Fernanda Velluzzi1, Gianni Secci1, Vincenzo Sepe2, Catherine Klersy3, Marion Shattock4, Richard Foxon5, Marco Songini6, Stefano Mariotti1, Mattia Locatelli7, Gian Franco Bottazzo7, Andrea Loviselli8. 1. Department of Medical Sciences "Mario Aresu", University of Cagliari, AOU, SS 554, Monserrato, Cagliari, Italy. 2. Unit of Nephrology, Dialysis, Transplantation, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 3. Service of Biometry and Clinical Epidemiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 4. Department of Immunology, St Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK. 5. School of Biomedical and Health Science, King's College, London, UK. 6. Diabetes Unit, Brotzu Hospital, Cagliari, Italy. 7. Scientific Directorate, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy. 8. Department of Medical Sciences "Mario Aresu", University of Cagliari, AOU, SS 554, Monserrato, Cagliari, Italy. alovise@medicina.unica.i.
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.
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.
Entities:
Keywords:
Anti-insula autoantibodies; Epidemiology of T1DM; Prediction of T1DM
Authors: R Rodia; F Pani; G Caocci; G La Nasa; M P Simula; O Mulas; F Velluzzi; A Loviselli; S Mariotti; F Boi Journal: J Endocrinol Invest Date: 2021-07-20 Impact factor: 4.256