1. DCCT
OVMC LANDMARK TRIALS SERIES
The Diabetes Control and Complications Trial (DCCT).
“The effect of intensive treatment of diabetes on the
development and progression of long term
complications in insulin-dependent diabetes mellitus.”
New England Journal of Medicine.1993; 329:977-986
2. The Diabetes Control and Complications Trial (DCCT)
Summarized by: Maria Morkos, MD; Laxmi Suthar, MD
3. BACKGROUND
Insulin dependent diabetes mellitus
causes much morbidity and
mortality, including many long term
microvascular and neurological
complications
Up until this study it was unclear if
tight glycemic control could
decrease or prevent such
complications
4. CLINICAL QUESTION
How would intensive diabetes
management compare with
conventional therapy in regards to the
development and progression of early
vascular and neurologic complications
of IDDM?
retinopathy
nephropathyneuropathy
5. DESIGN
Analysis: intention to treat; chi-square test, Wilcoxon rank-sum test
Randomized, unblinded, multicenter design (29 centers in United States)
N= 1441
Group 1: 726 primary prevention
Group 2: 715 secondary intervention
Participants in each group were randomized to either conventional or intensive
treatment
Median follow-up: 6.5 years
Outcomes: microvascular complications (neuropathy, nephropathy,
retinopathy)
6. POPULATION
Inclusion Criteria
13-39 years old
T1DM defined by C-peptide deficiency
Primary prevention group
T1DM 1-5 years
No retinopathy
Urinary albumin excretion <40 mg/24
hours
Secondary intervention group
T1DM 1-15 years
Mild-moderate non-proliferative
retinopathy
Exclusion Criteria
Hypertension
Hyperlipidemia
Severe diabetic complications
7. INTERVENTIONS
Intensive therapy
>3 insulin injections/day, or use of an insulin pump
Goal pre-prandial blood glucose 70-120; goal post-prandial <180
Goal A1c <6.05%
Conventional therapy
1-2 daily insulin injections
Adjustments to insulin only to avoid sx of hypo/hyperglycemia or ketonuria
8. RESULTS
In primary prevention group, intensive insulin therapy (compared to conventional therapy) reduced
adjusted mean relative risk of developing
retinopathy by 76%
microalbuminuria by 34%
clinical neuropathy by 69%
In secondary intervention group, intensive insulin therapy (compared to conventional tx) reduced
adjusted mean relative risk of worsened
retinopathy by 54%
microalbuminuria by 43%
clinical neuropathy by 57%
9. RESULTS
Mean blood glucoses were
155+/-30 mg/dL in intensive tx group
231 +/- 55 mg/dL in conventional tx group
Hypoglycemia 3x higher in intensive group
Increased weight gain in intensive group
No differences in macrovascular events
No difference in mortality
10. CRITICISMS
Follow-period (6.5 years) was too short to evaluate for macrovascular outcomes
Did not look at patients with severe microvascular complications
Limited age range
Excluded pts with HTN and HLD (?applicability)
Types of insulin were not standardized
Unblinded trial
11. BOTTOM LINE
In Type 1 diabetics, intensive
therapy with insulin slows
progression of microvascular
complications (nephropathy,
neuropathy, and retinopathy)
12. DISCUSSION QUESTIONS
What were the two arms of the study, in general terms?
What outcomes/endpoints did the study look at?
What were two negative outcomes in the intensive therapy group?
What were two outcomes that did not differ between the two groups (intensive
and conventional therapy groups)?
13. DISCUSSION ANSWERS
What were the two arms of the study, in general terms?
ANSWER: primary prevention (early T1DM) and secondary intervention (more progressed T1DM)
What outcomes/endpoints did the study look at?
ANSWER: microvascular complications (retinopathy/nephropathy/neuropathy)
What were two negative outcomes in the intensive therapy group?
ANSWER: higher risk of hypoglycemia and weight gain
What were two outcomes that did not differ between the two groups (intensive and
conventional therapy groups)?
ANSWER: macrovascular events and mortality
14. BOARD-LIKE QUESTION
57 yo M with a history of DM and CAD is
evaluated for b/l burning sensation in his
feet for the last 6 months. The sensation
worsens at night. His A1c’s were <7% for the
last two years but previously were 8-9%
(prior to switching to insulin two years ago).
Medications are regular insulin, NPH insulin,
aspirin, metoprolol, atorvastatin, and
lisinopril.
PE findings are compatible with distal
polyneuropathy. Labs including CBC are wnl.
(Adapted from MKSAP)
QUESTION
Which of the following is the most
appropriate management of this patient’s
neuropathy?
A. Amitriptyline
B. Duloxetine
C. Nerve conduction study
D. Vitamin B12 measurement
15. BOARD-LIKE QUESTION
Educational Objective:
Manage diabetic neuropathy
Key Point:
- Damage to small nerve fibers leads to
pain/numbness/burning/tingling;
damage to large nerve fibers leads to
abnormal vibration sensation and
proprioception.
- Amitriptyline in a patient like this one
with CAD increases the risk for
arrhythmias, heart block, and sudden
death.
- NCS not necessary in classic stocking-
glove distribution; B12 measurement
unnecessary since labs are wnl.
QUESTION
Which of the following is the most
appropriate management of this patient’s
neuropathy?
A. Amitriptyline
B. Duloxetine
C. Nerve conduction study
D. Vitamin B12 measurement
16. REFERENCES
The effect of intensive treatment of diabetes on the development and progression of long term
complications in insulin-dependent diabetes mellitus (1993). New England Journal of Medicine, 329:977-
986. doi 10.1056/NEJM199309303291401