The 30+ year DCCT-EDIC trial provided important insights into the long-term effects of intensive glycemic control in type 1 diabetes patients. The DCCT found that intensive control significantly reduced the risk of developing diabetic complications compared to conventional treatment. The EDIC observational follow-up study found these benefits were durable, and intensive control continued to have beneficial effects on complications even after glycemic control was relaxed. Together, DCCT-EDIC established intensive glycemic control as the standard of care for type 1 diabetes and demonstrated its benefits in both preventing and delaying complications over the long term.

1. DCCT- EDIC
THE THIRTY PLUS YEARS TRIAL
LESSONS AND OUTCOMES
DCC = DIABETES CONTROL AND COMPLICATIONS TRIAL
EDIC = EPIDEMIOLOGY OF DIABETES INTERVENTIONS AND COMPLICATIONS STUDY
Mohammad Daoud , MD
Consultant Endocrinologist –ABIM
KAMC-NGHA , Jeddah

2. DM is Not a Number
DM= A Cardiovascular Disease
Complications : Micro / Macro
Hidden Faces of :
Sexual dysfunction ,Diabetic foot
Depression

3. Barriers
Therapeutics ,Physicians (Inertia) and Patients
Legacy effect
The key is: Rx Glycemia and other CVD risk factors simultaneously

4. WHAT ABOUT TYPE 1 DM PATIENTS…
DOES THE SAME CONCEPTS APPLY ?

5. DCCT –EDIC
Overview

6. DCCT/EDIC: Overview
• The DCCT was designed to test the glucose hypothesis and
determine whether the complications of type 1 diabetes
could be prevented or delayed (1982–1993)
• The EDIC observational follow-up study determined the
durability of the DCCT effects on the more-advanced stages
of diabetes complications including cardiovascular disease
(1994–present)
Nathan et al. Diabetes Care 2014;37:9–16
AIMS: determine whether conventional therapy and intensive
treatment program prevent or delay the appearance of early
background retinopathy (primary prevention) and would prevent the
progression of early retinopathy to more advanced forms of
retinopathy (secondary intervention)
DCCT : Diabetes Control and Complications Trial;
EDIC : Epidemiology of Diabetes Interventions and Complications

7. Initial DCCT Results Presented at ADA 1993
•Initial results of the DCCT were presented in 1993 at
the 53rd Scientific Sessions of the American Diabetes
Association in Las Vegas, NV, USA
• The significance of the findings was instantly apparent
• Results meant that there was no more guessing on what the
standards of treatment should be
• Initial results ushered in a new paradigm of treatment
•No one could predict what was to come of the DCCT
over the next 20 years!
ADA, American Diabetes Association

8. DCCT/EDIC: Timelines and Key Publications
1982 1994 2013
EDIC (20 years)
1993
DCCT (10 years)
1992
Design and
methodology
considerations
for the
feasibility
phase, 1986
Results of
feasibility
study, 1987
First DCCT
results,
1993
Key publications Implementation
of treatment
protocols in the
DCCT, 1995
Adverse events
in the DCCT,
1995
Relationship of
HbA1c to the
risk of
development
and progression
of retinopathy,
1995 Pregnancy
outcomes, 1996
Hypoglycaemia,
1997
Design of EDIC,
1999
Retinopathy
and
nephropathy
four years after
intensive
therapy, 2000
Effect of
intensive
therapy on
microvascular
complications,
2002
Effect of
glycaemic
exposure on the
risk of
microvascular
complications,
2008
Effects of prior
intensive insulin
therapy on
cardiac
autonomic
nervous system
function, 2009
Effect of prior
intensive insulin
treatment on
peripheral
neuropathy,
2010
The DCCT/EDIC at 30 years,
2014
Results presented
at ADA, 1993

9. DCCT / EDIC
DESIGN AN METHODS

10. Patients
•Eligibility criteria
•13–39 years of age
•Type 1 diabetes diagnosed based on clinically-accepted criteria
•Fasting C-peptide <0.2 nmol/L
•Generally healthy
•No history of cardiovascular disease
•No hypertension (blood pressure <140/90 mmHg)
•No dyslipidaemia
•No neuropathy requiring treatment
Nathan et al. Diabetes Care 2014;37:9–16

11. Patients
•Primary prevention cohort (n=726)
•Type 1 diabetes of 1–5 years’ duration
•No detectable retinopathy
•Urinary albumin <40 mg/24 hours
Nathan et al. Diabetes Care 2014;37:9–16
•Secondary intervention cohort (n=715)
•Type 1 diabetes of 1–15 years’ duration
•Very mild-moderate non-proliferative retinopathy
•Urinary albumin 200 mg/24 hours

12. Interventions and Metabolic Goals
•Conventional group (n=730)
• Aim: to avoid symptoms of
hyper/hypoglycaemia
• 1 or 2 insulin injections per day
• Daily self-monitoring
• Pregnant women treated intensively
• Diet and exercise education
• Quarterly visits
Nathan et al. Diabetes Care 2014;37:9–16
•Intensive group (n=711)
• Aim: symptom-free + plasma glucose
3.9–6.7 mmol/L before meals, <10
mmol/L after meals, >4.0 mmol/L at
03:00 a.m. and HbA1c <6.05 %
• ≥3 insulin injections/day or insulin pump
• ≥4 daily blood glucose tests
• Hospitalisation for initiation
• Frequent dietary instructions
• Monthly clinic visits

13. Study Design
DCCT Research Group. N Engl J Med 1993;329:977–86; Nathan et al. Diabetes Care 2014;37:9–16
Primary prevention (n=726)
(No detectable retinopathy)
Secondary prevention (n=715)
(Very mild-moderate
nonproliferative retinopathy)
1441 patients
Randomisation Randomisation
Conventional
(n=378)
Conventional
(n=352)
Intensive
(n=348)
Intensive
(n=363)
DCCT
(1982–1993)
EDIC
(1994–present)
All patients offered intensive treatment (n=1394)
Observational follow-up until 2012 (n=1284)

14. DCCT/EDIC: Outcome Measurements
Nathan et al. Diabetes Care 2014;37:9–16
Frequency
Complication DCCT EDIC Defined outcomes
Retinopathy: 7-field
stereoscopic and fundus
photography
6 months
1/4 cohort/year,
entire cohort
year 4
Three-step progression*, CSME, severe
NPDR, PDR
Renal function
Albumin excretion#
Serum creatinine
(eGFR†)
Annual
Annual
Alternate years‡
Annual
Albuminuria: micro ≥40 mg/24 h,
macro >300 mg/24 h
eGFR: <60 mL/min/1.73 m2
Neuropathy
History, examination,
and NCS
Autonomic
Cardiac
Urologic (ED)
MNSI + monofilament
Baseline, year 5,
and/or study
end
Baseline, every
2 years, end
–
–
Year 13/14
Years 13/14 and
16/17
Year 10
Annual
Confirmed clinical: abnormal exam and
abnormal NCS or autonomic study
R-R variation <15 or R-R <20 and
Valsalva ratio <1.5 or orthostatic
hypotension

15. DCCT/EDIC: Outcome Measurements (continued)
Nathan et al. Diabetes Care 2014;37:9–16
Frequency
Complication DCCT EDIC Defined outcomes
Cardiovascular
History
ECG
Ankle-brachial index
Carotid ultrasound
CT CAC
Cardiac MRI
Annual
Annual
Annual
–
–
–
Annual
Annual
Annual
Years 1, 6, and
12
Year 8
Year 15
Aggregate major*: fatal CVD,
nonfatal MI, and stroke,
hospitalised
Angina, vascular procedures
Agatston score >200
Cardiac structure, function, scars
Risk factors
HbA1c
Fasting lipids
Blood pressure
3 months
Annual
Annual
Annual
Alternate years†
Annual

16. Results of DCCT/EDIC
Patient characteristics and demographics

19. Clinical Characteristics
Nathan et al. Diabetes Care 2014;37:9–16
DCCT Baseline
(1983–1989)
N=1441
End of DCCT
(1993)
N=1422*
EDIC Year 18
(2010–2012)
N=1284*
Intensive
n=711
Convent.
n=730
Intensive
n=698
Convent.
n=717
Intensive
n=620
Convent.
n=597
Demographics
Age, years
Female, %
Diabetes duration, years
DCCT primary prevention cohort, %
Hypertension, % ¶
Hyperlipidaemia, % #
Current cigarette smoking, %
27.2 (7.1)
48.5
5.8 (4.2)
49.0
3.1
22.8
18.6
26.7 (7.1)
45.9
5.5 (4.1)
51.8
2.1
23.4
18.4
33.6 (7.0)
49.0
12.3 (4.9)
49.1
4.4
25.6
20.2
33.0 (7.0)
46.0
11.9 (4.8)
51.7
3.9
29.7
19.8
52.3 (6.9)
48.7
30.7 (5.0)
47.7
66.6
68.6
11.5
51.4 (6.9)†
45.7
30.2 (4.9)
50.6
68.8
68.2
10.7
Medical treatment
Glucose management
Pump or multiple daily injections (≥3), %
Glucose monitoring ≥4 times a day, %
Use of antihypertensive medication, % §
Any
ACE inhibitor or ARB
0
0
–
0
0
0
–
0
97.4
52.7
–
–
5.0‡
3.8‡
–
–
97.6
67.7
60.3
56.8
97.7
70.7
62.7
59.8
Data are mean (SD) unless otherwise indicated. *renal measurements (AER or eGFR) were completed for 1415 patients at DCCT closeout and 1217 patients at EDIC year 17 or
18 (1194 with AER at year 17 or 18 and 1187 with eGFR at year 18); †p=0.05 by the Wilcoxon rank sum test or x2 test; ‡p=0.01 by the Wilcoxon rank sum test or x2 test;
¶hypertension was defined by a systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or use of antihypertensive medications; #hyperlipidaemia was
defined by an LDL cholesterol level ≥130 mg/dL (3.4 mmol/L) or the use of lipid-lowering agents; §medication data were not collected during the DCCT. ACE inhibitors were
prohibited during the DCCT.
ACE, angiotensin-converting-enzyme; AER, albumin excretion rate; ARB, angiotensin II receptor blocker; LDL, low-density lipoprotein; convent, conventional

20. Clinical Characteristics (continued)
Nathan et al. Diabetes Care 2014;37:9–16
DCCT baseline
(1983–1989) N=1441
End of DCCT
(1993)
N=1422*
EDIC Year 18
(2010–2012) N=1284*
Intensive
n=711
Convent.
n=730
Intensive
n=698
Convent.
n=717
Intensive
n=620
Convent.
n=597
Physical examination
BMI, kg/m2
Obese (BMI ≥30 kg/m2), %
Systolic blood pressure, mmHg
Diastolic blood pressure, mmHg
Mean arterial pressure, mmHg
23.4(2.7)
1.3
114.5(11.3)
73.1(8.2)
86.9(8.2)
23.5(2.9)
1.9
114.6(11.4)
72.9(8.7)
86.8(8.6)
26.6(4.2)
18.6
116.3(11.7)
74.4(8.8)
88.3(8.9)
25.0 (3.1)‡
5.6‡
115.3(12.0)
74.3(8.8)
88.0(8.9)
29.1 (5.7)
36.1
122.4(15.4)
71.4(9.0)
88.4(9.8)
28.5 (5.1)
33.0
121.8(15.1)
71.3(8.8)
88.2(9.6)
Laboratory values
HbA1c, %
Plasma lipids, mg/dL
Total cholesterol
HDL cholesterol
LDL cholesterol
Triglycerides
9.1(1.6)
177.1(32.8)
50.8(12.3)
110.3(28.7)
80.8(43.3)
9.1(1.6)
175.7(33.6)
50.3(12.3)
109.1(29.4)
81.8(51.3)
7.2(0.9)
178.8(31.2)
50.8(12.8)
111.6(27.2)
82.0(51.6)
9.1(1.3)‡
183.4(36.6)
51.5 (12.9)
114.3(31.4)
87.8(54.0)†
8.0(1.0)
174.8(35.4)
61.9(19.4)
96.7(29.2)
81.1(50.6)
8.0(1.0)
172.1(36.4)
61.5(17.7)
94.7(29.5)
80.6(71.5)
Data are mean (SD) unless otherwise indicated. *renal measurements (AER or eGFR) were completed for 1415 patients at DCCT closeout and 1217 patients
at EDIC year 17 or 18 (1194 with AER at year 17 or 18 and 1187 with eGFR at year 18); †p=0.05 by the Wilcoxon rank sum test or x2 test; ‡p=0.01 by the
Wilcoxon rank sum test or x2 test
BMI, body mass index; HDL, high-density lipoprotein; convent, conventional

21. Clinical Characteristics: Complications
Nathan et al. Diabetes Care 2014;37:9–16
DCCT Baseline
(1983–1989) N=1441
End of DCCT
(1993)
N=1422*
EDIC Year 18
(2010–2012) N=1284*
Complication Intensive
n=711
Convent.
n=730
Intensive
n=698
Convent.
n=717
Intensive
n=620
Convent.
n=597
Eye
Retinopathy levels, %
No retinopathy (10/10)
Microaneurysm only (20/≤20)
Mild NPDR (35/≤35)
Moderate NPDR (43/≤43–53/53) Severe
PDR or worse (53/<53+)
49.0
35.0
11.6
4.5
0
51.8
27.8
15.2
5.1
0.1
28.3
39.7
21.2
8.2
2.6
‡
17.3
32.1
28.5
14.3
7.8
10.7
36.9
21.3
16.5
14.7
‡
4.7
26.8
18.3
19.6
30.7
Renal*
AER, %
0 to <30 mg/24 h
30 to <300 mg/24 h
≥300 mg/24 h or ESRD
eGFR (mL/min/1.73 m2)
Sustained eGFR <60 mL/min/ 1.73 m2, %
88.3
11.7
0
126.0(13.9)
0
90.0
10.1
0
126.2(14.6)
0
89.8
8.8
1.4
116.0(13.0)
0.1
‡
82.2
14.6
3.2
117.8 (13.7)‡
0.4
81.5
14.2
4.3
93.3(18.1)
3.2
‡
75.1
17.0
7.9
91.7(20.1)
5.3
Neuropathy
Confirmed clinical neuropathy, %
6.8 5.6 9.3 17.5
‡ 23.6 32.7
‡
Data are mean (SD) unless otherwise indicated. *renal measurements (AER or eGFR) were completed for 1415 patients at DCCT
closeout and 1217 patients at EDIC year 17 or 18 (1194 with AER at year 17 or 18 and 1187 with eGFR at year 18);
‡p=0.01 by the
Wilcoxon rank sum test or x2 test. Convent, conventional

22. Key DCCT Findings

23. Results of DCCT/EDIC
Glycaemic control & Major complications

24. A1c Reduction :Intensive Vs Conventional Management
0 2 4 6 8 10
Years from randomization
5 731 9
8
9
10
7
HbA1c(%)
6
0
Intensive
Conventional
DCCT Research Group. N.Eng.J.Med. 1993;329:977–986.
9.1%
7.2%

25. Intensive treatment leads to more effective glycaemic control
than conventional treatment
• DCCT intensive treatment did not achieve target HbA1c <6.05%
• 44% of patients reached target ≥1 time during trial
• Median HbA1c with intensive treatment was 7.2% Vs. 9.1% with
conventional treatment
Nathan et al. Diabetes Care 2014;37:9–16
Intensive – EDIC mean 8.0%Intensive – DCCT mean 7.2%
11
10
9
8
7
6
5
0 1 2 3 4 5 6 7 8 9 10
Conventional –
EDIC mean 8.0%
Conventional –
DCCT mean 9.1%
Study year
TrainingDCCT intervention EDIC observation
HbA1c(%)
1 2 3 4 5 6 7 8 11 12 13 14 15 16 17 189 10

26. 0
0.2
0.4
0.6
0.8
1.0
1.2
Risk of
retinopathy
Severe hypoglycaemia
120
60
0
per100patient-years
HbA1c (%)
DCCT: The Price of Improved Diabetic Control - Hypoglycaemia
per100patient-years
Adapted from DCCT Research Group. N Engl J Med 1993;329:977–86

28. Results of DCCT/EDIC
Diabetic Retinopathy and other ocular findings

29. DCCT: Delayed Onset and Progression of Diabetic Retinopathy
with Intensive vs. Conventional Treatment
Primary prevention cohort
(726 patients with no DR)
Secondary intervention cohort
(715 patients with mild DR)
 54% (p<0.001)
60
50
40
30
20
10
0
0 1 2 3 4
Study time (years)
5 6 7 8 9
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9
Conventional
Intensive
Cumulativeincidenceof
DRprogression(%)
Cumulativeincidenceof
DRprogression(%)
Conventional
Intensive
 76% (p<0.001)
Study time (years)
DCCT Research Group. N Engl J Med 1993;329:977–86

30. Persistent Benefit of Early Intensive vs. Conventional treatment
After 10 years of EDIC
observation, the benefit of early
intensive treatment persisted with
a 53% (p<0.0001) reduction in
the risk of further retinopathy
progression
Aiello et al. Diabetes Care 2014;37:17–23
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10
Conventional
Intensive
EDIC year
Cumulativeincidence(%)
Cumulative
Incidence (%)

31. Effect of DCCT Intensive Treatment on Prevalence of Diabetic
Retinopathy Complications
Aiello et al. Diabetes Care 2014;37:17–23
DCCT closeout
n=1211
EDIC year 4
n=1094
EDIC year 10
n=1211
Odds
reduction
(%)
p Odds
reduction
(%)
p Odds
reduction
(%)
p
≥3-step DR progression 76 <0.001 74 <0.001 57 <0.001
Severe NPDR or worse 66 <0.001 68 <0.001 58 <0.001
PDR or worse 64 <0.001 65 <0.001 58 <0.001
CSME 51 0.005 62 <0.001 38 0.009
PRP 60 <0.001 54 0.004 57 <0.001
PRP, pan-retinal photocoagulation

32. Greater Effect of Intensive vs. Conventional Treatment on
Prevalence of Any Major Eye Disease
Aiello et al. Diabetes Care 2014;37:17–23
Diabetes duration, years
Cumulativeincidence(%)
EDC, Pittsburgh Epidemiology of Diabetes Complications (EDC) study
EDC
DCCT – conventional therapy
DCCT – intensive therapy
Cumulative
Incidence (%)

36. Results of DCCT/EDIC
Kidney disease and related findings

37. Reduced Risk of Microalbuminuria and Macro-albuminuria with
Intensive vs. Conventional treatment
De Boer et al. Diabetes Care 2014;37:24–30
N (events) Risk reduction with
intensive
(%)
Proportion of effect
explained by DCCT HbA1c (%)
Intensive Conventional
Microalbuminuria
(AER ≥40 mg/24 h)
DCCT
EDIC years 1–8
110
39
166
87
39 % (21–52)
59 % (39–73)
99
91
Macroalbuminuria
(AER ≥300 mg/24 h)
DCCT
EDIC years 1–8
18
9
37
59
54 % (29–74)
84 % (67–92)
98
99

38. Continued Benefit of Intensive Treatment on
Cumulative Incidence of Persistent Microalbuminuria
De Boer et al. Diabetes Care 2014;37:24–30
80
60
40
20
0
0 5
Duration of diabetes (years)
10 15 20 25 30
Conventional
Intensive
Risk reduction with
intensive therapy=39%
(95% CI, 21–52%; p=0.001)
Cumulativeincidenceofpersistent
microalbuminuria(%)

39. Date of download: 3/15/2016
Copyright © 2016 American Medical
Association. All rights reserved.
From: Sustained Effect of Intensive Treatment of Type 1 Diabetes Mellitus on Development and Progression of
Diabetic Nephropathy: The Epidemiology of Diabetes Interventions and Complications (EDIC) Study
JAMA. 2003;290(16):2159-2167. doi:10.1001/jama.290.16.2159
Albuminuria defined as albumin excretion rate ≥208 µg/min,equivalent to 300 mg/24 h. A, Prevalence of clinical albuminuria at the end of
the Diabetes Control and Complications Trial (DCCT) and during the Epidemiologyof Diabetes Interventions and Complications (EDIC) study.
The differencesbetween the treatment groups are significant at each time point after DCCTclose-out (P<.01). B, Cumulative incidence of new
cases in the EDIC study for those participants in the intensive- and conventional-treatmentgroups with either normoalbuminuria or
microalbuminuria at the end of theDCCT. The difference in cumulative incidences is significant by the log-rank-test.(P<.001).

41. Reduced Risk of Impaired GFR and Hypertension with
Intensive vs. Conventional Treatment
Risk reduction with
intensive therapy=20%
(95% CI, 6–21%; p=0.006)
GFR Hypertension
De Boer et al. Diabetes Care 2014;37:24–30
Conventional
Intensive
Cumulativeincidenceof
hypertension(%)
0 5 10 15 20
80
60
40
20
0
Time from randomisation (years)
15
10
5
0
0 5 10 15 20
Time from randomisation (years)
25
Cumulativeincidenceof
impairedGFR(%)
Risk reduction with
intensive therapy=50%
(95% CI, 18–69%, p=0.006)
Conventional
Intensive

42. Reduced Risk of Impaired GFR and Hypertension with
Intensive vs. Conventional Treatment
Risk reduction with
intensive therapy=20%
(95% CI, 6–21%; p=0.006)
GFR Hypertension
De Boer et al. Diabetes Care 2014;37:24–30
Conventional
Intensive
Cumulativeincidenceof
hypertension(%)
0 5 10 15 20
80
60
40
20
0
Time from randomisation (years)
15
10
5
0
0 5 10 15 20
Time from randomisation (years)
25
Cumulativeincidenceof
impairedGFR(%)
Risk reduction with
intensive therapy=50%
(95% CI, 18–69%, p=0.006)
Conventional
Intensive

43. Date of download: 3/15/2016
Copyright © 2016 American Medical
Association. All rights reserved.
From: Sustained Effect of Intensive Treatment of Type 1 Diabetes Mellitus on Development and Progression of
Diabetic Nephropathy: The Epidemiology of Diabetes Interventions and Complications (EDIC) Study
JAMA. 2003;290(16):2159-2167. doi:10.1001/jama.290.16.2159
Prevalence of hypertension (defined as blood pressure >140/90 mmHg) at the end of the Diabetes Control and Complications Trial
(DCCT) and during the Epidemiology of Diabetes Interventions and Complications (EDIC)study for participants in the intensive vs
conventional-treatment groups.The aggregate odds reduction with intensive vs conventional therapy of emergent hypertension during the
EDIC study, adjusted for DCCT mean arterial pressure,was 40.4% (95% C.I, 33.7%-46.5%; P<.001).

44. Results of DCCT/EDIC
Neuropathy and related findings

45. Lower Prevalence of DPN and CAN with Intensive vs.
Conventional Treatment
During DCCT, the prevalence
of confirmed DPN increased
slightly among intensively
treated group participants
(from 7% to 9%), but
increased substantially in
conventionally treated
patients
(from 5% to 17%; p<0.001)
Martin et al. Diabetes Care 2014;37:31–8
Outcome measure Group
DCCT
baseline
DCCT
closeout
EDIC year
13/14
Clinically evident DPN
Intensive
Conventional
57 (10)
48 (8)
88 (15)*
128 (22)
204 (34)*
240 (41)
Abnormal nerve
conduction studies
Intensive
Conventional
185 (31)
196 (34)
164 (28)*
288 (50)
326 (54)*
401 (69)
Confirmed DPN
Intensive
Conventional
39 (7)
31 (5)
52 (9)*
97 (17)
152 (25)*
204 (35)
R-R variation <15
Intensive
Conventional
20 (3)
25 (4)
39 (7)
53 (10)
147 (24)†
178 (30)
CAN composite
Intensive
Conventional
24 (4)
31 (5)
43 (7)
57 (10)
179 (29)†
208 (35)
Adjusted R-R
variations ¶
Intensive
Conventional
49 ± 21
47 ± 21
42 ± 19†
39 ± 19
30 ± 17‡
26 ± 17
Data are presented as n (%) or mean ± SD. Clinically evident DPN is defined by signs and symptoms consistent with DPN. Abnormal nerve conduction studies are defined as abnormalities in at least
two anatomically distinct nerves. Confirmed DPN required the presence of clinically evident neuropathy and abnormal nerve conduction studies. CAN composite is defined by any of the following
conditions: R-R variation <15, R-R variation <20 in combination with Valsalva ratio ≤1.5 or postural hypotension. *p<0.001; †p<0.05; ‡p<0.01 for treatment group differences by the Wilcoxon
rank sum test or x2 test; ¶means adjusted for DCCT baseline age, sex, cohort assignment, and duration in the DCCT study
CAN, cardiovascular autonomic neuropathy; DPN; diabetic peripheral neuropathy

46. Lower Prevalence of DPN and CAN with Intensive vs.
Conventional Treatment
In EDIC, a 30% reduction in the risk of incident confirmed DPN was observed with
prior intensive therapy odds ratio [OR] 0.70 [95% CI: 0.52–0.93]
Martin et al. Diabetes Care 2014;37:31–8
*Incidence at DCCT closeout is among participants without the defined outcome at DCCT baseline. Incidence at
EDIC year 13/14 is among participants without the defined outcome at DCCT closeout. †p<0.001; ‡p=0.0125
former intensive vs. conventional
Outcome measure Group DCCT closeout* EDIC year 13/14
Clinically evident DPN
Intensive
Conventional
57 (11)†
96 (18)
145 (29)
154 (34)
Abnormal nerve
conduction studies
Intensive
Conventional
73 (18)†
137 (36)
195 (45)
151 (52)
Confirmed DPN
Intensive
Conventional
32 (6)†
75 (14)
117 (22)‡
136 (28)

47. Increased Prevalence and Incidence of DPN Outcomes with
Increased HbA1c
Martin et al. Diabetes Care 2014;37:31–8
Logistic regression models Mean HbA1c
/1% elevation
Prevalent
OR (95% CI)
Incident*
OR (95% CI)
Clinically evident DPN
DCCT
EDIC
1.17 (1.06–1.29)**
1.64 (1.44–1.88)**
1.07 (0.95–1.20)
1.74 (1.48–2.03)**
Abnormal nerve conduction
studies
DCCT
EDIC
1.43 (1.28–1.60)**
1.87 (1.61–2.18)**
1.14 (0.99–1.32)
1.96 (1.63–2.36)**
Confirmed DPN
DCCT
EDIC
1.35 (1.21–1.50)**
1.80 (1.56–2.07)**
1.24 (1.10–1.41)**
1.82 (1.55–2.14)**
Data are the proportional odds for a one-unit increase in DCCT or EDIC mean HbA1c on having the
outcome, given all other variables are held constant. *among participants with intact function at DCCT
closeout; **indicates significant increase in OR

48. Results of DCCT/EDIC
Cardiovascular outcomes

49. Reduced Incidence of Coronary Events with Intensive
vs. Conventional Treatment
Lachin et al. Diabetes Care 2014;37:39–43
Primary composite CVD
outcome
Fatal or non-fatal MI/stroke or
CV deathCumulativeincidence
ofevents(%)
Cumulativeincidence
ofevents(%)
Years from study entry
0.12
0.10
0.08
0.06
0.04
0.02
0.00
0 2 4 6 8 10 12 14 16 18 20
Years from study entry
0.12
0.10
0.08
0.06
0.04
0.02
0.00
0 2 4 6 8 10 12 14 16 18 20
Conventional
Intensive
Conventional
Intensive
The risk of primary composite
CVD outcome was reduced by 42%
(95% CI, 9–63%; p=0.016)
The risk of MACE was reduced by 57%
(95% CI, 12–79%; p=0.018)

50. 57% risk reduction
in non-fatal MI, stroke or CVD death*
(P = 0.02; 95% CI: 12–79%)
Cumulativeincidenceof
non-fatalMI,strokeor
deathfromCVD
Conventional
treatment
Intensive
treatment
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Years
0.06
0.04
0.02
0.00
Adapted from DCCT. N Engl J Med 1993; 329:977–986. DCCT/EDIC. JAMA 2002; 287:2563–2569.
DCCT/EDIC. N Engl J Med 2005; 353:2643–2653.
DCCT/EDIC: glycaemic control reduces the risk of non-fatal MI, stroke or death
from CVD in type 1 diabetes
0
7
1 6
HbA1C(%)
9
8
2 3 4 5 7 8 9
Conventional treatment
Intensive treatment
11 12 13 14 15 16 1710
*Intensive vs conventional treatment
DCCT (intervention period EDIC (observational follow-up)
DCCT (intervention period) EDIC (observational follow-up)
Years

51. Greater Reductions in Major Complication Risk with Intensive
vs. Conventional Treatment
DCCT intensive treatment reduced the early stages of
microvascular complications by 35–76% compared with
conventional treatment
Nathan et al. Diabetes Care 2014;37:9–16
0 20 40 60 80
3+ step development, primary
3+ step progression, secondary
Microalbuminuria
Macroalbuminuria
Neuropathy
Further 3+ step progression, primary
Further 3+ step progression, secondary
New microalbuminuria
New macroalbuminuria
New neuropathy (2007–08)
Severe eye disease
Reduced GFR
CVD events
Reduction in risk (%)
DCCT
1983–1993
EDIC
1994–2011
DCCT
+
EDIC

56. Costs
• Cost of treatment
- Intensive treatment Vs Conventional treatment
• Cost of treating side effects (e.g. hypoglycemia)
• Cost of treating diabetic complications

57. Costs of Therapy in the DCCT
Annual Therapy
MDI CSII Conventional
Inpatient 127 155 58
Outpatient 1,243 1,244 513
Case-management 548 554 116
Self-care 1,866 3,621 909
Side-effects of therapy 210 210 70
TOTAL $4,014 $5,784 $1,666

58. Costs of Complications of
Type 1 Diabetes
Laser therapy $948 / episode
ACE inhibitor $725 / yr
Blindness $1,911 / yr
Renal failure $46,207 / yr
Amputation $31,225 / episode
DCCT

59. Type of Health Care Costs by Treatment Group
Intensive Conventional
Treatment Side Effects Complications
DCCT

60. Costs and Effects of Intensive Therapy
Increased use of primary
diabetes care
Increased hypoglycemia
Increased weight gain
Lower incidence of
microvascular complications
Health care savings when
complications are delayed
or prevented
DCCT
Costs Effects

61. Cost-Effectiveness of Intensive Therapy in Type 1 Diabetes
DCCT Modeling Study
Years Free From Complication
(Projected Average)
Conventional
treatment
Intensive
treatment
Proliferative retinopathy 39.1 53.9
Blindness 49.1 56.8
Microalbuminuria 34.5 43.7
End-stage renal disease
(ESRD)
55.6 61.3
Neuropathy 42.3 53.2
Amputation 39.1 53.9
DCCT Research Group. JAMA. 1996;276:1409-1415

62. Average Number of Years Living Without ...
Conventional Intensive Difference
Proliferative Retin. 39.1 53.9 14.8
Macular Edema 44.7 52.9 8.2
Visual Acuity Loss 49.1 56.8 7.7
Overt Nephrop. 49.7 59.5 9.8
ESRD 55.6 61.3 5.8
LE Amputation 55.2 60.9 5.7
1st major comp. 37.0 52.2 15.2
DCCT

63. Treatment Duration
U.S.
Dollars
0
50000
100000
150000
200000
250000
$300000
1 5 10 15 20 25 30 35 40 45 50
Conventional
Intensive
DCCT
Cumulative Actual Cost of Conventional vs.
Intensive Therapy by Treatment Duration

64. ADA 2016

65. Summary
• Persistent benefit of early intensive treatment on progression of
diabetic retinopathy in the DCCT/EDIC
Substantial risk reduction in microvascular complications:
by 35-76%
-Development of PDR and incidence of major eye disease
-Microalbuminuria, macro-albuminuria ,reduction of GFR and
hypertension development
-Persistent benefit of intensive treatment on neuropathy
• Long-term benefit on progression of atherosclerosis and
cardiovascular disease during DCCT/EDIC
by 57% (MACE)

66. Summary (continued)
•The DCCT/EDIC = Achieving the best glycaemia control as close
to the non-diabetic range as safely possible….
Reduced all of the microvascular and cardiovascular
complications of diabetes
•Translating such findings into clinical care has substantially
improved the long-term health of people with type 1 diabetes
•Cost effectiveness ?!

67. Thank You
Any Questions ?