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Clinical evolution of beta cell function in youth with diabetes: the SEARCH for Diabetes in Youth study
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Details:
  • Pubmed ID:
    22990715
  • Pubmed Central ID:
    PMC4492685
  • Description:
    Aims/hypothesis

    Few studies have explored the epidemiology of beta cell loss in youth with diabetes. This report describes the evolution and major determinants of beta cell function, assessed by fasting C-peptide (FCP), in the SEARCH for Diabetes in Youth study.

    Methods

    Participants were 1,277 youth with diabetes (948 positive for diabetes autoantibodies [DAs] and 329 negative for DAs), diagnosed when aged <20 years, who were followed from a median of 8 months post diagnosis, for approximately 30 months. We modelled the relationship between rate of change in log FCP and determinants of interest using repeated measures general linear models.

    Results

    Among DA-positive youth, there was a progressive decline in beta cell function of 4% per month, independent of demographics (age, sex, race/ethnicity), genetic susceptibility to autoimmunity (HLA risk), HbA1c and BMI z score, or presence of insulin resistance. Among DA-negative youth, there was marked heterogeneity in beta cell loss, reflecting an aetiologically mixed group. This group likely includes youths with undetected autoimmunity (whose decline is similar to that of DA-positive youth) and youth with non-autoimmune, insulin-resistant diabetes, with limited decline (~0.7% per month).

    Conclusions/interpretation

    SEARCH provides unique estimates of beta cell function decline in a large sample of youth with diabetes, indicating that autoimmunity is the major contributor. These data contribute to a better understanding of clinical evolution of beta cell function in youth with diabetes, provide strong support for the aetiological classification of diabetes type and may inform tertiary prevention efforts targeted at high-risk groups.

  • Document Type:
  • Collection(s):
  • Funding:
    1U18DP002709/DP/NCCDPHP CDC HHS/United States
    1UL1RR026314-01)./RR/NCRR NIH HHS/United States
    M01 RR00069/RR/NCRR NIH HHS/United States
    M01RR00037/RR/NCRR NIH HHS/United States
    NIH P30 DK57516/DK/NIDDK NIH HHS/United States
    U01 DP000244/DP/NCCDPHP CDC HHS/United States
    U01 DP000245/DP/NCCDPHP CDC HHS/United States
    U01 DP000246/DP/NCCDPHP CDC HHS/United States
    U01 DP000247/DP/NCCDPHP CDC HHS/United States
    U01 DP000248/DP/NCCDPHP CDC HHS/United States
    U01 DP000250/DP/NCCDPHP CDC HHS/United States
    U01 DP000254/DP/NCCDPHP CDC HHS/United States
    U18 DP003256/DP/NCCDPHP CDC HHS/United States
    U18DP000247-06A1/DP/NCCDPHP CDC HHS/United States
    U18DP002708-01/DP/NCCDPHP CDC HHS/United States
    U18DP002710-01/DP/NCCDPHP CDC HHS/United States
    U18DP002714/DP/NCCDPHP CDC HHS/United States
    U48/CCU419249/PHS HHS/United States
    U48/CCU519239/PHS HHS/United States
    U48/CCU819241-3/PHS HHS/United States
    U48/CCU919219/PHS HHS/United States
    U58/CCU019235-4/PHS HHS/United States
    U58CCU919256/PHS HHS/United States
    UL1 RR029882/RR/NCRR NIH HHS/United States
    UL1 TR000077/TR/NCATS NIH HHS/United States
    UL1RR029882/RR/NCRR NIH HHS/United States
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