MODY, a type of diabetes that is easily overlooked

It is not the well-known type 1 or type 2 diabetes, nor is it related to gestational diabetes. About 8 million people in my country suffer from this type of diabetes, 80% of which are misdiagnosed as type 1 or type 2 diabetes, and 70% The patient has not received correct and effective treatment. It is a niche type of diabetes-juvenile-onset adult diabetes (also called MODY).

MODY is an inherited disease, which is inherited in an autosomal dominant manner and belongs to the category of single-gene inherited diseases. The age of onset is usually relatively early, and children or adolescents have the onset of the disease. The patients are generally younger than 25 years old, and the disease is relatively mild, usually lacking autoantibodies, and belongs to non-insulin-dependent diabetes. There are currently 14 known MODY subtypes, and different MODY subtypes have different clinical manifestations. The most common clinically in my country are MODY2 and 3.

It is currently believed that MODY is the most common form of monogenic diabetes, accounting for 2% to 5% of diabetes. This ratio is actually not low, but there are not many clinical diagnoses. Most of them are misdiagnosed as type 1 or type 2 diabetes and use insulin treatment. Considering that diabetes is basically regarded as a lifelong disease, which means that insulin may need to be used for life, which will cause a lot of inconvenience and pressure to patients. In fact, the treatment of MODY is relatively simple. Some of them can be treated with diet control or sulfonylureas to control blood sugar well. Therefore, if the diabetes mellitus can be diagnosed as MODY in the early stage, it may not require insulin or lifelong insulin therapy (maybe some patients with the prolonged course of the disease, the pancreatic islet cell function declines, and the later period still needs insulin therapy), then it will be given to the patient To reduce a lot of inconvenience and burden, this is the greatest significance of its diagnosis.

So, which diabetics need to be screened for MODY? The author recommends screening mainly for juvenile diabetic patients. If the age of onset is relatively young, blood sugar is slightly to moderately elevated, glycosylated hemoglobin <7.5%; or there are diabetic patients in two consecutive generations; or GAD antibody (GADA), insulinoma antigen 2A (IA-2A), zinc transporter 8A (ZnT8A) and insulin autoantibodies (IAA) are negative, you need to consider this disease and perform genetic testing.

Sweden has done a related survey to screen patients who were diagnosed with diabetes for the first time, patients aged 1 to 18 years old, and meet the above criteria, the results showed that MODY accounted for 1% to 4% of childhood diabetes. For patients with positive autoantibodies (at least one of the four autoantibodies is positive), genetic examination did not find that they carried the MODY gene. They also performed genetic tests on autoantibody-negative patients. 15% of patients were eventually diagnosed as MODY, with a prevalence of 1.2%. Some antibody-negative patients were diagnosed with type 1 diabetes, type 2 diabetes, or other types of diabetes, such as pancreas. Diabetes associated with cystic fibrosis. It can be seen that the examination of autoantibodies is very important.

In short, if you are a diabetic patient with an early onset, a clear family history, a normal weight, a negative islet autoantibody, and a glycosylated hemoglobin >Link
Monogenic diabetes

In 1999, the World Health Organization (WHO) released the etiological classification of diabetes. Among them, special types of diabetes include 8 subtypes such as pancreatic β-cell functional gene defects and genetic abnormalities in insulin action. As people’s understanding of diabetes is getting deeper and deeper, in 2019, the WHO classified the two subtypes of diabetes, which are gene defects in pancreatic β-cell function and genetic abnormalities in insulin action, as monogenic diabetes. Since then, monogenic diabetes has been officially named, referring to a heterogeneous disease caused by a single gene mutation that plays a key role in the development, function, or insulin signaling pathway of β cells. It mainly includes the following four types: juvenile-onset adult-onset diabetes (MODY); neonatal diabetes (NDM); diabetes-related genetic syndromes; and single-gene insulin resistance syndrome.