14.5% cases (234/1620). Sporadic PHPT occurs in 83% of cases (1592/1914). 326 patients (17%) had a suspicion for hereditary form of the disease: average age was 31.2 12.3 years. A genetic analysis was conducted in 61 patients (3.2%): showed the mutation in the MEN1 gene in 2.9% of cases (55/1914) and the mutation in the CDC73 gene in 0.3% of cases (6/1914) (HPT-JT syndrome). Parathyroid carcinoma was confirmed in 1.8% of all patients (35/1914). Surgical treatment was performed in 64.5% of patients (1234/1914). Remission was achieved in 94% of cases (1160/1234), in 6% of cases relapse after surgical treatment or persistence of PHPT was recorded. CONCLUSION: detection of PHPT in the Russian Federation raised in comparison to 2016, which is associated with an active start of registration of patients in the regions. At this stage, it is necessary to modify the principles of registration and control, to make a platform for gathering information and calculating the necessary volumes of medical care for PHPT patients.

Prevalence and risk factors of sleep breathing disorders in patients with acromegaly from Moscow region.

AIM: Assessment of prevalence and risk factors of sleep breathing disorders in patients with acromegaly from Moscow region. MATERIALS AND METHODS: Cardiorespiratory monitoring was executed to 55 patients with acromegaly (18 men and 37 women): 27 patients with de novo disease, 28 patients on treatment of acromegaly (including 18 patietns with uncontrolled and 10 - with controlled acromegaly). All subgroups did not differ on sex, BMI and age. Also 24-hour monitoring of arterial blood pressure was carried out in 39 patients (12 men and 27 women, 14 patients with de novo acromegaly, 15 and 10 patients with uncontrolled and controlled acromegaly, respectively). RESULTS: The high prevalence of sleep breathing disorders (SBD) was revealed in patients with acromegaly from Moscow Region. SBD was found in 92.6%, 83.5% and 70.0% patients with newly diagnosed, uncontrolled and controlled acromegaly, respectively. The majority of patients had severe/moderate SBD in all subgroups (78.8%, 72.2% and 60.0%, respectively). In patients with newly diagnosed and uncontrolled acromegaly index of apnea-hypopnea (31 and 38.5 respectively), number of apnoe episodes (76 and 72) and saturation level (93% and 93.5%) did not differ significantly while these parameters were better in patients with a controlled acromegaly (apnea-hypopnea index 20, apnea episodes 45.5 and saturation level 95%). The peak of desaturation was subphysiological in 91.7%, 86.7% and 77.8% of patients with newly diagnosed, uncontrolled and controlled acromegaly, respectively. Severity of SBD did not depend on GH and IGF-1 levels as well as acromegaly duration. Such all-population risk factors of SBD as BMI and age were valuable for patients with acromegaly, however gender did not matter. SBD were associated with lack of physiological decrease of systolic and diastolic night BP. CONCLUSION: Acromegaly per se is a strong risk factor of sleep breathing disorders. The high prevalence of sleep breathing disorders in patients with acromegaly even after achievement of control over a disease emphasized need of specialized treatment of these violations.

[Clinical and functional characteristics of giant pituitary adenomas in the population of patients in the Moscow region]. / Klinicheskie i funktsional'nye kharakteristiki gigantskikh adenom gipofiza v populiatsii patsientov Moskovskoi oblasti.

Benign pituitary tumors are the most common sellar neoplasms. Lesions larger than 39 mm in the maximum dimension are called giant. They are rare, and, therefore, there are few data on the clinical and morphological features of giant pituitary tumors with different hormonal activity. AIM: The aim of this study was to identify the clinical and functional features of giant pituitary tumors with different hormonal activity. MATERIAL AND METHODS: We analyzed data of clinical, laboratory, and instrumental examinations of 351 patients diagnosed with pituitary macroadenomas at the Moscow Regional Research Clinical Institute in the period between 2008 and 2017: there were 144 hormonally inactive pituitary adenomas and 207 hormonally active pituitary adenomas (65 prolactinomas and 142 somatotropinomas). RESULTS AND DISCUSSION: Among 351 patients with pituitary macroadenomas, there were 32 (9.1%) giant adenoma cases: 18 (12.5%) 144 patients with hormonally inactive pituitary adenomas and 14 (6.8%) 207 patients with hormonally active pituitary adenomas 6 (3.9%) 65 prolactinomas and 6 (2.9%) 142 somatotropinomas. The volume of giant adenomas was somewhat larger among somatotropinomas 48 926 [35 067; 97 650] mm3 and prolactinomas 36 872 [15 281; 75 102] mm3 compared to that of hormonally inactive pituitary adenomas 26 933 [21 910; 42 895] mm3. Tumors had predominant suprasellar and posterosellar growth (31 (97.8%) and 29 (90.6%) cases, respectively). The most common first patient complaints were visual impairments (59.4%) and headache and/or dizziness (43.8%). Correspondingly, due to these complaints, 16 (50%) patients first consulted an ophthalmologist. Hypopituitarism detected before any treatment was present in 16 (50%) patients. CONCLUSION: In most cases, visual impairments and headaches/dizziness were the first manifestations of giant pituitary adenomas; therefore, ophthalmologists and neurologists should always refer patients with these complaints to MRI. Patients with identified giant pituitary tumors should be referred to an endocrinologist for exclusion of hypopituitarism and, if necessary, timely prescription of hormonal therapy.

Effects of allogenic fetal pancreatic tissue transplantation on regeneration of islet cells in recipient rats with alloxan-induced diabetes mellitus.

The linear parameters and number of Langerhans islets were evaluated in rats with alloxaninduced diabetes mellitus after transplantation of fetal pancreatic tissue to the anterior chamber of the eye. The islets significantly increased in size by week 3 after surgery and a trend to an increase in their number was observed.

Prevalence of diabetes mellitus in patients with acromegaly.

Early carbohydrate metabolism disorders (ECMDs) and diabetes mellitus (DM) are frequently associated with acromegaly. We aimed to assess the prevalence of ECMDs in patients with acromegaly and to compare the results with those in adults without acromegaly using two population-based epidemiologic surveys. We evaluated 97 patients with acromegaly in several phases of their disease (mean age, 56 years and estimated duration of acromegaly, 12.5 years). An oral glucose tolerance test was done in those not yet diagnosed with DM to reveal asymptomatic DM or ECMDs (impaired glucose tolerance+impaired fasting glucose). Comparisons were made between patients with acromegaly and participants from the general adult population (n=435) and an adult population with multiple type 2 diabetes risk factors (n=314), matched for gender, age and BMI. DM was diagnosed in 51 patients with acromegaly (52.5%) and 14.3% of the general population (P<0.001). The prevalence of ECMDs was also higher in patients with acromegaly than in the general population and in the high-risk group; only 22% of patients with acromegaly were normoglycaemic. The prevalence of newly diagnosed ECMDs or DM was 1.3-1.5 times higher in patients with acromegaly compared with the high-risk group. Patients with acromegaly having ECMDs or DM were older, more obese and had longer disease duration and higher IGF1 levels (Z-score). Logistic regression showed that the severity of glucose derangement was predicted by age, BMI and IGF1 levels. In patients with acromegaly, the prevalence of DM and ECMDs considerably exceeds that of the general population and of a high-risk group, and development of DM depends on age, BMI and IGF1 levels.

[Risk of type 2 diabetes mellitus and acute cardiovascular disorders in patients with early disturbances of carbohydrate metabolism].

The aim of this work was to estimate the relative risk (RR) of type 2 diabetes mellitus (DM2) and cardiovascular diseases, total and cardiovascular mortality in patients with disturbances of carbohydrate metabolism revealed in the prospective study carried out in 2009 that included patients found to have disturbances of carbohydrate metabolism in 2006. We analysed the 3-year risk of development of type 2 diabetes mellitus, total and cardiovascular mortality. RR of DM2 was significantly increased in association with practically all early disturbances of carbohydrate metabolism. The most unfavourable combination is fasting glycemia and impaired glucose tolerance. Within 3 years after its determination, 33.3% of the patients developed DM2 while RR of DM2 increased 11-fold. Newly diagnosed DM2 increased RR of total mortality by 2.3 times. Fasting glycemia during 3 years increased RR of cardiovascular mortality by 3.2 times. Results of the study suggest the necessity of not only timely diagnosis of fasting glycemia and impaired glucose tolerance but also further monitoring and correction of carbohydrate metabolism in patients with this pathology as well as of the elaboration and implementation of a comprehensive program for the screening of disturbed carbohydrate metabolism in high-risk groups.

[Major risk factors of glucose metabolism abnormalities].

Using the data of population base study of adult residents of 2 districts of Moscow Region (2638 persons), prevalence is studied and influence on occurrence of glucose metabolism abnormalities of major risk factors is estimated. Influence of risk factors was estimated with Cox regression analyses. High prevalence undiagnosed glucose metabolism abnormalities among persons (24,9%) is taped; it is established that relative risk of diabetes mellitus type 2 significantly raised at persons is more than 50 years of age independently of BMI, at the same time first-degree obesity increased relative risk of diabetes mellitus type 2 in 4,3 times and third-degree obesity--in 9,0 times independently of age.

[Correlation of HBA(1c) and postprandial glycemia during a standard breakfast test in patients with type 2 diabetes mellitus receiving glibenclamide].

AIM: To analyze the effect of glibenclamide on carbohydrate metabolic parameters, glucose values after standard breakfast in particular, in patients with type 2 diabetes (T2D). SUBJECTS AND METHODS: Thirty patients aged 57.6 +/- 9.4 years with a 4.4 +/- 4.0-year history of T2D received glibenclamide in a daily dose of 10.9 +/- 4.4 mg in combination with diet therapy for 3 months. Venous plasma glycemia was determined before and at the end of the fasting test, 60 and 120 minutes after a standard breakfast test. The area under the glycemic curve was calculated using the trapezoidal method during the standard breakfast test. Out of all possible formulas reflecting a blood glucose increase in relative values during the test, there were two most acceptable formulas that were chosen for further calculations: (1) the contribution of postprandial glycemia exceeding fasting glycemia to postprandial glycemia exceeding 6.1 mmol/l (OS(1/2)); (2) that of postprandial glycemia exceeding the glycemia of 6.1 mmol/l to postprandial glycemia in the standard breakfast test (OS2/S). RESULTS: Follow 3-month therapy, glycated hemoglobin (HBA1c) decreased from 8.7 +/- 1.8 to 7.0 +/- 1.0% (p < 0.0001), fasting plasma glucose reduced from 9.8 +/- 2.7 to 8.3 +/- 1.7 mmol/l (p < 0.01); it decreased from 14.8 +/- 3.9 to 13.2 +/- 3.3 mmol/l (p < 0.01) and from 13.3 +/- 3.6 to 11.1 +/- 3.0 mmol/l (p < 0.02) 1 and 2 hours after the load test, respectively. There was a significant reduction in the total area under the glycemic curve (S)--from 1583.5 +/- 405.8 to 1375.7 +/- 320.1 mmol/l x rmin. However, there were no significant changes. There was a significant increase in the relative value OS(1/2) from 51.7 +/- 17.7 to 62.8 +/- 20.0% and a significant reduction in OS2/S. Analysis of the area in relative values (OS(1/2) and OS2/S) obviates the ambiguousness of the results obtained when analyzing the area in absolute values. CONCLUSION: Glibenclamide treatment causes a statistically significant reduction in fasting and postprandial plasma glucose levels, glycated hemoglobin, and relative area values during the standard breakfast test.

[Influence of age and body weight on plasma glucose levels during an oral glucose tolerance test in subjects without carbohydrate metabolic disturbances].

AIM: To evaluate the influence of age and body mass index (BMI) on fasting and postprandial (2 hours after glucose load) plasma glucose (FPG and PPG) levels in males and females. SUBJECTS AND METHODS: A screening for carbohydrate metabolic disturbances (by using an oral glucose tolerance test) was made in the stratified adult sample from two municipal districts of the Moscow Region. The data were statistically processed by the computer program SPSS 11.0. RESULTS: The mean FPG level in normoglycemic subjects was 5.26 +/- 0.43 mmol/l. There was a significant (p < 0.001) positive correlation between age and FPG: r = 0.11 in men and r = 0.17 in women. The mean PPG was 6.15 +/- 1.35 mmol/l; in males it was significantly lower than that in females. There was a significant correlation between age and PPG: r = 0.30 in males and r = 0.13 in females. A weak, but statistically significant correlation was found between FPG and body mass index (BMI) in women: r = 0.02. There was no significant correlation between FPG and BMI in men. No significant correlation was found between PPG and BMI in both males and females. A lower PPG level was 2 times more frequently observed in men than that in women (37.70 and 17.57%, respectively). CONCLUSION: Fasting and postprandial (2 hours after glucose load) plasma glucose levels increase with age in subjects without carbohydrate metabolic disturbances. A predictable plasma glucose level increase depending on age is described by the cubic regression model equation.

[Analysis of a continuous 24-hour glycemic curve by the symmetrization method].

The study included 18 patients (10 females and 8 males) with a not less than 2 year-history of type 1 diabetes (T1D), who had received insulin therapy since its diagnosis was established. The patients ' mean age was 32.9± 13.0 years; the mean duration of TID was 15.1+11.5 years; the mean daily dose of insulin was 40.1+16.0 units; the mean level of glycosylated hemoglobin (HbAJ was 9.4±2.1% (the normal value 4.4-4.9%). The glycemic curve symmetrization method proposed for statistical analysis of glycemic self-control is also quite suitable for the statistical monitoring of a continuous daily glycemic curve. The high and low glycemic indices calculated from the symmetrized glycemic data correlate well with the level of HbAk and with the duration of hypoglycemia and hyperglycemia and hence they may be used as additional criteria for a risk of diabetes complications. The criteria, calculated from the symmetrized data of glycemia for the risk of hyper- and hypoglycemia, adequately reflect the behavior of a continuous glycemic curve and may be used as integral indices of the efficiency of glucose-reducing therapy in clinical practice.

[Study of new capacities in the evaluation of glycemic control in patients with type 2 diabetes].

The purpose of the study was to comprehensively analyze glycemic control in type 2 diabetes (T2D) patients who were first given glucose-reducing therapy. Glidiab MB and Diabeton MB caused a comparable reduction in glycemic control parameters: the level of HbA1c, fasting glycemia, and mean glycemic levels as shown by the results of its continuous glucose monitoring system (CGMS) study. The lower glycemic level was not accompanied by weight gain and it improved lipid spectrum parameters. The readings of monthly self-control of glycemia were transformed to its deviation from the goal range (ADRR) that and the hyper- and hypoglycemia indices calculated from the continuous glycemic control were used to evaluate glycemic lability not reflected by HbA1c. In this connection ADRR may be used to evaluate the efficiency of sugar-reducing therapy and in the examined groups it proved to be low, which generally reflects the stable course of the disease in new cases of T2D. The mean glycemic value calculated from CGMS data virtually coincides with the mean glycemia estimated from glycemic self-control readings both on the day of continuous glucose monitoring and in the month to come before and after CGMS study. In this connection the latter is justified only when the continuous glycemic curve undergoes a complex analysis. The complex analysis of the continuous glycemic curve includes symmetrization of the continuous glycemia scale; calculation of hyper- and hypoglycemic indices, hourly diurnal hyperglycemic index and hourly glycemic variations (Poincare method). The use of this procedure could compare the glucose-reducing effect of the two drugs within the framework of a short-term study.

[Effect of orlistat on postprandial glycemia in the oral glucose tolerance test and on other metabolic parameters in patients with type 2 diabetes].

The impact of monotherapy with an enteric lipase inhibitor (orlistat) on postprandialglycemia in the oral glucose tolerance test (OGTT) and on other metabolic parameters was studied in obese patients with type 2 diabetes (T2D). The study included 26 patients aged S3.07±6.70 years, who had a 2.60±2.91-year history of mild T2D. All the patients were given orlistat, 120 mg, as a capsule thrice daily before meals. Orlistat treatment was performed along with a low-calorie (as high as 1200 kcal daily) diet whose keeping was monitored by an individual dietary diary. During orlistat therapy, significant reductions were found in body weight (BW), body mass index, and waist circumference. At the same time, just within the first month and most patients were observed to lose up to 5% of the В W, but by the end of treatment there was a weight reduction by more than 5% of the baseline. Orlistat therapy caused a significant decrease in the fasting and postprandial blood levels of glucose and, accordingly, glycated hemoglobin. Orlistat induced a significant reduction in the total level of total cholesterol and low-density lipoproteins. By the end of the study, there was a significant decrease in systolic and diastolic blood pressures.

[Comparative evaluation of the efficiency of monotherapy with metformin and orlistat in patients with type 2 diabetes].

The purpose of the study was to evaluate the efficacy of orlistat versus metformin on the time course of changes in body weight (BW), lipid metabolism, blood pressure (BP), glycated hemoglobin (HbA1c, the kinetic parameters of'the oral glucose tolerance test (OGTT), and insulinemia in patients with type 2 diabetes (T2D). Two groups of patients with mild T2D with overweight or obesity were selected. Group 1 comprised 25 patients aged 53.16±8.92 years, who had a 2.50±3.06-year history. In this group, all the patients were given metformin in the daily starting dose of 500 mg. Group 2 patients (n = 26) aged 53.07±6.70 years, who had a 2.60±2.91-year history, took orlistat (xenical) (F. Hoffman-La Roche, Switzerland) in a dose of 120 mg thrice daily with meals. In addition, to exclude the impact of the time course of changes in body mass index (BMI) on carbohydrate and fat metabolic parameters, the twin method was used to select from each group 12 patients with similar ВW changes, matched by age, gender, the history of T2D, and the time course of changes in all anthropometric indices. The study revealed that orlistat and metformin exerted a comparable beneficial effect on carbohydrate and lipid metabolisms, BP in overweight or obese patients with T2D. Orlistat produced a significantly more pronounced effect on BW than did metformin. Unlike, orlistat, metformin significantly lowered fasting blood glucose levels due to the known inhibitory effect of hepatic glucose hyperproduction in overweight or obese patients with T2D. By excluding the Impact of BW loss on carbohydrate metabolism in overweight or obese patients with T2D, orlistat had a more marked sugar-lowering effect evaluated by the level of HbA1c This may be accounted for by the fact that with the specific suppression of fat absorption, orlistat may diminish intestinal carbohydrate absorption.

[Impact of adjuvant therapy with lithium carbonate on the results of radioiodine treatment in patients with diffuse toxic goiter].

Thirty-eight patients with diffuse toxic goiter (Graves' disease) were treated with radioiodine. Before 131I therapy thyrotoxicosis compensation was achieved by antithyroid medication in all the patients. Antithyroid medication was discontinued 10 days before radioiodine treatment. After its withdrawal, the use of lithium carbonate successfully prevented the development of thyrotoxicosis before 131I therapy. The administration of the agent caused a reduction in the proportion of patients with thyrotoxicosis 1.5 months after 131I therapy. Lithium carbonate used 10 days before and 4 days after 131Itherapy exerted the most considerable effect, by reducing the volume of the thyroid gland. By month 3, hypothyroidism more promptly developed in lithium carbonate-untreated patients; by month 6, the rate of different treatment outcomes (hypothyroidism, euthyroidism, or thyrotoxicosis) did not virtually depend on any lithium carbonate treatment regiment.

[Efficiency of treatment for diffuse toxic goiter in relation to the estimated therapeutic activity of radioactive iodine].

Forty-eight patients with diffuse toxic goiter (Graves's disease) were treated with radioactive iodine in a dose of 5.3-30.0 mCi. A special formula considering the volume of the thyroid and post-24-hour capture of the diagnostic activity of radioactive iodine was used to calculate the optimum therapeutic activity. As a result, specific therapeutic activity (STA) correlated with specific activity and with the volume of thyroid. The high rate (33.3%) of recurrent thyrotoxicosis was observed when the calculated STA was less than 0 3 mCi/ml and reduced to 11.1% if a greater activity was applied. The use of the standard activity of radioactive iodine (10mCi) with a thyroid volume of up to 40 ml, as compared to that calculated by the formula results in the similar rate of ineffective radioiodine therapy for thyrotoxicosis at a lower incidence of euthyrosis.

[Correlation Level of HbA1с and postprandial glycemia in type 2 diabetes in the oral glucose tolerance test].

A number of today's analytical methods for postprandial glycemia in the oral glucose tolerance test (OGTT) still remain to be substantiated. The standard OGTT using 75 g of glucose was performed in 42 type 2 diabetes mellitus (DM-2) patients who received diet therapy. The concentration of Hb A1c has been found to correlate with absolute levels of glycemia during 1- and 2-hour OGTT. However, exclusion of fasting glycemia from the level of glycemia at 1 and 2 hours of OGTT leads to cession of the correlation of HbA1c with these values of the test. Only 7 out of the 8 today's parameters for calculating the areas under the glycemic curve in OGTT correlate with the level of HbA1c. Moreover, 5 out of these 7 parameters are equivalent (r - 1; p < 0.05). The recently proposed two new parameters for calculating the areas under the glycemic curve in OGTT, one of which is constant 6.1, have proved to be equivalent (r= 1; p < 0 05) and to be actually reduced to one. The correlation with Hb Ah holds if any other constants from 5 to 11 mmоl/l are inserted instead of the constant 6.1 for calculating the area, the highest coefficient correlation with Hb A1c is achieved at the constant equal to 6.1. The correlation usually detectable at DM-2 between the concentration of Hb A,c and the absolute level of postprandial glycemia (glycemic spike in particular) Is mainly determined by its implicit inclusion of fasting glycemia. A set of 4 nonequivalent OGTT parameters should be used when the relationship of diabetes mellitus complications to the OGTT parameters that correlate with HbA,cis studied. The constants 5.6 and 6.1 reflect different aspects of the development of complications in diabetes mellitus when they are included in the calculation of an area in OGTT.

[Postprandial glyсеmia, body weight, and cardiovascular parameters in diabetes type 2 in metformin monotherapy].

Twenty-five patients with type 2 diabetes (DM-2) and its moderate initial decompensation (8.83±1.85%) were examined. The mean age of the examinees was 53.16±8.92 years; the duration of the disease was 2.50±3.06 years. There were 18 females (mean age 54.11 ±9.67 years) whose disease duration was 2.71±3.08 years and 7 males (mean age 50.7 1±6.63 years) with a disease duration of 1.95±3.17 years. Before prescribing metformin, all the patients received diet therapy, but without making a special monitoring of the calorie content of a diet. All the patients were given metformin in an initial daily dose of 500 mg. Later on the daily dose of metformin was increased up to 1000-1500 mg. Metformin treatment was performed during low-calorie diet (as high as 1200 kcal daily); compliance was monitored by an individual dietary diary. In patients with DM-2, metformin exerted a positive effect on fasting glycemia (p = 0.001) and postprandial hyperglycemia (absolute and relative areas under the curve in the oral glucose tolerance test (OGTT)). At the same time there were no perceptible changes in the level of glycated hemoglobin (p = 0.533). Although metformin caused a noticeable decrease from 5.75±4.72 to 3.97±2.71, it was yet statistically insignificant (p = 0.181). In patients with DM-2, metformin therapy enhanced a low-calorie diet-induced body weight loss, most markedly within the first three months of therapy. At the same time, a meta-analysis has shown that this effect of metformin is rather moderate (p = 0.02). Metformin treatment for MD-2 during low-calorie diet improves lipid metabolism, by significantly decreasing the levels of total cholesterol and low-density lipoproteins, and lowers systolic blood pressure.

[Vascular topography of glycemia in diabetes mellitus type 1 and in norm (theoretical analysis)].

Glycemia level in peripheral circulation is the basic parameter of diabetes diagnosing as well as a criteria of treatment effectiveness. Also there are a lot of the experimental data concerns glucose metabolism in different parts of the circulation. This permits to calculate so called circulatory topography of glycemia--glucose level in different parts of the circulation. As a result of the calculation was shown that in DM1 glycemia level is elevated in insulin-independent tissues even when glycemia level is normal in clinically useful peripheral circulation. These results can explain the predisposal of DM1 patients to diabetic retinopathy and nephropathy because eyes and kidney are the insulin-independent tissues. The reason why changes circulatory topography of glycemia in DM1 is changes in prime insulin delivery in circulation: insulin medication input not in the portal vein of hepar as in normal state but in peripheral circulation. It was shown that stable glycemia level in DM1 could be reached only in case of hepatic insulin-resistance.

[Impaired glucose balance and seven diabetes mellitus subtypes detected by intravenous glucose tolerance test].

A new clinically suitable method has been developed to calculate the rate of blood glucose elimination and hepatic glucose production (HGP) by the results of intravenous glucose tolerance test (IGTT). A subpopulation of non-diabetic persons was identified in whom substantially increased HGP is compensated for high blood glucose elimination, which prevents the development of hyperglycemia in them. This abnormality is designated impaired glucose balance and may be referred to as an early prehyperglycemic stage of diabetes (prediabetes). The results of IGTT analysis correlate with the types of diabetes mellitus and the degree of carbohydrate metabolic disturbance, which allows one to recommend the proposed method for diagnosing diabetes and its types and assessing the degree of metabolic disturbances in diabetes. Four types of glucose imbalance may be identified from the ratio of the degree of impaired HGP to glucose elimination. As a result, a combination of 2 types of diabetes mellitus and 4 types of glucose imbalance makes it possible to divide the population of diabetes mellitus into 7 subgroups (subtypes), which may be subsequently of importance in optimizing sugar-reducing therapy. A computer program has been developed, which automatically calculates the glucose kinetics in IGTT according to the tatter's results and which is free available in the Internet at www.diabet.ru/Dreval/ivgtt_eng.exe .