Article

Diabetologia

, Volume 55, Issue 12, pp 3359-3368

Clinical evolution of beta cell function in youth with diabetes: the SEARCH for Diabetes in Youth study

  • D. DabeleaAffiliated withDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Denver Email author 
  • , E. J. Mayer-DavisAffiliated withDepartments of Nutrition and Medicine, University of North Carolina
  • , J. S. AndrewsAffiliated withDepartment of Biostatistical Sciences, Wake Forest School of Medicine
  • , L. M. DolanAffiliated withDepartment of Pediatrics, Cincinnati Children’s Hospital, University of Cincinnati College of Medicine
  • , C. PihokerAffiliated withDepartment of Pediatrics, University of Washington
  • , R. F. HammanAffiliated withDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Denver
  • , C. GreenbaumAffiliated withDiabetes Research Program, Benaroya Research Institute
  • , S. MarcovinaAffiliated withDepartment of Medicine, University of Washington
  • , W. FujimotoAffiliated withKuakini Medical Center
    • , B. LinderAffiliated withNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
    • , G. ImperatoreAffiliated withDepartment of Epidemiology, Colorado School of Public Health, University of Colorado DenverDivision of Diabetes Translation, Centers for Diseases Control and Prevention
    • , R. D’AgostinoJrAffiliated withDepartment of Biostatistical Sciences, Wake Forest School of Medicine

Abstract

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.

Keywords

Beta cell function Decline Determinants Epidemiology Type 1 diabetes Type 2 diabetes Youth