MODY2

MODY2, also known as GCK-MODY, is a form of monogenic diabetes caused by heterozygous mutations in the glucokinase gene (GCK). It is inherited in an autosomal dominant pattern and is one of the more common forms of maturity-onset diabetes of the young. The condition is typically characterized by mild, persistent hyperglycemia from birth.

Glucokinase acts as a glucose sensor in pancreatic beta cells and liver. When GCK is mutated, the threshold for insulin secretion is raised, leading to fasting hyperglycemia that is usually stable over time. Individuals with MODY2 generally have preserved pancreatic beta-cell function, normal body weight, and lack autoimmune markers, distinguishing it from type 1 and from many cases of type 2 diabetes. A strong multi-generational family history of mild hyperglycemia is common.

Clinical presentation and diagnosis: many people with MODY2 are asymptomatic and discovered through routine screening or family history. Diagnosis is confirmed by genetic testing identifying a pathogenic GCK mutation. HbA1c values tend to be mildly elevated, and fasting glucose tends to be consistently above the normal range without the marked fluctuations seen in other forms of diabetes.

Management and prognosis: most individuals with MODY2 do not require pharmacologic glucose-lowering therapy. Management focuses on routine monitoring and lifestyle measures. Pregnancy requires special consideration, as fetal genotype can influence management decisions and fetal growth; care is typically provided by specialists. Overall, MODY2 has a favorable prognosis with a normal or near-normal life expectancy and no inherent increase in microvascular complications beyond what mild hyperglycemia would predict.