The DCCT Landmark Trial The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-term Complications in Insulin Dependent Diabetes Mellitus

1. Grethel Fatima Castañeda, MD
With
Hannah Urbanozo-Corpuz, MD, FPCP, FPSEDM

2. 9 February 2017
Journal Club
GRETHEL FATIMA CASTAÑEDA, MD
WITH
HANNAH URBANOZO-CORPUZ, MD, FPCP, FPSEDM

3. What is the DCCT?
◦ Diabetes Control and Complications Trial (DCCT)
◦ major clinical study conducted from 1983 to 1993
◦ National Institute of Diabetes and Digestive and Kidney Diseases
◦ The study compared the effects of standard control of blood glucose versus
intensive control on the complications of diabetes.

4. Diabetes Control and Complications Trial
Conventional Treatment
◦ 1-2 insulin injections per day
Intensive Treatment
◦ > 3 insulin injections per day
◦ Insulin pump

5. DCCT (1983-1993)
◦ Study Design: parallel-arm, randomized clinical trial
◦ Study Population: 1441 IDDM, 13-39yrs old
◦ primary prevention cohort (726 no retinopathy)
◦ secondary intervention cohort (715 mild retinopathy)
◦ Intervention: (unmasked)
◦ Intensive arm: insulin pump or ≥ 3 daily insulin injections
◦ Conventional arm: 1-2 insulin injections

6. ELIGIBILITY CRITERIA
PRIMARY PREVENTION SECONDARY PREVENTION
MAJOR CRITERIA
Insulin dependence
13-39 y/o
No hypertension, hypercholesterolemia or severe diabetic
complications
IDDM for 1-5 years IDDM for 1-15 years
No retinopathy Mild to moderate retinopathy
Urine albumin <40mg in 24 hrs Urine albumin <200mg in 24 hrs

8. CLINICAL QUESTIONS
Primary prevention
◦ Will an intensive treatment
program prevent the
development of
retinopathy in patients with
no retinopathy?
Secondary intervention
◦ Will such an intervention
affect the progression of
early retinopathy to more
advanced forms of
retinopathy?

10. RESULTS
◦ 99% competed the study
◦ 11 died
◦ 32 inactive
◦ 8 lost to ff up
◦ 95 women, originally on conventional treatment transferred
to intensive treatment during pregnancy

12. How did intensive treatment affect
diabetic eye disease?
◦ All DCCT participants were monitored for diabetic retinopathy
◦ Study results showed that intensive therapy reduced the risk for
developing retinopathy by 76 percent.
◦ In participants who had some eye damage at the beginning of
the study, intensive management slowed the progression of the
disease by 54 percent.

15. How did intensive treatment affect
diabetic kidney disease?
◦ Participants in the DCCT were tested to assess the
development of diabetic kidney disease, or
nephropathy.
◦ Findings showed that intensive treatment prevented the
development and slowed the progression of diabetic
kidney disease by 56 percent.

18. How did intensive treatment affect
diabetic nerve disease?
◦ Participants in the DCCT were examined to
detect the development of nerve damage, or
diabetic neuropathy.
◦ Study results showed the risk of nerve damage
was reduced by 60 percent in people on
intensive treatment.

20. intensive
conventional
Abnormal

21. How did intensive treatment affect
diabetes-related cardiovascular
disease?
◦ Detection macrovascular events were unlikely due to
short time frame.
◦ Reduced development of hypercholesterolemia (LDL
>160mg/dl) by 34%

22. What are the risks of intensive
treatment?
◦ HYPOGLYCEMIA
◦ 3x increase both in the intensive and conventional
treatment groups
◦ 62 px in intensive vs 19 px in conventional treatment
◦ Seizure due to hypoglycemia - 16 px in intensive vs 5
px in conventional treatment
◦ 2 – vehicular accident
◦ Hospitalization due to hypoglycemia - 54 px in
intensive vs 36 px in conventional treatment

23. What are the risks of intensive
treatment?
◦ WEIGHT GAIN
◦ Body weight > 120% of IBW
◦ Increased by 33% in intensive treatment
◦ DKA
◦ 1.8 episodes in conventional treatment
◦ 2 episodes in intensive treatment

24. SUMMARY and RECOMMENDATIONS
◦ Intensive therapy delays the progression of clinically important retinopathy.
◦ There is transient worsening of retinopathy with intensive therapy which
occurred mainly on the first year of therapy.
◦ Intensive therapy reduced the risk of albuminuria and microalbuminuria.
◦ Whether the decrease in albuminuria and microalbuminuria result in the
decrease of renal insufficiency, follow-up of the entire cohort must be
done.

25. SUMMARY and RECOMMENDATIONS
◦ The ability of intensive therapy to reduce development of neuropathy
suggests that neuropathy may be preventable.
◦ Whether intensive therapy may reduce macrovascular complications
requires further investigation.
◦ Benefits of reducing hyperglycemia are extended to NIDDM patients

26. • IDDM patient are better treated with closely monitored
intensive therapy.
• Keeping blood glucose levels as close to normal as possible
slows the onset and progression of the eye, kidney, and
nerve damage caused by diabetes.
• The study demonstrated that any sustained lowering of
blood glucose helps, even if the person has a history of poor
control.
LEARNING POINTS