Leptin treatment prevents impaired hypoglycemic counterregulation induced by exposure to severe caloric restriction or exposure to recurrent hypoglycemia.

Hypoglycemia-associated autonomic failure (HAAF) is a maladaptive failure in glucose counterregulation in persons with diabetes (PWD) that is caused by recurrent exposure to hypoglycemia. The adipokine leptin is known to regulate glucose homeostasis, and leptin levels fall following exposure to recurrent hypoglycemia. Yet, little is known regarding how reduced leptin levels influence glucose counterregulation, or if low leptin levels are involved in the development of HAAF.

Consuming a ketogenic diet leads to altered hypoglycemic counter-regulation in mice.

Ketogenic diets (KDs) are becoming increasingly popular for the treatment of diabetes, yet they are associated with increased frequency of hypoglycemia. Here we report that mice fed a KD display blunted glucagon release to hypoglycemia and neuroglucopenia, suggesting that consuming a KD may increase the risk for iatrogenic hypoglycemia.