Effect of Fasting on Hypoglycemic Counterregulation in Type 1 Diabetes

Iatrogenic hypoglycemia is still considered to be the number one barrier to effective glycemic control in patients with type 1 diabetes (T1D). In a previous study, it was observed in people without diabetes that fasting can be detrimental to the hormonal and hepatic responses to insulin-induced hypoglycemia. In the experiments described herein, the impact fasting has on hypoglycemic counterregulation in people with T1D will be determined.

Because patients with type 1 diabetes (T1D) are required to estimate and administer their own insulin requirements, they frequently overestimate their needs. This often leads to debilitating insulin-induced hypoglycemia, which is the number one barrier to the safe, effective management of glycemia in this population. In addition to the difficulty estimating one's own insulin requirements after a meal, counterregulatory hormone responses to hypoglycemia are impaired in patients with T1D, thereby reducing hepatic glucose production (HGP) and increasing the depth and duration of the hypoglycemic episode. The discovery of ways by which counterregulatory responses to hypoglycemia can be improved in people with T1D is a priority. In previous experiments, it was observed that fasting reduces counterregulatory hormone secretion in healthy humans during insulin-induced hypoglycemia, thereby reducing hepatic glucose production (HGP). Therefore, the studies proposed herein will determine the effect of fasting on hypoglycemic counterregulation in people with T1D. It is hypothesized that fasting will diminish the hormonal and hepatic responses to insulin-induced hypoglycemia. Each subject will undergo two trials; one where they eat an isocaloric breakfast and lunch prior to an insulin-induced hypoglycemic challenge and a second one during which they remain fasted prior to the hypoglycemic challenge. This study design will allow assessment of the relationship between fasting and the counterregulatory responses to insulin-induced hypoglycemia in a population that is particularly vulnerable to low blood sugar.