Islet autoantibodies and residual beta cell function in type 1 diabetes children followed for 3–6 years

Sorensen, Jesper S.; Vaziri-Sani, Fariba; Maziarz, Marlena; Kristensen, Kurt; Ellerman, A.; Breslow, Norman E.; Lernmark, Åke; Pociot, Flemming; Brorsson, Caroline; Birkebæk, Niels H

doi:10.1016/j.diabres.2011.12.013

Cited by 17 publications

(33 citation statements)

References 30 publications

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“…Moreover, individuals with negative tests for ZnT8A represented a sizable proportion of those with two or more autoantibodies (118 of 237 [50%]). Reports describing T1D patients in the years after diagnosis suggest that ZnT8A autoantibodies are important to understanding pathogenesis (27–29). The particular significance of ZnT8A autoantibodies shows why specific types and levels of autoantibodies should be considered to avoid faulty determinations of eligibility for prevention trials.…”

Section: Discussionmentioning

confidence: 99%

The Prediction of Type 1 Diabetes by Multiple Autoantibody Levels and Their Incorporation Into an Autoantibody Risk Score in Relatives of Type 1 Diabetic Patients

et al. 2013

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OBJECTIVEWe assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D).RESEARCH DESIGN AND METHODSTrialNet Natural History Study participants (n = 784) were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those positive for at least one autoantibody were subsequently tested for ICA and ZnT8A. An autoantibody risk score (ABRS) was developed from a proportional hazards model that combined autoantibody levels from each autoantibody along with their designations of positivity and negativity.RESULTSThe ABRS was strongly predictive of T1D (hazard ratio [with 95% CI] 2.72 [2.23–3.31], P < 0.001). Receiver operating characteristic curve areas (with 95% CI) for the ABRS revealed good predictability (0.84 [0.78–0.90] at 2 years, 0.81 [0.74–0.89] at 3 years, P < 0.001 for both). The composite of levels from the five autoantibodies was predictive of T1D before and after an adjustment for the positivity or negativity of autoantibodies (P < 0.001). The findings were almost identical when ICA was excluded from the risk score model. The combination of the ABRS and the previously validated Diabetes Prevention Trial–Type 1 Risk Score (DPTRS) predicted T1D more accurately (0.93 [0.88–0.98] at 2 years, 0.91 [0.83–0.99] at 3 years) than either the DPTRS or the ABRS alone (P ≤ 0.01 for all comparisons).CONCLUSIONSThese findings show the importance of considering autoantibody levels in assessing the risk of T1D. Moreover, levels of multiple autoantibodies can be incorporated into an ABRS that accurately predicts T1D.

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Section: Discussionmentioning

confidence: 99%

The Prediction of Type 1 Diabetes by Multiple Autoantibody Levels and Their Incorporation Into an Autoantibody Risk Score in Relatives of Type 1 Diabetic Patients

et al. 2013

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“…The study group included 342 children and adolescents, of whom 97% were positive for one or more diabetes-specific autoantibodies at diabetes onset (29). Great diversity concerning RBF phenotype was observed.…”

Section: Discussionmentioning

confidence: 99%

“…Stimulated C-peptide level equal to or just higher than our lower detection limit may not affect the clinical outcome but may serve as an autoantigen stimulus (29). Schiffrin et al (19) found that 23% of 151 Canadian children and adolescents with type 1 diabetes onset during 1985–1988 had stimulated C-peptide >0.06 nmol/L at 3 years after diabetes onset.…”

Section: Discussionmentioning

confidence: 99%

“…HLA typing (DQB1) was performed as previously described (29). The HLA-DQB1 types were classified as follows: very high-risk genotypes (302/02); high-risk genotypes (302/302 and 302/X, where X is any allele except 02); moderate-risk genotypes (02/02 and 02/X, where X is any allele except 0302); and low-risk genotypes (604/x, 604/301, 603/304, 602/304, 602/301, 603/x, 602/x, 304/x, and 301/x).…”

Section: Methodsmentioning

confidence: 99%

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Residual β-Cell Function 3–6 Years After Onset of Type 1 Diabetes Reduces Risk of Severe Hypoglycemia in Children and Adolescents

et al. 2013

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OBJECTIVETo determine the prevalence of residual β-cell function (RBF) in children after 3–6 years of type 1 diabetes, and to examine the association between RBF and incidence of severe hypoglycemia, glycemic control, and insulin requirements.RESEARCH DESIGN AND METHODSA total of 342 children (173 boys) 4.8–18.9 years of age with type 1 diabetes for 3–6 years were included. RBF was assessed by testing meal-stimulated C-peptide concentrations. Information regarding severe hypoglycemia within the past year, current HbA1c, and daily insulin requirements was retrieved from the medical records and through patient interviews.RESULTSNinety-two children (27%) had RBF >0.04 nmol/L. Patients with RBF <0.04 nmol/L were significantly more likely to have severe hypoglycemia than patients with RBF >0.04 nmol/L (odds ratio, 2.59; 95% CI, 1.10–7.08; P < 0.03). HbA1c was significantly higher in patients with RBF <0.04 nmol/L compared with patients with RBF >0.04 nmol/L (mean, 8.49 ± 0.08% [69.3 ± 0.9 mmol/mol] vs. 7.92 ± 0.13% [63.1 ± 1.4 mmol/mol]; P < 0.01), and insulin requirements were significantly lower in patients with RBF >0.2 nmol/L (mean ± SE: 1.07 ± 0.02 vs. 0.93 ± 0.07 units/kg/day; P < 0.04).CONCLUSIONSWe demonstrated considerable phenotypic diversity in RBF among children after 3–6 years of type 1 diabetes. Children with RBF are at lower risk for severe hypoglycemia, have better diabetes regulation, and have lower insulin requirements compared with children without RBF. There appears to be a lower limit for stimulated RBF of ∼0.04 nmol/L that confers a beneficial effect on hypoglycemia and metabolic control.

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“…For example, it has been reported that the predominant factor associated with a rapid loss of RBF is young age . The causal effect of autoantibodies on RBF has remained unclear because of conflicting results . Human leukocyte antigen (HLA) genotype, a history of diabetic ketoacidosis (DKA) at diagnosis, C‐peptide levels at diagnosis, sex, and body mass index (BMI) are also factors that affect RBF after diagnosis in adolescents and young adults …”

Section: Introductionmentioning

confidence: 99%

Prognosis for residual islet β‐cell secretion function in young patients with newly diagnosed type 1 diabetes

Miao

Zhang

et al. 2019

Journal of Diabetes

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Background This study investigated possible predictors of residual islet β‐cell function (RBF) in young patients with newly diagnosed type 1 diabetes (T1D). Methods After analyzing RBF in 443 patients with T1D according to age at diagnosis and disease duration, 110 were followed‐up over 18‐60 months. A nomogram was developed by logistic regression to explore factors associated with long‐term RBF. Results Of the 443 T1D patients (mean [±SD] age 20.28 ± 5.50 years; mean [±SD] diabetes duration 28.5 ± 14.6 months), RBF was preserved in 64.3%. Independent predictors for poor RBF outcome among the 110 patients in the follow‐up cohort were age at onset (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.73‐0.92; P < 0.001), high‐risk human leukocyte antigen (HLA) status (OR 4.73; CI 1.28‐17.52; P = 0.020), female sex (OR 3.39; CI 1.03‐11.22; P = 0.045), and a history of diabetic ketoacidosis (DKA; OR 8.71; CI 2.31‐32.83; P < 0.001). Baseline glutamic acid decarboxylase (GAD) antibody, family history of diabetes, body mass index, insulin dosage, and C‐peptide and HbA1c levels were not associated with poor RBF outcome. Intensive glycemic control after T1D diagnosis may improve RBF within a mean (±SD) follow‐up of 35.1 ± 13.8 months. The calibration plot for the probability of 2‐, 3‐, and 4‐year RBF showed optimal agreement between nomogram‐predicted and actual observed probabilities. Conclusions Younger age of onset, female sex, higher HLA risk status, and a history of DKA were the main factors predicting long‐term poor preserved β‐cell function. Glycemic control could improve RBF during the course of diabetes. The nomogram provides an individualized risk estimate of RBF in patients with newly diagnosed T1D within Chinese Han populations.

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Islet autoantibodies and residual beta cell function in type 1 diabetes children followed for 3–6 years

Abstract: Islet autoantibodies and residual beta cell function in type 1 diabetes children followed for 3-6 years Sorensen, J. S.; Vaziri Sani, Fariba; Maziarz, M.; Kristensen, K.; Ellerman, A.; Breslow, N.; Lernmark, Åke; Pociot, F.; Brorsson, C.; Birkebaek, N. H.

Cited by 17 publications

References 30 publications

The Prediction of Type 1 Diabetes by Multiple Autoantibody Levels and Their Incorporation Into an Autoantibody Risk Score in Relatives of Type 1 Diabetic Patients

The Prediction of Type 1 Diabetes by Multiple Autoantibody Levels and Their Incorporation Into an Autoantibody Risk Score in Relatives of Type 1 Diabetic Patients

Residual β-Cell Function 3–6 Years After Onset of Type 1 Diabetes Reduces Risk of Severe Hypoglycemia in Children and Adolescents

Prognosis for residual islet β‐cell secretion function in young patients with newly diagnosed type 1 diabetes

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