Hypoglycemia

Hypoglycemia is dangerous and common event for many patients with diabetes. Although it is more common in DM1, many patients with DM2 will experience this problem. The Diabetes Control and Complications Trial (DCCT) identified hypoglycemia as a major concern, causing symptoms approximately 2 times a week in those with DM1. As patients live longer with DM2, they also develop an increased frequency of hypoglycemia, where 25% of patients using insulin for over 5 years experience this problem regularly. Much of our focus when caring for patients with diabetes is lowering their blood sugar in the hopes of preventing complications. Microvascular complications are reduced by improving glycemic control in both patients with DM1 and DM2, making it the focus of diabetes care. However, randomized trials targeting lower HbA1c levels (ex. ACCORD), found increased mortality in those randomized to tighter glucose control. Although not directly proven, this is likely a result of increased hypoglycemia. This highlights that severe symptoms can occur as a result of hypoglycemia. A study published in Diabetes Care found 100% of patients with DM1 experienced severe hypoglycemia at some point, requiring medical intervention. Recognizing the problem is an opportunity for prevention. Many diabetics with recurrent episodes lose the ability to sense hypoglycemia, putting them at risk for lower levels and additional risks. Symptoms can be broken down into two categories:


1. Neurogenic symptoms - tremor, palpitations, arousal, sweating, hunger (mediated through catecholamine and acetylcholine mechanisms).
2. Neuroglycopenic symptoms - cognitive impairment, coma, seizure and death.

Patient who experience recurrent hypoglycemia are at increased risk for developing hypoglycemia unawareness. This is when, despite hypoglycemia, patients lack symptoms to suggest a problem. Often the first symptom in these patients is confusion, which makes it hard for them to respond appropriately with increased sugar intake. Hypoglycemia unawareness can lead to hypoglycemia associated autonomic failure (HAAF), a form of autonomic insufficiency from recurrent hypoglycemia. In HAAF, patients are unable to mount an appropriate adrenergic response to low blood glucose. HAAF is associated with a significant risk of severe hypoglycemia (25x those without). If glucose levels improve and are maintained, patients will regain the function of their catecholamine axis in several weeks.

Definitions of hypoglycemia are different whether or not a diagnosis of diabetes is present.In those with diabetes any glucose less than 3.9 mmol is considered low. In those without diabetes the guidelines state that patients must have whipples triad:

1. Symptoms that may be explained by hypoglycemia
2. Documented hypoglycemia at the time of symptoms
3.Improvement of symptoms after taking glucose

There are many causes of hypoglycemia, and the approach is different in those with and without diabetes. The most common cause of low glucose is druge related. Several categories exist and can be separated by either "sick patients/medicated" or "well patients":

"Sick/medicated patient"
1. Drugs-insulin, alcohol
2. Critical illness- sepsis
3. Organ failure- renal/liver failure
4. Cortisol deficiency
5. Non-islet cell tumours
"Well patient"
1. Endogenous overproduction of insulin- insulinoma, nesidioblastosis
2. Autimmune- antibodies against endogenous insulin
3. Use of secretagogue- accidental, serruptitious etc.

More details regarding investigations for hypoglycemia and management of this illness in patients with diabetes can be found in the guidelines linked below.

Hypoglycemia guidelines