Epidemiology and risk factors of hypoglycaemia in type 1 DM

Hypoglycemia in type 1 diabetes is more or less unavoidably the consequence of the limitations of current insulin agents. The 'fire and forget' administration mode of exogenous insulin does not mimic endogenous insulin release as the latter may change rapidly in response to glucose levels. Some patients with type 1 diabetes are far more susceptible for hypoglycaemia than others, depending on factors such as the duration of diabetes. Thus, a newly diagnosed patient with some residual beta-cell function may not suffer from any hypoglycaemia.

Type 1 diabetes

Incidence of hypoglycaemia

Prospective studies have reported an average incidence of 2 episodes per patient per week. The distribution of episodes is much skewed, with some individuals reporting no events and others reporting multiple episodes per week. It is estimated that 85% of the type 1 diabetes patients have at least one episode per year. In unselected populations of people with type 1 diabetes, the estimated incidence of severe hypoglycaemia (usually defined as third party assistance) is ranging from 1.0 to > 3.0 episodes per patient per year.

Risk factors for mild hypoglycaemia

Hypoglycaemia is by definition the result of (relative) insulin excess and/or lack of glucose (availability). This may be due to missed meals, meals unexpectedly low in carbohydrates, exercise, miscalculated high insulin dose or hot weather (enhanced insulin uptake). However, conditions such as kidney failure and celiac disease should also be considered in this respect, because these lead to reduced clearance of insulin or reduced uptake of carbohydrates, respectively. Alcohol reduces the ability of the liver to form glucose (gluconeogenesis). Exercise may also increase the risk of hypoglycaemia, both during the activity itself and in the recovery period (up to 20 hours after exercise). It is believed that the duration of diabetes has little impact on the frequency of mild hypoglycaemia in patients with type 1 diabetes.

Risk factors for severe hypoglycaemia

There are several factors that increase the risk of severe hypoglycaemia in patients with type 1 diabetes:

  • strict glycaemic control, reflected by near normal glycated hemoglobin levels, is a risk factor severe hypoglycaemia. The Diabetes Control and Complications Trial DCCT) showed a quadratic relation beween HbA1c level and severe hypoglycaemia. The risk of severe hypoglycaemia increased with decreasing HbA1c levels. However, HbA1c is only one of the factors impacting on the risk of hypoglycaemia, along with many others (see below).
  • intensive insulin therapy may lead to an increased risk of severe hypoglycaemia, independent of HbA1c. The DCCT showed that patients with intensive insulin therapy had a higher risk of severe hypoglycaemia and this was not necessarily caused by lower HbA1c levels since patients in the control group had lower levels of hypoglycaemia even if they happened to have the same HbA1c.
  • a previous episode of hypoglycaemia
  • complete insulin deficiency (C-peptide negative). Residual beta-cell function has a protective effect, probably because the patient is not completely dependent on exogenous insulin and still partially able to modulate his/her own circulating insulin levels.
  • impaired awareness of hypoglycaemia
  • There is small effect for duration of diabetes. The observation that duration of diabetes has little impact on the risk of hypoglycaemia is probably due to the fact that very tight glycaemic control can be pursued or may be a reflection of the inability to accurately assess hypoglycaemic frequency.

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