One month of self-monitored blood glucose (SMBG) field data was used to calculate measures of glucose variability and risk of hypoglycemia, while the hyperinsulinemic, euglycemic and hypoglycemic clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia.

At 21:30h, an overnight insulin infusion was titrated to control the subjects' BG overnight between 100 and 150mg/dL by blood sampling for plasma glucose via a YSI analyzer every 30min and adjusting the rate of insulin infusion as needed. At the beginning of the clamp, the overnight insulin was replaced by an insulin infusion via a Harvard pump given as a 20mU/kg priming over a 10-min period, followed by a constant rate delivery of 1mU/kg/min until the end of the clamp. Blood was sampled for plasma glucose, and glucose was clamped at basal levels for the euglycemic control period of 150min via a variable-rate infusion of 20% dextrose. Then the glucose concentration was lowered at a rate of 1mg/dL/min to a minimum of 50mg/dL, where it was held constant for 30min. Finally, the glucose concentration was increased at a rate of 1mg/dL/min to 90mg/dL, where it was held for an additional 30min. Blood was sampled for epinephrine during euglycemia, hypoglycemia, and recovery.

Mean maximum epinephrine response during induced hypoglycemia is the average of subjects' maximum concentration of all epinephrine measurements taken at plasma glucose level lower than 70mg/dL.

Low blood glucose index (LBGI) is a metric to calculate the risk for hypoglycemia based on frequency and extent of past events based on SMBG readings. In studies, the LBGI typically accounted for 40-55% of the variance of future significant hypoglycemia in the subsequent 3-6 months. The LBGI has established risk categories: Low Risk, LBGI < 2.5; Moderate Risk, 2.5 < LBGI < 5; and High Risk, LBGI > 5, indicating an over 10-fold increase in future severe hypoglycemia from the lowest to the highest risk category.

Mean maximum epinephrine response during induced hypoglycemia is the average of subjects' maximum concentration of all epinephrine measurements taken at plasma glucose level lower than 70mg/dL.

Average Daily Risk Range (ADRR) is associated with glycemic variability and risk of both hyper- and hypoglycemia.

Low Risk, ADRR < 20; Moderate Risk, 20 < ADRR < 40; and High Risk,ADRR > 40.

Subjects with type 1 diabetes performed self-monitoring of blood glucose (SMBG) for a month, followed by an inpatient hyperinsulinemic euglycemic and hypoglycemic clamp. SMBG field data were used to calculate measures of glucose variability and risk of hypoglycemia, while the clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia.

Mean maximum epinephrine response during induced hypoglycemia is the average of subjects' maximum concentration of all epinephrine measurements taken at plasma glucose level lower than 70mg/dL.

Low blood glucose index (LBGI) is a metric to calculate the risk for hypoglycemia based on frequency and extent of past events based on SMBG readings. In studies, the LBGI typically accounted for 40-55% of the variance of future significant hypoglycemia in the subsequent 3-6 months. The LBGI has established risk categories: Low Risk, LBGI < 2.5; Moderate Risk, 2.5 < LBGI < 5; and High Risk, LBGI > 5, indicating an over 10-fold increase in future severe hypoglycemia from the lowest to the highest risk category.

3 participants did not have adequate epinephrine data.

Subjects with type 1 diabetes performed self-monitoring of blood glucose (SMBG) for a month, followed by an inpatient hyperinsulinemic euglycemic and hypoglycemic clamp. SMBG field data were used to calculate measures of glucose variability and risk of hypoglycemia, while the clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia.