scholarly journals The epidemiology and genetic analysis of children with idiopathic type 1 diabetes in the state of Qatar

2021 ◽  
Author(s):  
Tasneem Abdel-Karim ◽  
Basma Haris ◽  
Houda Afyouni ◽  
Shayma Mohammed ◽  
Amel Khalifa ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Wolfram Syndrome ◽  
Insulin Requirement ◽  
Monogenic Diabetes ◽  
C Peptide ◽  
Peptide Level ◽  
Uncertain Significance ◽  
Age Of Diagnosis ◽  
History Of

Abstract Background To study the epidemiology, describe the clinical characteristics and report results of genetic studies in pediatric patients with idiopathic type 1 diabetes. Methods Prospective study of type 1 diabetes patients attending Sidra Medicine from 2018-2020. Autoantibodies (GAD65, IAA, IA-2A and ZnT8) measured and genetic testing undertaken in patients negative for autoantibodies to rule out monogenic diabetes. Demographic and clinical data of patients with idiopathic type 1 diabetes compared to patients with autoimmune type 1 diabetes. Results 1157 patients had type 1 diabetes of which 63 were antibody negative. Upon genome sequencing, four had MODY, two had Wolfram syndrome, one had H syndrome and three had variants of uncertain significance in MODY genes. 53 patients had idiopathic type 1 diabetes. The most common age of diagnosis was 10-14 years and C-peptide level was low but detectable in 30 patients (56.6%) and normal in 23 patients (43.4%) The average BMI was in the normal range and 33% of the patients had history of DKA. Conclusions 4% of children have Idiopathic type 1 diabetes. There were statistically significant differences in the C-peptide level and insulin requirement between the two groups. DKA was less common in the idiopathic group. Mutations in MODY genes suggest the importance of autoantibody testing and genetic screening for known causes of monogenic diabetes in idiopathic type 1 diabetes. The mechanism of idiopathic type 1 diabetes is not known but could be due to defects in antibody production or due to autoantibodies that are not yet detectable or discovered.

scholarly journals Pembrolizumab-induced fulminant type 1 diabetes with C-peptide persistence at first referral

2020 ◽  
Vol 2020 ◽  
Author(s):  
Kazuhisa Kusuki ◽  
Saya Suzuki ◽  
Yuzo Mizuno
Keyword(s):  
Type 1 Diabetes ◽  
Blood Glucose ◽  
Fulminant Type 1 Diabetes ◽  
C Peptide ◽  
Outpatient Visits ◽  
Peptide Level ◽  
Life Threatening ◽  
History Of ◽  
Fulminant Type

Summary A 72-year-old man with no history of diabetes was referred to our department due to hyperglycemia during pembrolizumab treatment for non-small-cell lung carcinoma. His blood glucose level was 209 mg/dL, but he was not in a state of ketosis or ketoacidosis. Serum C-peptide levels persisted at first, but gradually decreased, and 18 days later, he was admitted to our hospital with diabetic ketoacidosis (DKA). The patient was diagnosed with fulminant type 1 diabetes (FT1D) induced by pembrolizumab. According to the literature, the insulin secretion capacity of a patient with type 1 diabetes (T1D) induced by anti-programmed cell death-1 (anti-PD-1) antibody is depleted in approximately 2 to 3 weeks, which is longer than that of typical FT1D. Patients with hyperglycemia and C-peptide persistence should be considered for hospitalization or frequent outpatient visits with insulin treatment because these could indicate the onset of life-threatening FT1D induced by anti-PD-1 antibodies. Based on the clinical course of this patient and the literature, we suggest monitoring anti-PD-1 antibody-related T1D. Learning points: Immune checkpoint inhibitors, such as anti-PD-1 antibodies, are increasingly used as anticancer drugs. Anti-PD-1 antibodies can cause immune-related adverse events, including T1D. FT1D, a novel subtype of T1D, is characterized by the abrupt onset of hyperglycemia with ketoacidosis, a relatively low glycated hemoglobin level and depletion of C-peptide level at onset. In patients being treated with anti-PD-1 antibody, hyperglycemia with C-peptide level persistence should be monitored through regular blood tests. Because of C-peptide persistence and mild hyperglycemia, it is possible to miss a diagnosis of life-threatening FT1D induced by anti-PD-1 antibody. In particular, in patients who have no history of diabetes, hyperglycemia without DKA is likely to be the very beginning of anti-PD-1 antibody-induced T1D. Therefore, such patients must be considered for either hospitalization or frequent outpatient visits with insulin injections and self-monitoring of blood glucose.

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 Monogenic causes in the Type 1 Diabetes Genetics Consortium cohort; low genetic risk for autoimmunity in case selection

2021 ◽  
Author(s):  
Luc Marchand ◽  
Meihang Li ◽  
Coralie Leblicq ◽  
Ibrar Rafique ◽  
Tugba Alarcon-Martinez ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Genetic Risk ◽  
Large Scale ◽  
Wolfram Syndrome ◽  
Monogenic Diabetes ◽  
Therapeutic Implications ◽  
Pathogenic Variants ◽  
Affected Parent ◽  
Diabetes Genetics

Abstract: Hypothesis About 1% of patients clinically diagnosed as type 1 diabetes have non-autoimmune monogenic diabetes. The distinction has important therapeutic implications but, given the low prevalence and high cost of testing, selecting patients to test is important. We tested the hypothesis that low genetic risk for type 1 diabetes can substantially contribute to this selection. Methods As proof of principle, we examined by exome sequencing families with two or more children, recruited by the Type 1 Diabetes Genetics Consortium and selected for negativity for two autoantibodies and absence of risk HLA haplotypes. Results We examined 46 families that met the criteria. Of the 17 with an affected parent, seven (41.2%) had actionable monogenic variants. Of 29 families with no affected parent, 14 (48.3%) had such variants, including five with recessive pathogenic variants of WFS1 but no report of other features of Wolfram syndrome. Our approach diagnosed 55.8% of the estimated number of monogenic families in the entire T1DGC cohort, by sequencing only 11.1% of the autoantibody-negative ones. Conclusions Our findings justify proceeding to large-scale prospective screening studies using markers of autoimmunity, even in the absence of an affected parent. We also confirm that non-syndromic WFS1 variants are common among cases of monogenic diabetes misdiagnosed as type 1 diabetes.

scholarly journals Inverse relationship between glomerular hyperfiltration and C-peptide level in Type 1 diabetes

2014 ◽  
Vol 04 (01) ◽  
pp. 50-53 ◽  
Author(s):  
Anissa Messaaoui ◽  
Sylvie Tenoutasse ◽  
Christian Mélot ◽  
Harry Dorchy
Keyword(s):  
Type 1 Diabetes ◽  
Inverse Relationship ◽  
Glomerular Hyperfiltration ◽  
C Peptide ◽  
Peptide Level

scholarly journals Stimulated urine C-peptide creatinine ratio vs serum C-peptide level for monitoring of β-cell function in the first year after diagnosis of Type 1 diabetes

2016 ◽  
Vol 33 (11) ◽  
pp. 1564-1568 ◽  
Author(s):  
D. Tatovic ◽  
S. Luzio ◽  
G. Dunseath ◽  
Y. Liu ◽  
M. Alhadj Ali ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
First Year ◽  
Creatinine Ratio ◽  
Β Cell ◽  
C Peptide ◽  
Peptide Level ◽  
Β Cell Function

scholarly journals An Unusual Form of Type 1 Diabetes With an Elevated Proinsulin Level

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A456-A456
Author(s):  
Jana Havranova ◽  
Thomas Gallagher ◽  
Mohammad Ishaq Arastu
Keyword(s):  
Type 1 Diabetes ◽  
Family History ◽  
Hypoglycemic Agents ◽  
Past Medical History ◽  
Strong Family History ◽  
Oral Hypoglycemic Agents ◽  
Peptide Level ◽  
History Of ◽  
Proinsulin Level

Abstract Introduction: Diabetes is one of the most prevalent diseases in the world. We recognize the three most common types of diabetes: type1, type2 and gestational diabetes. It is estimated that around 425 million of people worldwide have diabetes and about 90% of those represent type 2 diabetes. The most common types of diabetes are polygenic -- they are caused by a defect in multiple genes. Monogenic diabetes is caused by a mutation in a single gene. We currently have over 10 different types of monogenic diabetes called MODY (Maturity Onset Diabetes of the Young). Sun et al. states that over the past few years, 30 different insulin gene mutations were reported to cause a new syndrome called MIDY (Mutant INS-gene-induced Diabetes of Youth). Most of these mutations lead to proinsulin misfolding in the endoplasmic reticulum. We present a rare case of a young obese female with an elevated proinsulin level and low C-peptide level diagnosed with type 1 diabetes requiring therapy with insulin. Case Description: A 21 year old female with past medical history of chronic diarrhea initially presented with a complaint of dry mouth, dizziness, excessive urination, and thirst. She was found to have hyperglycemia of 203 mg/dL, A1C 8.3, and negative ketones. Patient had a strong family history of diabetes. She had a family history of: father with type 1 diabetes; mother with a past medical history of gestational diabetes who became diabetic postpartum; and three of the patient’s grandparents with a history of diabetes. Patient was started on the oral hypoglycemic agents metformin and glipizide, but she only had partial response to these medications. Because of her strong family history and incomplete response to oral hypoglycemic agents, additional testing was performed. Patient was found to have a low C-peptide level (1.6 ng/mL), elevated proinsulin (72.9 pmol/L), positive GAD antibody (10.3 units/mL) and negative islet cell autoantibody. Patient had a very good response to insulin and subsequently became insulin dependent. She is currently on an insulin pump. Conclusion: Sun et al. reports that proinsulin misfolding causes beta cell failure. Increased misfolding occurs under certain pathological conditions that are currently unknown. We think that there might be some increased proinsulin misfolding abnormality that might be occurring in this patient. There are most likely many epigenetic modifiers that would trigger certain individuals to be more prone to this phenomena of misfolded proinsulin. Future research in diabetes may one day yield antibodies that would specifically recognize misfolded proinsulin in the plasma. Further research is required to elucidate how defective proinsulin folding may lead to beta cell dysfunction and subsequent evolution of diabetes mellitus.

scholarly journals C-peptide level and clinical parameters in children with new onset type 1 diabetes

2017 ◽  
Vol 16 (4) ◽  
pp. 263-268
Author(s):  
Leszek Szewczyk ◽  
◽  
Robert Piekarski ◽  
Anna M. Bury ◽  
◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Clinical Parameters ◽  
C Peptide ◽  
Onset Type ◽  
Peptide Level ◽  
New Onset
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