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

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

InterventionClinical goals for both groups - avoidance of symptoms of hyperglycaemia and hypoglycaemia.

Conventional Intensive

R/V by health care team 1x every 3 months,

one or two insulin injections per day,

monitor either urine or blood glucose without specific numeric glucose targets,

hospitalized to initiate therapy seen at least monthly thereafter by the

health care team# additional specific targets:

• Pre-prandial 70-120 mg/dl (3.9-6.67 mmol/l)• Post-prandial <180 mg/dl (<10 mmol/l) • 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

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 9 years

Number of

Rate Relative risk

95% Cl

Hypoglycaemic 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 ofINTENSIVE

Percentage Number of

n 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

AGE

Adolescent 103 44.7 207 27.80 92 81.5 603 85.74 3.08 1.97-4.84

Adult 627 33.3 685 16.99 619 62.0 2,293 56.90 3.35 2.63-4.26

Comparison (2)CONVENTIONAL

Percentage Number ofINTENSIVE

Percentage Number of

n with event events Rate n with event events Rate RR 95% CI

Stimulated C-peptide (pmol/ml)

<0.20 565 37.5 787 20.79 572 68.5 2,598 66.94 3.22 2.56-4.05

>0.20 165 26.1 105 10.61 139 48.2 298 34.99 3.30 1.94-5.62

IDDM duration (years)

<6 469 30.1 457 15.64* 436 61.0 1,522 54.87 3.51 2.5.5-4.83

6-10 128 48.4 232 25.91 119 67.2 574 67.00 2.59 1.74-3.84

>10 133 39.1 203 21.19 156 72.4 800 72.56 3.42 2.33-5.04

HbA1c at eligibility screening (%)

<7.825 189 45.0 327 27.22 171 59.1 607 56.93 2.09 1..37-3.19

7.82.5- 8.819 185 38.9 232 18.82 175 67.4 682 58.65 3.12 2.15-4.51

8.820- 10.099 166 30.7 176 16.07 192 68.8 898 66.39 4.13 2.79-6.13

10.100+ 190 24.7 157 12.60 173 62.4 709 61.59 4.89 3.05-7.83

Insulin (U/kg)

<0.635 373 27.6 290 12.41 345 55.9 1,090 49.26 3.97 2.73-5.76

>0.635 357 42.6 602 24.68 366 72.7 1,806 71.66 2.90 2.25-3.75

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