title: Low levels of C-peptide have clinical significance for established Type 1 diabetes.
abstract: OBJECTIVE
  To determine whether the low C-peptide levels (< 50 pmol/l) produced by the pancreas for decades after onset of Type 1 diabetes have clinical significance.
  
  
  METHODS
  We evaluated fasting C-peptide levels, duration of disease and age of onset in a large cross-sectional series (n = 1272) of people with Type 1 diabetes. We then expanded the scope of the study to include the relationship between C-peptide and HbA1c control (n = 1273), as well as diabetic complications (n = 324) and presence of hypoglycaemia (n = 323). The full range of C-peptide levels was also compared with 1,5-Anhydroglucitol, a glucose responsive marker.
  
  
  RESULTS
  C-peptide levels declined for decades after diagnosis, and the rate of decline was significantly related to age of onset (P < 0.0001), after adjusting for disease duration. C-peptide levels > 10 pmol/l were associated with protection from complications (e.g. nephropathy, neuropathy, foot ulcers and retinopathy; P = 0.03). Low C-peptide levels were associated with poor metabolic control measured by HbA1c (P < 0.0001). Severe hypoglycaemia was associated with the lowest C-peptide levels compared with mild (P = 0.049) or moderate (P = 0.04) hypoglycaemia. All levels of measurable C-peptide were responsive to acute fluctuations in blood glucose levels as assessed by 1,5-Anhydroglucitol (P < 0.0001).
  
  
  CONCLUSIONS
  Low C-peptide levels have clinical significance and appear helpful in characterizing groups at-risk for faster C-peptide decline, complications, poorer metabolic control and severe hypoglycaemia. Low C-peptide levels may be a biomarker for characterizing at-risk patients with Type 1 diabetes.
authors.affiliation: Immunobiology Laboratory, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Kuhtreiber
authors.affiliation: Immunobiology Laboratory, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
authors.forename: S L L
authors.initials: SL
authors.lastname: Washer
authors.forename: E
authors.initials: E
authors.lastname: Hsu
authors.affiliation: Immunobiology Laboratory, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Immunobiology Laboratory, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Reinhold
authors.affiliation: Immunobiology Laboratory, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Burger
authors.affiliation: Department of Biostatistics, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Immunobiology Laboratory, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Faustman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood*; D002648:Child; D003430:Cross-Sectional Studies; D003847:Deoxyglucose / Q000097:blood / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D003847:Deoxyglucose; D006442:Glycated Hemoglobin; C006584:1,5-anhydroglucitol