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Prediction of type 1 diabetes in Sardinian schoolchildren using islet cell autoantibodies: 10-year follow-up of the Sardinian schoolchildren type 1 diabetes prediction study

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Abstract

Aims

Stable genetic background makes individuals from the Mediterranean island of Sardinia ideal to define the predictive power of islet-related autoantibodies (IRAs): glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase-like antibodies (IA-2A), islet cell antibodies (ICA) to identify T1DM progressors. The aims of the present study were: (1) determination of IRAs reference limits in healthy non-diabetic Sardinian schoolchildren (SSc). (2) Predictive power evaluation of IRAs as single or combined determination to identify islet to identify T1DM progressors.

Methods

Between 1986 and 1994, 8448 SSc were tested for IRAs. All were followed up for 10 years. The predictive power of single or combination of IRAs was determined as hazard ratio (HR), sensitivity, specificity, area under the ROC curve, negative and positive predictive value (NPV, PPV).

Results

All 43 progressors to T1DM, but three showed at least one autoantibody positivity. HR for any single-autoantibody positivity was 55.3 times greater when compared to SSc negative for all IRAs. Any single autoantibody performed at least 64.9 % sensitivity with PPV always lower than 16 %. The best performing combination was ICA, plus IA-2A (showing 52.6 % sensitivity, 99.8 % specificity, 0.76 area under the ROC curve, 51.3 % PPV and 99.8 % NPV.

Conclusions

Determination of IRAs reference limits in healthy SSc by standard statistical methods is crucial to establish the power of IRAs as progression markers to T1DM. Our data offer a solid rationale for future testing of ICA and IA-2A as routine laboratory markers to identify individuals at high risk of T1DM in the general population.

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Abbreviations

SSc:

Sardinian schoolchildren

FH:

Family history

TD:

Thyroid disease

T1DM:

Type 1 diabetes mellitus

IRAs:

Islet-related autoantibodies

ICA:

Islet cell antibodies

GADA:

Glutamic acid decarboxylase antibodies

IA-2A:

Protein tyrosinephosphatase-like IA-2

IAA:

Insulin autoantibodies

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Acknowledgment

S.M. was supported by Ministero della Salute (Rome, Italy, Grant No. ICS 120.2/RF99.17).

Conflict of interest

The authors declare that there is no conflict of interest associated with this manuscript.

Ethical standard

The study protocol conformed to the principles of the Declaration of Helsinki and was approved by Department of Medical Sciences “Mario Aresu” University of Cagliari, Ethics Committee.

Human and Animal Rights

This article does not contain any studies with human or animal subjects performed by any of the authors.

Informed consent

Informed consent was obtained from all patients for being included in the study.

Author information

Authors and Affiliations

  1. Department of Medical Sciences “Mario Aresu”, University of Cagliari, AOU, SS 554, Monserrato, Cagliari, Italy

    Fernanda Velluzzi, Gianni Secci, Stefano Mariotti & Andrea Loviselli

  2. Unit of Nephrology, Dialysis, Transplantation, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Vincenzo Sepe

  3. Service of Biometry and Clinical Epidemiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Catherine Klersy

  4. Department of Immunology, St Bartholomew’s and the Royal London School of Medicine and Dentistry, London, UK

    Marion Shattock

  5. School of Biomedical and Health Science, King’s College, London, UK

    Richard Foxon

  6. Diabetes Unit, Brotzu Hospital, Cagliari, Italy

    Marco Songini

  7. Scientific Directorate, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy

    Mattia Locatelli & Gian Franco Bottazzo

Authors
  1. Fernanda Velluzzi
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  2. Gianni Secci
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  3. Vincenzo Sepe
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  4. Catherine Klersy
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  5. Marion Shattock
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  6. Richard Foxon
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  7. Marco Songini
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  8. Stefano Mariotti
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  9. Mattia Locatelli
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  10. Gian Franco Bottazzo
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  11. Andrea Loviselli
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Consortia

The Sardinian Autoimmunity Study Group

Corresponding author

Correspondence to Andrea Loviselli.

Additional information

Managed by Massimo Porta.

The Sardinian Autoimmunity Study Group is given in the “Appendix”.

Appendix

Appendix

The author group is part of the Sardinia Autoimmunity Study Groups’, which include:

General Management

Overall Scientific and Administrative Responsibility: M. Songini (Cagliari), GF. Bottazzo (Rome)

General Co - ordinator: M. Locatelli (Rome);

The Immnunological and Genetic Study Group: Responsible: G.F. Bottazzo (Cagliari-Rome), E. Bonifacio (Milano).

Local Overall Responsibility: M. Songini (Cagliari)

The Epidemiology Study Group, The Statistical Group: Responsible: M. Songini (Cagliari);

The School Children Study Group: Responsibles: A. Loviselli, F. Velluzzi (Cagliari);

Co - ordinator: S. Mariotti (Cagliari);

Physicians and Laboratory Personnel: A. Pilo, G. Pinna, G. Secci, A. Taberlet.

Field workers: P. Mele, M.A. Calia, R. Mastinu, A. Pilleri, S. Serra, M. Diliberto, E. Rizzolo, N. Costantini.

Family GPs in the Provinces: L. Curreli, Serramanna (Ca), A. Trincas, Cabras (Or), M. Lara, S. Melis, L. Melis, G. Uggias, M. Incollu, Baunei (Og), S. Serra, Urzulei (Og), A. Seoni, S. Monni, Villagrande (Og), M. Muntoni, Ulassai (Og), M. Moi, Perdasdefogu (Og), F. Calzone, I. Ena, A. Manca, Bitti (Og), A. Lai, E. Floris, Tertenia (Og), M. Orrù, G. Melis, G. Mou, A. Deplano, Jerzu (Og).

CAD Sardinia:CAD Cagliari, CAD Sassari, CAD Oristano, CAD Nuoro, CAD Lanusei-Tortolì, CAD Olbia, CAD Tempio, CAD Carbonia, CAD Iglesias, CAD Quartu S.E., CAD Senorbì, CAD San Gavino M., CAD Bosa, CAD Isili, CAD Alghero, CAD Tempio Pausania, CAD Ozieri, CAD Santa Teresa di Gallura, CAD LA Maddalena, CAD Arzachena, CAD Bono, CAD Muravera, CAD Siniscola-Orosei, CAD Oristano.

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Velluzzi, F., Secci, G., Sepe, V. et al. Prediction of type 1 diabetes in Sardinian schoolchildren using islet cell autoantibodies: 10-year follow-up of the Sardinian schoolchildren type 1 diabetes prediction study. Acta Diabetol 53, 73–79 (2016). https://doi.org/10.1007/s00592-015-0751-y

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  • DOI: https://doi.org/10.1007/s00592-015-0751-y

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