Defining hypoglycemia to improve its study
Hypoglycemia refers to a drop in blood glucose (sugar) levels and occurs when there is too much insulin circulating in the bloodstream for the body’s needs at a specific time. Possible causes include a mistake in the dose of the injected insulin, overestimating the amount of carbohydrates ingested, physical activity, etc. Hypoglycemia can cause a range of symptoms that vary in intensity and onset from one individual to another. Symptoms include hunger, sweating, shaking and nausea and can affect the ability to concentrate and even cause a loss of consciousness.
To conduct research on hypoglycemia, it must first be defined properly. Various international organizations have recently revised the definition of hypoglycemia, especially in terms of its severity levels. Diabetes Canada, in its 2018 Clinical Practice Guidelines, maintains the usual nomenclature by distinguishing between mild, moderate, and severe. These Guidelines define severe hypoglycemia as a blood glucose level below 2.8 mmol/L and an inability to treat oneself. The American Diabetes Association prefers not to set a glycemic threshold, pointing out that any abnormal blood sugar level can be harmful. Moreover, a recent position paper by the American Diabetes Association and the European Association for the Study of Diabetes has proposed a three-level classification for hypoglycemia (see Table 1) that avoids defining a blood glucose value for the third level, which corresponds to severe hypoglycemia. In any case, the main criterion for severe hypoglycemia is that the affected person requires the help of someone else to treat it.
Table I. Blood glucose levels proposed by the American Diabetes Association and the European Association for the Study of Diabetes, 2017
| Level 1 | Blood glucose of 3.9 mmol/L or less. |
| Level 2 | Blood glucose below 3.0 mmol/L, low enough be considered serious hypoglycemia, which is clinically important. |
| Level 3 | Severe hypoglycemia with cognitive impairment, requiring the assistance of others to treat. |
Studies report that, each year, 10% of people with type 1 diabetes experience an episode of severe hypoglycemia. Severe hypoglycemia greatly affects the quality of life of patients and their loved ones.
Factors that can increase the risk of severe hypoglycemia:
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Hypoglycemia in real life
Although we would like to be able to define hypoglycemia scientifically, definitions do not always resonate with people living with type 1 diabetes on a daily basis. The seriousness of a hypoglycemic episode can vary depending on the context in which it occurs, regardless of a person’s blood sugar value at the time. For example, hypoglycemia may be more serious if it occurs at work or while driving a car.
On average, people with type 1 diabetes report experiencing three to four episodes of mild or moderate hypoglycemia every week. This number may be higher because some people do not feel every episode of their hypoglycemia. The fear of hypoglycemia is one of the main barriers to achieving optimal glycemic (blood glucose) control in people with type 1 diabetes.
The potential of technology to reduce the risk of hypoglycemia
Some technological breakthroughs have given people with type 1 diabetes more flexibility and freedom in managing their disease. The advent of continuous glucose monitoring systems (Dexcom® and Enlite®) and, more recently, FreeStyle Libre (also called a flash glucose monitoring system) have revolutionized the way blood glucose is measured. These devices make it possible to measure blood glucose more frequently, without fingersticks, and provide trend curves that help their users better understand the fluctuations in their blood glucose so they can adjust their treatment accordingly. Continuous glucose monitoring and the flash system can help improve glycemic control (HbA1C) while reducing the time spent in a hypoglycemic state. For example, studies done on FreeStyle Libre have shown a 46% decrease in the time spent in a state of hypoglycemia, especially in people whose glycemic control is poor.
An insulin pump can also be a useful tool to reduce hypoglycemia and prevent severe episodes. The insulin pump is able to program different basal insulin infusion rates during a single day. The pump also has a function to calculate the bolus dose (the insulin dose injected at meals). It can even estimate the amount of active insulin still circulating to help calculate the doses to inject. In addition, when coupled with a continuous blood glucose monitor (Medtronic system), insulin infusion can be automatically suspended in the event of a drop in a person’s blood sugar.
Despite their proven benefits, these new technologies are not accessible to everyone, mainly because of their cost and the current reimbursement policies in effect. In addition, to be used to their full potential, a health professional must provide instruction at the start and then on a periodic basis. For example, it is necessary to learn how to modify the pump’s settings to prevent certain kinds of hypoglycemia from occurring. Unfortunately, some patients lack support and not all health care professionals have the time or are comfortable recommending these technologies or providing the required instruction.
Pharmacological progress in reducing hypoglycemia
Since its first therapeutic use in 1921, insulin used for the treatment of diabetes has made significant pharmacological advances. Thus, ultra-rapid insulin analogues are now available that take less than five minutes to act, while others (long-acting basal insulins) have an increasingly flat action profile. These make it possible to further mimic the action of the pancreas of nondiabetic people and potentially reduce the risk of hypoglycemia.
The opposite of insulin is glucagon. Used as an emergency medication in cases of severe hypoglycemia, glucagon is also seeing pharmacological advances that could benefit people with type 1 diabetes. Usually, during severe hypoglycemia, glucagon is injected into a muscle by a third party to raise blood sugar levels very quickly. However, a new method of administration – via the nose – is currently being studied. This simpler approach might reduce emergency room visits for severe hypoglycemia.
Towards the reduction of hypoglycemia
So many technological and pharmacological advances with the potential to reduce the risk of hypoglycemia are encouraging. Nevertheless, the BETTER team believe that it is essential to properly define hypoglycemia, understand patients’ experience with the therapy, the technology and hypoglycemia, and to facilitate education about these products.