Key facts about glucose homeostasis

Sugar (more specifically glucose) is the main source of energy of our cells.  In fasting conditions, blood glucose levels range from 4 to 5 mmol/l.  Maintaining optimal circulating glucose levels is key to stay healthy.

The regulation and maintenance of blood glucose levels or glycemia is a complex mechanism involving the participation of the whole body, especially the gastro-intestinal tract, the endocrine system, the liver, the muscles, the adipose tissue as well as the nervous system.  Among all factors and hormones that are implicated in the maintenance of optimal circulating glucose level, insulin is key to this process.  Produced and released by the pancreatic beta-cells that are localized within the pancreatic islets (the endocrine part of the pancreas), insulin level in the blood rise concomitantly after nutrient load in the organism.  Insulin has an important mission:  it distributes glucose coming from the digestion of the food to various organs, including liver (where glucose is stored for future needs), skeletal muscles and the fat (where it is consumed for energy expenditure) and allows the blood glucose concentrations to decrease down to normal level.  In contrary, in periods of fasting, when blood glucose levels are reduced, other cells localized within the pancreatic islets, called alpha-cells, will release glucagon, another hormone that favors the production of glucose from the liver, to supply the organism in energy.

When glucose homeostasis is deficient and when the hormones (especially insulin) regulating this process are not able to play their role anymore, unhealthy conditions and metabolic diseases can develop.  Among them, diabetes, defined as chronic hyperglycemia (high blood glucose) results in typical symptoms such as glucosuria, polyphagia, polydypsia, polyuria, ketoacidosis, dramatic and rapid weight loss as well as changes in energy metabolism.

Diabetes, a debilitating disease

Diabetes or diabetes mellitus (diabetes means siphon in Greek and mellitus means honey or sweet in Latin) is the most common metabolic disease worldwide.  According to World Health Organization (WHO), in 2014, the disease affected already 422 millions people, which represents 1 person out of 11.  In 2016, 1.6 million patients died of diabetes and its complications.

The diagnosis of diabetes, as established by the WHO, consists in measuring the blood sugar level.  In healthy people, fasting glycemia is less than 6.1 mmol/l, and under 7.8 mmol/l 2 hours after ingestion of a 75 g glucose solution (oral glucose tolerance test or OGTT).  In contrary, diabetic patients have their glycemia higher than 7 mmol/l in fasting conditions, and more than 11 mmol/l after the OGTT.

There are several types of diabetes recognized :

  1.  diabetes type 1, representing 10% of the cases.  It is an auto-immune disease, that leads to the specific and progressive loss of insulin-producing beta cells within the pancreas and therefore to a state of insulin deficiency It typically appears in young people in their childhood, but can also develop in adults before 40 years of age.
  2.  diabetes type 2, representing about 85-90% of the cases.  It is a mutifactorial and heterogeneous disease and develops as a consequence of altered function of insulin-producing cells and the progressive decreased sensitivity of peripheral organs to the hormone insulin (insulin resistance)This form of the disease can develop in children and adolescents but mostly in adults and elderly people.
  3.  gestational diabetes – represents 2-7% of the cases.  It develops at the end of the second trimester of pregnancy.  It is the result of the increased adipose mass occurring during pregnancy in a population of women, and has for consequence, a temporary hyperglycemia, that in most cases disappears after the birth of the child.
  4.  rare forms of diabetes also exist and represent 1-2% of cases.  These are subclasses of type 2 diabetes and can appear as a consequence of an infection, malnutrition, surgery or specific genetic syndromes.

How to combat diabetes ?

The treatment of diabetes is mainly based on quotidian insulin injections in insulin-deficient individuals suffering from type 1 diabetes.  Type 2 diabetic patients are not dependent on insulin at the beginning of their condition.  However, in progressive stages of type 2 diabetes, insulin-producing beta-cells die due to the enormous metabolic stress they encounter, and patients need to control their metabolism by receiving insulin therapy.  In cases where beta-cells are still present, but show a defect in their function, the treatment of diabetes supports drugs which boost insulin secretion (e.g sulfonylureas) and therapies, which increase insulin sensitivity (metformin, usually prescribed to overweight or obese individuals).

Importantly, besides their every day medications allowing diabetic patients to tightly control their blood glucose levels, they are also submitted to severe diet, regular physical activity and should avoid stress.

One of the treatment of type 1 diabetes is transplantation of pancreatic islets coming from healthy donors, allowing to decrease patient’s insulin dependence and improving their quality of life.  However, this procedure is still rare due to the limited number of donors and the complex procedure of islet isolation from the pancreas.  In addition, it requires a tight preparation for the patient to undergo a delicate surgery consisting in transplanting donor islets in the liver.