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HDL cholesterol as a diagnostic tool for clinical differentiation of GCK ‐MODY from HNF1A ‐MODY and type 1 diabetes in children and young adults
Author(s) -
Fendler Wojciech,
Borowiec Maciej,
Antosik Karolina,
Szadkowska Agnieszka,
Deja Grazyna,
JaroszChobot Przemyslawa,
Mysliwiec Malgorzata,
Wyka Krystyna,
Pietrzak Iwona,
Skupien Jan,
Malecki Maciej T.,
Mlynarski Wojciech
Publication year - 2011
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2011.04052.x
Subject(s) - medicine , endocrinology , diabetes mellitus , hnf1a , triglyceride , cholesterol , glucokinase , type 2 diabetes
Summary Introduction 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 m m offered significantly better diagnostic efficiency than total cholesterol (cut‐off value 4·51 m m ; 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.