Ever wondered about the possibility that if you are diabetic you don’t need to be similar to other diabetic patients? Yes, if your body is unable to utilize glucose in the body there are chances that you are suffering from type 1 or type 2 diabetes.
But that’s not all. There also exists a possibility that you are suffering from genetic type diabetes. This genetic type is usually known as mature onset diabetes of youth that also passes on from generation to generation as an autosomal dominant disorder. You will be learning more about them in this article.
What are the types of MODY and how do they occur?
MODY is a disorder that occurs due to mutation in any particular gene in your body. You should know that as of today 14 types of MODY are detected worldwide.
Why is it important to differentiate MODY types? Can you think of any possible reason?
This is because the types differ in terms of age of onset, clinical course and its progression, hyperglycemia type, and response towards treatment options.
The major 6 types of MODY are as follows:
1. GCK MODY (Type 2)
As the name suggests, GCK gene mutation is responsible for this type. GCK is the gene that is responsible for glucose conversion to glucose-6- phosphate which you know is responsible for controlling glucose-mediated insulin secretion and can lead to either hyperglycemia or hypoglycemia.
This is the type which becomes more severe with age and the symptoms you can experience can vary. In the majority, it is found to be asymptomatic and is found in gestational diabetes during pregnancy and the weight of the baby depends on whether the mutation is seen in the mother or baby.
There can be two cases as follows:
a. When both mother and fetus have GCK mutations
In this case, during the increase in blood glucose levels if the mother will increase the insulin secretion in the fetus. This will normalize the glucose levels of the baby. Hence, the baby would be of normal weight.
b. When only the mother is having GCK mutation
If only the mother is having a mutation in GCK. There is an increase in blood glucose levels in the mother’s blood only and not in the fetus so the increased secretion of insulin in the mother due to high glucose levels will lead to an increase in baby weight which would be 500 grams more than the normal body weight.
2. HNF-1 α-MODY (Type-3 MODY)
You should be aware that this factor is expressed in the liver, kidney, intestine, and pancreatic β cells hence the removal of this gene from the human DNA can give rise to defective glucose-induced insulin secretion leading to diabetes. Heterozygous mutation of this gene in your body leads to the formation of defective glucose that is why there is progressive insulin deficiency leading to mild hyperglycemia in childhood and diabetes in adults. If you have hyperglycemia, it is progressive and deteriorating in microvascular and macrovascular complications that are similar to those in Type-1 and Type-2 diabetes.
HNF-1α mutation in your body can lead to postprandial glycosuria that means you are going to excrete an excess of glucose in urine due to renal dysfunction and a low threshold for glucose absorption. This mutation does not have any influence on the fetus as insulin secretion is normal in the baby.
3. HNF-4 α MODY (Type-1 MODY)
This gene HNF-4 α is expressed in your liver, pancreas, and kidney and regulates the genes for glucose transport and metabolism. Heterozygous mutation in this gene leads to macrosomia in the fetus leading to a larger and heavier size of the baby in pregnant women due to high levels of insulin in the blood but cells of the body are not sensitive to this high insulin in your blood.
4. HNF-1 β MODY (TYPE-5)
The transcription factor responsible for the organogenesis of the kidney, genitourinary tract, liver, lungs, gut, and pancreas in your body is HNF 1β. This mutation can lead to various problems in your body other than hyperglycemia like you can suffer from renal dysplasia, renal cysts, and renal malformations.
Renal dysfunction in your body would appear before you reach 45 years of age. You would be able to understand the reverse that in this type of MODY the birth weight of the fetus decreases due to lower insulin levels in the fetus body.
To be more specific MODY-5 is responsible for dyslipidemia, low LDL, high levels of HDL so if you are having this mutation in your body, you might have these additional problems.
5. PDX-1 MODY (Type-4)
If you have this homeodomain-containing transcription factor you can have both homozygous and heterozygous mutation.
If you are having the homozygous mutation, you can have pancreas agenesis, hypoplasia, and permanent neonatal diabetes while if you have heterozygous mutation you can suffer from a beta-cell impairment, hyperglycemia, and permanent neonatal diabetes mellitus.
6. NEUROD1-MODY (MODY-6)
This gene in your body is a basic loop helix transcription factor and is responsible for neuronal and pancreatic development in your body. If you lack this gene, you can have a poor response to glucose.
If you are having homozygous mutation you can suffer from neonatal diabetes, neurological abnormalities, and learning difficulties while in the case of heterozygous mutation you can develop diabetes either in childhood or even as an adult.
How to Differentiate MODY From TYPE-1 And TYPE-2 Diabetes?
As you are aware of the fact, that Type-1 diabetes occurs due to the destruction of pancreatic beta cells as these cells are no more capable of producing sufficient amount of insulin that is being needed in the body to utilize the glucose you consume, while the fact that MODY is genetic disorder there is no pancreatic beta-cell destruction, hence due to genetic mutation in the gene which is responsible for insulin production, your cells produce insulin which does not work properly as it would have done.
So, here is what you’ve got to do just go for an anti-beta cell antibody test, it’ll help you know whether you are having antibodies that are responsible for pancreatic beta-cell destruction or not. If yes, you are suffering from Type-1 diabetes, but if your body is having these antibodies that means your pancreas is working and secreting enough insulin, it’s just not working because of the genetic mutation in your genes.
Some similarities are seen in MODY and Type-1 diabetes, this is because, when you have Type-2 diabetes you have insulin resistance implying that you are having high insulin levels which are not working. In this scenario, genetic testing is the key as in the case of MODY you would not be having insulin resistance.
You can differentiate between Type-2 diabetes and MODY based on some key symptoms like type-2 patients are generally obese while MODY patients are non-obese but can be obese due to sedentary lifestyle.
What Are The Diagnostics Tests For MODY?
As now you know, the diagnostic test for confirming whether you are suffering from MODY is anti-beta cell antibody testing. The basis for testing must be:
Non-obese people with hyperglycemia
No beta cell autoimmunity evidence
Absence of beta-cell function.
Family history of diabetes.
Absence of insulin resistance.
What Are the Different Treatment Strategies?
When it comes to treatment the basic treatment is similar to Type-1 and Type-2 diabetes which is insulin and oral hypoglycemic agents. Your medications vary based on the type of MODY.
Type Of MODY | Drugs Treatment |
HNF-4 α | Sensitive to sulfonylurea |
GCK | No medication, or Diet |
HNF-1 α | Sensitive to sulfonylurea |
PDX1 | Diet or Oral antidiabetic or insulin |
HNF-1β | Insulin |
NEUROD-1 | Oral antidiabetic or insulin |
Is Treatment Different From TYPE-1 and TYPE-2 Diabetes?
This question is clear now that the treatment is similar but differs from the type of MODY you are dealing with. If you have Type-1 diabetes you would be on long-term insulin treatment, but it’s not true for MODY you can be on insulin treatment, and sometimes, it won’t be a long-term treatment. Although there are no permanent cures or preventive care for MODY, still it can be managed and predicted with the help of medical sciences.
Conclusion
If you are obese and diabetic it'll be helpful to have genetic testing, as you cannot differentiate whether you are suffering from type-2 diabetes or have genetic alterations in the body. One just can't predict with open eyes whether he/she is affected by MODY or not. Some specific symptoms distinguish MODY from generic Diabetes and it's essential to have a clear picture of the same to provide better medical support. Though medications are available for MODY, then again it varies with the type of MODY you're dealing with. Also, the abnormality of the glucose level in the body caused by MODY just couldn't be cured that easily with treatments, but it could give a steady halt to this disease with proper medications and a proper health care plan.
References
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2019:12 Dovepress https://www.dovepress.com/diabetes-metabolic-syndrome-and-obesity-targets-and-therapy-journal
Content Credits
Rashi Bahuguna
Author
Harshita Karodiwal
Editor
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