Causes of Type 1 Diabetes

Type 1 diabetes is an autoimmune disease. The immune system—which is actually responsible for defending against pathogens—attacks the body’s own insulin-producing cells, the beta cells in the islets of Langerhans in the pancreas. If most or all of the insulin-producing cells are destroyed, glucose from the diet is no longer transferred from the blood into the body’s cells, as this process requires insulin. The result: Blood sugar levels rise.

It is not yet fully understood why the immune system turns against the body’s own cells in some individuals and not in others. At the DZD, intensive research is being conducted into the causes of type 1 diabetes. It is now known that genetics play a major role. Studies have identified numerous genes that are involved in the development of type 1 diabetes. However, family history also has an impact. People who have a family history of diabetes as well as one or more risk genes have the highest risk of developing type 1 diabetes. 

However, in addition to genetic factors, environmental factors can also influence the development of autoimmune diseases like type 1 diabetes. Research is currently being conducted into the potential role of diet in early childhood, the gut microbiome and viral infections in the first years of life.

Type 1 diabetes: Causes and development (diabinfo.de)

Causes of Type 2 Diabetes

Unlike type 1 diabetes, patients with type 2 diabetes initially still produce a sufficient quantity of insulin. At first, the insulin-producing beta cells of the pancreas work normally. The rise in blood sugar associated with type 2 diabetes occurs because insulin no longer acts properly on the cell walls. This is known as insulin resistance. Consequently, not enough glucose is transferred from the blood into the tissue, resulting in an elevated blood sugar concentration accompanied by an energy deficiency in the cells. To compensate for insulin resistance and lower the blood sugar level, the pancreas increases insulin production. This leads to the gradual exhaustion of the insulin-producing beta cells in the pancreas, which causes insulin production to decrease. This results in insulin deficiency.

Genetic factors also play a role in the development of type 2 diabetes. In addition to the already known risk genes, DZD researchers have managed to identify over 50 new genes that have an effect on metabolism. People whose mother or father has type 2 diabetes have an approximately 1.7 times higher risk of developing type 2 diabetes over the course of their lives compared to those without a family predisposition. The risk is almost three times higher if both parents have the disease.

However, the risk of diabetes is not only influenced by the genetic code itself, but also by “epigenetics.” Lifestyle—an unhealthy diet, smoking, overweight—can lead to epigenetic changes in the DNA, which influence the extent to which certain genes are read. Because such changes also occur in oocytes and sperm, they can be passed on to offspring. DZD researchers have shown that the diet of the mother as well as that of the father—even before the conception of the child—influences whether the offspring develops overweight or type 2 diabetes later on.
Further information:

Research news: You Are What Your Parents Ate!

Press release: Father's Diet Before Conception Influences Children's Health

Nevertheless, even with a genetic predisposition and epigenetic changes, other risk factors must also be present in order for type 2 diabetes to manifest. An unhealthy lifestyle with a poor diet, overweight and a lack of physical activity plays an important role in this.       

Furthermore, studies by DZD researchers indicate that food at unfavorable times, such as at night during shift work, disrupt the circadian rhythm and could increase the risk for overweight and type 2 diabetes.

Research news: Insulin Directly Regulates the Circadian Clock in Adipose Tissue

Insulin Resistance

Unhealthy lifestyle factors can lead to insulin resistance in individuals with a corresponding genetic predisposition. Although the beta cells in the pancreas still produce insulin in sufficient quantities, its full effect is no longer achieved at the cell walls in the body. The cells become insensitive to insulin. Consequently, the glucose from the diet does not reach the cells but remains in the blood.

Decreased Insulin Production

Although the insulin-producing beta cells still work at the onset of type 2 diabetes, insulin production also becomes impaired as the disease progresses. In individuals with type 2 diabetes, the pancreas produces an excessive amount of insulin in order to overcome existing insulin resistance. This high effort leads to the increasing exhaustion of the beta cells, until they are no longer able to produce enough insulin.

Type 2 diabetes: Causes and development (diabinfo.de)

The Role of GLP-1

Endogenous gut hormones, such as GLP-1 (glucagon-like peptide-1) also play an important role in type 2 diabetes. This hormone binds to specific receptors in the brain and ensures that the body responds appropriately to the intake of carbohydrates, such as by triggering the secretion of insulin from the pancreas and thus regulating blood sugar levels. However, endogenous gut hormones also influence the feeling of satiation and thereby food intake. In people with type 2 diabetes, GLP-1 is no longer produced in sufficient quantities, meaning that this process no longer works properly. New findings, including by the DZD, have led to the development of drugs that can mimic the effect of GLP-1 and other peptide hormones and thus compensate for the deficit.

Press release: New Approach for the Development of a Drug Treatment for Obesity and Type 2 Diabetes

The Role of the Liver and Brain

Current studies show that the brain and liver can also influence the development of type 2 diabetes. Regions of the brain that are responsible for food intake or metabolism respond to insulin. It is suspected that the hormone acts on the brain and inhibits the feeling of hunger, thus potentially preventing the development of overweight. On the other hand, insulin resistance in certain areas of the brain has a negative impact on metabolism.

Studies by the DZD not only suggest that people with an insulin-sensitive brain lose weight more easily when they have a healthy diet and exercise, but also that less fat accumulates in their abdominal area, i.e., where it particularly increases the risk for type 2 diabetes.

Besides abdominal fat, however, excessive fat in the liver also impairs metabolism and can contribute to the development of type 2 diabetes. A fatty liver promotes the development of insulin resistance associated with type 2 diabetes.

Various organs therefore play a role in the development of diabetes. However, the pancreas, brain, liver and the intestines do not contribute to this independently of one another—rather, they interact with one other. This is referred to as “organ crosstalk.”

Research news: Brain Insulin Sensitivity Determines Body Weight and Fat Distribution