dcct landmark trial

Grethel Fatima Castañeda, MD With

Hannah Urbanozo-Corpuz, MD, FPCP, FPSEDM

9 February 2017

Journal Club

GRETHEL FATIMA CASTAÑEDA, MD WITH

HANNAH URBANOZO-CORPUZ, MD, FPCP, FPSEDM

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.

Diabetes Control and Complications Trial

Conventional Treatment

◦ 1-2 insulin injections per day

Intensive Treatment

◦ > 3 insulin injections per day

◦ Insulin pump

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

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

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?

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

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.

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.

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.

intensive

conventional

Abnormal

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%

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

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

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.

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

•  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