Gene Corner

Mutations in one of the two copies of the GCK gene result in blood sugars that are mildly elevated above normal levels. These blood sugars are often in the range of “impaired glucose tolerance” or consistent with “mild” diabetes. GCK is a gene that codes for an enzyme, known as glucokinase, which helps the body produce insulin in response to increases in blood sugar.

GCK functions as the ‘glucose sensor’ of the beta cell. In the image below, it is seen as the first step linking an increase in blood glucose levels to the release of insulin. For people who have GCK-MODY, only one of their two GCK genes functions normally. The result is that their blood glucose level has to be higher for GCK to start the process of releasing insulin. This is one of the most common forms of MODY, it is estimated to affect about 1 in every 1000 people.

gene

Image source: Fajans SS, Bell GI, Polonsky KS. “Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young.” N Engl J Med. 2001 Sep 27;345(13):971-80.

Presentation:

People with GCK-MODY have stable, mild fasting hyperglycemia (~99-140 mg/dL) and hemoglobin A1c values that typically range from 5.6-7.6%. Often elevated blood sugars are picked up incidentally by health care providers during an exam for an unrelated reason such as a sports physical. GCK-MODY can also be picked up in pregnancy and mistaken for gestational diabetes.

Distinguishing GCK-MODY from Type 1 and Type 2 Diabetes can sometimes be difficult.

Features that make us suspect GCK-MODY include:

  • Persistent, fasting sugars of 100-140 mg/dL (5.6-7.5 mmol/L) for many years without worsening
  • 2 or 3 generations of diabetes in a family
  • Stable HbA1c that ranges between 5.6- 7.6%
  • Lack of obesity or signs of insulin resistant that would be expected in type 2 diabetes
  • Lack of beta-cell autoantibodies that would be expected in type 1 diabetes
  • Persistently detectable C-Peptide (meaning the body is making it’s own insulin)
  • No history of diabetic ketoacidosis

Treatment:

Treatment for GCK-MODY is rarely needed and a study of people with GCK-MODY showed that diabetes medications don’t alter the HbA1c.

However, women with GCK-MODY may require treatment when pregnant and decisions regarding treatment are based on whether the baby is likely to also have GCK-MODY. If you or a family member become pregnant and have GCK-MODY, please do not hesitate to contact us.

Inheritance:

Mutations can occur spontaneously but usually are passed on from a parent to a child. If a parent has GCK-MODY, there is a 50% chance that a child will inherit the mutation and also have GCK-MODY. Finding a GCK mutation in a patient’s family may reveal other family members who also have GCK-MODY.