Objective. To estimate performance characteristics and diagnostic value of immunofluorescent islet cell antibody (ICA) assay, immunoradiometric glutamic acid decarboxylase antibody (GADA) assay, and ELISA tyrosine phosphatase IA-2 antibody (IA-2A) and insulin antibody (IA) assays.Research Design and Methods. Antibodies were tested in 438 children and adolescents with newly diagnosed diabetes mellitus (DM) type 1, and in 891 subjects without DM type 1. ICA were determined by the classic indirect immunofluorescent method recommended by the Juvenile Diabetes Foundation International, GADA were determined with the Immunotech IRMA Anti-GAD kit, and IA-2A and IA were determined with Medizym Anti-IA2 and Orgentec Anti-Insulin ELISA kits, respectively. Sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of the tests were estimated with contingency tables. Diagnostic accuracy was estimated from areas under receiver operating curves (AUC).Results. ICA test was of the greatest diagnostic value (Se=88%, Sp=96%, PPV=96%, NPV=94%, AUC=0,94), followed by IA-2A (Se=66%, Sp=98%, PPV=98%, NPV=59%, AUC=0,82) and GADA (Se=73%, Sp=84%, PPV=75%, NPV=83%, AUC=0,79). IA test exhibited a very low Se (4,3%) and lacked diagnostic accuracy (AUC=0,5).Conclusions. We recommend to use ICA, IA-2A and GADA tests surveyed in our study for diagnosis of DM type 1 and differential diagnosis of DM. We don’t recommend IA testing with an Orgentec Anti-Insulin ELISA kit for usage in clinical practice.
Backgraund: Children with type 1 diabetes mellitus (T1DM) need more insulin late in the evening (reverse dawn phenomenon (RDP)), and adolescents need more insulin yearly in the morning (dawn phenomenon (DP)); these cause blood glucose variability. Modern long acting insulin analogues allow to achieve satisfactory glycemic control.Aims: To study the characteristics of insulin therapy in children and adolescents with T1DM using insulin analogues detemir and degludec to overcome blood glucose variability caused by DP and RDP in different age periods.Materials and methods: We analyzed medical documents of 200 patients using detemir, admitted to pediatric endocrinology department in 2013–2019, at mean age 9.0 years (5.4; 13.0), with T1DM for 1.3 years (0.5; 3.0); and medical documents of 50 patients switched to degludec in 2018–2019 at mean age 12.0 years (10.5; 14.5) with T1DM for 3.0 years (1.5; 6.0). Before degludec they were on intensive insulin therapy with glargine (22), detemir (26), or insulin pump (2); 16 patients (32%) presented with clinical characteristics of DP, and 5 (10%) — RDP.Results: 67 children of 108 (62%) aged 1–9 years had redistribution of detemir doses to daytime; 58 adolescents of 92 (63%) aged 10–17 лет — to nighttime. Patients switched to degludec demonstrated decrease in HbA1с from 8.7% (7.8; 9.9) to 8.0% (7.4; 9.0) (р<0.001); fasting blood glucose from 9.8 mmol/l (7.4; 11.7) to 7.7 mmol/l (6.4; 8.6) (р<0.001); within-day variability from 35.2% (31.6; 40.9) to 23.5% (19.7; 28.6) (р<0.001); daily insulin dose from 0.98 U/kg/day (0.82; 1.14) to 0.87 U/kg/day (0.75; 1.07) (р=0.002). Sub-groups of patients with DP and RDP demonstrated decrease in fasting blood glucose (from 11.5 mmol/l (9.8; 13.8) to 7.5 mmol/l (6.6; 9.1) (р<0.001)), and late evening blood glucose (from 11.0 mmol/l (10.2; 11.2) to 8.0 mmol/l (6.7; 9.5) (р= 0.03)) correspondently. Achieved levels of glycemic control did not differ between sub-groups of patients initially using glargine or detemir.Conclusions: Compensation of T1DM may be complicated due to DP and RDP. Switching to degludec allowed to achieve better glycemic control and lowering of blood glucose variability caused by DP and DRP.
Objective. To estimate performance characteristics and diagnostic value of immunofluorescent islet cell antibody (ICA) assay, immunoradiometric glutamic acid decarboxylase antibody (GADA) assay, and ELISA tyrosine phosphatase IA-2 antibody (IA-2A) and insulin antibody (IA) assays.Research Design and Methods. Antibodies were tested in 438 children and adolescents with newly diagnosed diabetes mellitus (DM) type 1, and in 891 subjects without DM type 1. ICA were determined by the classic indirect immunofluorescent method recommended by the Juvenile Diabetes Foundation International, GADA were determined with the Immunotech IRMA Anti-GAD kit, and IA-2A and IA were determined with Medizym Anti-IA2 and Orgentec Anti-Insulin ELISA kits, respectively. Sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of the tests were estimated with contingency tables. Diagnostic accuracy was estimated from areas under receiver operating curves (AUC).Results. ICA test was of the greatest diagnostic value (Se=88%, Sp=96%, PPV=96%, NPV=94%, AUC=0,94), followed by IA-2A (Se=66%, Sp=98%, PPV=98%, NPV=59%, AUC=0,82) and GADA (Se=73%, Sp=84%, PPV=75%, NPV=83%, AUC=0,79). IA test exhibited a very low Se (4,3%) and lacked diagnostic accuracy (AUC=0,5).Conclusions. We recommend to use ICA, IA-2A and GADA tests surveyed in our study for diagnosis of DM type 1 and differential diagnosis of DM. We don’t recommend IA testing with an Orgentec Anti-Insulin ELISA kit for usage in clinical practice.
BACKGROUND: Liraglutide was approved for treatment of obesity in children and adolescents since 12 years. Due to gastrointestinal (GI) side effects not all patients reach maximal dose; this can affect the efficacy of obesity treatment.AIM: To study efficacy and tolerability of liraglutide in adolescents with obesity.MATERIALS AND METHODS: We analyzed medical data of adolescents with simple obesity and GI comorbidities before and in 3 months after start of liraglutide (BMI SDS; obesity complications; liraglutide side effects, and maximal doses), duration of therapy, reasons for discontinuation, and BMI SDS in 3–6 months after discontinuation.RESULTS: Liraglutide was administered for 10 adolescents (7 girls, 3 boys) 15.4 (13.5; 16.2) years with BMI SDS 3.3 (2.9; 3.7). Three months of treatment led to significant (p=0.001) decrease of BMI SDS till 2.8 (2.6; 3.5). Maximal dose of liraglutide was 3.0 mg (6 patients), 2.4 mg (2), 1.8 mg (1), and 1.2 mg (1). No correlation between maximal dose and BMI ΔSDS was detected. While dose titration patients complained of nausea (9), diarrhea (3), obstipation (1), and flatulence (1). In majority of cases complains were not dose-dependent. Only in 1 patient nausea and diarrhea that did not allow to increase liraglutide dose above 1.2 mg; additional investigation after discontinuation of therapy revealed GI infection.Therapy was discontinued in 3 months by 2 patients (1 — side effects, 1 — satisfactory result), in 4–5 months by 3 patients (1 — relapse of excessive weight gain, 2 — financial reasons), in 6 months by 1 patient (satisfactory result); 4 continued therapies. In 3–6 months after discontinuation of therapy BMI SDS increased and did not significantly differ from basal.CONCLUSION: Liraglutide is effective for treatment of obesity in adolescents and well tolerated by majority of patients. In case of pronounced adverse events additional GI investigation is recommended. Patients can discontinue treatment not only due to side effects, but also when they achieve their goal, and due to financial reasons.
BACKGROUND: In coexistence of diabetes mellitus type 1 (DM1) with severe autoimmune and inflammatory diseases some patients need simultaneous administration of insulin and glucocorticoids (GC). GC therapy in patients with DM1 can worsen glycemic control. AIM: To determine characteristics of insulin therapy of DM1 in children and adolescents receiving GC. DESCRIPTION OF CLINICAL CASES: We observed 5 patients with DM1 receiving GC for juvenile idiopathic arthritis (JIA), juvenile systemic sclerosis (JSS), juvenile dermatomyositis (JDM), ulcerative colitis (UC), and reactive arthritis (RA). Intra-articular administration of GC did not significantly influence glycemic control. In case of GC pulse therapy hyperglycemia and increased insulin requirements were recognized in 36 hours after GC receipt, persisted from few hours up to 3 days after each administration. While therapy with oral GC in high doses the worst glycemic control was registered in daylight hours. To overcome insulin resistance change of time of injection and 10%-increase of long-acting insulin analogue, additional injections of ultrashort-acting insulin analogues, temporal prescription of short-acting human insulin were used. While GC therapy insulin daily dose was individual and could reach 2.0 U/kg. After transition to maintaining doses of GC or discontinuation of GC therapy patients returned to standard or relatively low insulin requirements. Levels of glycosylated hemoglobin differed significantly among patients at different stages of treatment, were maximal while long-term therapy with high doses of oral GC, but mostly depended on patients compliance. CONCLUSION: Bettering of glycemic control while receiving GC can be reached by timely dose correction of insulin therapy, selection of individual schemes, taking into account time of receipt and pharmacokinetic characteristics of GC. Adherence of the patient and his family to treatment of DM1 plays an important role in glycemic control.
BACKGROUND: Diagnostics of growth hormone deficiency (GHD) and secondary adrenal insufficiency (SAI) is based on estimation of peak GH and cortisol concentrations in provocation tests. Russian consensus on diagnostics and treatment of hypopituitarism in children and adolescences recommends to measure GH and cortisol concentrations in every time-point of insulin test (IT). Glucagon test (GT) is discussed in literature as alternative to IT.AIMS: To estimate the possibility to use provocation GT for diagnostics of SAI and GHD in children and adolescents.MATERIALS AND METHODS: We investigated blood and urine cortisol levels, IT, and GT in 20 patients 6.5–17.8 years (Me 13.0 (10.4; 15.3)) after surgery and/or radiology and/or chemical therapy of head and neck tumors; remission for 0.4–7.5 years (Ме 2.1 (1.5; 5.2)).RESULTS: With cut-off point 550 nmol/L sensitivity and specifity of IT was 100% and 60%, GT — 100% and 53% respectively. Minimal cortisol cut-off level for GT with sensitivity 100% was 500 nmol/L, maximal with specifity 100% — 400 nmol/L.Early morning cortisol levels did not exceed 250 nmol/l in 2 patients with SAI; and were above 500 nmol/l in 8 patients without SAI while primary or repeated examination.GHD was reviled by IT in all patients. Maximal GH concentrations in GT and IT did not differ significantly (p>0.05) but GT results of 4 patients exceeded or met cut-off for this test (7 ng/ml).GT was characterized by less severity compared with IT.CONCLUSIONS: For diagnostics of SAI by GT we can advise cut-off points of cortisol level 500 (sensitivity 100%, specifty 53%) and 400 nmol/L (sensitivity 80%, specifity 100%). Measuring of cortisol levels in 2–3 early morning blood samples allows to exclude or to suspect SAI in half of patients before tests. GH peaks in GT can exceed similarly data in IT that needs future investigation.
Obesity is one of the socially significant diseases of our time and is a generally recognized risk factor for the development of carbohydrate metabolism disorders, including type 2 diabetes mellitus (DM), the prevalence of which in the pediatric population is rapidly increasing.Aim of the study. To demonstrate the most frequent types of carbohydrate metabolism disorders in children and adolescents with obesity.Materials and methods. 123 obese patients under 18 years old were examined and the structure of obesity complications was analyzed.Results. Carbohydrate metabolism disorders were identified in 24 patients (19%): impaired fasting glycemia (IFG) (8 girls, 6 boys (11%)), type 2 DM (6 girls, 3 boys (7%)), and type 1 DM (1 boy (1%)). Descriptions of 4 clinical cases are given: 1) patient, 17 years old, with constitutional-exogenous obesity of 3rd degree, arterial hypertension (AH), dyslipidemia and nonalcoholic fatty liver disease (NAFLD) and a history of transient IFG; 2) patient, 16 years old, with morbid obesity, NAFLD, AH, polycystic ovarian syndrome (PCOS), type 2 DM, compensated on metformin therapy; 3) patient, 17 years old, with constitutional-exogenous obesity of the 3rd degree, AH, dyslipidemia, NAFLD, type 2 DM (on insulin pump therapy), complicated by diabetic nephropathy and diabetic polyneuropathy; 4) patient, 12 years old, with type 1 DM, manifested against the background of obesity.Conclusion. When screening for obesity complications in children and adolescents, carbohydrate metabolism disorders may be detected in one in five patients. Prediabetes in childhood can be transient. When a child with obesity is identified, differential diagnosis of type 1 and type 2 DM should be made. It is necessary to teach patients with type 2 DM the skills of self-monitoring on a par with patients with type 1 DM and motivate them to control glycemia regularly at home.
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