Genes Matter
Diabetes is a disease with a high incidence in today’s society. In Spain, for example, it affects 14% of the population. One of the most common doubts about this pathology is whether it can be transmitted from parents to children. Therefore, in this article we want to clarify whether diabetes is hereditary or not, explaining the different types that exist, their origins, treatments and most frequent complications.
How does the body control sugar levels?
Before dealing with diabetes, let us briefly review how our blood sugar levels are controlled internally, so that we can better understand the origin of this pathology. The pancreas plays a fundamental role in the control of blood sugar levels (glycemia) since it is the organ that, among many other important functions, produces insulin, the hormone responsible for regulating the level of glucose in the blood.
The process is:
When we eat, blood glucose levels rise.
The body produces insulin, which has the function of diverting the sugar present in the blood to tissues and muscles for use or storage.
If everything is working properly, blood sugar levels drop and normalize relatively quickly after each meal.
Normal blood glucose and insulin levels (non-diabetic) for 24 hours.
Diabetes: when blood glucose control fails
The problem arises when the pancreas does not produce enough insulin (type 1 diabetes) or when the body does not react (becomes resistant) to its presence (type 2 diabetes). In these cases, sugar levels do not normalize after meals and this causes various problems, both in the short and long term.
Sustained high blood sugar levels (hyperglycemia) damage the blood vessels and increase the risk of stroke, kidney disease, visual disturbances or neurological problems. For this reason, if you suffer from diabetes, it is necessary to keep a strict control of blood glucose levels to avoid the onset of diabetic coma and the development of other health problems in the short and long term.
What is diabetic coma?
A diabetic coma is a complication of diabetes that occurs when blood glucose levels increase (hyperglycemia) or decrease (hypoglycemia) excessively, causing loss of consciousness and lack of response to stimuli. This situation can be fatal, so the sufferer requires immediate attention.
Some symptoms that may suggest hyperglycemia are thirst, frequent urination, fatigue, dry mouth or nausea and vomiting. Symptoms related to hypoglycemia, however, are tremors or nervousness, fatigue, weakness, sweating, slurred speech, hunger or nausea. In patients who have had diabetes for a long time, what is called “asymptomatic hypoglycemia”, i.e. a decrease in glucose levels that does not cause symptoms, can sometimes occur.
Diabetes is hereditary according to its type
In our blog articles such as Diseases and types of genetic inheritance or Hereditary genetic diseases: the most frequent and the rarest, we explained that hereditary genetic diseases are those caused by alterations in one or more genes that pass from generation to generation. But is this the case of diabetes? The answer is that it depends on the type of diabetes, although we think of diabetes as a single pathology, the causes are different and their degree of heritability varies. The main types are:
Next, we will see the main characteristics of each type of diabetes and their degree of heritability.
Type 1 diabetes
Type 1 diabetes occurs because the pancreas does not produce enough insulin to control blood glucose. This can occur for different reasons:
Genetic predisposition
The development of type 1 diabetes is due to the interaction of genetic factors with environmental factors. Therefore, it is not the disease that is inherited, but the probability of having it. This increased risk of having type 1 diabetes does not depend on a single gene, but is probably a consequence of the interaction of several of them (known or unknown), something we know as “polygenic inheritance”. In the case of identical twins, if one has this type of diabetes, there is a 50% probability that the other will also develop it.
Environmental factors
As in other diseases, in type 1 diabetes there are external environmental factors that can intervene in the development of the pathology, mainly in genetically predisposed people, such as:
Viruses
Autoimmunity
In certain cases, the body itself attacks the insulin-producing cells of the pancreas (pancreatic beta cells), causing diabetes.
Type 2 diabetes
This type of diabetes is known as “adult-onset diabetes” and is the most common in people over 40 years of age. The problem is that the body becomes resistant to insulin, although production is initially correct. Generally, the body, in order to try to compensate for this lack of sensitivity, increases insulin production, however, over time, this overexertion has consequences and the pancreatic beta cells reduce insulin production.
In type 2 diabetes the hereditary factor has more weight than in type 1 diabetes, but we are still talking about predisposition. In other words, what is inherited is the risk of presenting it, but in this case there is also “polygenic inheritance” and environmental factors that influence the development of the pathology. If one twin has type 2 diabetes, the probability that the other twin will have it is 80%.
Lifestyle
80% of people with type 2 diabetes are obese and sedentary. These two factors decrease insulin sensitivity, which is why it is so important to lead an active life and maintain an adequate weight to prevent the development of diabetes.
Type 1.5 diabetes
Type 1.5 diabetes has characteristics of both type 1 and type 2 diabetes. It is more technically referred to as Latent Autoimmune Diabetes of Adults (LADA). In this type of diabetes, autoimmune cells attack pancreatic cells (as in type 1 diabetes), although the disease does not appear until adulthood (as in type 2 diabetes). In fact, about 10% of type 2 diabetes cases are actually LADA cases and therefore do not respond to type 2 diabetes treatment, with which they are usually misdiagnosed.
Diabetes type MODY
This type of diabetes is named after Maturity Onset Diabetes of the Young and generally appears before the age of 25. In this case, it is a monogenic disease, that is, it is caused by an alteration or mutation in a specific gene.
There are different types of MODY, and each of them is related to a different gene. In general, these genetic alterations affect the maturation of the beta cells of the pancreas and, therefore, insulin production. Between 1% and 2% of diabetic patients in Europe have this type of diabetes, although they are usually misdiagnosed as type 1 or 2 diabetes.
MODY 1
This type is due to mutations in the HNF4A gene, and accounts for 10% of MODY cases. When there are mutations in this gene, there is a reduction in insulin production. These patients do not respond well to sulfonylureas, a drug used to treat diabetes by increasing insulin secretion by the beta cells of the pancreas.
MODY 2
This type is due to mutations in the glucokinase (GK) gene. Between 30% and 50% of cases of MODY diabetes are MODY 2, making this type the most frequent along with MODY 3. In this case the mutations alter the body’s ability to detect elevated glucose levels, which hinders appropriate insulin production. MODY 2 diabetes is considered mild and only about 5% of patients have complications. In fact, at the time of diagnosis they usually have high glucose values but no other symptoms.
MODY 3
This type is due to mutations in the HNF1A gene and accounts for 30% to 50% of patients with MODY. In this case patients have elevated glucose levels that increase over time leading, in many cases, to diabetes complications. The average age of diagnosis is usually 14 years. Many cases are incorrectly confused with type 1 diabetes and treated with insulin when they usually respond well to sulfonylureas.
MODY 4
This type, which accounts for about 1% of MODY type diabetes, is due to mutations in the PDX1 gene, which plays a key role in the development of the pancreas.
MODY 5
This other type is due to mutations in the HNF1B gene, and accounts for 5% of cases of MODY type diabetes. In addition to all those listed, there are other much less frequent types of MODY diabetes, caused by different genes:
MODY6 type (NEUROD1 gene)
Type MODY 7 (KLF11 gene)
Type MODY 8 (CEL gene)
Type MODY 9 (PAX4 gene)
Type MODY 10 (INS gene)
Type MODY 11 (BLK gene)
Type MODY 12 (ABCC8 gene)
Type MODY 13 (KCNJ11 gene)
Gestational diabetes
Gestational diabetes occurs in 10% of pregnant women and can affect fetal development and increase the risk associated with pregnancy. Its origin is multifactorial, i.e. it depends on both genes and the environment.
Although the hereditary factor had been known for some time, it was not until 2019, when the first specific gene directly involved in the development of gestational diabetes was identified: PAX8. This finding is the result of the research work of scientists from the Institute of Medical and Molecular Genetics of La Paz together with the Andalusian Center for Molecular Biology and Regenerative Medicine-Cabimer, of the University of Seville.
Why does blood glucose tend to increase during pregnancy?
The normal physiological mechanisms of pregnancy lead to the production of human placental lactogen (HPL) or human chorionic somatomammotropin, a hormone whose function is to ensure that the baby receives an adequate supply of energy. To achieve this, it exerts the opposite effect to that of insulin, i.e., it favors the permanence of glucose in the blood, which is why there is a greater probability of presenting elevated levels during pregnancy.
To detect pregnant women with abnormally high glucose levels, all pregnant women are screened between 24 and 28 weeks. Gestational diabetes usually resolves after delivery.
Secondary diabetes
Secondary diabetes is a consequence of external agents or other primary pathologies, such as hemochromatosis or Cushing’s disease. There is also the possibility of secondary hyperglycemia due to the ingestion of certain drugs.
Can I prevent diabetes?
14% of the Spanish population has diabetes, which makes this pathology one of the most prevalent. Diabetes arouses great interest in the general population since in many types it is possible to prevent its development through lifestyle habits.
In this article we have tried to explain the hereditary nature of the different types of diabetes. Although genetic inheritance plays an important role in the development of this pathology, in most cases it is produced by a combination of genes, immune and environmental factors, which makes our lifestyle a useful tool in the prevention of some types of diabetes.
In other cases, genes play a determining role in the development of diabetes, as occurs in MODY type diabetes, and genetic testing is important for a correct diagnosis of the disease.
From Veritas we try to help to transmit the importance of genetics in the prevention and diagnosis of diseases, we hope to have helped you to better understand this pathology so frequent nowadays! If you want more information, contact Veritas and solve all your doubts.
Bibiana Palao - Directora Departamento Científico
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