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. 2012 Dec;55(12):3359-68.
doi: 10.1007/s00125-012-2719-6. Epub 2012 Sep 20.

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

D Dabelea  1 , E J Mayer-Davis, J S Andrews, L M Dolan, C Pihoker, R F Hamman, C Greenbaum, S Marcovina, W Fujimoto, B Linder, G Imperatore, R D'Agostino Jr
Affiliations

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

D Dabelea et al. Diabetologia. 2012 Dec.

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), HbA(1c) 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.

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Conflict of interest statement

Duality of interest The authors declare that there is no duality of interest associated with this manuscript.

Figures

Fig. 1
Fig. 1
Estimated mean FCP levels and rate of monthly decline among youth with positive DA status at baseline; (a) age at diagnosis of diabetes <10; (b) age at diagnosis ≥10. Black symbols, HLA susceptible; grey symbols, HLA not susceptible; diamonds, NHW race/ethnicity; triangles, other race. Multivariate mixed model predicting log-transformed FCP over time based on diabetes duration, age at diagnosis of diabetes, sex, race/ethnicity, HLA risk group, baseline HbA1c, BMI z score, site and time-varying fasting glucose (FPG). Estimates and rate of decline (95% CIs) are shown for an average baseline HbA1c of 8% (63.93 mmol/mol), BMI z score of 0.6 and an average time-dependent FPG of 9.2 mmol/l. The data under the graph present the number of FCP data points available in various time intervals
Fig. 2
Fig. 2
Estimated mean FCP levels and rate of monthly decline among youth with negative DA status at baseline; (a) age at diagnosis of diabetes <10; (b) age at diagnosis ≥10. Black symbols, HLA susceptible; grey symbols, HLA not susceptible; diamonds, NHW race/ethnicity; triangles, other race. Multivariate mixed model predicting log-transformed FCP over time based on diabetes duration, age at diagnosis of diabetes, sex, race/ethnicity, HLA risk group, baseline HbA1c, BMI z score, site and time-dependent fasting glucose (FPG) levels. Estimates and rates of decline (95% CIs) are shown for an average baseline HbA1c of 7.5% (58.47 mmol/mol) and BMI z score of 1.3 and an average time-dependent FPG of 7.3 mmol/l. The data under the graph present the number of FCP data points available in various time intervals
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