title: HDL cholesterol as a diagnostic tool for clinical differentiation of GCK-MODY from HNF1A-MODY and type 1 diabetes in children and young adults.
abstract: BACKGROUND
  Confirmation of monogenic diabetes caused by glucokinase mutations (GCK-MODY) allows pharmacogenetic intervention in the form of insulin discontinuation. This is especially important among paediatric and young adult populations where GCK-MODY is most prevalent.
  
  
  METHODS
  The study evaluated the utility of lipid parameters in screening for patients with GCK-MODY. Eighty-nine children with type 1 diabetes and 68 with GCK-MODY were screened for triglyceride (TG), total and HDL cholesterol levels. Standardization against a control group of 171 healthy children was applied to eliminate the effect of development. Clinical applicability and cut-off value were evaluated in all available patients with GCK-MODY (n = 148), hepatocyte nuclear factor 1-alpha-MODY (HNF1A MODY) (n = 37) or type 1 diabetes (n = 221).
  
  
  RESULTS
  Lower lipid parameter values were observed in GCK-MODY than in patients with type 1 diabetes. Standard deviation scores were -0·22 ± 2·24 vs 1·31 ± 2·17 for HDL cholesterol (P < 0·001), -0·16 ± 2·14 vs 0·60 ± 1·77 for total cholesterol (P = 0·03) and -0·57 ± 0·97 vs-0·22 ± 0·97 for TG (P = 0·05). Validation analysis confirmed that HDL cholesterol was the best parameter for GCK-MODY selection [sensitivity 87%, specificity 54%, negative predictive value (NPV) 86%, positive PV 56%]. A threshold HDL concentration of 1·56 mm offered significantly better diagnostic efficiency than total cholesterol (cut-off value 4·51 mm; NPV 80%; PPV 38%; P < 0·001). TG did not offer a meaningful cut-off value.
  
  
  CONCLUSIONS
  HDL cholesterol levels measured in individuals with likely monogenic diabetes may be useful in screening for GCK-MODY and differentiation from T1DM and HNF1A-MODY, regardless of treatment or metabolic control.
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Fendler
authors.forename: Maciej
authors.initials: M
authors.lastname: Borowiec
authors.forename: Karolina
authors.initials: K
authors.lastname: Antosik
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szadkowska
authors.forename: Grazyna
authors.initials: G
authors.lastname: Deja
authors.forename: Przemyslawa
authors.initials: P
authors.lastname: Jarosz-Chobot
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Mysliwiec
authors.forename: Krystyna
authors.initials: K
authors.lastname: Wyka
authors.forename: Iwona
authors.initials: I
authors.lastname: Pietrzak
authors.forename: Jan
authors.initials: J
authors.lastname: Skupien
authors.forename: Maciej T
authors.initials: MT
authors.lastname: Malecki
authors.forename: Wojciech
authors.initials: W
authors.lastname: Mlynarski
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D004252:DNA Mutational Analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D005941:Glucokinase / Q000235:genetics*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D009154:Mutation; D011237:Predictive Value of Tests; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D008076:Cholesterol, HDL; D051538:Hepatocyte Nuclear Factor 1-alpha; D014280:Triglycerides; D002784:Cholesterol; D005941:Glucokinase