Type 1 Diabetes and the Six Missing Hormones

Type 1 diabetes (T1D) is an autoimmune disease in which the immune system misses its target and destroys the insulin-producing beta cells. Since insulin is a vital hormone, people with T1D must take multiple injections of insulin daily.

Actually, insulin isn’t the only hormone affected; there are several other hormones that are either missing or dysfunctional in T1D.  

Cells destruction

The pancreas has two main functions: 

• It helps with digestion by producing enzymes that are released into the digestive tract. This capacity, called the “exocrine function,” is usually functional in T1D.  
• It produces hormones in small structures, called Langerhans’ islets or pancreatic islets (endocrine function). Adults have between 750,000 and 1,500,000 islets.

Five types of cells are found in these islets:

• Beta cells (65% to 80% of total cells)
• Alpha cells (15% to 20%)
• Delta cells (3% to 10%)
• Gamma cells (less than 5%)
• Epsilon cells (less than 1%)

In people who don’t have diabetes, these cells are constantly communicating with each other within the islets, secreting several hormones that help keep blood sugar levels within a very narrow range. 

The six missing hormones and their roles

The autoimmune attack that causes T1D not only destroys the insulin-producing cells (beta cells), but also leads to broader islet damage or complete destruction. As a result, the hormones usually secreted by these cells can’t be secreted and function as they should. 

Here are the main points:

• Insulin is produced by the beta cells. It allows the cells to use glucose (blood sugar) as an energy source. In people who don’t have T1D, insulin is naturally secreted in precise amounts to prevent blood sugar from rising. 
• Amylin and insulin are produced by the beta cells, simultaneously and in the same amount. Amylin’s main role is to slow the emptying of the stomach, to promote satiety (feeling full) and to decrease the release of glucagon. These combined effects limit the rise in blood sugar after meals. 
• Glucagon is produced by the alpha cells; its main role is to increase blood sugar levels. In people who don’t have diabetes, the pancreas’s beta cells automatically adjust the release of glucagon: less glucagon after a meal, more glucagon when blood sugar levels go down. The breakdown of these cells and of local insulin production in the pancreas leads to dips and spikes in glucagon production, which increases the risk of hypoglycemia. 
• Pancreatic polypeptide is produced by the gamma cells, but its role is not yet fully understood. It promotes satiety and helps insulin to act on the liver to store sugar as glycogen. For people with T1D, the intake of pancreatic polypeptide may help reduce insulin requirements.
• Somatostatin is produced by the delta cells, decreasing the secretion of glucagon and insulin to maintain blood sugar balance after meals.
• Ghrelin is produced by the epsilon cells. It stimulates the appetite, increases fat storage and stimulates the release of growth hormone, which increases blood sugar. It was recently found that the production of ghrelin in people with T1D is atypical. However, the levels of ghrelin produced by the pancreas are very modest compared to those produced by the gastrointestinal tract.

Treatment options in T1D

People with T1D balance their lack of insulin secretion with multiple daily insulin injections or insulin infusion with an insulin pump. However, although some insulin pumps now make it easier to manage the administration of insulin, people with T1D still need to manually adjust their insulin doses based on multiple factors (e.g., number of carbohydrates consumed, physical activity, sick days).

Should some of the other hormones mentioned above also be replaced to improve and/or simplify the management of blood glucose levels?

To reduce glucagon secretion after meals, certain drugs are used for treating type 2 diabetes, but aren’t yet approved for T1D—although studies with encouraging results are underway. 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. A pump capable of injecting microdoses of glucagon in addition to insulin is currently being developed in the United States. This type of treatment could significantly reduce the risk of hypoglycemia.

An amylin treatment (Symlin^Ⓡ) has been available in the United States since 2005; however, because of its side effects (e.g., increased hypoglycemia, nausea) and the need for additional injections at mealtime mean, this treatment is not widely used by people with T1D. A treatment is currently under study to combine insulin and amylin in a single injection. 

Except for insulin and emergency glucagon treatment, there is currently no treatment to replace the other missing hormones, although research is ongoing. It’s easy to see why it’s so difficult for people living with T1D to keep their blood sugar levels within the recommended range.

While it’s not clear whether replacing the missing hormones would be helpful, further research will be needed to determine whether this type of treatment could facilitate the management of blood sugar levels in people with T1D.  

References :

• T1D Exchange, “The Six Dysfunctional Hormones of Type 1 Diabetes” , consulté le 7 février 2023, https://t1dexchange.org/t1d-hormones/  
• Levetan, Claresa & Pierce, Susan. (2012). Distinctions Between the Islets of Mice and Men: Implications for New Therapies for Type 1 and 2 Diabetes. Endocrine practice: official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 19. 1-36.  
• Levetan, Claresa. (2010), Distinctions between islet neogenesis and β-cell replication: Implications for reversal of Type 1 and 2 diabetes. Journal of Diabetes, 2: 76-84. 
• Levetan, Claresa. (2022), Frederick Banting’s observations leading to the potential for islet neogenesis without transplantation. Journal of diabetes. 14, 2: 104-110.  
• Holdstock C, Ludvigsson J, Karlsson FA. (2004), Abnormal ghrelin secretion in new-onset childhood Type 1 diabetes. Diabetologia. 47: 150–1. 
• Rabiee, Atoosa et al. “Pancreatic polypeptide administration enhances insulin sensitivity and reduces the insulin requirement of patients on insulin pump therapy.” Journal of diabetes science and technology vol. 5,6 1521-8. 1 Nov. 2011, doi:10.1177/193229681100500629
• Diabetes in control, «How Glucagon Impacts Type 1 Diabetes and Vice Versa», consulté le 21 octobre 2021, https://www.diabetesincontrol.com/how-glucagon-impacts-type-1-diabetes-and-vice-versa/
• Whitehouse, Fred et al. “A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes.” Diabetes care vol. 25,4 (2002): 724-30. doi:10.2337/diacare.25.4.724
• Taleb, Nadine, & Rémi Rabasa-Lhoret. “Can somatostatin antagonism prevent hypoglycaemia during exercise in type 1 diabetes?.” Diabetologia vol. 59,8 (2016): 1632-5. doi:10.1007/s00125-016-3978-4
• Beta Bionics, “Beta Bionics has developed the world’s first bionic pancreas”, consulté le 9 février 2023, https://www.betabionics.com/our-technology/