Family history of diabetes, autoimmunity, and risk factors for cardiovascular disease among children with diabetes in the SEARCH for Diabetes in Youth Study

Abstract

While type 1 diabetes and type 2 diabetes (T2D) are considered etiologically distinct, mixed features of autoimmunity and insulin resistance are increasingly common. We explored a familial contribution to this admixture by evaluating diabetes family history (FH) and its relationship to diabetes type, ethnicity, age at diagnosis, and cardiovascular risk factors in SEARCH for Diabetes in Youth Study participants. Diabetes FH was assessed by questionnaire, with FH categories defined by relative's(s') age at diagnosis as follows: <25 (early FH), >/=25 (later FH), and both <25 and >/=25 (mixed FH). Diabetes type was classified based on a biochemical algorithm using diabetes autoantibodies and fasting C-peptide (FCP). A positive FH was common in all diabetes types, particularly T2D (83%). Minorities were more likely to have a positive FH than non-Hispanic Whites [odds ratio (OR) 1.96, 95% confidence interval (CI) 1.69-2.27]. The likelihood of having an early FH decreased with age at diagnosis (OR 0.95, 95% CI 0.93-0.98), and the likelihood of having a later/mixed or any positive FH increased with age (OR 1.03, 95% CI 1.01-1.04; OR 1.03, 95% CI 1.02-1.05, respectively). Higher FCP concentrations and less desirable values for almost all cardiovascular risk factors were associated with a later/mixed FH. The association between a later/mixed FH and FCP, body mass index, waist circumference, triglycerides, and high-density lipoprotein remained significant in a subgroup of autoimmune participants. Later FH confers cardiovascular risk factors in diabetic youth, including those youth with islet cell autoimmunity. This characterization of diabetes FH may provide a better understanding of familial contributors to diabetes.