title: Most people with long-duration type 1 diabetes in a large population-based study are insulin microsecretors.
abstract: OBJECTIVE
  Small studies using ultrasensitive C-peptide assays suggest endogenous insulin secretion is frequently detectable in patients with long-standing type 1 diabetes (T1D), but these studies do not use representative samples. We aimed to use the stimulated urine C-peptide-to-creatinine ratio (UCPCR) to assess C-peptide levels in a large cross-sectional, population-based study of patients with T1D.
  
  
  METHODS
  We recruited 924 patients from primary and secondary care in two U.K. centers who had a clinical diagnosis of T1D, were under 30 years of age when they received a diagnosis, and had a diabetes duration of >5 years. The median age at diagnosis was 11 years (interquartile range 6-17 years), and the duration of diabetes was 19 years (11-27 years). All provided a home postmeal UCPCR, which was measured using a Roche electrochemiluminescence assay.
  
  
  RESULTS
  Eighty percent of patients (740 of 924 patients) had detectable endogenous C-peptide levels (UCPCR >0.001 nmol/mmol). Most patients (52%, 483 of 924 patients) had historically very low undetectable levels (UCPCR 0.0013-0.03 nmol/mmol); 8% of patients (70 of 924 patients) had a UCPCR ≥0.2 nmol/mmol, equivalent to serum levels associated with reduced complications and hypoglycemia. Absolute UCPCR levels fell with duration of disease. Age at diagnosis and duration of disease were independent predictors of C-peptide level in multivariate modeling.
  
  
  CONCLUSIONS
  This population-based study shows that the majority of long-duration T1D patients have detectable urine C-peptide levels. While the majority of patients are insulin microsecretors, some maintain clinically relevant endogenous insulin secretion for many years after the diagnosis of diabetes. Understanding this may lead to a better understanding of pathogenesis in T1D and open new possibilities for treatment.
authors.affiliation: National Institute for Health Research, Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, U.K.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Oram
authors.affiliation: National Institute for Health Research, Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, U.K. Department of Blood Sciences, Royal Devon and Exeter NHS Foundation Trust, Exeter, U.K.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: McDonald
authors.affiliation: National Institute for Health Research, Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, U.K.
authors.forename: Beverley M
authors.initials: BM
authors.lastname: Shields
authors.affiliation: National Institute for Health Research, Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, U.K.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Hudson
authors.affiliation: National Institute for Health Research, Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, U.K.
authors.forename: Maggie H
authors.initials: MH
authors.lastname: Shepherd
authors.affiliation: National Institute for Health Research, Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, U.K.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hammersley
authors.affiliation: Division of Cardiovascular and Diabetes Medicine, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, U.K.
authors.forename: Ewan R
authors.initials: ER
authors.lastname: Pearson
authors.affiliation: National Institute for Health Research, Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, U.K. a.t.hattersley@exeter.ac.uk.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
mesh_terms: D000328:Adult; D002096:C-Peptide / Q000378:metabolism; D002648:Child; D003404:Creatinine / Q000652:urine; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D019518:Postprandial Period / Q000502:physiology; D013997:Time Factors; D055815:Young Adult
chemical_list: D002096:C-Peptide; D007328:Insulin; D003404:Creatinine