McKeigue PM, Spiliopoulou A, McGurnaghan S, et al. - Via a cross-sectional study, researchers investigated the correlation of detectable C-peptide secretion in type 1 diabetes (T1D) to clinical characteristics and to the genetic architecture of diabetes. Prevalence of detectable C-peptide differed from 19% to 92% in those with onset prior to the age of 15 and duration > 15 years, as well as in those with onset following the age of 35 and duration < 5 years. In C-peptide levels, 29% of the variation was accounted for by correlation with male sex, late age at onset, and short duration. Adjusted for sex, age at onset and duration, the SNP heritability of residual C-peptide secretion was estimated at 26%. For T1D, the genotypic risk score was inversely related to detectable C-peptide secretion (ie, the most strongly correlated loci were the HLA and INS gene regions). A risk score for T1D on the basis of the HLA DR3 and DQ8-DR4 serotypes was strongly correlated with early age at onset, and inversely related to C-peptide persistence. For C-peptide—but not age at onset—there were strong relationships with risk scores for T1D and type 2 diabetes that was based on SNPs in the HLA region but not considered for by HLA serotype. Therefore, in people with clinically diagnosed T1D, the persistence of C-peptide secretion differs widely. C-peptide persistence is affected by variants in the HLA region that are distinctive from those deciding the risk of early-onset T1D. For diabetes, known risk loci account for only a small proportion of the genetic influences on C-peptide persistence.