Hypoglycemia Risk and Glucose Variability Indices Derived from Routine Self-Monitoring of Blood Glucose Are Related to Laboratory Measures of Insulin Sensitivity and Epinephrine Counterregulation

Background: The widely held assumptions that in type 1 diabetes glucose variability may correlate with insulin sensitivity and impaired epinephrine counterregulation have not been studied directly. Here we investigate possible relationships between outpatient measures of glucose variability and risk for hypoglycemia with physiological characteristics: insulin sensitivity and hypoglycemia counterregulation. Methods: Thirty-four subjects with type 1 diabetes (14 women, 20 men; 37 +/- 2.1 years old; glycosylated hemoglobin [HbA1c], 7.6 +/- 0.21%) 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. Spearman partial correlations adjusted for age, duration of diabetes, body mass index, gender, and HbA1c were used to assess the relationship between the field indices of glucose variability and the physiological characteristics of diabetes. Results: Two glucose variability measures correlated positively (P<0.01) with insulin sensitivity: the Average Daily Risk Range (ADRR) (rho = 0.5) and the Glycemic Lability Index (rho = 0.48). The Low Blood Glucose Index, a measure of the risk for hypoglycemia, and the ADRR correlated negatively with maximum epinephrine response during hypoglycemia: rho = -0.46, P<0.01 and rho = -0.4, P = 0.03, respectively. Conclusions: Higher insulin sensitivity and lower epinephrine response during hypoglycemia are related to increased glucose variability (as quantified by the ADRR), irrespective of HbA1c and other patient characteristics. Lower epinephrine relates to risk for hypoglycemia as well.