Nocturnal hypoglycemia: answering the challenge with long-acting insulin analogs

Abstract

Background: Nocturnal hypoglycemia may be the most common type of hypoglycemia in individuals with diabetes using insulin and is particularly worrisome because it often goes undetected and may lead to unconsciousness and even death in severe cases.

Objectives: The prevalence, causes, and consequences of nocturnal hypoglycemia as well as detection and prevention strategies are reviewed, including the use of long-acting insulin analogs, which offer more physiologic and predictable time-action profiles than traditional human basal insulin.

Data sources: A total of 307 publications (151 PubMed; 104 Adis; 52 BIOSIS) were reviewed.

Review methods: Relevant trials were found by searching for "(detemir OR glargine) AND nocturnal AND (hypoglycemia OR hypoglycaemia) AND diabetes." To capture trials that may not have specified "nocturnal" in the title or abstract text but still reported nocturnal hypoglycemia data, a supplemental search of PubMed using "(detemir OR glargine) AND (nocturnal OR hypoglycemia OR hypoglycaemia) AND diabetes" was undertaken.

Results: A review of these trials found that patients with type 1 and type 2 diabetes mellitus have a lower risk for nocturnal hypoglycemia when receiving long-acting insulin analogs (insulin detemir or insulin glargine), provided that glycemic control is comparable to that provided by traditional human basal insulin. Long-acting insulin analogs may be the best option to provide basal insulin coverage in patients who do not choose or require continuous subcutaneous insulin infusion.

Conclusions: Randomized clinical trials suggest that the long-acting insulin analogs are associated with a lower risk for nocturnal hypoglycemia than neutral protamine Hagedorn without sacrificing glycemic control.

Figure 1

The cycle of frequent hypoglycemia, illustrating the impact of impaired counterregulation that exists in diabetes. Sleep, with reduced cognition and sympathetic output, and other behavioral factors contribute. Frequent hypoglycemic episodes, whether daytime or nighttime, can lead to impaired sympathoadrenal responses, symptom loss, and hypoglycemia unawareness, and eventually, may lead to severe hypoglycemia. Figure adapted from Fanelli et al. Copyright John Wiley & Sons Limited. Reproduced with permission.