One-hour postload plasma glucose levels as a new criterion for assessing insulin secretion in obese children

BACKGROUND: Incidence of Type 2 Diabetes Mellitus (T2DM) and associated dysglycemic conditions, increasing the risk of diabetes development, continues to rise worldwide, most notably due to ever-growing obesity rate. Early identification of the persons who are exposed to the risk of T2DM development holds much significance for prevention of both this disease and associated cardiometabolic complications.AIM: To study characteristics of insulin secretion and insulin sensitivity among obese children and adolescents versus the glycemic level 60 minutes (GL60) after the standard oral glucose tolerance test (OGTT).METHODS: This open-label comparative cross-sectional study involved 613 children in the age between 6 and 17.9 years old with constitutive-exogenous obesity, divided into 2 groups: 173 patients with GL60 level ≥ 8.6 mmol/L and 440 children with GL60 level < 8.6 mmol/L. They underwent a screening for dyslipidemia, non-alcoholic fatty liver disease, arterial hypertension and impaired glucose tolerance (IGT). Insulin secretion was evaluated on the basis of maximal (IRI max), average level (IRI avg) of insulin in the course of OGTT and insulinogenic index (IGI), insulin resistance (IG) — by Matsuda index.RESULTS: The groups were comparable in the terms of age, sex, sexual maturation stage and obesity level. Children with GL60 level ≥ 8.6 mmol/L were characterized by higher IR (Matsuda 2.8 ± 2.3 vs 3.5 ± 2.2, р < 0.01), hyperinsulinemia (IRI max 190.0 ± 59.5 vs 157.1 ± 63.4 μU/ml, р < 0.001, IRI avg 115.3 ± 59.7 vs 90.2 ± 54.1 μU/ml, p < 0.001) along with low IGI value (1.84 ± 1.62 vs 2.61 ± 1.3, р < 0.01), which is indicative of the first phase insulin secretion impairment. The lowest IGI values were found among the "GL60 level ≥ 8.6 mmol/L" group patients with IGT (1.4 ± 0.9). Besides, the patients with GL60 level ≥ 8.6 mmol/L are characterized by the higher rate of metabolic complications in the form of impaired glucose tolerance, arterial hypertension, fatty hepatosis and steatohepatitis.CONCLUSIONS: GL60 level ≥ 8.6 mmol/L can be used as an additional marker for metabolically complicated obesity among children and adolescents with a high risk of the carbohydrate metabolism disorder development

Long-term glycemic control and factors, associated with response to pump insulin therapy in children

Background: In recent years, pump-based insulin therapy, also known as continuous subcutaneous insulin infusion (CSII), has become a common treatment for children with type 1 diabetes mellitus (T1DM). Despite the fact that, in general, children with type 1 diabetes achieve the best glycemic control indices during pump therapy, while there is a significant heterogeneity of metabolic outcomes among individual patients, many children with CSII do not reach the target level of HbA1c.Objective: To assess the level of glycemic control and factors associated by withdrawal of use, the response to treatment with prolonged use of CSII in children with type 1 diabetes.Materials and methods: The study included 458 children aged 1 to 18 years, treated to pump therapy at least 3 years before the study, the presence of the analyzed data in the register.Results: The level of HbA1c decreased by -0.7% compared with the primary endpoint, which was accompanied by an increase in the number of patients who reached the target level of HbA1c (<7.5%) from 17% to 36%. The best response was observed for patients under 6 years of age with HbA1c over 9% for pump insulin therapy, as well as in patients who regularly use additional bolus and basal functions and CGM. The main reason for stopping the use of the insulin pump is the inconvenience of using and wearing — 47.7%. Risk factors for pump abandonment: later age of start treatment on CSII and frequent episodes of severe hypoglycemia.Conclusion: According to the results of the study, it was shown that pump therapy is an effective method of insulin therapy, which allows to achieve a lower level of HbA1c compared to the initial values

Remote monitoring of adolescents with type 1 diabetes mellitus using a mobile application

Background: The prevalence of type 1 diabetes mellitus (T1DM) in childhood is increasing every year. Adolescence is the most challenging age for achieving optimal metabolic control of T1DM. Telemedicine has already been shown to be ­effective in children with the condition, but there are not enough studies in adolescents. The use of mobile apps may be associated with better glycemic control in patients with type 1 diabetes.Aims: To assess the effectiveness and safety of a model of medical care for adolescents with type 1 diabetes using remote counseling and a mobile application.Materials and methods: Were included adolescents aged ≥14 and 18 years with a T1DM duration> 3 months, a glycated hemoglobin level (HbA1c)> 7%. The duration of the study was 26 weeks. There were 3 face-to-face and at least 4 remote visits using a mobile application. All patients underwent standard examination and anthropometry, study of HbA1c, registration and analysis of indicators, assessment and correction of the treatment. The quality of life of adolescents was assessed at baseline and at the end of the study. Adolescents and physicians were interviewed about program evaluation.Results: 56 patients were included, 7 adolescents withdrew. HbA1c significantly decreased by the 12th week of the study (–0.3%; p = 0.005), by the end of the study the change in HbA1c was –0.5% (p <0.001). There was an increase in the percentage of glucose measurements in the target range (+5.3 pp; p = 0.016) and a decrease in blood glucose variability (-3.1 pp; p =  0.015). There was a significant improvement in both the total assessment of the quality of life by patients (+2.9 points; p = 0.008) and individual components of its indicators: attitude to diabetes (+3.0 points; p = 0.049), attitude to treatment (+4.6 points; p = 0.010) and communication with others (+4.5 points; p = 0.015). The majority of doctors and patients assessed their participation in the study positively. The incidence of adverse events did not change significantly during the study from baseline.Conclusion: Remote counseling using a mobile app is a safe and effective approach for adolescents with T1DM in terms of glycemic control and quality of life, and provides convenience and speed of interaction

Characteristics of blood pressure level in children with different body weight

BACKGROUND: Essential arterial hypertension (AH) develops more often in children with accompanying risk factors — obesity, overweight, positive heredity and genetic predisposition.AIM: Study of peculiarities of arterial hypertension clinical course in adolescents with normal body weight, overweight and obesity.MATERIALS AND METHODS: The study was conducted on children with arterial hypertension who received treatment in two hospitals in Voronezh in 2016–2020. A retrospective analysis of the children’s case histories was carried out taking into account the anamnesis, clinical laboratory and instrumental examination data and the pharmacotherapy. Some children underwent polymerase chain reaction genetic testing to determine pathological alleles of genes regulating blood pressure (BP).RESULTS: 96 patients aged 9 to 17 took part in the study. The group with normal body weight included 38 children (39.6%), median age 16.4 (aged 10.7; 17.9), with overweight — 33 people (34.4%), median age 15.2 (aged 12.0; 17.9), with obesity — 25 children (26.0%), median age 14.5 (aged 9.2; 17.9). Obese children developed arterial hypertension at earlier age (p = 0.023). According to blood pressure daily monitoring (BPDM), pathological values of systolic blood pressure (SBP) during the day (above the 95th percentile) among children with normal body weight were observed in 17 patients (44.7%), with excess body weight — in 14 people (42.4%), with obesity — in 16 people (64%), p = 0.031. Accurate difference values between the groups were obtained in terms of time index (TI) of SBP at night (p = 0.006). Time index of diastolic BP during the day > 50% was observed only in the obese children group — 4 people (16%) (p = 0.042). Pathological alleles of the angiotensinogen gene (AGT: 704 T>C), aldosterone synthase gene (CYP11B2: -344 C>T) and endothelial nitrogen synthase type 3 (NOS3: -786 T> C) were identified most frequently during genetic testing in some patients.CONCLUSION: Children with obesity developed earlier arterial hypertension compared to the same-age children with normal body weight and more often had unfavorable type of arterial hypertension according to BPDM. These results can be used to choose individual therapy and to develop special attention as regards certain target organs damage

C-peptide levels and the prevalence of islets autoantibodies in children with type 1 diabetes mellitus with different duration of the disease

BACKGROUND: Type 1 diabetes mellitus (T1DM) is characterized by the development of absolute insulin deficiency. In some patients residual insulin secretion may persist for a long time. C-peptide is a widely used to measure the pancreatic beta cells function, in clinical practice and in research studies.AIM: To assess C-peptide levels and presence of islets autoantibodies (Ab) in children with different duration of T1DM and to identify factors associated with the preserved secretion.MATERIALS AND METHODS: Single-center cross-sectional study including data from 703 cases of children with T1DM, examined in the Endocrinology Research Center in 2016-2020, who was underwent a study of C-peptide levels and was positive for one or more islets antibodies (ZnT8, IA-2, GAD, ICA, IAA). There were 3 groups of patients: 1st — T1DM duration < 1 year, 2nd — from 1 to 5 years, 3rd — > 5 years.RESULTS: The median of the fasting C-peptide level in the 1st group was 0.6 ng/ml [0.27; 1.09]; in the 2nd group — 0.2 ng/ml [0.01; 0.8]; in the 3rd group — 0.01 ng/ml [0.01; 0.037]. The preserved secretion of C-peptide (> 0.6 ng/ml) was determined in 51.4% in the 1st group, in 31.4% — in the 2nd group and in 11.4% in the 3rd group. In patients with obesity during the first year from the T1DM diagnosis C-peptide levels above 1.1 ng/ml was determined significantly more often (65.2%), as well as at the period of 1 to 5 years of the disease (35.7%), compared with children with normal BMI (18.5% and 14.5%, respectively) or overweight (15.7% and 19%, respectively), p <0.01. A negative correlation was found between C-peptide levels and the duration of T1DM (r = -0.489, p = 0.000), the daily dose of insulin (r = -0.637, p = 0.000), a positive association was found with the age of diagnosis of T1DM (r = 0.547, p = 0.000). The frequency of the presence of one type of islets autoantibodies in all groups was 29.5%, 2 types — 33.6%, 3 and more types — 36.9%. The titer of IA-2, ZnT8 decreased with the disease duration (p <0.05 and p <0.01, respectively), while the titer of ICA increased (p <0.01). No associations between the types, number, antibodies titer and C-peptide levels, age of disease manifestation were found.CONCLUSION: C-peptide levels in children with T1DM in groups with older age at diagnosis and with obesity is significantly higher for the first 5 years of the disease. The study have shown the titer of IA-2, ZnT8 is decreasing with the disease duration, in turn, the frequency of detection of ICA increases. No association between C-peptide levels and the type, number and titer of antibodies were found

The Scientific Advisory board resolution: Implementation of intermittently scanned Continuous Glucose monitoring in clinical practice to improve glycemic control

The Scientific Advisory Board chaired by Academician of the Russian Academy of Sciences, Peterkova V.A. was held 26 of November in Moscow to discuss the possibilities of continuous glucose monitoring technology (CGM) implementation into routine clinical practice in Russia in order to improve glycemic control in patients with diabetes mellitus (DM).The main aims for Advisory board were to determine the most significant indicators and parameters for CGM to be implemented in practice from a practical point of view of LMWH, necessary for implementation in clinical practice, for different patients groups with diabetes.The following questions and topics were raised within the discussion: the importance of additional indicators beyond glycated hemoglobin (HbA1c) for glycemic control assessment in diabetes patients, CGM positioning in International and Russian clinical guidelines, the accuracy of CGM devises and approaches to its assessment, the role of education programs for diabetic patients, including trainings in correct use and data interpretation and analysis of CGM data obtained, clinical evidence analysis for CGM in randomized trials and real world evidence

Non-immune diabetes mellitus in children due to heterozygous mutations in the glucokinase gene (GCK-MODY): data of 144 patients

BACKGROUND: Monogenic diabetes mellitus (MDM) is a rare form of diabetes mellitus (DM) which caused by one or more mutations in one of the genes that cause pancreatic β-cell dysfunction. Despite the sufficient knowledge of the most common subtypes of MODY, cases of MDM are undiagnosed and classified as type 1 diabetes mellitus and type 2 diabetes mellitus.AIM: To study the clinical, laboratory characteristics, as well as age-related features of GCK-MODY in children.MATERIALS AND METHODS: The studied population is patients with GCK-MODY under the age of 18 years. The diagnosis was confirmed by genetic test, a heterozygous mutation was identificated in the GCK gene.RESULTS: MODY-GCK was verified in 144 patients (131 probands and 13 siblings) under the age of 18 years. Missense mutations were detected in 80.2% (n=105). Mutation was detected in one case in 59.6%. The most common missense mutations were p.G261R (n=7) and p.G258C (n=6). The age of diagnosis of carbohydrate metabolism disorders was 7.6 years [4.0; 11.2]. In 72.2% carbohydrate metabolism disorders were diagnosed accidentally, in 16.7% the examination was provided due to a family history of diabetes, 11.1% had clinical symptoms of diabetes. Fasting glycemia at diagnosis was 6.8 mmol / l [6.4; 7.3], HbA1c — 6.4% [6.1; 6.7]. At examination, the level of fasting glycemia corresponded to normal values in 16.4% of patients, impaired fasting glycemia — in 57.8%, diabetic — in 25.8%. In 62.3% of patients was impaired glucose tolerance, in 18.9% — to diabetic values, and in 11.7% of patients — to a normal level at 120 minutes during the oral glucose tolerance test. A moderate positive correlation was found between the age of examination and the levels of fasting glycemia (r=0.347, p<0.01), C-peptide (r=0.656, p<0.001), and insulin (r=0.531, p<0.001). Insulin resistance (IR) (HOMA index) was detected in 21 patients (14.5%), obesity — in 6 patients (4.2%). In 9 patients (6.25%) was revealed a moderate increase in the titer of specific pancreatic antibodies (AT). The presence of IR, obesity, AT did not affect the level of HbA1c. In 92.3% diet was priscribed, in 4.2% insulin was prescribed, 2.1% — metformin, 1.4% — sulfonylureas.CONCLUSION: In children, disorders of carbohydrate metabolism in GCK-MODY are diagnosed accidentally, asymptomatically at any age from birth, and are characterized by a combination of impaired fasting glycemia and impaired glucose tolerance and, as a rule, do not require antihyperglycemic therap

Comparative assessment of energy metabolism, body composition and metabolic features in children with hypothalamic and simple obesity

Background: Hypothalamic obesity often develops after surgical treatment of craniopharyngioma and is characterized by rapid weight gain, high frequency of metabolic disorders, body composition specificity and resistance to standard lifestyle modification approaches and medication therapy of obesity. Recent studies show that one of the mechanisms, explaining weight gain in these children is decrease in resting energy expenditure (REE).Aims: To compare REE, body composition parameters, and the frequency of metabolic disorders in children with hypothalamic and simple obesity.Materials and methods: The study included 60 obese children aged 7 to 17 years, divided into two groups. The study group included 20 children with hypothalamic obesity, developed after craniopharyngioma treatment. The control group consisted of 40 children with simple obesity. Body composition, REE, and metabolic disorders were associated in all children.Results: Children with hypothalamic obesity showed a significant decrease of resting energy expenditure. The average decrease in REE was 13.1%, but in single patients it reached 33.4%. The percentage of fat mass in hypothalamic and simple obesity does not differ significantly (39.7% [36.2; 42.6] vs 38.8 % [35.9; 43.2]; p=0.69). Screening for metabolic disorders revealed a high prevalence of metabolic disorders in hypothalamic obesity: impaired glucose tolerance - in 10%; dyslipidemia - 55%, insulin resistance-50%, non-alcoholic fatty liver disease - 60 %.Conclusions: Children with hypothalamic obesity showed a significant decrease of resting energy expenditure. When planning a diet in this group of patients it is preferable to use indirect calorimetry. Hypothalamic obesity even at an early age is associated with a high frequency of metabolic disturbance. Hypothalamic obesity in children is not associated with more pronounced hyperinsulinemia and insulin resistance compared to the simple obesity

The use of Flash glucose monitoring in children with type 1 diabetes mellitus in real clinical practice

BACKGROUND: In 2018, a Frestyle Libre flash glucose monitoring system (FGM) appeared in Russia and became a potential alternative to the traditional CGM. Studies carried out to date have shown the advantages of FGM over SMBG, but only a few of them relate to real clinical practice, especially in children with type 1 diabetes.OBJECTIVE: To evaluate the efficacy of FGM in children with T1DM in relation to glycemic control indicators, the occurrence of severe hypoglycemia and diabetic ketoacidosis, as well as the satisfaction of patients and their parents with the use of FGM.MATERIALS AND METHODS: Single-center, prospective, observational cohort study. Children 4–18 years old with T1DM and HbA1c level less than 10.0% were invited to participate in the study on intensified insulin therapy (by MDI or CSII). The duration of the patient’s participation in the study was 6 months. At baseline and every 3 months thereafter, face-to-face consultations were conducted with an assessment of the general condition, HbA1c study, an assessment of glycemic indicators, progress in relation to glycemic control targets and correction of the therapy. A total of 228 patients (110 boys and 118 girls) who met the inclusion criteria were included in the study. The median age was 11.2 (8.6–14.7) years, the duration of type 1 diabetes was 3.8 (2–7.1), 136 patients received insulin therapy by CSII for 1.3 (0.8–2.6) years.RESULTS: In the general group of patients, 3 and 6 months after the start of FGM use, the HbA1c values decreased statistically significantly by 0.2%. In addition, the number of children with HbA1c <7.5% increased by 6.1 and 4.9% at 3 and 6 months, respectively, but these changes were not statistically significant. The number of cases of DKA when using FGM decreased by 74%, and the number of cases of severe hypoglycemia by 83%, thus the number of episodes decreased by 4 and 6 times, respectively. Patients and / or their parents rated the ease of use and their experience with FGM on a scale from 0 (strongly agree) to 4 (strongly disagree). The majority of children and parents positively (0 or 1) assessed the convenience of installing and wearing the sensor (72.7–98.2%) using the FGM system in general (75.0–96.4%) and in comparison with the SMBG glucometer (92.3–98.2%).CONCLUSION: The installation and use of FGM is convenient and comfortable for the vast majority of children and parents, while compared to SMBG, the use of FGM is more convenient and simpler, and glucose measurement is much faster and less painful

The role of specific pancreatic antibodies in the differential diagnosis of complete clinical and laboratory remission of type 1 diabetes mellitus and MODY in children

BACKGROUND: T1D is characterized by autoimmune destruction of pancreatic β-cells, which develops due to genetic and environmental risk factors. Shortly after initiating the treatment with insulin, 80% of children with T1D may require smaller doses of insulin and develop clinical and laboratory remission of the disease so called «honeymoon». The issue of whether there is a need of differential diagnosis between autoimmune DM and non-immune forms of DM raises in cases of preclinical diagnosis of T1D and laboratory remission for more than 6 months.AIM: To study the clinical, immunological, genetic characteristics of T1D remission phase and MODY in children, to determine the diagnostic criteria for T1D and MODY in children.MATERIALS AND METHODS: A single-centre, cross sectional noncontrolled comparative study of two independent cohorts. Data of 150 children examined in the Endocrinology Research Center (January 2016–June 2021). First cohort included patients with complete clinical and laboratory remission of T1D (n=36), second cohort included patients with MODY, confirmed by genetic study (n=114).RESULTS: The median age of diabetes manifestation was significantly higher in patients with T1D — 11.25 years [8.33; 13.78] than in patients with MODY — 7.5 years [4.6; 12.2] (p=0.004). In patients with T1D remission the level of glycated hemoglobin was 6.0% [5.6; 6.4], in group with MODY — 6.5% [6.2; 6.7] (p<0.001). Patients with monogenic diabetes had impaired fasting glucose — 6.27 mmol/l [5.38; 6.72], while patients with remission phase had normoglycemia — 5.12 mmol/l [4.17; 5.87]. The oral glucose tolerance test was perform to all patients, two-hour glucose level did not significantly differ in two groups (p=0.08). A strong family history of diabetes in patients with MODY registered more often (93% vs. 66.7%). A positive autoantibody titer detected more often in patients with remission of T1D (77.8%) than in patients with MODY (11.4%). In addition, no more than 1 type of autoantibodies was detected in patients with MODY.CONCLUSION: Antibodies ZnT8 and IA2 showed the greatest significance for the differential diagnosis of T1D and MODY in cases with long absents of insulin requirement in children with diabetes mellitus. Genetic test is recommended in seronegative cases. If only one type of AT is detected, specialist should decide on the need to do diagnostic genetic test based on a comprehensive analysis of the patient’s clinic characteristics, including family history, manifestation and blood glucose levels