Many doctors and researchers believe that maturity-onset diabetes of the young, or MODY, is a subgroup of Type 2 diabetes (T2D) and that it is frequently misdiagnosed as such. Because many doctors are unaware of the differences, it is estimated that over 90% of MODY patients receive a false diagnosis of T2D. Mody accounts for one to two percent of all instances of diabetes. Given the similarities between MODY and T2D and the ongoing research into their differences, the terminology currently in use may be rather ambiguous. For instance, a variant of MODY can be caused by mutations or damage to at least six separate genes. Nevertheless, only three (MODY1, MODY2, and MODY3) are officially acknowledged as types of MODY (see below). Some do not acknowledge the others. Due to the diseases’ rarity, there are certain distinguishing features of MODY that can set it apart from other types of diabetes. However, these are not as frequently identified. Because different kinds of MODY respond better to different treatments, these distinctions can be significant.
The Fundamentals
MODY is a single-gene disorder that is monogenic in nature and can be inherited from one parent to another. There are currently six identified genes that can result in MODY when they are mutated or changed. The names of these genes are:
- The gene HNF4A (MODY1): Encodes the protein known as Hepatocyte Nuclear Factor-4 Alpha. This gene’s protein turns on and off other genes. Babies that carry this gene frequently have macrosomia at birth, meaning they weigh more than nine pounds. Early in childhood, they might also experience low blood sugar. Adults with diabetes may not exhibit symptoms until middle age or beyond, but they will still need to manage their blood sugar levels, either with insulin or with prescription drugs.
- Glucokinase (MODY2): Parts of the body’s glucose metabolism are carried out by glucokinase. Blood glucose (blood sugar) levels rise when the glucokinase gene is disrupted because insufficient glucokinase is produced. Due to its moderate nature, this type of MODY is frequently only identified during routine screening. On the other hand, during pregnancy, this type of MODY may be substantial. Insulin may be administered if this kind of diabetes is discovered during pregnancy, but not all doctors will write a prescription for it—many would rather advise “watchful waiting” and closer observation of both the mother and the fetus.
- The gene HFN1A (MODY3): Encodes the protein known as Hepatic Nuclear Factor 1 Alpha. The quantity of insulin the pancreas produces is reduced by mutations in this gene. Approximately 70% of all MODY instances are caused by mutations in this gene, making it the most prevalent cause of MODY3.
- IPF1 (MODY4): The gene known as PDX-1, or insulin promotor factor 1, is involved in the formation and proliferation of pancreatic beta cells. It also has a role in promoting the activation of the insulin-coding gene.
- The gene HFN1B (MODY5): Is responsible for producing the protein Hepatocyte Nuclear Factor-1 Beta. This gene’s mutations result in a kind of MODY that is linked to kidney cyst development and diabetes. People who have a mutation in the HFN1B gene are frequently diagnosed with kidney cyst formation, genital tract anatomic deformities, and elevated blood uric acid levels, which can induce gout in even very young children, rather than diabetic symptoms. Diabetes or MODY is frequently diagnosed later.
- The gene NEUROD1 (MODY6): Codes for the protein Neurogenic Differentiation 1, which facilitates the synthesis of proteins from other genes. Insulin production is decreased when NEUROD1 is disrupted because it controls the expression of the insulin gene.
- Although several different genes have been proposed as the etiology of MODY, opinions on these genes are divided.
T2D and T1D are not the same as MODY. Some of the more notable variations are listed in the following table.
| MODY | Type 2 Diabetes | Type 1 Diabetes | |
| Number of genes involved | 1 | Many | Multiple HLA genes and others |
| Age when symptoms first appear | Usually younger than 25 years of age | Usually older than 40 years of age | Usually younger than 8-12 years of age |
| Can it be inherited | Yes—MODY can be passed on to children. One of the key features of MODY is a parent and a grandparent with diabetes | Not completely– the risk of T2D is passed on to children. Also dependent on environmental factors. | Not completely—the risk of T1D is passed on to children. Also dependent on environmental factors. |
| Obese vs. Non-obese | Non-obese | Obese | Often non-obese |
| Associated with Metabolic Syndrome (Diabetes + high blood pressure+ high blood lipids (triglycerides)) | No | Yes | Greater risk of other autoimmune diseases (eg. thyroid disease, Celiac disease) |
Identification of the MODY Types
Genetic testing is typically required for the diagnosis of MODY. This often entails a blood test, and the turnaround time for the results is four to eight weeks. Sometimes, the period of time can be substantially shorter. A mouth swab may be obtained less frequently for genetic testing. Otherwise, normal screening for blood sugar levels is typically how MODY is found.
MODY symptoms
A lot of the time, MODY symptoms are rather moderate. As previously shown, regular testing frequently reveals MODY. When it comes to symptoms, increased thirst and urination, inexplicable weight gain, sluggish healing, and recurrent infections are all hallmarks of MODY, but they may be subtle enough to be missed.
Handling of the MODY Forms
HNF4A (MODY1): Usually reacts favorably to sulfonylurea-containing oral medications. Medications like glipizide (Glucotrol®), glimepiride (Amaryl®), and glyburide (Micronase®, Diabeta®, Glynase®) are examples of sulphonylureas. The earliest class of diabetic drugs, known as sulfonylureas, work by encouraging the pancreas to generate more insulin. While taking these drugs can postpone the need for insulin injections, full control may occasionally require insulin injections as well.
Glucokinase (MODY2): This type of diabetes is less severe and is typically not treated with insulin or medicine, with the exception of pregnancy, when closer observation is usually required. Patients with MODY2 can frequently lead very healthy lives by controlling their diets and exercising.
HFN1A (MODY3): Patients with this kind of MODY react favorably to sulphonylurea therapy, a class of diabetic medication. Insulin injections may not be necessary as long as these drugs are taken as prescribed.
IPF1 (MODY4): Sulfonylureas are often well-tolerated by MODY4 patients.
MODY5 and MODY6: insulin treatment is frequently required, even for the less prevalent types of MODY, and may even be necessary shortly after diagnosis. Kidney cysts and other conditions need to be treated in MODY5.
Controlling blood sugar is crucial since all forms of MODY, with the exception of MODY 2, have the same risks of consequences (nerve damage, eye involvement, heart disease, kidney disease, etc.) as T1D and T2D.