14-fold increased prevalence of rare glucokinase gene variant carriers in unselected Danish patients with newly diagnosed type 2 diabetes

Anette P Gjesing; Line Engelbrechtsen; Anne Cathrine B Thuesen; Christian T Have; Mette Hollensted; Niels Grarup; Allan Linneberg; Jens Steen Nielsen; Lotte B Christensen; Reimar W Thomsen; Kristoffer E Johansson; Matteo Cagiada; Sarah Gersing; Rasmus Hartmann-Petersen; Kresten Lindorff-Larsen; Allan Vaag; Henrik T Sørensen; Ivan Brandslund; Henning Beck-Nielsen; Oluf Pedersen; Jørgen Rungby; Torben Hansen

doi:10.1016/j.diabres.2022.110159

14-fold increased prevalence of rare glucokinase gene variant carriers in unselected Danish patients with newly diagnosed type 2 diabetes

Anette P Gjesing^*
, Line Engelbrechtsen
, Anne Cathrine B Thuesen
, Christian T Have
, Mette Hollensted
, Niels Grarup
, Allan Linneberg
, Jens Steen Nielsen
, Lotte B Christensen
, Reimar W Thomsen
, Kristoffer E Johansson
, Matteo Cagiada
, Sarah Gersing
, Rasmus Hartmann-Petersen
, Kresten Lindorff-Larsen
, Allan Vaag
, Henrik T Sørensen
, Ivan Brandslund
, Henning Beck-Nielsen
, Oluf Pedersen

Jørgen Rungby, Torben Hansen^*

^*Corresponding author af dette arbejde

7 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Artikelnummer	110159
Tidsskrift	Diabetes Research and Clinical Practice
Vol/bind	194
ISSN	0168-8227
DOI	https://doi.org/10.1016/j.diabres.2022.110159
Status	Udgivet - 1 dec. 2022

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10.1016/j.diabres.2022.110159Licens: CC BY

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Gjesing, A. P., Engelbrechtsen, L., Cathrine B Thuesen, A., Have, C. T., Hollensted, M., Grarup, N., Linneberg, A., Steen Nielsen, J., Christensen, L. B., Thomsen, R. W., Johansson, K. E., Cagiada, M., Gersing, S., Hartmann-Petersen, R., Lindorff-Larsen, K., Vaag, A., Sørensen, H. T., Brandslund, I., Beck-Nielsen, H., ... Hansen, T. (2022). 14-fold increased prevalence of rare glucokinase gene variant carriers in unselected Danish patients with newly diagnosed type 2 diabetes. Diabetes Research and Clinical Practice, 194, Artikel 110159. https://doi.org/10.1016/j.diabres.2022.110159

14-fold increased prevalence of rare glucokinase gene variant carriers in unselected Danish patients with newly diagnosed type 2 diabetes. / Gjesing, Anette P; Engelbrechtsen, Line; Cathrine B Thuesen, Anne et al.
I: Diabetes Research and Clinical Practice, Bind 194, 110159, 01.12.2022.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Gjesing, AP, Engelbrechtsen, L, Cathrine B Thuesen, A, Have, CT, Hollensted, M, Grarup, N, Linneberg, A, Steen Nielsen, J, Christensen, LB, Thomsen, RW, Johansson, KE, Cagiada, M, Gersing, S, Hartmann-Petersen, R, Lindorff-Larsen, K, Vaag, A, Sørensen, HT, Brandslund, I, Beck-Nielsen, H, Pedersen, O , Rungby, J & Hansen, T 2022, '14-fold increased prevalence of rare glucokinase gene variant carriers in unselected Danish patients with newly diagnosed type 2 diabetes', Diabetes Research and Clinical Practice, bind 194, 110159. https://doi.org/10.1016/j.diabres.2022.110159

@article{4ac5d6051e384fcba8ad8445bedb5c94,

title = "14-fold increased prevalence of rare glucokinase gene variant carriers in unselected Danish patients with newly diagnosed type 2 diabetes",

abstract = "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.",

keywords = "Complications, Glucokinase, Macrovascular, Microvascular, MODY, Monogenic diabetes",

author = "Gjesing, \{Anette P\} and Line Engelbrechtsen and \{Cathrine B Thuesen\}, Anne and Have, \{Christian T\} and Mette Hollensted and Niels Grarup and Allan Linneberg and \{Steen Nielsen\}, Jens and Christensen, \{Lotte B\} and Thomsen, \{Reimar W\} and Johansson, \{Kristoffer E\} and Matteo Cagiada and Sarah Gersing and Rasmus Hartmann-Petersen and Kresten Lindorff-Larsen and Allan Vaag and S{\o}rensen, \{Henrik T\} and Ivan Brandslund and Henning Beck-Nielsen and Oluf Pedersen and J{\o}rgen Rungby and Torben Hansen",

note = "Copyright {\textcopyright} 2022. Published by Elsevier B.V.",

year = "2022",

month = dec,

day = "1",

doi = "10.1016/j.diabres.2022.110159",

language = "English",

volume = "194",

journal = "Diabetes Research and Clinical Practice",

issn = "0168-8227",

publisher = "Elsevier Ireland Ltd",

}

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

PY - 2022/12/1

Y1 - 2022/12/1

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

UR - https://www.scopus.com/pages/publications/85143917075

U2 - 10.1016/j.diabres.2022.110159

DO - 10.1016/j.diabres.2022.110159

M3 - Journal article

C2 - 36400171

SN - 0168-8227

VL - 194

JO - Diabetes Research and Clinical Practice

JF - Diabetes Research and Clinical Practice

M1 - 110159

ER -

14-fold increased prevalence of rare glucokinase gene variant carriers in unselected Danish patients with newly diagnosed type 2 diabetes

Abstract

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