Questions About Hypoglycaemia

The IHSG has proposed a three-tiered classification, as explained in the box below.

IHSG classification: proposed glucose levels when reporting hypoglycaemia in clinical trials

Level 1 Level 2 Level 3
A glucose alert value of 3.9 mmol/L (70 mg/dL) or less. This need not be reported routinely in clinical studies, although this would depend on the purpose of the study. This is to be called a hypoglycaemia alert level. A glucose level of 3.0 mmol/L (54 mg/dL) is sufficiently low to indicate serious, clinically important hypoglycemia. Severe hypoglycemia, as defined by the ADA, denotes severe cognitive impairment requiring external assistance for recovery.

The American Diabetes Association has defined hypoglycaemia in diabetes as “all episodes of an abnormally low plasma glucose concentration that expose the individual to potential harm” – a definition that avoids linking hypoglycaemia to a specific number.

While acknowledging the variability of response to glucose levels, the IHSG also sees value in a numerical threshold for clinically and health-economically significant hypoglycaemia. After numerous discussions, IHSG members reached a consensus that a glucose level of 3.0 mmol/L (54 mg/dL) is sufficiently low to indicate serious, clinically important hypoglycaemia.

In clinical trials, 3.9 mmol/L (70 mg/dL) is often set as a threshold for hypoglycaemia. The IHSG views this figure as an “alert value” rather than an upper limit of hypoglycaemia, because it does not necessarily incur symptoms or long-term harm. As such, it may not be necessary to report it routinely in clinical trials.

When blood glucose drops significantly within a few minutes, people may experience symptoms of hypoglycaemia even at higher absolute blood glucose levels than expected. This can also happen in people who have persistently elevated blood glucose levels and poor glycaemic control.

Both inpatient and outpatient hypoglycaemia have been linked to a higher mortality rate. However, it is not yet known whether hypoglycaemia directly impacts mortality or whether it simply reflects more severe disease (associated with a higher mortality rate).

Current inpatient guidelines suggest a patient-centered approach, with tighter control advised for some patients and less intensive control for severely ill or elderly patients. The goal, in each case, is to weigh the risks of hypo- and hyperglycaemia and aim for the level of glycaemic control that best balances these risks.

Repeated episodes of hypoglycaemia (typically in the context of insulin therapy) may lead to impaired awareness of hypoglycemia (IAH), defined as a diminished ability to perceive the onset of hypoglycemia. Not surprisingly, IAH raises the risk of severe hypoglycaemia.

That said, total loss of hypoglycemia symptoms is uncommon; most people with IAH retain a few neuroglycopenic symptoms, though they may only perceive them at very low glucose levels. Some people who experience recurrent hypoglycaemia never develop IAH.

Many studies have found an inverse correlation between intensity of glucose control (as reflected by HbA1c) and hypoglycaemia risk. This risk rises most significantly in patients with HbA1c values within the non-diabetic range.  However, several recent reports have failed to show this inverse relationship, indicating that hypoglycaemia can occur at any level of glycaemic control.

In some individuals, a higher HbA1c may result from suboptimal diabetes self-management, which could also raise the risk of hypoglycaemia. For example, a single overdose of insulin can cause blood glucose levels to fall into the hypoglycaemic range, even in patients with higher baseline glucose levels.

  • Frail or cognitively impaired elderly patients: Hypoglycaemia carries a greater risk in these populations, so avoiding hypoglycaemia takes precedence over achieving glycaemic targets. Depending on the level of frailty, glycaemic targets may be raised to HbA1c less than or equal to 8.5% and fasting or preprandial glucose to 5.0 to 12.0 mmol/L (90 to 216 mg/dL). People with established cardiovascular disease have a higher risk of serious outcomes if they develop hypoglycaemia, so glycaemic targets should be less stringent in this group.
  • Patients with impaired awareness of hypoglycaemia (IAH): several weeks of avoidance of hypoglycemia may improve awareness in many patients. Thus, patients with IAH and/or recurrent hypoglycaemia may benefit from short-term relaxation of glycaemic targets.
  • Hospitalized patients: It is appropriate to relax glucose targets for most patients in hospital, whether in ICU or general-ward settings.

Doctors have a duty to inform their patients with diabetes about hypoglycaemia. Topics to cover include:

  • Symptoms and risk factors
  • Short- and long-term consequences of severe hypoglycaemia
  • Medication regimens that may increase and lower the risk of hypoglycaemia
  • Simple strategies to reduce the risk
  • How to self-treat and when to ask for help

If the patient has impaired awareness of hypoglycaemia (IAH), the doctor should advise the patient to stop driving until the condition is reversed.

Questions About IHSG

Yes. IHSG created its materials with the intention of sharing them freely. Downloadable materials are available in the “Resources” section. You can also contact IHSG here to request materials.

Yes. You can use the materials to educate other health professionals, whether in presentations or informal discussions. Some materials may also help in your discussions with patients.

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Yes. You can connect to the IHSG members here

IHSG will regularly update this website with educational resources. Either individually or in small groups, IHSG members will continue to prepare and give talks on hypoglycaemia at major endocrinology/diabetes conferences.