Different types of MODY
Type 3 diabetes mellitus includes, for example, genetic disorders and endocrinological diseases associated with diabetes. Some of the most important genetic diabetes disorders are monogenic, non-immunologically caused forms of diabetes mellitus. Up to 2% of patients with diabetes have such a MODY (Maturity Onset Diabetes of the Young). A monogenic disorder is caused by a defect in a single gene (mono-gene). It is estimated that more than 80% remain undetected and are incorrectly classified as type 1 or type 2 diabetes. More than 13 different types of MODY are known. Here, only the most common MODY types will be discussed: MODY 1–3.

Most common: MODY 3
MODY 3 is the most common form of monogenic diabetes, accounting for 60% of cases. In MODY 3, the gene for the transcription factor HNF1A is affected. Transcription refers to the production of RNA from a DNA template. DNA is a chain of building blocks (nucleic acids) that contains the genetic information in all living organisms. RNA is a copy of the DNA template that translates the genetic information into the production of proteins. Transcription factors are proteins that influence RNA formation. The transcription factor HNF1A is involved in glucose metabolism and in the production of glucose transporters GLUT 1 and GLUT 2, which transport glucose across the cell membrane.

Mutations (changes in genetic material) in this gene cause a mild increase in blood glucose levels and a pronounced rise in glucose during the oral glucose tolerance test, which is used to diagnose diabetes mellitus. Patients often also have very low CRP levels and elevated HDL levels. For most patients, dietary modification is sufficient. Some can achieve good blood glucose control for years with sulfonylureas. In a few cases, insulin therapy is required.

Second most common: MODY 2
The second most common form is MODY 2, accounting for 20% of cases. The glucokinase gene is affected. Glucokinase is an enzyme (a catalyst that accelerates chemical reactions) that attaches a phosphate group to the sixth carbon of the glucose molecule, forming glucose-6-phosphate. In the pancreas, there is a blood glucose sensing system in which glucokinase plays a crucial role.

A defect in this gene leads to mildly elevated fasting blood glucose levels and slightly elevated HbA1c levels. To diagnose gestational diabetes, an oral glucose tolerance test is often performed. A moderate, slightly excessive rise in glucose in this test is often misinterpreted as gestational diabetes, but in up to 5% of such cases, it is actually MODY 2. In most cases, dietary modification alone is sufficient for treatment.

Less common: MODY 1
MODY 1 accounts for 5–10% of monogenic diabetes cases. The gene for the transcription factor HNF4A is affected. In children, the defect in this transcription factor gene does not yet manifest. Mutations in this gene lead to a gradual decline in insulin production in young adults. Patients also have elevated LDL cholesterol, low lipoprotein(a) levels, and low HDL cholesterol.

Patients can be treated for years with sulfonylureas or other oral antidiabetic drugs. In advanced stages, insulin therapy becomes necessary.