scholarly journals Алгоритм доклинической диагностики сахарного диабета 1-го типа как основа для создания Реестра ДААт-позитивных детей и подростков Украины с прогнозированным развитием заболевания

2019 ◽  
Vol 24 (3) ◽  
pp. 203-216
Author(s):  
M.D. Tron’ko ◽  
K.P. Zak ◽  
V.V. Popova
Keyword(s):  
Type 1 Diabetes ◽  
Children And Adolescents ◽  
Pancreatic Beta Cells ◽  
State Institution ◽  
Tolerance Test ◽  
The State ◽  
Immunological Study ◽  
C Peptide ◽  
Study Results

Aim — The establishment of mechanisms for T1D development at early and late preclinical stages of disease formation in children and adolescents. Material and methods. At the State Institution «V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine» mentioned the Program «Immunity in the preclinical period of T1D development» was initiated, on the basis of which the Register of marker-positive children with predictable development of type 1 diabetes was created, which includes 612 children aged from 7 to 15 years with burdened heredity, in which the titer of diabetes-associated autobodies (DAA), cytokines, levels of basal and postprandial glycemia and secretion of C-peptide at preclinical and clinical stages of T1D development in children and adolescents based on the performed clinical and immunological study. Results. The new data have been obtained at the State Institution «V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine», which allowed to substantially supplement the existing ideas about the type 1 diabetes (T1D) pathogenesis. As a result of the performed study, a group of marker-positive children with burdened heredity and a predicted risk of developing the disease was formed. It was found that an increased titer of DAA was observed in 162 (35.45%) of 457 children with burdened heredity with no less than two times determination of DAA presence in them, mainly GADA and IA‑2A, the clinical debut was manifested in 86 (53.08%) of them from 6 months to 16 years (27.4±4.3 months). The formula of combined occurrence and values of simultaneously increased DAA titers to islet autoantigens, namely IA‑2A + GADA, was determined, which is a predictor of both the duration of preclinical stage of T1D development and the debut rate. Impaired cytokine production (increase of the level of proinflammatory cytokines IL‑1α, IL‑6 and TNFα, IL‑8 and IL‑16 while reducing the concentration of IL‑4 in the PB) as key factors of the T1D pathogenesis, which determine the rate of T1D debut, and the aggressiveness of its course were also established. It was found that the early preclinical period of T1D development in DAA+ children was characterized by the presence of dysglycemia in the form of increased glycemia in 2 hour after the glucose tolerance test and a slight decrease in secretion of stimulated C-peptide; in addition, dysglycemia in the form of impaired fasting glycemia was added in DAA+children in the late preclinical period, and a decrease in both basal and stimulated secretion of the C-peptide was determined, indicating that the potential of pancreatic beta cells was depleted.

scholarly journals Concentration of diabetes-associated autoantibodies against islet autoantigens (IA-2A, GADA, IAA), levels of basal and postprandial glycemia, and secretory state of basal and stimulated C-peptide in the preclinical period of type 1 diabetes development in children and adolescents as immunological, metabolic and hormonal predictors of the clinical onset of the disease

2019 ◽  
Author(s):  
Mykola Tronko ◽  
Boris Mankovskyi ◽  
Vyktoryia Popova
Keyword(s):  
Type 1 Diabetes ◽  
Children And Adolescents ◽  
Genetic Predisposition ◽  
Pancreatic Beta Cells ◽  
Preclinical Stage ◽  
C Peptide ◽  
Postprandial Glycemia ◽  
Clinical Onset ◽  
Diabetes Development

Materials and methods. Based on clinical and immunological studies, in this study, we present data on the establishment of mechanisms that are responsible for the development of early and late pre-clinical stages of the type 1 diabetes (T1D), obtained by studying diabetes-associated autoantibodies (DAAb) and the levels of basal and postprandial glycemia, and C-peptide secretion at the preclinical stage of T1D development in children and adolescents. Results. As a result we were able to form a group of marker-positive children with a genetic predisposition and an increased predicted risk of developing the diease. A total of 474 practically healthy normoglycemic children and adolescents aged 7 to 18 years were examined. An elevated titre of DAAb, mainly GADA and IA-2A was found in 94 (25.68 %) of 366 children with a genetic predisposition for at least of two determinants of DAAb, and the clinical onset of T1D manifesting in 68 (72.34 %) of them from 6 months to 15 years (30.9 ± 3.2 months). The formula of combined occurrence and values of simultaneously elevated titres of DAAb against islet autoantigens, namely, IA-2A + GADA, which is a predictor of the duration of the preclinical stage of T1D, was determined. Conclusions. It was established that the early preclinical development of T1D in DAAb + children was characterized by the presence of dysglycemia in the form of elevated glycemia 2 hours after the glucose tolerance test and a steady decrease in the secretion of stimulated C-peptide; additionally, dysglycemia was jointed as impaired fasting glycemia, and there was a decrease in both basal and stimulated secretions of C peptide, indicating the depletion of the potential of pancreatic beta-cells. Key words: type 1 diabetes (T1D), children and adolescents, diabetes-associated autoantibodies (DAAb), autoantibodies against glutamic acid decarboxylase (GADA), autoantibodies against tyrosine phosphatase (IA-2A), basal and postprandial glycemia, basal and stimulated C-peptide. For citation: Tronko MD, Mankovskyi BM, Popova VV, Zak KP. Concentration of diabetes-associated autoantibodies against islet autoantigens (IA-2A, GADA, IAA), levels of basal and postprandial glycemia, and secretory state of basal and stimulated C-peptide in the preclinical period of type 1 diabetes development in children and adolescents as immunological, metabolic and hormonal predictors of the clinical onset of the disease. Journal of the National Academy of Medical Sciences of Ukraine. 2019;25(3):285–95

scholarly journals Associations of HbA1c with the timing of C‐peptide responses during the oral glucose tolerance test at the diagnosis of type 1 diabetes

2019 ◽  
Vol 20 (4) ◽  
pp. 408-413
Author(s):  
Heba M. Ismail ◽  
Carmella Evans‐Molina ◽  
Linda A. DiMeglio ◽  
Dorothy J. Becker ◽  
Ingrid Libman ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
C Peptide

scholarly journals Urine C-Peptide Creatinine Ratio Is a Noninvasive Alternative to the Mixed-Meal Tolerance Test in Children and Adults With Type 1 Diabetes

Diabetes Care ◽  
2011 ◽  
Vol 34 (3) ◽  
pp. 607-609 ◽  
Author(s):  
R. E. J. Besser ◽  
J. Ludvigsson ◽  
A. G. Jones ◽  
T. J. McDonald ◽  
B. M. Shields ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Tolerance Test ◽  
Creatinine Ratio ◽  
Mixed Meal ◽  
C Peptide ◽  
Meal Tolerance Test ◽  
Mixed Meal Tolerance Test

scholarly journals Low-dose ATG/GCSF in Established Type 1 Diabetes: A Five-Year Follow-up Report

2021 ◽  
Author(s):  
Andrea Lin ◽  
Jasmine A. Mack ◽  
Brittany Bruggeman ◽  
Laura M. Jacobsen ◽  
Amanda L. Posgai ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Low Dose ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Modeling Framework ◽  
C Peptide ◽  
Recent Onset

Previously, we demonstrated low-dose anti-thymocyte globulin (ATG) and granulocyte colony stimulating factor (GCSF) immunotherapy preserved C-peptide for two years in a pilot study of subjects with established type 1 diabetes (n=25). Herein, we evaluated the long-term outcomes of ATG/GCSF in study participants with five years of available follow-up data (n=15). The primary endpoint was area under the curve (AUC) C-peptide during a two-hour mixed-meal tolerance test (MMTT). After five years, there were no statistically significant differences in AUC C-peptide when comparing subjects who received ATG/GCSF versus placebo (p = 0.41). A modeling framework based on mean trajectories in C-peptide AUC over five years, accounting for differing trends between groups, was applied to re-categorize responders (n=9) and non-responders (n=7). ATG/GCSF reponders demonstrated nearly unchanged HbA1c over five years [mean (95% CI) adjusted change = 0.29% (-0.69%, 1.27%)], but the study was not powered for comparisons against non-responders 1.75% (-0.57%, 4.06%) and placebo 1.44% (0.21%, 2.66%). These data underscore the importance of long-term follow up in previous and ongoing phase 2 trials of low-dose ATG in recent-onset type 1 diabetes.

Decline of C-peptide during the first year after diagnosis of Type 1 diabetes in children and adolescents

2013 ◽  
Vol 100 (2) ◽  
pp. 203-209 ◽  
Author(s):  
Johnny Ludvigsson ◽  
Annelie Carlsson ◽  
Ahmed Deli ◽  
Gun Forsander ◽  
Sten-A. Ivarsson ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Children And Adolescents ◽  
First Year ◽  
C Peptide

scholarly journals Baseline Assessment of Circulating microRNAs Near Diagnosis of Type 1 Diabetes Predicts Future Stimulated Insulin Secretion

2020 ◽  
Author(s):  
Ada Admin ◽  
Isaac Snowhite ◽  
Ricardo Pastori ◽  
Jay Sosenko ◽  
Shari Messinger Cayetano ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Type 1 Diabetes ◽  
Insulin Secretion ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Tolerance Test ◽  
Circulating Micrornas ◽  
C Peptide ◽  
Impaired Insulin

Type 1 diabetes is an autoimmune disease resulting in severely impaired insulin secretion. We investigated whether circulating microRNAs (miRNAs) are associated with residual insulin secretion at diagnosis and predict the severity of its future decline. We studied 53 newly diagnosed subjects enrolled in placebo groups of TrialNet clinical trials. We measured serum levels of 2,083 miRNAs using RNAseq technology, in fasting samples from the baseline visit (<100 days from diagnosis), during which residual insulin secretion was measured with a mixed meal tolerance test (MMTT). Area under the curve (AUC) C-peptide and peak C-peptide were stratified by quartiles of expression of 31 miRNAs. After adjustment for baseline C-peptide, age, BMI and sex, baseline levels of miR-3187-3p, miR-4302, and the miRNA combination of miR-3187-3p/miR-103a-3p predicted differences in MMTT C-peptide AUC/peak levels at the 12-month visit; the combination miR-3187-3p/miR-4723-5p predicted proportions of subjects above/below the 200 pmol/L clinical trial eligibility threshold at the 12-month visit. Thus, miRNA assessment at baseline identifies associations with C-peptide and stratifies subjects for future severity of C-peptide loss after 1 year. We suggest that miRNAs may be useful in predicting future C-peptide decline for improved subject stratification in clinical trials.

scholarly journals Low-dose ATG/GCSF in Established Type 1 Diabetes: A Five-Year Follow-up Report

2021 ◽  
Author(s):  
Andrea Lin ◽  
Jasmine A. Mack ◽  
Brittany Bruggeman ◽  
Laura M. Jacobsen ◽  
Amanda L. Posgai ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Low Dose ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Modeling Framework ◽  
C Peptide ◽  
Recent Onset

Previously, we demonstrated low-dose anti-thymocyte globulin (ATG) and granulocyte colony stimulating factor (GCSF) immunotherapy preserved C-peptide for two years in a pilot study of subjects with established type 1 diabetes (n=25). Herein, we evaluated the long-term outcomes of ATG/GCSF in study participants with five years of available follow-up data (n=15). The primary endpoint was area under the curve (AUC) C-peptide during a two-hour mixed-meal tolerance test (MMTT). After five years, there were no statistically significant differences in AUC C-peptide when comparing subjects who received ATG/GCSF versus placebo (p = 0.41). A modeling framework based on mean trajectories in C-peptide AUC over five years, accounting for differing trends between groups, was applied to re-categorize responders (n=9) and non-responders (n=7). ATG/GCSF reponders demonstrated nearly unchanged HbA1c over five years [mean (95% CI) adjusted change = 0.29% (-0.69%, 1.27%)], but the study was not powered for comparisons against non-responders 1.75% (-0.57%, 4.06%) and placebo 1.44% (0.21%, 2.66%). These data underscore the importance of long-term follow up in previous and ongoing phase 2 trials of low-dose ATG in recent-onset type 1 diabetes.

1343-P: A Comparison of C-Peptide and Glucose Responses between Children and Adolescents Who Progress to Type 1 Diabetes (T1D)

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1343-P
Author(s):  
HEBA M. ISMAIL ◽  
BRANDON M. NATHAN ◽  
JERRY P. PALMER ◽  
LINDA DIMEGLIO ◽  
JAY M. SOSENKO
Keyword(s):  
Type 1 Diabetes ◽  
Children And Adolescents ◽  
C Peptide

Salivary interleukin-8 levels in children suffering from Type 1 diabetes mellitus

2013 ◽  
Vol 37 (4) ◽  
pp. 377-380 ◽  
Author(s):  
D Dakovic ◽  
M Colic ◽  
S Cakic ◽  
I Mileusnic ◽  
Z Hajdukovic ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Children And Adolescents ◽  
Statistical Significance ◽  
Control Group ◽  
Healthy Children ◽  
Study Results ◽  
Type 1 Dm

Objective: The aim of this study was to investigate the differences between the salivary levels of IL-8 in patients with Type 1 diabetes mellitus (DM) with (DM+P) or without (DM-P) concomitant periodontitis and healthy subjects. The correlations between the levels of these cytokines and clinical periodontal parameters were also established. Methods: Twenty children and adolescents with Type 1 DM (10 diagnosed with periodontitis, 10 presenting no signs of periodontitis) and a control group consisting of 20 healthy children and adolescents aged 7-18 years were recruited for this study. Results: The Salivary IL-8 level was statistically significantly (p&lt;0.005) elevated in subjects with Type 1 DM (474.47 ± 716.76) compared to non-diabetic control group (101.99 ± 68.32). There was no difference (p≯0.05) in the salivary IL-8 level when subjects with Type 1 DM with concomitant periodontitis were compared to diabetics without periodontitis. When the salivary IL-8 level in subjects with Type 1 DM was correlated with the clinical parameters, no statistical significance was found. Conclusion: An elevated salivary IL-8 level in subjects with Type 1 DM without concomitant periodontitis plays a major role in the development of diabetic micro and macroangiopathy and pathogenesis of atherosclerosis. Consequently, this may offer a basis for the assessment of risk, prophylaxis and treatment of diabetic complications.

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