Blood glucose awareness training and epinephrine responses to hypoglycemia during intensive treatment in type 1 diabetes

OBJECTIVE - To determine the effect of blood glucose awareness training (BGAT) on epinephrine and symptom responses to hypoglycemia in patients with type 1 diabetes enrolled in an intensive diabetes treatment (IDT) program. RESEARCH DESIGN AND METHODS - A total of 47 subjects with uncomplicated diabetes (duration 9 ± 3 years; HbA(1c) 9.0 ± 1.2%; reference range 4-6%) enrolled in a 4-month outpatient IDT program were randomized to classes in BGAT (n = 25) (BGAT group) or cholesterol awareness (n = 22) (control group). Subjects underwent stepped hypoglycemic clamp studies before and at completion of IDT. Plasma glucose was lowered from 6.7 mmol/l (base-line) to 4.4, 3.9, 3.3, 2.8, and 2.2 mmol/l over 190 min. Symptoms, counterregulatory hormones, and ability of the subject to estimate their glucose level were assessed at each plateau. At home, subjects used a handheld computer to first estimate and then measure and record blood glucose levels for 70 trials over a 4-week period immediately before IDT and again immediately following the educational intervention. RESULTS - HbA(1c) decreased in both BGAT group (9.1 ± 1.4 to 7.9 ± 1.1%; P < 0.001) and control group (9.0 ± 1.1 to 7.8 ± 0.8%; P < 0.001) (NS between groups). Frequency of hypoglycemia (<3.9 mmol/l) increased in both groups, from 0.45 ± 0.06 to 0.69 ± 0.07 episodes per day (P < 0.001) in the BGAT group and from 0.50 ± 0.08 to 0.68 ± 0.06 episodes per day (P < 0.05) in the control group (NS between groups). Epinephrine responses after IDT were greater in the BGAT group (repeated measure analysis of variance [ANOVA], F = 3.5, P < 0.05). A separate analysis of subjects (n = 26) most at risk for hypoglycemia (HbA(1c) after IDT <7.8% or an HbA(1c) improvement of >2 percentage points) showed that frequency of hypoglycemia increased in both the groups: from 0.50 ± 0.09 to 0.80 ± 0.11 episodes per day (P < 0.01) in the BGAT group (n = 14) and from 0.43 ± 0.11 to 0.75 ± 0.07 episodes per day (P < 0.05) in the control group (n = 12) (NS between groups). However, the epinephrine response in control subjects decreased with IDT while the response in the BGAT subjects was preserved (repeated measure ANOVA, F = 4.4, P < 0.02). CONCLUSIONS - BGAT is a useful intervention to decrease blunting of counterregulatory responses associated with improved glycemic control and may modify the severity of hypoglycemia associated with improved glycemic control in type 1 diabetes.