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Antibodies to oxidized insulin improve prediction of type 1 diabetes in children with positive standard islet autoantibodies

Strollo, Rocky (author)
Univ Campus Biomed Roma, Italy
Vinci, Chiara (author)
Univ Campus Biomed Roma, Italy; Queen Mary Univ London, England
Napoli, Nicola (author)
Univ Campus Biomed Roma, Italy; IRCCS Ist Ortoped Galeazzi, Italy
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Fioriti, Elvira (author)
Univ Campus Biomed Roma, Italy
Maddaloni, Ernesto (author)
Univ Campus Biomed Roma, Italy
Åkerman, Linda (author)
Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten,Region Östergötland, Klinisk immunologi och transfusionsmedicin
Casas, Rosaura (author)
Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten
Pozzilli, Paolo (author)
Univ Campus Biomed Roma, Italy; Queen Mary Univ London, England
Ludvigsson, Johnny (author)
Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten,Region Östergötland, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus
Nissim, Ahuva (author)
Queen Mary Univ London, England
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 (creator_code:org_t)
2019-02-18
2019
English.
In: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 35:4
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • BackgroundAntibodies to posttranslationally modified insulin (oxPTM‐INS‐Ab) are a novel biomarker of type 1 diabetes (T1D). Here, we evaluated whether oxPTM‐INS‐Ab can improve T1D prediction in children with positive standard islet autoantibodies (AAB).MethodsWe evaluated sensitivity, specificity, accuracy, and risk for progression to T1D associated with oxPTM‐INS‐Ab and the standard islet AAB that include insulin (IAA), GAD (GADA), and tyrosine phosphatase 2 (IA‐2A) in a cohort of islet AAB‐positive (AAB+) children from the general population (median follow‐up 8.8 years).ResultsoxPTM‐INS‐Ab was the most sensitive and specific autoantibody biomarker (74% sensitivity, 91% specificity), followed by IA‐2A (71% sensitivity, 91% specificity). GADA and IAA showed lower sensitivity (65% and 50%, respectively) and specificity (66% and 68%, respectively). Accuracy (AUC of ROC) of oxPTM‐INS‐Ab was higher than GADA and IAA (P = 0.003 and P = 0.017, respectively), and similar to IA‐2A (P = 0.896). oxPTM‐INS‐Ab and IA‐2A were more effective than IAA for detecting progr‐T1D when used as second‐line biomarker in GADA+ children. Risk for diabetes was higher (P = 0.03) among multiple AAB+ who were also oxPTM‐INS‐Ab+ compared with those who were oxPTM‐INS‐Ab–. Importantly, when replacing IAA with oxPTM‐INS‐Ab, diabetes risk increased to 100% in children with oxPTM‐INS‐Ab+ in combination with GADA+ and IA‐2A+, compared with 84.37% in those with IAA+, GADA+, and IA‐2A+ (P = 0.04).ConclusionsAntibodies to oxidized insulin (oxPTM‐INS‐Ab), compared with IAA which measure autoantibodies to native insulin, improve T1D risk assessment and prediction accuracy in AAB+ children.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Keyword

biomarker; insulin autoantibodies; posttranslational modifications; prediction; type 1 diabetes

Publication and Content Type

ref (subject category)
art (subject category)

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