Clinical implications of the glucokinase impaired function - GCK MODY today

Physiol Res. 2020 Dec 22;69(6):995-1011. doi: 10.33549/physiolres.934487. Epub 2020 Nov 2.


Heterozygous inactivating mutations of the glucokinase (GCK) gene are causing GCK-MODY, one of the most common forms of the Maturity Onset Diabetes of the Young (MODY). GCK-MODY is characterized by fasting hyperglycemia without apparent worsening with aging and low risk for chronic vascular complications. Despite the mild clinical course, GCK-MODY could be misdiagnosed as type 1 or type 2 diabetes. In the diagnostic process, the clinical suspicion is often based on the clinical diagnostic criteria for GCK-MODY and should be confirmed by DNA analysis. However, there are several issues in the clinical and also in genetic part that could complicate the diagnostic process. Most of the people with GCK-MODY do not require any pharmacotherapy. The exception are pregnant women with a fetus which did not inherit GCK mutation from the mother. Such a child has accelerated growth, and has increased risk for diabetic foetopathy. In this situation the mother should be treated with substitutional doses of insulin. Therefore, distinguishing GCK-MODY from gestational diabetes in pregnancy is very important. For this purpose, special clinical diagnostic criteria for clinical identification of GCK-MODY in pregnancy are used. This review updates information on GCK-MODY and discusses several currently not solved problems in the clinical diagnostic process, genetics, and treatment of this type of monogenic diabetes.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / enzymology*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Glucokinase / genetics*
  • Glucokinase / metabolism
  • Heterozygote
  • Humans
  • Hyperglycemia / enzymology*
  • Hyperglycemia / genetics
  • Hyperglycemia / pathology
  • Mutation*
  • Pregnancy


  • Glucokinase

Supplementary concepts

  • Maturity-Onset Diabetes of the Young, Type 2