title: High-sensitivity C-reactive protein does not improve the differential diagnosis of HNF1A-MODY and familial young-onset type 2 diabetes: A grey zone analysis.
abstract: OBJECTIVE
  Low plasma levels of high-sensitivity C-reactive protein (hs-CRP) have been suggested to differentiate hepatocyte nuclear factor 1 alpha-maturity-onset diabetes of the young (HNF1A-MODY) from type 2 diabetes (T2D). Yet, differential diagnosis of HNF1A-MODY and familial young-onset type 2 diabetes (F-YT2D) remains a difficult challenge. Thus, this study assessed the added value of hs-CRP to distinguish between the two conditions.
  
  
  METHODS
  This prospective multicentre study included 143 HNF1A-MODY patients, 310 patients with a clinical history suggestive of HNF1A-MODY, but not confirmed genetically (F-YT2D), and 215 patients with T2D. The ability of models, including clinical characteristics and hs-CRP to predict HNF1A-MODY was analyzed, using the area of the receiver operating characteristic (AUROC) curve, and a grey zone approach was used to evaluate these models in clinical practice.
  
  
  RESULTS
  Median hs-CRP values were lower in HNF1A-MODY (0.25mg/L) than in F-YT2D (1.14mg/L) and T2D (1.70mg/L) patients. Clinical parameters were sufficient to differentiate HNF1A-MODY from classical T2D (AUROC: 0.99). AUROC analyses to distinguish HNF1A-MODY from F-YT2D were 0.82 for clinical features and 0.87 after including hs-CRP. For the grey zone analysis, the lower boundary was set to miss<1.5% of true positives in non-tested subjects, while the upper boundary was set to perform 50% of genetic tests in individuals with no HNF1A mutation. On comparing HNF1A-MODY with F-YT2D, 65% of patients were classified in between these categories - in the zone of diagnostic uncertainty - even after adding hs-CRP to clinical parameters.
  
  
  CONCLUSIONS
  hs-CRP does not improve the differential diagnosis of HNF1A-MODY and F-YT2D.
authors.affiliation: Department of Genetics, AP-HP, Hôpital Pitié-Salpétrière, Université Pierre-et-Marie-Curie, 47-83, boulevard de l'Hôpital, 75013 Paris, France. Electronic address: christine.bellanne-chantelot@psl.aphp.fr.
authors.forename: C
authors.initials: C
authors.lastname: Bellanné-Chantelot
authors.affiliation: Unit of Biostatistics and Epidemiology, AP-HP, Hôtel Dieu; Unit Research APEMAC, EA 4360, Université Paris-Descartes, Sorbonne Paris Cité, Lorraine Université, 75004 Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Coste
authors.affiliation: Department of Diabetology, AP-HP, Hôpital Pitié-Salpétrière, Université Pierre-et-Marie-Curie, 75013 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Ciangura
authors.affiliation: Department of Medical Biochemistry, AP-HP, Hôpital Pitié-Salpétrière, 75013 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Fonfrède
authors.affiliation: Department of Genetics, AP-HP, Hôpital Pitié-Salpétrière, Université Pierre-et-Marie-Curie, 47-83, boulevard de l'Hôpital, 75013 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Saint-Martin
authors.affiliation: Department of Diabetology, AP-HP, Hôpital Lariboisière, 75010 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Bouché
authors.affiliation: Department of Endocrinology, CHU de Brest, 29609 Brest, France.
authors.forename: E
authors.initials: E
authors.lastname: Sonnet
authors.affiliation: Department of Nutrition, Metabolic diseases, Endocrinology, AP-HM, Hôpital de la Timone, Aix-Marseille Université, 13385 Marseille, France.
authors.forename: R
authors.initials: R
authors.lastname: Valéro
authors.affiliation: Department of Diabetology, AP-HP, Hôpital Cochin, Université Paris-Descartes, 75014 Paris, France.
authors.forename: D-J
authors.initials: DJ
authors.lastname: Lévy
authors.affiliation: Department of Diabetology, AP-HP, Hôpital Cochin, Université Paris-Descartes, 75014 Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Dubois-Laforgue
authors.affiliation: Department of Diabetology, AP-HP, Hôpital Cochin, Université Paris-Descartes, 75014 Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Timsit
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000032:analysis*; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000145:classification* / Q000175:diagnosis* / Q000453:epidemiology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D055815:Young Adult
chemical_list: D002097:C-Reactive Protein
keywords: C-reactive protein; Grey zone analysis; HNF1A; MODY; ROC analysis