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.


METHODS
A total of 47 subjects with uncomplicated diabetes (duration 9 +/- 3 years: HbA1c 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 (baseline) 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
HbA1c 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 (HbA1c after IDT < 7.8% or an HbA1c 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.
Kinsley
B T
BT
Section of Diabetes and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Weinger
K
K
Bajaj
M
M
Levy
C J
CJ
Simonson
D C
DC
Quigley
M
M
Cox
D J
DJ
Jacobson
A M
AM
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001364:Awareness; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy* / Q000534:rehabilitation; D004837:Epinephrine / Q000097:blood*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010353:Patient Education as Topic; D010465:Perception; D012307:Risk Factors
D000324:Adrenocorticotropic Hormone; D001786:Blood Glucose; D002784:Cholesterol; D004837:Epinephrine; D006442:Glycated Hemoglobin; D019382:Human Growth Hormone; D006854:Hydrocortisone; D007004:Hypoglycemic Agents; D007328:Insulin