Using spatio-temporal surveillance data to test the infectious environment of children before type 1 diabetes diagnosis

Abstract Aims/hypothesis Among white European children developing type 1 diabetes, the otherwise common HLA haplotype DR15-DQ6 is rare, and highly protective. Adult-onset type 1 diabetes is now known to represent more overall cases than childhood onset, but it is not known whether DR15-DQ6 is protective in older-adult-onset type 1 diabetes. We sought to quantify DR15-DQ6 protection against type 1 diabetes as age of onset increased. Methods In two independent cohorts we assessed the proportion of type 1 diabetes cases presenting through the first 50 years of life with DR15-DQ6, compared with population controls. In the After Diabetes Diagnosis Research Support System-2 (ADDRESS-2) cohort (n = 1458) clinician-diagnosed type 1 diabetes was confirmed by positivity for one or more islet-specific autoantibodies. In UK Biobank (n = 2502), we estimated type 1 diabetes incidence rates relative to baseline HLA risk for each HLA group using Poisson regression. Analyses were restricted to white Europeans and were performed in three groups according to age at type 1 diabetes onset: 0–18 years, 19–30 years and 31–50 years. Results DR15-DQ6 was protective against type 1 diabetes through to age 50 years (OR < 1 for each age group, all p < 0.001). The following ORs for type 1 diabetes, relative to a neutral HLA genotype, were observed in ADDRESS-2: age 5–18 years OR 0.16 (95% CI 0.08, 0.31); age 19–30 years OR 0.10 (0.04, 0.23); and age 31–50 years OR 0.37 (0.21, 0.68). DR15-DQ6 also remained highly protective at all ages in UK Biobank. Without DR15-DQ6, the presence of major type 1 diabetes high-risk haplotype (either DR3-DQ2 or DR4-DQ8) was associated with increased risk of type 1 diabetes. Conclusions/interpretation HLA DR15-DQ6 confers dominant protection from type 1 diabetes across the first five decades of life. Graphical abstract

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Prevalence of autoantibodies in type 1 diabetes mellitus pediatrics in Mazandaran, North of Iran

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0396 ◽

2020 ◽

Vol 33 (10) ◽

pp. 1299-1305

Author(s):

Daniel Zamanfar ◽

Mohsen Aarabi ◽

Monireh Amini ◽

Mahila Monajati

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Serum Level ◽

Type 1 Diabetes Mellitus ◽

Children And Adolescents ◽

Statistical Significance ◽

Pancreatic Beta Cell ◽

Eligible Patient ◽

Diabetes Diagnosis

AbstractObjectivesType 1 diabetes is an autoimmune disease. Its most important immunologic markers are pancreatic beta-cell autoantibodies. This study aimed to determine diabetes mellitus antibodies frequency among children and adolescents with type 1 diabetes.MethodsThis descriptive study evaluated the frequency of four diabetes autoantibodies (glutamic acid decarboxylase 65 autoantibodies [GADA], islet cell autoantibodies [ICA], insulin autoantibodies [IAA], tyrosine phosphatase–like insulinoma antigen-2 antibodies [IA-2A]) and their serum level in children and adolescents diagnosed with type 1 diabetes mellitus at the diabetes department of Bou-Ali-Sina Hospital and Baghban Clinic, Sari, Iran, from March 2012 to March 2018. The relationship between the level of different antibodies and age, gender, and diabetes duration were determined. A two-sided p value less than 0.05 indicated statistical significance.ResultsOne hundred forty-two eligible patient records were screened. The average age at diabetes diagnosis was 4.2 ± 4.4 years. The median duration of diabetes was 34.0 (12.7–69.7) months. 53.5% of patients were female, and 81.7% of them had at least one positive autoantibody, and ICA in 66.2%, GADA in 56.3%, IA-2A in 40.1%, and IAA in 21.8% were positive. The type of the autoantibodies and their serum level was similar between females and males but there was a higher rate of positive autoantibodies in females. The level of IA-2A and ICA were in positive and weak correlation with age at diagnosis.ConclusionsMore than 80% of pediatric and adolescent patients with type 1 diabetes were autoantibody-positive. ICA and GADA were the most frequently detected autoantibodies. The presence of antibodies was significantly higher in females.

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Continuous subcutaneous insulin infusion alters microRNA expression and glycaemic variability in children with type 1 diabetes

Scientific Reports ◽

10.1038/s41598-021-95824-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Emma S. Scott ◽

Andrzej S. Januszewski ◽

Luke M. Carroll ◽

Gregory R. Fulcher ◽

Mugdha V. Joglekar ◽

...

Keyword(s):

Type 1 Diabetes ◽

Continuous Subcutaneous Insulin Infusion ◽

Insulin Infusion ◽

Diabetes Diagnosis ◽

Subcutaneous Insulin ◽

Glycaemic Variability ◽

Altered Expression ◽

C Peptide

AbstractTo determine whether continuous subcutaneous insulin infusion (CSII) vs. multiple daily injections (MDI) therapy from near-diagnosis of type 1 diabetes is associated with reduced glycaemic variability (GV) and altered microRNA (miRNAs) expression. Adolescents (74% male) within 3-months of diabetes diagnosis (n = 27) were randomized to CSII (n = 12) or MDI. HbA1c, 1-5-Anhydroglucitol (1,5-AG), high sensitivity C-peptide and a custom TaqMan qPCR panel of 52 miRNAs were measured at baseline and follow-up (median (LQ-UQ); 535 (519–563) days). There were no significant differences between groups in baseline or follow-up HbA1c or C-peptide, nor baseline miRNAs. Mean ± SD 1,5-AG improved with CSII vs. MDI (3.1 ± 4.1 vs. − 2.2 ± − 7.0 mg/ml respectively, P = 0.029). On follow-up 11 miRNAs associated with diabetes vascular complications had altered expression in CSII-users. Early CSII vs. MDI use is associated with lower GV and less adverse vascular-related miRNAs. Relationships with future complications are of interest.

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The Frequency and Immunodominance of Islet-Specific CD8+ T-cell Responses Change after Type 1 Diabetes Diagnosis and Treatment

Diabetes ◽

10.2337/db07-1594 ◽

2008 ◽

Vol 57 (5) ◽

pp. 1312-1320 ◽

Cited By ~ 71

Author(s):

E. Martinuzzi ◽

G. Novelli ◽

M. Scotto ◽

P. Blancou ◽

J.-M. Bach ◽

...

Keyword(s):

Type 1 Diabetes ◽

T Cell ◽

T Cell Responses ◽

Cd8 T Cell ◽

Diagnosis And Treatment ◽

Diabetes Diagnosis ◽

Cell Responses

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Association and Familial Coaggregation of Type 1 Diabetes and Eating Disorders: A Register-Based Cohort Study in Denmark and Sweden

10.2337/figshare.14040212 ◽

2021 ◽

Author(s):

Ashley E. Tate ◽

Shengxin Liu ◽

Ruyue Zhang ◽

Zeynep Yilmaz ◽

Janne T. Larsen ◽

...

Keyword(s):

Eating Disorders ◽

Type 1 Diabetes ◽

Anorexia Nervosa ◽

Eating Disorder ◽

Eating Behaviors ◽

Diabetes Diagnosis ◽

Disordered Eating Behaviors ◽

Increased Risk ◽

Clinical Diagnoses

OBJECTIVE To ascertain the association and co-aggregation of eating disorders and childhood-onset type 1 diabetes in families. RESEARCH DESIGN AND METHODS Using population samples from national registers in Sweden (n= 2 517 277) and Demark (n= 1 825 920) we investigated the within-individual association between type 1 diabetes and EDs, and their familial co-aggregation among full siblings, half-siblings, full cousins, and half-cousins. Based on clinical diagnoses we classified eating disorders (EDs) into: any eating disorder (AED), anorexia nervosa and atypical anorexia nervosa (AN), and other eating disorder (OED). Associations were determined with hazard ratios (HR) with confidence intervals (CI) from Cox regressions. RESULTS <pre>Swedish and Danish individuals with a type 1 diabetes diagnosis had a greater risk of receiving an ED diagnosis (HR [95% CI] Sweden: AED 2.02 [1.80 – 2.27], AN 1.63 [1.36 – 1.96], OED 2.34 [2.07 – 2.63]; Denmark: AED 2.19 [1.84 – 2.61], AN 1.78 [1.36 – 2.33], OED 2.65 [2.20 – 3.21]). We also meta-analyzed the results: AED 2.07 [1.88 – 2.28], AN 1.68 [1.44 – 1.95], OED 2.44 [2.17 – 2.72]. There was an increased risk of receiving an ED diagnosis in full siblings in the Swedish cohort (AED 1.25 [1.07 – 1.46], AN 1.28 [1.04 – 1.57], OED 1.28 [1.07 – 1.52]), these results were non-significant in the Danish cohort.</pre> CONCLUSION Patients with 1 diabetes are at a higher risk of subsequent EDs; however, there is conflicting support for the relationship between having a sibling with type 1 diabetes and ED diagnosis. Diabetes healthcare teams should be vigilant for disordered eating behaviors in children and adolescents with type 1 diabetes.

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10-Year Incidence of Diabetic Ketoacidosis at Type 1 Diabetes Diagnosis in Children Aged Less Than 16 Years From a Large Regional Center (Hangzhou, China)

Frontiers in Endocrinology ◽

10.3389/fendo.2021.653519 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wei Peng ◽

Jinna Yuan ◽

Valentina Chiavaroli ◽

Guanping Dong ◽

Ke Huang ◽

...

Keyword(s):

Type 1 Diabetes ◽

Abdominal Pain ◽

Diabetic Ketoacidosis ◽

Primary Care Physicians ◽

Clinical Symptoms ◽

Diabetes Diagnosis ◽

Regional Center ◽

Retrospective Audit ◽

Number Of Patients

BackgroundDiabetic ketoacidosis (DKA) is a potentially life-threatening complication of type 1 diabetes (T1D), and a leading cause of death in children aged <15 years with new-onset T1D.Aimsi) to assess the incidence of DKA in children and adolescents newly diagnosed with T1D over a 10-year period at a large regional center in China; and ii) to examine the clinical symptoms and demographic factors associated with DKA and its severity at diagnosis.MethodsWe carried out a retrospective audit of a regional center, encompassing all youth aged <16 years diagnosed with T1D in 2009–2018 at the Children’s Hospital, Zhejiang University School of Medicine (Hangzhou, China). DKA and its severity were classified according to ISPAD 2018 guidelines.Results681 children were diagnosed with T1D, 50.1% having DKA at presentation (36.0% mild, 30.0% moderate, and 33.9% severe DKA). The number of patients diagnosed with T1D progressively rose from approximately 39 cases/year in 2009–2010 to 95 cases/year in 2017–2018 (≈2.5-fold increase), rising primarily among children aged 5–9 years. DKA incidence was unchanged but variable (44.8% to 56.8%). At T1D diagnosis, 89% of patients reported polyuria and 91% polydipsia. Children presenting with DKA were more likely to report vomiting, abdominal pain, and particularly fatigue. DKA was most common among the youngest children, affecting 4 in 5 children aged <2 years (81.4%), in comparison to 53.3%, 42.7%, and 49.3% of patients aged 2–4, 5–9, and ≥10 years, respectively. Children with severe DKA were more likely to report vomiting, fatigue, and abdominal pain, but less likely to report polyuria, polydipsia, and polyphagia than those with mild/moderate DKA. Rates of severe DKA were highest in children aged <2 years (51.1%).ConclusionsThe number of children diagnosed with T1D at our regional center increased over the study period, but DKA rates were unchanged. With 9 of 10 children reporting polyuria and polydipsia prior to T1D diagnosis, increasing awareness of this condition in the community and among primary care physicians could lead to earlier diagnosis, and thus potentially reduce rates of DKA at presentation.

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Intestinal Delivery of Proinsulin and IL-10 via Lactococcus lactis Combined With Low-Dose Anti-CD3 Restores Tolerance Outside the Window of Acute Type 1 Diabetes Diagnosis

Frontiers in Immunology ◽

10.3389/fimmu.2020.01103 ◽

2020 ◽

Vol 11 ◽

Author(s):

Dana P. Cook ◽

João Paulo Monteiro Carvalho Mori Cunha ◽

Pieter-Jan Martens ◽

Gabriele Sassi ◽

Francesca Mancarella ◽

...

Keyword(s):

Type 1 Diabetes ◽

Lactococcus Lactis ◽

Low Dose ◽

Acute Type ◽

Diabetes Diagnosis ◽

Intestinal Delivery

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A Time-Friendly, Feasible Measure of Nutrition Knowledge in Type 1 Diabetes: The Electronic Nutrition and Carbohydrate Counting Quiz (eNCQ)

Journal of Diabetes Science and Technology ◽

10.1177/1932296818778608 ◽

2018 ◽

Vol 13 (1) ◽

pp. 68-74

Author(s):

Arwen M. Marker ◽

Amy E. Noser ◽

Nicole Knecht ◽

Mark A. Clements ◽

Susana R. Patton

Keyword(s):

Type 1 Diabetes ◽

Glycemic Control ◽

Nutrition Education ◽

Diabetes Management ◽

Clinical Care ◽

Nutrition Knowledge ◽

Diabetes Diagnosis ◽

Carbohydrate Counting ◽

One Year

Background: Greater knowledge about nutrition and carbohydrate counting are associated with improved glycemic control and quality of life in youth with type 1 diabetes (T1D). However, limited assessments of nutrition and carbohydrate knowledge have been developed, and existing measures can be time-consuming, overly broad, or not conducive to routine clinical use. To fill this gap, we developed and examined the feasibility of administering the electronic Nutrition and Carbohydrate Counting Quiz (eNCQ). Method: Ninety-two caregivers and 70 youth with T1D (mean age 12.5 years; mean time since diagnosis 5 years; English speaking) completed the 19-item eNCQ via tablet during a routine clinical visit. Completion time and item completion rates were used to assess feasibility. Relationships between eNCQ scores and patient demographics, diabetes management, and health outcomes were examined. Results: Participants took 10 minutes, on average, to complete the eNCQ. Total and Carbohydrate subscale scores (youth report) were negatively correlated with youth hemoglobin A1c (total r = –.38, carbohydrate r = –.38, Ps < .05), indicating that greater nutrition knowledge related to better glycemic control. Nutrition knowledge scores were generally high, but knowledge was negatively related to time since diabetes diagnosis ( r = –.276, P < .05). Conclusions: Findings support feasibility of the eNCQ to assess nutrition knowledge in routine clinical care. Following additional acceptability and validity testing, the eNCQ may identify families in need of further nutrition education. Nutrition assessment is particularly indicated for youth over one year since T1D diagnosis, as these families displayed lower nutrition knowledge and may need continuing education to maintain diabetes-specific nutrition knowledge over time.

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The Effect of Ethnicity in the Rate of Beta-Cell Functional Loss in the First 3 Years After Type 1 Diabetes Diagnosis

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa348 ◽

2020 ◽

Vol 105 (12) ◽

pp. e4393-e4406 ◽

Cited By ~ 1

Author(s):

Mustafa Tosur ◽

Mario A Cleves ◽

Jay M Sosenko ◽

Ingrid Libman ◽

David A Baidal ◽

...

Keyword(s):

Type 1 Diabetes ◽

Beta Cell ◽

Clinical Diagnosis ◽

Area Under The Curve ◽

Diabetes Diagnosis ◽

Z Score ◽

C Peptide ◽

Functional Loss ◽

Intervention Trials

Abstract Objective We set forth to compare ethnicities for metabolic and immunological characteristics at the clinical diagnosis of type 1 diabetes (T1D) and assess the effect of ethnicity on beta-cell functional loss within 3 years after clinical diagnosis. Research Methods and Design We studied participants in TrialNet New Onset Intervention Trials (n = 624, median age = 14.4 years, 58% male, 8.7% Hispanic) and followed them prospectively for 3 years. Mixed meal tolerance tests (MMTT) were performed within 6 months following clinical diagnosis and repeated semiannually. Unless otherwise indicated, analyses were adjusted for age, sex, BMI Z-score, and diabetes duration. Results At T1D clinical diagnosis, Hispanics, compared with non-Hispanic whites (NHW), had a higher frequency of diabetic ketoacidosis (DKA) (44.7% vs 25.3%, OR = 2.36, P = 0.01), lower fasting glucose (97 vs 109 mg/dL, P = 0.02) and higher fasting C-peptide (1.23 vs 0.94 ng/mL, P = 0.02) on the first MMTT, and higher frequency of ZnT8 autoantibody positivity (n = 201, 94.1% vs 64%, OR = 7.98, P = 0.05). After exclusion of participants in experimental arms of positive clinical trials, C-peptide area under the curve (AUC) trajectories during the first 3 years after clinical diagnosis were not significantly different between Hispanics and NHW after adjusting for age, sex, BMI-z score, and DKA (n = 413, P = 0.14). Conclusion Despite differences in the metabolic and immunological characteristics at clinical diagnosis of T1D between Hispanics and NHW, C-peptide trajectories did not differ significantly in the first 3 years following clinical diagnosis after adjustment for body mass index and other confounders. These findings may inform the design of observational studies and intervention trials in T1D.

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