Impaired hypoglycemia awareness in diabetes: epidemiology, mechanisms and therapeutic approaches

Impaired awareness of hypoglycemia (IAH) is a frequent complication of insulin therapy. Up to half insulin-treated individuals with type 1 and type 2 diabetes report the problems with hypoglycemia awareness, and 1525% of patients have a permanent IAH. A recurrent hypoglycemia is a cornerstone in IAH formation. The repeated episodes of hypoglycemia impair neurohumoral response to hypoglycemia, reduce its symptoms and induce inadequate brain adaptation to low glucose levels. In this regard, the IAH phenomenon can be considered as an example of "metabolic memory" in diabetes. The IAH is associated with episodes of severe hypoglycemia, fear of hypoglycemia and cognitive dysfunction. These associates can be combined into IAH syndrome. Development of IAH becomes a serious barrier in diabetes management. A growing body of evidence indicates that IAH is a reversible condition. If the syndrome is present, the hypoglycemia avoidance should be primary goal of the treatment. Structured training under specialized programs with psychological support is the most reasonable therapeutic approach to IAH amending. Technological approaches, including continuous subcutaneous insulin infusion, real-time continuous glucose monitoring, closed-loop insulin delivery systems ("artificial pancreas"), and islet transplantation also showed efficacy in hypoglycemia awareness improvement in some clinical studies. The diabetes management in patients with IAH is time-consuming and expensive. Therefore, step-by-step approach, from insulin personalization and therapeutic training to advanced medical technologies, should be recommended for these patients.