TY - JOUR
T1 - 14-fold increased prevalence of rare glucokinase gene variant carriers in unselected Danish patients with newly diagnosed type 2 diabetes
AU - Gjesing, Anette P.
AU - Engelbrechtsen, Line
AU - Cathrine B. Thuesen, Anne
AU - Have, Christian T.
AU - Hollensted, Mette
AU - Grarup, Niels
AU - Linneberg, Allan
AU - Steen Nielsen, Jens
AU - Christensen, Lotte B.
AU - Thomsen, Reimar W.
AU - Johansson, Kristoffer E.
AU - Cagiada, Matteo
AU - Gersing, Sarah
AU - Hartmann-Petersen, Rasmus
AU - Lindorff-Larsen, Kresten
AU - Vaag, Allan
AU - Sørensen, Henrik T.
AU - Brandslund, Ivan
AU - Beck-Nielsen, Henning
AU - Pedersen, Oluf
AU - Rungby, Jørgen
AU - Hansen, Torben
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022
Y1 - 2022
N2 - Aims: Rare variants in the glucokinase gene (GCK) cause Maturity-Onset Diabetes of the Young (MODY2/GCK-MODY). We investigated the prevalence of GCK variants, phenotypic characteristics, micro- and macrovascular disease at baseline and follow-up, and treatment among individuals with and without pathogenic GCK variants. Methods: This is a cross-sectional study in a population-based cohort of 5,433 individuals without diabetes (Inter99 cohort) and in 2,855 patients with a new clinical diagnosis of type 2 diabetes (DD2 cohort) with sequencing of GCK. Phenotypic characteristics, presence of micro- and macrovascular disease and treatment information were available for patients in the DD2 cohort at baseline and after an average follow-up of 7.4 years. Results: Twenty-two carriers of potentially deleterious GCK variants were found among patients with type 2 diabetes compared to three among 5,433 nondiabetic individuals [OR = 14.1 (95 % CI 4.2; 47.0), p = 8.9*10-6]. Patients with type 2 diabetes carrying GCK variants had significantly lower waist circumference, hip circumference and BMI, compared to non-carriers. Three GCK variant carriers with diabetes had microvascular complications during follow-up. Conclusions: Approximately 0.8% of Danish patients with newly diagnosed type 2 diabetes carry non-synonymous variants in GCK and resemble patients with GCK-MODY. Glucose-lowering treatment cessation should be considered in this subset of diabetes patients.
AB - Aims: Rare variants in the glucokinase gene (GCK) cause Maturity-Onset Diabetes of the Young (MODY2/GCK-MODY). We investigated the prevalence of GCK variants, phenotypic characteristics, micro- and macrovascular disease at baseline and follow-up, and treatment among individuals with and without pathogenic GCK variants. Methods: This is a cross-sectional study in a population-based cohort of 5,433 individuals without diabetes (Inter99 cohort) and in 2,855 patients with a new clinical diagnosis of type 2 diabetes (DD2 cohort) with sequencing of GCK. Phenotypic characteristics, presence of micro- and macrovascular disease and treatment information were available for patients in the DD2 cohort at baseline and after an average follow-up of 7.4 years. Results: Twenty-two carriers of potentially deleterious GCK variants were found among patients with type 2 diabetes compared to three among 5,433 nondiabetic individuals [OR = 14.1 (95 % CI 4.2; 47.0), p = 8.9*10-6]. Patients with type 2 diabetes carrying GCK variants had significantly lower waist circumference, hip circumference and BMI, compared to non-carriers. Three GCK variant carriers with diabetes had microvascular complications during follow-up. Conclusions: Approximately 0.8% of Danish patients with newly diagnosed type 2 diabetes carry non-synonymous variants in GCK and resemble patients with GCK-MODY. Glucose-lowering treatment cessation should be considered in this subset of diabetes patients.
KW - Complications
KW - Glucokinase
KW - Macrovascular
KW - Microvascular
KW - MODY
KW - Monogenic diabetes
U2 - 10.1016/j.diabres.2022.110159
DO - 10.1016/j.diabres.2022.110159
M3 - Journal article
C2 - 36400171
AN - SCOPUS:85143917075
VL - 194
JO - Diabetes Research and Clinical Practice. Supplement
JF - Diabetes Research and Clinical Practice. Supplement
SN - 1572-1671
M1 - 110159
ER -