HDL cholesterol as a diagnostic tool for clinical differentiation of GCK-MODY from HNF1A-MODY and type 1 diabetes in children and young adults.

摘要

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 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.