Prediction of type 1 diabetes among siblings of affected children and in the general population

Siljander, Heli; Veijola, Riitta; Reunanen, Antti; Virtanen, Suvi Μ.; Åkerblom, Hans K.; Knip, Mikael

doi:10.1007/s00125-007-0799-5

Cited by 50 publications

(40 citation statements)

References 11 publications

(15 reference statements)

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“…This is a limitation of our study. However, familial and non-familial cases of type 1 diabetes were shown not to differ in genetic, autoimmune and metabolic characteristics [37]; neither were there differences in disease-specific sensitivity of antibody markers between first-degree relatives and the general population [38]. Therefore, it is likely that our results in relatives can be extrapolated to the general population.…”

Section: Discussionmentioning

confidence: 69%

Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients

Gorus

Balti

Vermeulen

et al. 2012

Clinical and Experimental Immunology

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SummaryIn first-degree relatives of type 1 diabetic patients, we investigated whether diabetes risk assessment solely based on insulinoma antigen 2 (IA-2) and zinc transporter 8 (ZnT8) antibody status (IA-2A, respectively, ZnT8A) is as effective as screening for three or four autoantibodies [antibodies against insulin (IAA), glutamate decarboxylase 65 kDa (GAD) glutamate decarboxylase autoantibodies (GADA) and IA-2A with or without ZnT8A] in identifying children, adolescents and adults who progress rapidly to diabetes (within 5 years). Antibodies were determined by radiobinding assays during follow-up of 6444 siblings and offspring aged 0-39 years at inclusion and recruited consecutively by the Belgian Diabetes Registry. We identified 394 persistently IAA + , GADA + , IA-2A + and/or ZnT8A + relatives (6·1%). After a median follow-up time of 52 months, 132 relatives developed type 1 diabetes. In each age category tested (0-9, 10-19 and 20-39 years) progression to diabetes was significantly quicker in the presence of IA-2A and/or ZnT8A than in their joint absence (P < 0·001). Progression rate was age-independent in IA-2A + and/or ZnT8A + relatives but decreased with age if only GADA and/or IAA were present (P = 0·008). In the age group mainly considered for immune interventions until now (10-39 years), screening for IA-2A and ZnT8A alone identified 78% of the rapid progressors (versus 75% if positive for Ն 2 antibodies among IAA, GADA, IA-2A and ZnT8A or versus 62% without testing for ZnT8A). Screening for IA-2A and ZnT8A alone allows identification of the majority of rapidly progressing prediabetic siblings and offspring regardless of age and is more cost-effective to select participants for intervention trials than conventional screening.

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Section: Discussionmentioning

confidence: 69%

Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients

Gorus

Balti

Vermeulen

et al. 2012

Clinical and Experimental Immunology

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“…The prediction of type 1 diabetes has so far been based mainly on the presence of islet autoantibodies in individuals at increased genetic risk [3,20,21]. In this study we assessed for the first time the development of dysglycaemia in an OGTT to predict the presentation of type 1 diabetes in a populationderived cohort of autoantibody-positive children.…”

Section: Discussionmentioning

confidence: 99%

OGTT and random plasma glucose in the prediction of type 1 diabetes and time to diagnosis

et al. 2015

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Aims/hypothesis We assessed the utility of the OGTT and random plasma glucose concentrations in predicting the time to diagnosis of type 1 diabetes. Methods A population-derived cohort of 14,876 newborns with HLA-conferred risk of type 1 diabetes were invited to regular follow-up for islet autoantibodies. When two or more autoantibodies were detected, an OGTT was performed once a year and random plasma glucose analysed twice a year. During follow-up, 567 children developed multiple autoantibodies, 255 (45%) of whom were diagnosed with type 1 diabetes, while 312 remained non-diabetic by December 2011.Results Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were risk factors for type 1 diabetes (HR 3.2 [95% CI 1.5, 7.0] and 8.3 [95% CI 6.0, 11.5], respectively). When a random plasma glucose value ≥7.8 mmol/l was observed, the HR for diabetes was 6.0 (95% CI 4.3, 8.6). The median time to diagnosis after the detection of IFG was 5.2 years (interquartile range [IQR] 3.4, 6.3); after IGT, 0.7 years (IQR 0.3, 1.9); and, after a random plasma glucose ≥7.8 mmol/l, 1.0 years (IQR 0.3, 1.5). In a retrospective analysis, both OGTT-derived 2 h plasma glucose and random plasma glucose started to increase 1.5 years before diagnosis (p<0.001 and p=0.004, respectively). Conclusions/interpretation Dysglycaemia detected in an OGTT or based on random plasma glucose is a useful marker in the prediction of time to onset of type 1 diabetes in high-risk children. Random plasma glucose is a simple and low-cost measurement with comparable predictive characteristics to that of OGTT-derived 2 h glucose.

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“…The prediction of type 1 diabetes has so far been based mainly on the presence of islet autoantibodies in subjects who are at increased genetic risk (8,26,27). Young age at seroconversion also has a clear impact on the risk of progression to clinical disease (17).…”

Section: Discussionmentioning

confidence: 99%

HbA1c Predicts Time to Diagnosis of Type 1 Diabetes in Children at Risk

et al. 2014

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Prediction of type 1 diabetes is based on the detection of multiple islet autoantibodies in subjects who are at increased genetic risk. Prediction of the timing of diagnosis is challenging, however. We assessed the utility of HbA1c levels in predicting the clinical disease in genetically predisposed children with multiple autoantibodies. Cord blood samples from 168,055 newborn infants were screened for class II HLA genotypes in Finland, and 14,876 children with increased genetic risk for type 1 diabetes were invited to participate in regular follow-ups, including screening for diabetes-associated autoantibodies. When two or more autoantibodies were detected, HbA1c levels were analyzed at each visit. During follow-up, multiple (two or more) autoantibodies developed in 466 children; type 1 diabetes was diagnosed in 201 of these children (43%, progressors), while 265 children remained disease free (nonprogressors) by December 2011. A 10% increase in HbA1c levels in samples obtained 3–12 months apart predicted the diagnosis of clinical disease (hazard ratio [HR] 5.7 [95% CI 4.1–7.9]) after a median time of 1.1 years (interquartile range [IQR] 0.6–3.1 years) from the observed rise of HbA1c. If the HbA1c level was ≥5.9% (41 mmol/mol) in two consecutive samples, the median time to diagnosis was 0.9 years (IQR 0.3–1.5, HR 11.9 [95% CI 8.8–16.0]). In conclusion, HbA1c is a useful biochemical marker when predicting the time to diagnosis of type 1 diabetes in children with multiple autoantibodies.

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Prediction of type 1 diabetes among siblings of affected children and in the general population

Cited by 50 publications

References 11 publications

Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients

Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients

OGTT and random plasma glucose in the prediction of type 1 diabetes and time to diagnosis

HbA1c Predicts Time to Diagnosis of Type 1 Diabetes in Children at Risk

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