| 1. |
- Knip, Mikael, et al.
(author)
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Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes The TRIGR Randomized Clinical Trial
- 2018
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In: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 319:1, s. 38-48
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Journal article (peer-reviewed)abstract
- IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes.
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| 2. |
- Strollo, Rocky, et al.
(author)
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Antibodies to oxidized insulin improve prediction of type 1 diabetes in children with positive standard islet autoantibodies
- 2019
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In: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 35:4
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Journal article (peer-reviewed)abstract
- 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.
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| 3. |
- Strollo, Rocky, et al.
(author)
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Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children
- 2017
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In: Diabetologia. - : SPRINGER. - 0012-186X .- 1432-0428. ; 60:8, s. 1467-1474
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Journal article (peer-reviewed)abstract
- Aims/hypothesis We have shown that autoimmunity to insulin in type 1 diabetes may result from neoepitopes induced by oxidative post-translational modifications (oxPTM). Antibodies specific to oxPTM-insulin (oxPTM-INS-Ab) are present in most newly diagnosed individuals with type 1 diabetes and are more common than autoantibodies to native insulin. In this study, we investigated whether oxPTM-INS-Ab are present before clinical onset of type 1 diabetes, and evaluated the ability of oxPTM-INS-Ab to identify children progressing to type 1 diabetes. Methods We used serum samples collected longitudinally from the All Babies in Southeast Sweden (ABIS) cohort tested for the gold standard islet autoantibodies to insulin (IAA), GAD (GADA), tyrosine phosphatase 2 (IA-2A) and zinc transporter 8 (ZnT8A). We studied 23 children who progressed to type 1 diabetes (progr-T1D) and 63 children who did not progress to type 1 diabetes (NP) after a median follow-up of 10.8 years (interquartile range 7.7-12.8). Of the latter group, 32 were positive for one or more islet autoantibodies (NP-AAB(+)). oxPTM-INS-Ab to insulinmodified by (OH)-O-center dot or HOCl were measured by our developed ELISA platform. Results Antibodies to at least one oxPTM-INS were present in 91.3% of progr-T1D children. oxPTM-INS-Ab co-existed with GADA, IA-2A, IAA or ZnT8A in 65.2%, 56.5%, 38.9% and 33.3% progr-T1D children, respectively. In addition, oxPTM-INS-Ab were present in 17.4%, 26.1%, 38.9% and 41.6% of progr-T1D children who were negative for GADA, IA-2A, IAA and ZnT8A, respectively. (OH)-O-center dot-INS-Ab were more common in progr-T1D children than in NP-AAB+ children (82.6% vs 19%; p amp;lt; 0.001) and allowed discrimination between progr-T1D and NP-AAB(+) children with 74% sensitivity and 91% specificity. None of the NP-AAB(-) children were positive for oxPTM-INS-Ab. Conclusions/interpretation oxPTM-INS-Ab are present before the clinical onset of type 1 diabetes and can identify children progressing to type 1 diabetes.
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