What causes diabetes?

Diabetes Mellitus is a common yet serious condition where your blood glucose levels (BGL) are not regulated by your body well enough. This can lead to your BGL’s being too high or too low, both of which are dangerous. Scientists are figuring out the causes of diabetes. Type 2 develops due to your body’s resistance to insulin, mainly caused by an unhealthy lifestyle. However, the development of Type 1 Diabetes Mellitus is being researched more and more. In fact, recent research has shown that the chance of developing diabetes has increased in patients after COVID-19 infection. Does COVID-19 increase the risk? And if so, how does it do this?

Insulin is a peptide based hormone, responsible for the conversion of glucose into glycogen. Glycogen can then be stored in liver and muscles cells until they are needed. By converting glucose to glycogen, BGL’s are reduced to prevent hyperglycaemia (high BGL) and ensures that when glucose is needed during exercise it can be converted back from glycogen stores, preventing hypoglycaemia (low BGL). Thus, insulin is essential for control of BGL.

Insulin is secreted by cells in the pancreas called beta cells. The beta cells are triggered to release vesicles of insulin when glucose enters the cell so a high BGL will cause beta cells to release more insulin. The insulin is released directly into the bloodstream where it binds to receptors on the target cells (liver cells) and causes an enzyme cascade for the conversion of glucose to glycogen, known as glycogenesis. The glycogen is then stored in the liver cells, until glycolysis (conversion of glycogen to glucose) happens when glucose is needed during exercise.

The image shows a liver cell that has a receptor for insulin on its membrane. The insulin will bind to receptors causing the activation of the enzyme Adenylyl Cyclase inside the cell which then (after an enzyme cascade) allows the glucose transport protein channels to open. Glucose enters and is converted into glycogen.

Source: John Hopkins University

This system works well in people without diabetes. In diabetics, this pathway is interrupted, preventing the storage of glucose as glycogen.

Source: LiveScience

There are a number of different causes for Type 1 diabetes:

  1. Autoimmune reaction – the T cells (immune cells) recognise antigens on pancreatic cells and destroy the beta cells.
  2. Inflammation – infection from a pathogen causes an inflammatory response by our body’s immune system which causes damage to organs, including the pancreatic tissues. Many COVID-19 patients have complications due to the “Cytokine Storm” caused by a high concentration of cytokines in the blood.
  3. The pancreatic cells are attacked by the virus itself. For example with COVID-19, the ACE-2 receptors that the coronavirus used to enter and infect cells are found on pancreatic cells. The virus could damage the beta cells and prevent them from producing or secreting insulin.
  4. Scientists are also researching whether genetics may be the reason for some people being more likely to develop diabetes. The DNA sequence of a person would lead to certain glycoproteins and receptors being expressed on their cell membranes. Thus, they may express a certain receptor on beta cells that is particularly susceptible to a viral attack, leading to damage to beta cells.
  5. A virus could indirectly harm the beta cells. A virus attacks the small blood vessels that supply oxygenated blood to beta cells. Without the oxygen, the beta cells will be unable to respire or function.

Aside from COVID-19, there is a particular group of viruses known to trigger diabetes (small traces of the virus have been found in people diagnosed with diabetes). These are called Human Enteroviruses (HEVs). HEV’s infect the gut and trigger a strong immune response. The antigens (molecules that the immune system uses to recognise viruses) on HEV’s are similar to the antigens on beta cells. Therefore, the immune system attacks its own cells.

These causes mainly relate to Type 1 diabetes because it is caused by damage to beta cells. In contrast, Type 2 diabetes is due to the liver cells becoming resistant to insulin due to high concentrations of glucose in the blood (unhealthy diet or lifestyle being risk factors for this). So the causes of Type 2 diabetes are more well known and diabetes can even be reversed with lifestyle changes in some cases. However, scientists are still researching the cause of diabetes to reach a treatment. So far there is no treatment and diabetics have to rely on BGL monitors, insulin injections and, in rare cases, a pancreatic transplant.

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