1. Hypoglycemia in the diabetes
control and complications trial
The Diabetes Control and Complications Trial Research Group
Diabetes (1997)
Diabetes and Endocrine Study Day 2013/12/19
Buckfast Abbey Conference Centre
Andrzej Rys
2. Patients/Population
•
•
•
multicentre, randomized clinical trial, 26 clinics across the U.S. + 3 in Canada
patients with IDDM from 1983 to 1989 and followed them until 1993.
1,441 patients randomly assigned to receive intensive (n = 711)/con-ventional (n = 730) Rx
3. Intervention
Clinical goals for both groups - avoidance of symptoms of hyperglycaemia and
hypoglycaemia.
Conventional
Intensive
R/V by health care team 1x
hospitalized to initiate therapy
every 3 months,
seen at least monthly thereafter by the
one or two insulin injections per
health care team#
day,
additional specific targets:
monitor either urine or blood
• Pre-prandial 70-120 mg/dl (3.9-6.67 mmol/l)
glucose without specific numeric
• Post-prandial <180 mg/dl (<10 mmol/l)
glucose targets,
• 03:00 am (tested 1x/week) >65 mg/dl
(>3.61 mmol/l)
Choice of either:
•
•
MDI regimen
continuous subcutaneous insulin infusion
with an external pump
4. Comparison (1)
Conventional (n = 730)
Intensive (n = 711)
Percentage of patients with an event
Percentage of patients with an event
At
study
end
Cumulative
at 9 years
Number
of
Rate
At study
end
Cumulative at Number
9 years
of
Rate
Relativ
e risk
95% Cl
Hypoglycaemi
c events
34.9
41.3
892
18.7
64.6
72.8
2,896
61.2
3.285
(2.65,4.05)
Coma and/or
seizure
18.8
25.5
257
5.4
38.1
47.4
770
16.3
3.02
(2.36,3.86)
Hypoglycaemia risk
CONVENTIONAL
Percentage Number of
n
INTENSIVE
Percentage Number of
with event
events
Rate
n
with event
events
Rate
RR
95% CI
Sex
Male
395
33.9
373
14.63
366
66.4
1,535
63.59
4.35
3.20-5.90
Feniale
335
36.1
519
23.31
345
62.6
1,361
58.69
2.52
1.87-3.38
Adolesce 103
nt
44.7
207
27.80
92
81.5
603
85.74
3.08
1.97-4.84
Adult
33.3
685
16.99
619
62.0
2,293
56.90
3.35
2.63-4.26
AGE
627
6. Outcomes
• Hypoglycemia - the most frequent adverse effect of intensive
therapy of IDDM
• DCCT rate of hypoglycaemic episodes (16.3 per 100 patient-years
in the intensive therapy group) and episodes of loss of
consciousness (11%) were in the range reported elsewhere
• 65% of patients in the intensive group vs. 35% of patients in the
conventional group ≥1 episode of severe hypoglycemia by the study
end
• Intensive treatment - increased risk of multiple episodes within the
same patient (e.g., 22% ≥ 5 episodes of severe hypoglycemia within
the first 5 years of follow- up vs. 4% in the conventional group)
• Both treatment groups - increased risk of subsequent episodes after
1st episode
• Both treatment groups - ~ 30% experienced a 2nd episode within the
4 months fol-lowing the 1st episode
Editor's Notes
Group characteristics:Slighlty more menAvarage age 26 – 27Mainly caucasianMinority ovewightNo significant differences in stimulated C-paptide, HBA1c at eligibility screening, insulin dosage
There were 3,788 episodes of severe hypoglycemia (requiring assistance); 1,027 of these episodes were associated with coma and/or seizure.The overall rates of severe hypoglycemia were 61.2 per 100 patient-years vs. 18.7 per 100 patient-years in the intensive and conventional treatment groups, respectively, with a relative risk (RR) of 3.28. The relative risk for coma and/or seizure was 3.02 for intensive therapy.When baseline patient characteristics were examined for effects on the risk of severe hypoglycemia, the relative risk of hypoglycemia for intensive versus conventional treatment was >2 for all subgroups. Several subgroups defined by baseline characteristics, including males, adolescents, and subjects with no residual C-peptide or with a prior history of hypoglycemia, had a particularly high risk of severe hypoglycemia in both treatment groups.
65% of patients in the intensive group vs. 35% of patients in the conventional group ≥1 episode of severe hypoglycemia by the study end. Cumulative incidence of successive episodes indicated that intensive treatment was also associated with an increased risk of multiple episodes within the same patient (e.g., 22% experienced five or more episodes of severe hypoglycemia within the first 5 years of follow- up vs. 4% in the conventional group). Within both treatment groups, patients who experienced severe hypoglycemia were at increased risk of subsequent episodes. Approximately 30% of patients in each group experienced a second episode within the 4 months following the first episode of severe hypoglycemia.
