Residual β cell function in long-term type 1 diabetes associates with reduced incidence of hypoglycemia

BACKGROUND: We investigated residual β cell function in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study participants with an average 35-year duration of type 1 diabetes mellitus (T1DM). METHODS: Serum C-peptide was measured during a 4-hour mixed-meal tolerance test. Associations with metabolic outcomes and complications were explored among non-responders (all C-peptide values after meal0.2), intermediate (\u3e0.03 to ≤0.2), and low (≥ 0.003 to ≤0.03). RESULTS: Of the 944 participants, 117 (12.4%) were classified as responders. Residual C-peptide concentrations were associated with higher DCCT baseline concentrations of stimulated C-peptide (P value for trend = 0.0001). Residual C-peptide secretion was not associated with current or mean HbA1c, HLA high-risk haplotypes for T1DM, or the current presence of T1DM autoantibodies. The proportion of subjects with a history of severe hypoglycemia was lower with high (27%) and intermediate (48%) residual C-peptide concentrations than with low (74%) and no (70%) residual C-peptide concentrations (P value for trend = 0.0001). Responders and non-responders demonstrated similar rates of advanced microvascular complications. CONCLUSION: β Cell function can persist in long-duration T1DM. With a peak C-peptide concentration of \u3e0.03 nmol/L, we observed clinically meaningful reductions in the prevalence of severe hypoglycemia. TRIAL REGISTRATION: ClinicalTrials.gov NCT00360815 and NCT00360893. FUNDING: Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (DP3-DK104438, U01 DK094176, and U01 DK094157)