Glucagon: Friend or Foe for People With Type 1 Diabetes?

Blood sugar (glucose) management is a complex matter. A total of five hormones, including insulin and glucagon, are required to balance glucose levels. Insulin is secreted by the pancreas and lowers blood glucose. Glucagon is also produced by the pancreas, but it contributes to releasing glucose reserves in the muscles and liver in order to increase blood sugar levels when they decline, such as when we’re sleeping or exercising.

Insulin and glucagon play a complementary role in maintaining blood glucose within normal range. These hormones are regulated by our diets, as well as certain physical stress factors, such as fasting, exercising, anxiety and illness, which can all increase or decrease their secretion.

In the case of type 1 diabetes (T1D), the immune system destroys the insulin-producing beta cells in the pancreas. But what is the impact of T1D on glucagon production?

Excess or deficient glucagon production

In people with T1D, the pancreas is unable to offset the effect of any excess insulin administered and does not release enough glucagon to avoid hypoglycemia. This insufficient production of glucagon by the pancreas considerably increases the risk of severe hypoglycemia (inability to self-treat hypoglycemia, which can lead to loss of consciousness).

But glucagon can also be produced in excess quantities. For instance, this can happen after a meal, where the presence of excess glucagon amplifies any hyperglycemia.

The body does not produce enough glucagon when the person needs it, and too much when it’s unnecessary. This demonstrates the complexity of managing blood sugar levels in type 1 diabetes.

The root of the problem

The glucagon-producing alpha cells of the pancreas are not attacked by the immune system, unlike insulin-producing beta cells. However, beta cells play a role in the regulation of glucagon secretion. The breakdown of these cells and of local insulin production in the pancreas leads to dips and spikes in glucagon production.

The search for solutions

Some medications that are normally used for type 2 diabetes can decrease post-meal glucagon secretion, such as DPP-4 inhibitors (e.g., Januvia, Onglyza), or the glucagon-induced release of glucose reserves in the liver, such as biguanides (e.g., metformin). These drugs have not been approved for T1D, but they are sometimes prescribed for “extra-label” uses. Studies are ongoing to assess whether these drugs help to manage blood sugar levels in people with T1D.

However, there is currently no medication to compensate insufficient glucagon secretion when glucose levels decrease, except for nasal or injectable glucagon, which are emergency drugs administered by another person in the event of severe hypoglycemia. Research is being conducted to develop a mini dose of glucagon in a pen (like an insulin pen, but with glucagon) that a person could self-administer in small quantities in case of imminent risk of hypoglycemia. Insulin pumps containing both insulin and glucagon (dual-hormone pumps) are also under development

Other potential indirect solutions are also being studied, such as the possibility of doing high-intensity physical exercise or taking certain amino acids (via proteins) to increase glucagon production in order to offset decreasing blood glucose levels.

Overcoming the lack of glucagon when blood sugar levels go down seems to be the key to further improve blood sugar management and decrease hypoglycemia episodes in people with T1D.