[Early intensification of glucose-lowering therapy: VERIFY lessons and real clinical practice on the example of the Moscow region diabetes register data].

BACKGROUND: The prevalence of T2DM is steadily increasing not only among the elderly, but also at a young age. T2DM is preceded by a long period of significant metabolic changes with the development of insulin resistance and в-cell dysfunction. To reduce the prevalence of complications, treatment is needed which affects several pathophysiological mechanisms underlying the disease. Monotherapy with metformin at the onset of T2DM is often insufficient. The VERIFY study demonstrated the advantage of early administration of a combination of vildagliptin and metformin in relation to the glycemic durability compared to the sequential intensification of metformin with vildagliptin in patients with type 2 diabetes. AIMS: To assess the current situation in terms of the incidence of T2DM complications and the structure of the prescribing glucose lowering drugs based on the data from the Diabetes Register (DR) of the Moscow Region. To demonstrate the advantages of early combination therapy in patients with newly diagnosed T2DM using clinical cases. MATERIALS AND METHODS: The data from the DR of the Moscow region, which is part of the National Diabetes Register of the Russian Federation, were used for the analysis. The data of 6,096 patients with T2DM who died in 2019 were evaluated for building the structure of the causes of death of patients with T2DM. The pattern of glucose-lowering therapy was analyzed based on data of 226,327 patients with T2DM (for 2020), as well as separately of 14,379 patients with newly diagnosed T2DM in 2019. Clinical cases are described based on the data of two patients with T2DM, available in the DR database and outpatient records. RESULTS: In patients with young onset T2DM (<40 years), the prevalence of severe complications is higher than in the general population of patients with T2DM: blindness is in 5.9 times, end-stage chronic renal failure in 2.9 times, lower limb amputations in 6.4 times more. When prescribing glucose lowering drugs, monotherapy is prevalent, mostly metformin. In double combination, metformin is used in 96.22% of cases. In the structure of glucose lowering drugs, with newly diagnosed T2DM, combination therapy is used less frequently than in patients with T2DM in general. Of the drugs of the IDP-4 group, vildagliptin is most often prescribed - 46.25% (including of a fixed combination with metformin - 12.22%). Clinical cases reflect a rapid clinical outcome: a decrease in HbA1c to the target in 6 months, the absence of hypoglycemia or other side effects, and positive weight dynamics. CONCLUSIONS: A fairly large propotion of patients with T2DM are on monotherapy with glucouse lowering drugs. Early prescription of the combination of metformin plus vildagliptin provides a longer maintenance of glycemic control without increasing the risk of hypoglycemia and weight gain for patients with newly diagnosed T2DM.

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.