title: Urinary C-peptide creatinine ratio is a practical outpatient tool for identifying hepatocyte nuclear factor 1-{alpha}/hepatocyte nuclear factor 4-{alpha} maturity-onset diabetes of the young from long-duration type 1 diabetes.
abstract: OBJECTIVE
  Hepatocyte nuclear factor 1-α (HNF1A)/hepatocyte nuclear factor 4-α (HNF4A) maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 diabetes, and patients are inappropriately treated with insulin. Blood C-peptide can aid in the diagnosis of MODY, but practical reasons limit its widespread use. Urinary C-peptide creatinine ratio (UCPCR), a stable measure of endogenous insulin secretion, is a noninvasive alternative. We aimed to compare stimulated UCPCR in adults with HNF1A/4A MODY, type 1 diabetes, and type 2 diabetes.
  
  
  METHODS
  Adults with diabetes for ≥ 5 years, without renal impairment, were studied (HNF1A MODY [n = 54], HNF4A MODY [n = 23], glucokinase MODY [n = 20], type 1 diabetes [n = 69], and type 2 diabetes [n = 54]). The UCPCR was collected in boric acid 120 min after the largest meal of the day and mailed for analysis. Receiver operating characteristic (ROC) curves were used to identify optimal UCPCR cutoffs to differentiate HNF1A/4A MODY from type 1 and type 2 diabetes.
  
  
  RESULTS
  UCPCR was lower in type 1 diabetes than HNF1A/4A MODY (median [interquartile range]) (<0.02 nmol/mmol [<0.02 to <0.02] vs. 1.72 nmol/mmol [0.98-2.90]; P < 0.0001). ROC curves showed excellent discrimination (area under curve [AUC] 0.98) and identified a cutoff UCPCR of ≥ 0.2 nmol/mmol for differentiating HNF1A/4A MODY from type 1 diabetes (97% sensitivity, 96% specificity). UCPCR was lower in HNF1A/4A MODY than in type 2 diabetes (1.72 nmol/mmol [0.98-2.90] vs. 2.47 nmol/mmol [1.4-4.13]); P = 0.007). ROC curves showed a weak distinction between HNF1A/4A MODY and type 2 diabetes (AUC 0.64).
  
  
  CONCLUSIONS
  UCPCR is a noninvasive outpatient tool that can be used to discriminate HNF1A and HNF4A MODY from long-duration type 1 diabetes. To differentiate MODY from type 1 diabetes of >5 years' duration, UCPCR could be used to determine whether genetic testing is indicated.
authors.affiliation: Peninsula National Institute for Health Research Clinical Research Facility, Peninsula Medical School, University of Exeter, Exeter, UK.
authors.forename: Rachel E J
authors.initials: RE
authors.lastname: Besser
authors.forename: Maggie H
authors.initials: MH
authors.lastname: Shepherd
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: McDonald
authors.forename: Beverley M
authors.initials: BM
authors.lastname: Shields
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Knight
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D002096:C-Peptide / Q000652:urine*; D003404:Creatinine / Q000652:urine*; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000378:metabolism*; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D002096:C-Peptide; C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D007328:Insulin; D003404:Creatinine