scholarly journals Insulin-Like Growth Factor-1 at Diagnosis and during Subsequent Years in Adolescents with Type 1 Diabetes

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Simona I. Chisalita ◽  
J. Ludvigsson
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Secretion ◽  
Insulin Treatment ◽  
Insulin Dose ◽  
Newly Diagnosed ◽  
Blood Samples ◽  
C Peptide ◽  
Endogenous Insulin ◽  
High Hba1c

Background. Type 1 diabetes (T1D) in adolescents is associated with alterations in the insulin-like factor system probably caused both by a deranged metabolism and insulinopenia in the portal vein. Objective. To study how the circulating IGF-1 is affected at diagnosis and during subsequent years in adolescents with T1D. Methods. Ten girls and ten boys with type 1 diabetes (T1D), aged 13.0 ± 1.4 (mean ± SD) years at diagnosis, took part in the study. Blood samples were drawn at diagnosis and after 3, 9, 18, and 48 months. HbA1c, total IGF-1, and C-peptide were measured. Results. At diagnosis, the patients had high HbA1c, low IGF-1, and measurable C-peptide. After the start of insulin treatment, maximal improvement in glycemic control and IGF-1 occurred within 3 months and then both tended to deteriorate, that is, HbA1c to increase and IGF-1 to decrease. C-peptide decreased with time, and after 4 years, half of the patients were C-peptide negative. At diagnosis, C-peptide correlated positively to IGF-1 (r=0.50; p<0.03). C-peptide correlated negatively with insulin dose (U/kg) after 18 and 48 months from diagnosis (r=−0.48; p<0.03 and r=−0.72; p<0.001, resp.). Conclusions. In conclusion, our results show that in newly diagnosed adolescents with type 1 diabetes and deranged metabolism, the IGF-1 level is low and rapidly improves with insulin treatment but later tends to decrease concomitantly with declining endogenous insulin secretion.

scholarly journals Measurement Of Peak C-Peptide At Diagnosis Informs Glycemic Control But Not Hypoglycemia In Adults With Type 1 Diabetes

2021 ◽  
Author(s):  
Alice L J Carr ◽  
Richard A Oram ◽  
Shannon M Marren ◽  
Timothy J McDonald ◽  
Parth Narendran ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Dose ◽  
Glucose Monitoring ◽  
Glycemic Variability ◽  
Newly Diagnosed ◽  
C Peptide ◽  
Glucose Levels ◽  
Normal Glucose ◽  
The Impact

Abstract Context High residual C-peptide in longer duration type 1 diabetes associates with fewer hypoglycemic events and reduced glycemic variability. Little is known about the impact of C-peptide close-to-diagnosis. Objective Using continuous glucose monitoring (CGM) data from a study of newly diagnosed adults with type 1 diabetes, we aimed to explore if variation in C-peptide close-to-diagnosis influenced glycemic variability and risk of hypoglycemia. Design We studied newly diagnosed adults with type 1 diabetes who wore a Dexcom G4 CGM for 7 days as part the EXTOD study. We examined the relationship between peak stimulated C-peptide and glycemic metrics of variability and hypoglycemia for 36 CGM traces from 23 participants. Results For every 100 pmol/l increase in peak C-peptide, percentage time spent range 3.9-10 mmol/l was increased by 2.4% [95% CI: 0.5,4.3], p=0.01) with a reduction in time spent in level 1 hyperglycemia (&gt; 10 mmol/l) and level 2 hyperglycemia (&gt; 13.9 mmol/l) by 2.6% [95% CI: -4.9, -0.4, p=0.02) and 1.3% [95% CI: -2.7, -0.006], p= 0.04) respectively. Glucose levels were on average lower by 0.19 mmol/l ([95 % CI: -0.4,0.02], p=0.06) and standard deviation reduced by 0.14 [95% CI: -0.3, -0.02], p=0.02). Hypoglycemia was not common in this group and no association was observed between time spent in hypoglycemia (p=0.97) or hypoglycemic risk (p=0.72). There was no association between peak C-peptide and insulin dose adjusted HbA1c (IDAA1c, p=0.45). Conclusions C-peptide associates with time spent in normal glucose range and with less hyperglycemia, but not risk of hypoglycemia in newly diagnosed people with type 1 diabetes.

scholarly journals Pancreas-protective effect of rituximab for acute-onset type 1 diabetes in the honeymoon period: a case report

2016 ◽  
Vol 2016 ◽  
Author(s):  
Akira Kurozumi ◽  
Yosuke Okada ◽  
Tadashi Arao ◽  
Yusuke Miyazaki ◽  
Maiko Yoshikawa ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Secretion ◽  
Protective Effect ◽  
Hba1c Level ◽  
Insulin Dose ◽  
Acute Onset ◽  
Onset Type ◽  
Endogenous Insulin Secretion ◽  
Endogenous Insulin

Summary A randomized controlled study of rituximab demonstrated that the drug protects pancreatic function in patients with acute-onset type 1 diabetes mellitus (AOT1DM). However, the mechanism of this protective effect is poorly understood. We examined the effects of rituximab in two patients with AOT1DM in the honeymoon period and the mechanism of these effects. Case 1 was a 40-year-old man and Case 2 was a 45-year-old man, both diagnosed with AOT1DM. Various tests indicated intact capacity for endogenous insulin secretion and that they were in the honeymoon phase of AOT1DM. Treatment with rituximab protected against pancreatic β-cell damage and maintained somewhat the endogenous insulin secretion. In Case 2, HbA1c level was maintained below 6.5% up to 24 months after treatment. However, in Case 1, the patient showed a gradual increase in HbA1c level starting around 9 months but fell at 12 months to >9.0% and required an insulin dose about twice greater than that of Case 2. High spleen tyrosine kinase (Syk) levels were recorded in the two patients before rituximab administration and after the treatment, the levels were further increased in Case 1, but decreased in Case 2. Both patients require continuous careful follow-up for glycemic control, insulin secretion capacity, and adverse reactions in the future. Although the clinical relevance of high Syk levels in AOT1DM patients remains unclear, the difference in the change in Syk level between the two patients may explain the different clinical courses. Learning points We described the pancreas-protective effect of rituximab in two patients with acute-onset type 1 diabetes mellitus in the honeymoon period and investigated the possible mechanism of action. The present study demonstrated that treatment with rituximab maintained endogenous insulin secretion capacity for 2 years in the two patients. The phosphorylated-spleen tyrosine kinase (p-Syk) data suggest that the differences in HbA1c level and the required insulin dose between the two patients could be due to reactivation or nonreactivation of β-cells.

scholarly journals Metabolic bone markers can be related to preserved insulin secretion in children with newly diagnosed type 1 diabetes

2020 ◽  
Vol 26 (1) ◽  
pp. 10-16
Author(s):  
Małgorzata Szymańska ◽  
Izabela Michałus ◽  
Marcin Kaszkowiak ◽  
Krystyna Wyka ◽  
Danuta Chlebna-Sokół ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Secretion ◽  
Bone Markers ◽  
Newly Diagnosed ◽  
Metabolic Bone

Partial remission in children and adolescents with type 1 diabetes: an analysis based on the insulin dose-adjusted hemoglobin A1c

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Emine Ayça Cimbek ◽  
Aydın Bozkır ◽  
Deniz Usta ◽  
Nazım Ercüment Beyhun ◽  
Ayşenur Ökten ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Partial Remission ◽  
Hemoglobin A1c ◽  
Insulin Dose ◽  
Age At Onset ◽  
Insulin Requirement ◽  
C Peptide ◽  
Factors Associated ◽  
Daily Insulin

Abstract Objectives Most patients with type 1 diabetes (T1D) experience a transient phase of partial remission (PR). This study aimed to identify the demographic and clinical factors associated with PR. Methods This was a longitudinal retrospective cohort study of 133 children and adolescents with T1D. PR was defined by the gold standard insulin dose-adjusted hemoglobin A1c (HbA1c) (IDAA1c) of ≤9. Results Remission was observed in 77 (57.9%) patients. At diagnosis, remitters had significantly higher pH (7.3 ± 0.12 vs. 7.23 ± 0.15, p=0.003), higher C-peptide levels (0.45 ± 0.31 ng/mL vs. 0.3 ± 0.22, p=0.003), and they were significantly older (9.3 ± 3.6 years vs. 7.3 ± 4.2, p=0.008) compared with non-remitters. PR developed more frequently in patients without diabetic ketoacidosis (DKA) (p=0.026) and with disease onset after age 5 (p=0.001). Patients using multiple daily insulin regimen were more likely to experience PR than those treated with a twice daily regimen (63.9 vs. 32%, p=0.004). Only age at onset was an independent predictor of PR (OR: 1.12, 95% CI: 1-1.25; p=0.044). Remitters had lower HbA1c levels and daily insulin requirement from diagnosis until one year after diagnosis (p<0.001). PR recurred in 7 (9%) patients. The daily insulin requirement at three months was lower in remitters with PR recurrence compared to those without (0.23 ± 0.14 vs. 0.4 ± 0.17 U/kg/day, p=0.014). Conclusions Addressing factors associated with the occurrence of PR could provide a better comprehension of metabolic control in T1D. The lack of DKA and higher C-peptide levels may influence PR, but the main factor associated with PR presence was older age at onset. PR may recur in a small proportion of patients.

scholarly journals Systemic TNFα correlates with residual β-cell function in children and adolescents newly diagnosed with type 1 diabetes

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Anne Julie Overgaard ◽  
Jens Otto Broby Madsen ◽  
Flemming Pociot ◽  
Jesper Johannesen ◽  
Joachim Størling
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Disease Onset ◽  
Newly Diagnosed ◽  
Β Cell ◽  
Entire Study ◽  
C Peptide ◽  
Disease Remission ◽  
Β Cell Function

Abstract Background Type 1 diabetes (T1D) is caused by immune-mediated destruction of the β-cells. After initiation of insulin therapy many patients experience a period of improved residual β-cell function leading to partial disease remission. Cytokines are important immune-modulatory molecules and contribute to β-cell damage in T1D. The patterns of systemic circulating cytokines during T1D remission are not clear but may constitute biomarkers of disease status and progression. In this study, we investigated if the plasma levels of various pro- and anti-inflammatory cytokines around time of diagnosis were predictors of remission and residual β-cell function in children with T1D followed for one year after disease onset. Methods In a cohort of 63 newly diagnosed children (33% females) with T1D with a mean age of 11.3 years (3.3–17.7), ten cytokines were measured of which eight were detectable in plasma samples by Mesoscale Discovery multiplex technology at study start and after 6 and 12 months. Linear regression models were used to evaluate association of cytokines with stimulated C-peptide. Results Systemic levels of tumor necrosis factor (TNF)-α, interleukin (IL)-2 and IL-6 inversely correlated with stimulated C-peptide levels over the entire study (P < 0.05). The concentrations of TNFα and IL-10 at study start predicted stimulated C-peptide level at 6 months (P = 0.011 and P = 0.043, respectively, adjusted for sex, age, HbA1c and stage of puberty). Conclusions In recent-onset T1D, systemic cytokine levels, and in particular that of TNFα, correlate with residual β-cell function and may serve as prognostic biomarkers of disease remission and progression to optimize treatment strategies. Trial Registration The study was performed according to the criteria of the Helsinki II Declaration and was approved by the Danish Capital Region Ethics Committee on Biomedical Research Ethics (journal number H-3-2014-052). The parents of all participants gave written consent.

scholarly journals Type 1 diabetes can present before the age of 6 months and is characterised by autoimmunity and rapid loss of beta cells

Diabetologia ◽  
2020 ◽  
Vol 63 (12) ◽  
pp. 2605-2615 ◽  
Author(s):  
Matthew B. Johnson ◽  
◽  
Kashyap A. Patel ◽  
Elisa De Franco ◽  
William Hagopian ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Secretion ◽  
Genetic Risk ◽  
Early Onset ◽  
Genetic Risk Score ◽  
Neonatal Diabetes ◽  
Pathogenic Variant ◽  
Rapid Loss ◽  
C Peptide

Abstract Aims/hypothesis Diabetes diagnosed at <6 months of age is usually monogenic. However, 10–15% of affected infants do not have a pathogenic variant in one of the 26 known neonatal diabetes genes. We characterised infants diagnosed at <6 months of age without a pathogenic variant to assess whether polygenic type 1 diabetes could arise at early ages. Methods We studied 166 infants diagnosed with type 1 diabetes at <6 months of age in whom pathogenic variants in all 26 known genes had been excluded and compared them with infants with monogenic neonatal diabetes (n = 164) or children with type 1 diabetes diagnosed at 6–24 months of age (n = 152). We assessed the type 1 diabetes genetic risk score (T1D-GRS), islet autoantibodies, C-peptide and clinical features. Results We found an excess of infants with high T1D-GRS: 38% (63/166) had a T1D-GRS >95th centile of healthy individuals, whereas 5% (8/166) would be expected if all were monogenic (p < 0.0001). Individuals with a high T1D-GRS had a similar rate of autoantibody positivity to that seen in individuals with type 1 diabetes diagnosed at 6–24 months of age (41% vs 58%, p = 0.2), and had markedly reduced C-peptide levels (median <3 pmol/l within 1 year of diagnosis), reflecting rapid loss of insulin secretion. These individuals also had reduced birthweights (median z score −0.89), which were lowest in those diagnosed with type 1 diabetes at <3 months of age (median z score −1.98). Conclusions/interpretation We provide strong evidence that type 1 diabetes can present before the age of 6 months based on individuals with this extremely early-onset diabetes subtype having the classic features of childhood type 1 diabetes: high genetic risk, autoimmunity and rapid beta cell loss. The early-onset association with reduced birthweight raises the possibility that for some individuals there was reduced insulin secretion in utero. Comprehensive genetic testing for all neonatal diabetes genes remains essential for all individuals diagnosed with diabetes at <6 months of age.

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