Increase in Prevalence of Diabetic Ketoacidosis at Diagnosis Among Youth With Type 1 Diabetes: The SEARCH for Diabetes in Youth Study

Objective: We previously reported a high (~30%), but stable prevalence of DKA at youth-onset diagnosis of type 1 diabetes (2002 and 2010). Given the changing demographics of youth-onset type 1 diabetes, we sought to evaluate temporal trends in the prevalence of DKA at diagnosis of type 1 diabetes from 2010 to 2016 among youth <20 years of age and evaluate whether any change observed was associated with changes in sociodemographic distribution of those recently diagnosed. Research Design and Methods: We calculated prevalence of DKA within 1 month of type 1 diabetes diagnosis by year and evaluated trends over time (2010-2016) (n=7,612 incident diabetes cases, mean (SD) age 10.1 (4.5) at diagnosis). To assess whether trends observed were attributable to the changing distribution of sociodemographic factors among youth with incident type 1 diabetes, we estimated an adjusted relative risk (aRR) of DKA in relation to calendar year, adjusting for age, sex, race/ethnicity, income, education, health insurance status, language, season of diagnosis, and SEARCH site. Results: DKA prevalence increased from 35.3% (95% CI: 32.2, 38.4) in 2010, to 40.6% (95% CI: 37.8, 43.4) in 2016 (p for trend=0.01). Adjustment for sociodemographic factors did not substantively change the observed trends. We observed a 2% annual increase in prevalence of DKA at or near diagnosis of type 1 diabetes (crude RR: 1.02; 95% CI: 1.01, 1.04 and aRR: 1.02; 95% CI: 1.01, 1.04; p=0.01 for both). Conclusions: Prevalence of DKA at or near type 1 diabetes diagnosis has increased from 2010 to 2016, following the high but stable prevalence observed from 2002-2010. This increase does not seem to be attributable to the changes in distribution of sociodemographic factors over time.

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Alterations in Biomarkers Related to Glycemia, Lipid Metabolism, and Inflammation up to 20 Years Before Diagnosis of Type 1 Diabetes in Adults: Findings From the AMORIS Cohort

10.2337/figshare.16967647 ◽

2021 ◽

Author(s):

Katharina Herzog ◽

Tomas Andersson ◽

Valdemar Grill ◽

Niklas Hammar ◽

Håkan Malmström ◽

...

Keyword(s):

Type 1 Diabetes ◽

Uric Acid ◽

Lipid Metabolism ◽

Cox Regression ◽

Acute Onset ◽

Diabetes Risk ◽

Diabetes Incidence ◽

Diabetes Diagnosis ◽

Incident Type

Objective: Type 1 diabetes is described to have an acute onset, but autoantibodies can appear several years preceding diagnosis. This suggests a long preclinical phase, which may also include metabolic parameters. Here we assessed whether elevations in glycaemic, lipid, and other metabolic biomarkers were associated with future <a>type 1 diabetes</a> risk in adults. Research Design and Methods: We studied 591,239 individuals from the Swedish AMORIS cohort followed from 1985-1996 to 2012. Through linkage to national patient, diabetes, and prescription registers, we identified incident type 1 diabetes. Using Cox regression models, we estimated hazard ratios for biomarkers at baseline and incident type 1 diabetes. We additionally assessed trajectories of biomarkers during the 25 years before type 1 diabetes diagnosis in a nested case-control design. Results: We identified 1,122 type 1 diabetes cases during follow-up (average age at diagnosis: 53.3 years). The biomarkers glucose, fructosamine, triglycerides, the apolipoprotein B/A-I ratio, uric acid, alkaline phosphatase, and BMI were positively associated with type 1 diabetes risk. A higher apolipoprotein A-I was associated with a lower type 1 diabetes incidence. Already 15 years before diagnosis, type 1 diabetes cases had higher mean glucose, fructosamine, triglycerides, and uric acid levels compared to controls. Conclusion: Alterations in biomarker levels related to glycaemia, lipid metabolism, and inflammation are associated with clinically diagnosed type 1 diabetes risk, and these may be elevated many years preceding diagnosis.

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Alterations in Biomarkers Related to Glycemia, Lipid Metabolism, and Inflammation up to 20 Years Before Diagnosis of Type 1 Diabetes in Adults: Findings From the AMORIS Cohort

10.2337/figshare.16967647.v1 ◽

2021 ◽

Author(s):

Katharina Herzog ◽

Tomas Andersson ◽

Valdemar Grill ◽

Niklas Hammar ◽

Håkan Malmström ◽

...

Keyword(s):

Type 1 Diabetes ◽

Uric Acid ◽

Lipid Metabolism ◽

Cox Regression ◽

Acute Onset ◽

Diabetes Risk ◽

Diabetes Incidence ◽

Diabetes Diagnosis ◽

Incident Type

Objective: Type 1 diabetes is described to have an acute onset, but autoantibodies can appear several years preceding diagnosis. This suggests a long preclinical phase, which may also include metabolic parameters. Here we assessed whether elevations in glycaemic, lipid, and other metabolic biomarkers were associated with future <a>type 1 diabetes</a> risk in adults. Research Design and Methods: We studied 591,239 individuals from the Swedish AMORIS cohort followed from 1985-1996 to 2012. Through linkage to national patient, diabetes, and prescription registers, we identified incident type 1 diabetes. Using Cox regression models, we estimated hazard ratios for biomarkers at baseline and incident type 1 diabetes. We additionally assessed trajectories of biomarkers during the 25 years before type 1 diabetes diagnosis in a nested case-control design. Results: We identified 1,122 type 1 diabetes cases during follow-up (average age at diagnosis: 53.3 years). The biomarkers glucose, fructosamine, triglycerides, the apolipoprotein B/A-I ratio, uric acid, alkaline phosphatase, and BMI were positively associated with type 1 diabetes risk. A higher apolipoprotein A-I was associated with a lower type 1 diabetes incidence. Already 15 years before diagnosis, type 1 diabetes cases had higher mean glucose, fructosamine, triglycerides, and uric acid levels compared to controls. Conclusion: Alterations in biomarker levels related to glycaemia, lipid metabolism, and inflammation are associated with clinically diagnosed type 1 diabetes risk, and these may be elevated many years preceding diagnosis.

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1316-P: Celiac Disease in Youth with Type 1 Diabetes: Association with Age at Diabetes Diagnosis

Diabetes ◽

10.2337/db20-1316-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 1316-P

Author(s):

ERIN ALVING ◽

KRISTEN CARLIN ◽

DALE LEE ◽

ALISSA J. ROBERTS ◽

JANE DICKERSON ◽

...

Keyword(s):

Type 1 Diabetes ◽

Celiac Disease ◽

Diabetes Diagnosis

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DR15-DQ6 remains dominantly protective against type 1 diabetes throughout the first five decades of life

Diabetologia ◽

10.1007/s00125-021-05513-4 ◽

2021 ◽

Author(s):

Nicholas J. Thomas ◽

John M. Dennis ◽

Seth A. Sharp ◽

Akaal Kaur ◽

Shivani Misra ◽

...

Keyword(s):

Type 1 Diabetes ◽

Major Type ◽

Diabetes Incidence ◽

Diabetes Diagnosis ◽

Risk Haplotype ◽

Adult Onset ◽

Uk Biobank ◽

Onset Type ◽

Increased Risk

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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Geographic Clustering of Acute Complications and Sociodemographic Factors in Adults with Type 1 Diabetes

Canadian Journal of Diabetes ◽

10.1016/j.jcjd.2016.08.224 ◽

2017 ◽

Vol 41 (2) ◽

pp. 132-137 ◽

Cited By ~ 1

Author(s):

Sonia Butalia ◽

Alka B. Patel ◽

Jeffrey A. Johnson ◽

William A. Ghali ◽

Doreen M. Rabi

Keyword(s):

Type 1 Diabetes ◽

Sociodemographic Factors ◽

Geographic Clustering ◽

Acute Complications

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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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