HOMA2-B enhances assessment of type 1 diabetes risk among TrialNet Pathway to Prevention participants.

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  • Additional Information
    • Corporate Authors:
      Type 1 Diabetes TrialNet Study Group
    • Source:
      Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0006777 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0428 (Electronic) Linking ISSN: 0012186X NLM ISO Abbreviation: Diabetologia Subsets: MEDLINE
    • Publication Information:
      Original Publication: Berlin Springer Verlag
    • Subject Terms:
      Diabetes Mellitus, Type 1* ; Diabetes Mellitus, Type 2* ; Insulin Resistance*/physiology; Adolescent ; Adult ; Autoantibodies ; Blood Glucose/metabolism ; Child ; Child, Preschool ; Humans ; Insulin ; Young Adult
    • Abstract:
      Aims/hypothesis: Methods to identify individuals at highest risk for type 1 diabetes are essential for the successful implementation of disease-modifying interventions. Simple metabolic measures are needed to help stratify autoantibody-positive (Aab+) individuals who are at risk of developing type 1 diabetes. HOMA2-B is a validated mathematical tool commonly used to estimate beta cell function in type 2 diabetes using fasting glucose and insulin. The utility of HOMA2-B in association with type 1 diabetes progression has not been tested.
      Methods: Baseline HOMA2-B values from single-Aab+ (n = 2652; mean age, 21.1 ± 14.0 years) and multiple-Aab+ (n = 3794; mean age, 14.5 ± 11.2 years) individuals enrolled in the TrialNet Pathway to Prevention study were compared. Cox proportional hazard models were used to determine associations between HOMA2-B tertiles and time to progression to type 1 diabetes, with adjustments for age, sex, HLA status and BMI z score. Receiver operating characteristic (ROC) analysis was used to test the association of HOMA2-B with type 1 diabetes development in 1, 2, 5 and 10 years.
      Results: At study entry, HOMA2-B values were higher in single- compared with multiple-Aab+ Pathway to Prevention participants (91.1 ± 44.5 vs 83.9 ± 38.9; p < 0.001). Single- and multiple-Aab+ individuals in the lowest HOMA2-B tertile had a higher risk and faster rate of progression to type 1 diabetes. For progression to type 1 diabetes within 1 year, area under the ROC curve (AUC-ROC) was 0.685, 0.666 and 0.680 for all Aab+, single-Aab+ and multiple-Aab+ individuals, respectively. When correlation between HOMA2-B and type 1 diabetes risk was assessed in combination with additional factors known to influence type 1 diabetes progression (insulin sensitivity, age and HLA status), AUC-ROC was highest for the single-Aab+ group's risk of progression at 2 years (AUC-ROC 0.723 [95% CI 0.652, 0.794]).
      Conclusions/interpretation: These data suggest that HOMA2-B may have utility as a single-time-point measurement to stratify risk of type 1 diabetes development in Aab+ individuals.
      (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
    • References:
      JAMA. 2013 Jun 19;309(23):2473-9. (PMID: 23780460)
      Diabetes Care. 2012 Jun;35(6):1213-8. (PMID: 22446173)
      Cancer. 1950 Jan;3(1):32-5. (PMID: 15405679)
      Diabetes Res Clin Pract. 1995 Aug;28 Suppl:S151-7. (PMID: 8529508)
      Ann N Y Acad Sci. 2008 Dec;1150:14-24. (PMID: 19120262)
      Diabetes. 2012 Jun;61(6):1331-7. (PMID: 22618768)
      JCI Insight. 2018 Aug 9;3(15):. (PMID: 30089716)
      Diabetologia. 2002 Dec;45(12):1658-66. (PMID: 12488955)
      Endokrynol Pol. 2014;65(3):176-80. (PMID: 24971917)
      Am J Transplant. 2018 Apr;18(4):990-997. (PMID: 29218834)
      Diabetes Care. 1999 May;22(5):818-22. (PMID: 10332688)
      Pediatr Diabetes. 2019 May;20(3):263-270. (PMID: 30628751)
      Pediatr Diabetes. 2009 Apr;10(2):97-104. (PMID: 18823409)
      Diabet Med. 1998 Apr;15(4):290-6. (PMID: 9585393)
      Diabetes Care. 2014 Jan;37 Suppl 1:S14-80. (PMID: 24357209)
      Diabetes Care. 2015 Feb;38(2):271-6. (PMID: 25519451)
      Diabetes Care. 2015 Oct;38(10):1964-74. (PMID: 26404926)
      Diabetes Care. 1998 Dec;21(12):2191-2. (PMID: 9839117)
      N Engl J Med. 2019 Aug 15;381(7):603-613. (PMID: 31180194)
      Diabetes Care. 2007 Sep;30(9):2314-20. (PMID: 17536068)
      Diabetologia. 2004 Oct;47(10):1661-7. (PMID: 15480539)
      Diabetes. 1999 Sep;48(9):1779-86. (PMID: 10480608)
      Clin Chem. 1995 Aug;41(8 Pt 2):1248-55. (PMID: 7628115)
      Diabetes Res Clin Pract. 1998 Sep;41(3):191-6. (PMID: 9829348)
      Diabetologia. 2021 Apr;64(4):836-844. (PMID: 33496819)
      N Engl J Med. 2002 May 30;346(22):1685-91. (PMID: 12037147)
      Diabetes Care. 2008 Oct;31(10):1966-71. (PMID: 18628574)
      JAMA. 2020 Jan 28;323(4):339-351. (PMID: 31990315)
      Diabetes Care. 2011 Sep;34(9):1897-901. (PMID: 21750277)
      Diabetes Care. 2017 Nov;40(11):1494-1499. (PMID: 28860125)
      Pediatr Diabetes. 2011 Mar;12(2):85-90. (PMID: 20522170)
      Clin Chim Acta. 2011 Nov 20;412(23-24):2128-31. (PMID: 21843518)
      Diabetes Care. 2009 Sep;32(9):1603-7. (PMID: 19487644)
      Diabetes Care. 2020 Jan;43(1):5-12. (PMID: 31753960)
      Diabetes Care. 2004 Jun;27(6):1487-95. (PMID: 15161807)
      Diabetologia. 2019 Jan;62(1):24-27. (PMID: 30426167)
      Diabetologia. 2020 Mar;63(3):588-596. (PMID: 31768570)
      Diabetologia. 1985 Jul;28(7):412-9. (PMID: 3899825)
      J Autoimmun. 2016 Jul;71:88-96. (PMID: 27068279)
    • Grant Information:
      U01 DK085476 United States DK NIDDK NIH HHS; U01 DK085453 United States DK NIDDK NIH HHS; I01 BX001733 United States BX BLRD VA; U01 DK106993 United States DK NIDDK NIH HHS; U01 DK103282 United States DK NIDDK NIH HHS; UC4 DK106993 United States DK NIDDK NIH HHS; U01 DK061042 United States DK NIDDK NIH HHS; U01 DK085509 United States DK NIDDK NIH HHS; UC4 DK117009 United States DK NIDDK NIH HHS; R01 DK093954 United States DK NIDDK NIH HHS; R01 DK127308 United States DK NIDDK NIH HHS; UC4 DK104166 United States DK NIDDK NIH HHS; R21 DK119800 United States DK NIDDK NIH HHS; U01 DK061010 United States DK NIDDK NIH HHS; U01 DK127786 United States DK NIDDK NIH HHS; U01 DK085466 United States DK NIDDK NIH HHS; U01 DK103153 United States DK NIDDK NIH HHS; U01 DK061058 United States DK NIDDK NIH HHS; U01 DK106984 United States DK NIDDK NIH HHS; U01 DK085499 United States DK NIDDK NIH HHS; U01 DK107013 United States DK NIDDK NIH HHS; U01 DK103266 United States DK NIDDK NIH HHS; R01 DK127236 United States DK NIDDK NIH HHS; U01 DK127382 United States DK NIDDK NIH HHS; P30 DK097512 United States DK NIDDK NIH HHS; U01 DK107014 United States DK NIDDK NIH HHS; U01 DK106994 United States DK NIDDK NIH HHS; U01 DK061034 United States DK NIDDK NIH HHS; U01 DK085461 United States DK NIDDK NIH HHS; U01 DK103180 United States DK NIDDK NIH HHS; U01 DK085465 United States DK NIDDK NIH HHS; U01 DK085504 United States DK NIDDK NIH HHS
    • Contributed Indexing:
      Keywords: Autoantibody; Biomarker; HOMA2-B; Risk prediction; TrialNet Pathway to Prevention; Type 1 diabetes
    • Accession Number:
      0 (Autoantibodies)
      0 (Blood Glucose)
      0 (Insulin)
    • Publication Date:
      Date Created: 20211013 Date Completed: 20220331 Latest Revision: 20230102
    • Publication Date:
      20231215
    • Accession Number:
      PMC8752172
    • Accession Number:
      10.1007/s00125-021-05573-6
    • Accession Number:
      34642772