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Diabetes Mellitus


Types

Main types:

Type 1 diabetes mellitus: insulin dependent.

Type 2 diabetes mellitus: non-insulin dependent.

There are a number of specific types of diabetes mellitus, including:
  • Diabetes mellitus arising from a mutation in the gene for insulin.
  • Maturity onset diabetes of the young (MODY), etc.

Clinical signs

Type 1 (insulin dependent) diabetes mellitus

This is thought to result from the formation of autoantibodies against the cells in the pancreas that produce insulin - these cells are known as pancreatic beta cells.

The cells are destroyed and therefore it is necessary to supply the patient with exogenous insulin, which is administered by injection.

People with a specific histocompatibility (tissue type) site (DR3 and DR4) have an increased genetic risk. There is evidence that certain viral diseases constitute the trigger for the onset of diabetes mellitus.

The age of onset of diabetes of this type is relatively low, usually before the age of 15. The initial signs include excessive thirst and urination (polydypsia and polyuria), loss of weight, weakness, abdominal pain, very high blood sugar level and low blood insulin. Sometimes there are complications of increased levels of blood acids (a condition known as acidosis) that are life-threatening and require administration of sugar.

Over the years, long-term complications including eye damage and kidney damage appear. Stabilizing diabetes mellitus is important to reduce the risk of these complications and to prevent hypoglycemic (low blood sugar) episodes caused by temporary surpluses of insulin.

Type 2 (non-insulin dependent) diabetes mellitus

The blood insulin level of these patients is increased due to a reduced response of the insulin receptors in the cells. The body thus increases the blood insulin level to achieve the desired effect. Insulin resistance of cells increases with obesity.

The age of onset in this type of diabetes mellitus is relatively advanced, usually after the age of 30. The initial signs include excessive thirst and urination (polydypsia and polyuria), loss of weight, weakness, abdominal pain, very high blood sugar level and high blood insulin.

Over the years, long-term complications including eye damage and kidney damage appear. Stabilizing diabetes mellitus is important to reduce the risk of these complications. Treatment includes a low-sugar diet and medication involving pills to reduce the blood sugar level (hypoglycemics) rather than insulin.


Specific types of diabetes

MODY

This type of diabetes appears before the age of 25, is controlled for at least two years without having to administer insulin, and is not accompanied by production of acids in the blood (ketosis).

The type arising from a mutation in the insulin gene

In this type, the blood proinsulin and insulin levels are high, but there is a defect in the structure of the insulin itself. This means that the natural insulin in these patients is not sufficiently effective. Treatment usually involves a low-sugar diet and oral hypoglycemics (drugs that reduce blood sugar).

Inheritance pattern

Type 1 - multifactorial inheritance. Here a number of genes act together, possibly also with environmental factors. Viruses may be a minor environmental factor. The histocompatibility (tissue type) site plays a role with regard to genetic susceptibility. There are probably additional genes that are important in the genetic predisposition to develop diabetes mellitus.

Type 2 - multifactorial inheritance. Here diabetes and a high-sugar diet act as environmental catalysts. The genetic predisposition is undoubtedly more significant than in type 1.

In some families with diabetes, such as the type that results from a mutation in the insulin gene and in MODY, where it is an isolated finding rather than being part of a syndrome, the inheritance pattern is autosomal dominant.

Penetrance

Not known

Associated features that can be demonstrated in tests performed during pregnancy

Specific findings cannot be demonstrated in pregnancy.

What is the risk of recurrence in a subsequent pregnancy?

In diabetes type 1

Both siblings and children of patients with diabetes mellitus have a 4 - 5% risk of also having diabetes.

The risk can be better measured, thereby raising or lowering the statistical risk, based on the genetic resemblance of the patient and his or her relatives in the histocompatibility site (known in humans as HLA). This risk is especially high if a person tested in the family of a diabetes patient has HLA type DR3 or DR4. This site is particularly associated with this type of diabetes mellitus. For example, if there is a child who has the same HLA as his affected brother, his risk for developing diabetes is 10% - 20%. Conversely, if there is no HLA similarity between these brothers, the risk for the brother developing diabetes mellitus is approximately 1%.

The risk for more distant relatives depends on the number of affected individuals in the family, the degree of relationship between the relatives and the affected individuals, etc. This risk is established within genetic counseling.

In other, non-syndromic genetic types of diabetes (the type resulting from a mutation in the insulin gene and MODY):

The risk for offspring and siblings is up to 50%. Recently it has been shown that some cases of MODY are sporadic.

The risk for more distant relatives depends on the number of affected individuals in the family, the degree of relationship between the relatives and the affected individuals, etc. This risk is established within genetic counseling.

Molecular genetic information

The gene for the disease and its location

In type 1 diabetes mellitus: the tissue type gene complex known as HLA on chromosome 6.

In type 2 diabetes mellitus: a number of sites that play a role in the genetic predisposition for this type of diabetes have been found: the insulin receptor site on chromosome 19p, apolipoprotein B on chromosome 2p, apolipoprotein A1 on chromosome 11q, the HepG21 gene on chromosome 1p, and others. The number of sites associated with diabetes mellitus is increasing.

In diabetes mellitus of other, non-syndromic genetic types: in the type resulting from a mutation in the gene for insulin, the gene for proinsulin is involved. In the type known as MODY, a gene associated with this has recently been found.

Genetic testing

Diagnostic testing

For diabetes mellitus types 1 and 2, there are currently no reliable molecular tests. In specific families with many affected individuals, linkage analysis can be considered in a research setting. See also Indirect testing for genetic markers in a family that has one or several patients - when there are a number of different genes that can each cause the disease - the gene, or most of the genes not having been located / identified / mapped - multifactorial diseases.

Carrier testing

There is no reliable carrier test for type 1 or type 2 diabetes mellitus.

Fetal testing

There is no diagnostic molecular test that can be performed in the fetus or newborn.


Diabetes Mellitus


 
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