417disorders have different etiology, treatment strategy, associated comorbidities,
and prognosis. The important differentiating features between the two disorders
are summarized in the table given below.Parameters MODY T2DM in young
Inheritance Monogenic
(autosomal dominant)PolygenicFamily history Present in ≥3 generation Present
Penetrance 80–95 % Variable (10–40 %)
Pathophysiology β-cell dysfunction Insulin resistance and β-cell
dysfunction
Phenotype Nonobese Commonly obese
Features of insulin
resistanceAbsent Commonly presentTreatment Sulfonylureas Metformin- Why does glucokinase gene mutation lead to MODY in some and neonatal dia-
betes in others?
Glucokinase is highly expressed in pancreatic β-cells and hepatocytes. It con-
verts glucose to glucose–6–phosphate by the transfer of phosphate from ATP,
the rate-limiting step in glucose metabolism. Therefore, glucokinase is a key
enzyme which regulates the rate of entry of glucose into the glycolytic pathway
and its subsequent metabolism in β-cell. Heterozygous mutations of glucoki-
nase gene result in partial deficiency of this enzyme and manifests as MODY 2,
whereas homozygous mutations of this gene result in permanent neonatal dia-
betes mellitus.- What are the characteristics of MODY 2?
In contrast to most other forms of MODY where onset of hyperglycemia occurs
during or after adolescence, MODY 2 is characterized by the presence of
hyperglycemia since birth. In addition, these individuals have mildly elevated
fasting plasma glucose and minimal rise in glucose after OGTT (∆ rise in glu-
cose <54 mg/dl). The most affected individuals are asymptomatic and are
detected during screening (e.g., during pregnancy). Microvascular complica-
tions are rare in individuals with MODY 2 and majority can be controlled on
diet alone.12 Diabetes in the Young