Diabetes Care Volume 37, January 2014 9

DCCT/EDIC 30TH ANNIVERSARY

The Diabetes Control and David M. Nathan, for the DCCT/EDIC
Research Group*

Complications Trial/Epidemiology
of Diabetes Interventions and
Complications Study at 30 Years:
Overview

OBJECTIVE
The Diabetes Control and Complications Trial (DCCT) was designed to test the
glucose hypothesis and determine whether the complications of type 1 diabetes
(T1DM) could be prevented or delayed. The Epidemiology of Diabetes Interven-
tions and Complications (EDIC) observational follow-up determined the durability
of the DCCT effects on the more-advanced stages of diabetes complications in-
cluding cardiovascular disease (CVD).

RESEARCH DESIGN AND METHODS

The DCCT (1982–1993) was a controlled clinical trial in 1,441 subjects with T1DM
comparing intensive therapy (INT), aimed at achieving levels of glycemia as close
to the nondiabetic range as safely possible, with conventional therapy (CON),
which aimed to maintain safe asymptomatic glucose control. INT utilized three or
more daily insulin injections or insulin pump therapy guided by self-monitored
Diabetes Control and Complications Trial/
glucose. EDIC (1994–present) is an observational study of the DCCT cohort. Epidemiology of Diabetes Interventions and
Complications Data Coordinating Center, George
RESULTS Washington University, Biostatistics Center,
The DCCT followed >99% of the cohort for a mean of 6.5 years and demonstrated a Bethesda, MD
35–76% reduction in the early stages of microvascular disease with INT, with a Corresponding author: David M. Nathan,
median HbA1c of 7%, compared with CONV, with a median HbA1c of 9%. The major [email protected].
adverse effect of INT was a threefold increased risk of hypoglycemia, which was Received 7 September 2013 and accepted 25
September 2013.
not associated with a decline in cognitive function or quality of life. EDIC showed a
Clinical trial reg. nos. NCT00360815 and
durable effect of initial assigned therapies despite a loss of the glycemic separa-
NCT00360893, clinicaltrials.gov.
tion (metabolic memory) and demonstrated that the reduction in early-stage
*A complete list of participants in the DCCT/EDIC
complications during the DCCT translated into substantial reductions in severe Research Group can be found in N Engl J Med
complications and CVD. 2011;365:2366–2376.
© 2014 by the American Diabetes Association.
CONCLUSIONS See http://creativecommons.org/licenses/by-
DCCT/EDIC has demonstrated the effectiveness of INT in reducing the long-term nc-nd/3.0/ for details.
complications of T1DM and improving the prospects for a healthy life span. See accompanying articles, pp. 5, 8,
Diabetes Care 2014;37:9–16 | DOI: 10.2337/dc13-2112 17, 24, 31, 39, and 44.
10 DCCT/EDIC at 30 Years: Overview Diabetes Care Volume 37, January 2014

The plight of people with type 1 Institutes of Health (NIH) to “initiate and recruitment began. Recruitment ended
diabetes changed dramatically with the support a 5-year clinical study to assess in 1989, and the DCCT was halted by its
introduction of insulin therapy in 1922 the effects of treatment of juvenile- independent oversight committee in
(1). Type 1 diabetes was transformed onset diabetes on the development of 1993, approximately 1 year ahead of
from a uniformly fatal disease in the microvascular and macrovascular schedule, owing to the uniform and
preinsulin era, with mortality occurring complications.” conclusive results achieved (10). The
either acutely from diabetic original CON group was taught INT,
The advances necessary to perform a
ketoacidosis or subsequently from and the entire cohort was invited to
definitive clinical trial were finally in
inanition owing to a chronic catabolic join a long-term observational study
place by the early 1980s. These
state, to a chronic degenerative disease. named the Epidemiology of Diabetes
included: the ability to manage glucose
In the first 15 to 20 years of insulin Interventions and Complications (EDIC)
levels in the near-normal range using
therapy, a host of complications that (11). EDIC is now in its 20th year.
multiple daily injection (MDI) therapy or
had never been seen before was
continuous subcutaneous insulin
discovered in people with long-term
infusion (CSII) with external pumps, RESEARCH DESIGN AND METHODS
diabetes (2). These complications,
guided by self-monitoring of blood The eligibility criteria have been
affecting the eyes, kidneys, and
glucose (SMBG); the means of described in detail (8,10). Briefly, in
peripheral nervous system, were
measuring chronic glycemia objectively order to address the primary prevention
collectively called microvascular
and accurately with the glycated and secondary intervention questions,
complications, to distinguish them from
hemoglobin (HbA1c) assay; and the following eligibility criteria were
the less diabetes-specific but highly
objective measures of long-term used: age 13–39 years with type 1
prevalent macrovascular disease
complications. With these tools diabetes diagnosed based on clinically
complications. Microvascular disease
available and with generous support accepted criteria and with fasting
and peripheral neuropathy resulted in
from the National Institute of Arthritis, c-peptide concentrations ,0.2 nmol/L.
blindness, kidney failure, and
Diabetes, and Digestive and Kidney The subjects had to be generally healthy
amputations (3); and macrovascular
Diseases, which later became the with no history of cardiovascular disease
disease, exacerbated by renal
National Institute of Diabetes and (CVD) and without hypertension (blood
dysfunction and autonomic neuropathy,
increased the risk for myocardial
Digestive and Kidney Diseases (NIDDK), pressure ,140/90 mmHg) or
21 centers were selected in 1982 to plan dyslipidemia (8), and those with
infarctions and stroke to levels that and conduct a study that would test
were 10-fold or more than in the age- neuropathy requiring treatment were
what had become known as the excluded. Additionally, the primary
matched nondiabetic population (2,3). “glucose hypothesis.” Practically stated, prevention cohort had to have a duration
The pathoetiology of the microvascular the glucose hypothesis posited that of 1–5 years with no evidence of
complications was vigorously debated achieving near-normal glucose would retinopathy on fundus photography and
during the mid-20th century (4–6). ameliorate the long-term complications an albumin excretion rate (AER) ,40 mg
Some practitioners considered the of diabetes. Over the course of more per 24 h. The secondary intervention
complications a result of nonphysiologically than a year, the investigators planned cohort could have a longer duration of
controlled hyperglycemia; others thought the Diabetes Control and diabetes (1–15 years) and had to have at
that they were a glycemia-independent Complications Trial (DCCT) (8). The two least one microaneurysm in either eye.
feature of diabetes. Perhaps the most primary aims of the DCCT consensus This cohort could have an AER as high as
sensible opinion regarding the role protocol were to determine whether, 200 mg per 24 h. Subjects in the primary
of glucose control, expressed by compared with conventional therapy prevention cohort and those in the
R.D. Lawrence, the preeminent (CON), an intensive treatment program secondary intervention cohort with
diabetologist of his time and who had designed to achieve glycemic control ,5 years duration could have 2-h
type 1 diabetes himself, was as follows: as close to the nondiabetic range as stimulated c-peptide levels as high
“The attempt to keep the blood sugar safely possible would prevent or delay as 0.5 nmol/L; otherwise, it had to be
constantly normal may be ideal in the appearance of early background #0.2 nmol/L.
theory, but in practice it is very difficult retinopathy (primary prevention) and
to achieve and makes the diabetic life would prevent the progression of
DCCT Interventions and Metabolic
unnecessarily hard without adequate early retinopathy to more advanced
Goals
benefit” (7). forms of retinopathy (secondary The clinical goals for both treatment
The devastating consequences of the intervention). groups included absence of frequent
long-term complications led in part to After the successful completion of a symptoms of hyperglycemia or frequent
the formation of the National Diabetes 1-year feasibility phase, during which a or severe hypoglycemia, defined as
Commission by an Act of Congress (PL substantial separation of HbA1c levels requiring assistance from another
93-354). In 1975, the Commission issued between the intensive therapy (INT) person. DCCT INT aimed to achieve
The Long-Range Plan to Combat (“experimental”) and CON (“standard”) HbA1c levels that were ,2 SD above
Diabetes, which included the groups was achieved (9), an additional the mean value determined for
recommendation for the National eight centers were added, and full-scale similarly aged nondiabetic volunteers
care.diabetesjournals.org Nathan 11

(,6.05%, 42.6 mmol/mol). HbA1c was lente, and beef ultralente insulin for reading center (13), was the primary
measured monthly to aid adjustment basal delivery in MDI regimens. There outcome used for power and
of INT and quarterly as a process was no single MDI or CSII regimen, sample-size calculations. Similarly
outcome in both therapy groups. Only and clinic staff and participants important outcomes were
the quarterly results were used for worked together to individualize the nephropathy and retinopathy. The
study data. INT was adjusted based on regimens to match lifestyle factors measurements and their frequency
four or more SMBG tests with the and achieve the SMBG and HbA 1c and definitions of outcomes are
following self-monitored glucose goals (12). included in Table 1.
targets: premeals 70–120 mg/dL (3.9– CON was consistent with standard
6.7 mmol/L) and 2-h postmeals ,180 care in the 1980s and usually included EDIC Design and Outcomes
mg/dL (10 mmol/L). In addition, a weekly one or two daily injections of insulin In the wake of the successful completion
3:00 A.M. blood glucose was to be .65 with daily urine or SMBG. The only of the DCCT (10), the DCCT investigators
mg/dL (3.6 mmol/L) in order to protect numeric glycemic target was if HbA1c and the NIDDK decided that longer-
against otherwise unappreciated exceeded 13.5%, the mean +2 SD of term follow-up would provide
nocturnal hypoglycemia. To achieve the cohort’s baseline value, in which important information regarding the
the glycemic goals, participants case treatment was intensified durability of the original DCCT INT
randomly assigned to INT used at least independent of whether the subject effects and, in particular, the effects of
three insulin injections per day (MDI) had symptoms. INT on the more-advanced stages of
or CSII. The subjects and DCCT clinic complications and CVD (11). After the
staff chose which modality to use. The Outcomes end of the DCCT and before initiating
insulins used were those that were Retinopathy, which was measured the long-term follow-up called EDIC, all
available at the time: clear zinc objectively with stereoscopic fundus of the CON participants were offered
(regular) insulin for premeal boluses photography and graded with training in INT. In addition, diabetes care
and in the insulin pump and NPH, standardized methods by a central was returned to the subjects’ own care

Table 1—Major outcome measurements

Frequency
Complication DCCT EDIC Defined outcomes
Retinopathy: 7-field stereoscopic 6 months 1/4 cohort/year, Three-step progression*, CSME,
and fundus photography entire cohort year 4 severe NPDR, PDR
Renal function
Albumin excretion+ Annual Alternate years‡ Albuminuria: micro $40 mg/24 h,
macro .300 mg/24 h
Serum creatinine (eGFR@) Annual Annual eGFR: ,60 mL/min/1.73 m2
Neuropathy
History, examination, and NCS Baseline, year 5, and/or study end Year 13/14 Confirmed clinical: abnormal exam
and abnormal NCS or autonomic study
Autonomic
Cardiac Baseline, every 2 years, end Years 13/14 and 16/17 R-R variation ,15 or R-R ,20 and
Valsalva ratio ,1.5 or orthostatic
hypotension
Urologic (ED) d Year 10
MNSI + monofilament d Annual
Cardiovascular
History Annual Annual Aggregate major#: fatal CVD,
nonfatal MI, and stroke, hospitalized
ECG Annual Annual Angina, vascular procedures
Ankle-brachial index Annual Annual
Carotid ultrasound d Years 1, 6, and 12
CT CAC d Year 8 Agatston score .200
Cardiac MRI d Year 15 Cardiac structure, function, scars
Risk factors
HbA1c 3 months Annual
Fasting lipids Annual Alternate years‡
Blood pressure Annual Annual
*Based on modified Airlie House criteria (13); +based on a 4-h timed collection; @ calculated based on Modification of Diet in Renal Disease equation,
#adjudicated by reviewers masked to treatment assignment HbA1c; ‡during EDIC, albumin excretion and fasting lipids were measured in alternate
years. CAC, coronary artery calcification; CSME, clinically significant macular edema; CT, computed tomography; ED, erectile dysfunction; eGFR,
estimated GFR; MI, myocardial infarction; MNSI, Michigan neuropathy screening instrument; MRI, magnetic resonance imaging; NCS, nerve
conduction study; NPDR, nonproliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy.
12 DCCT/EDIC at 30 Years: Overview Diabetes Care Volume 37, January 2014

Table 2—Clinical characteristics of DCCT/EDIC participants at DCCT baseline, DCCT closeout, and EDIC year 18
DCCT baseline (1983–1989) End of DCCT (1993) EDIC year 18 (2010–2012)
(N = 1,441) (N = 1,422)* (N = 1,284)*
INT CON INT CON INT CON
n 711 730 698 717 620 597
Demographics
Age (years) 27.2 (7.1) 26.7 (7.1) 33.6 (7.0) 33.0 (7.0) 52.3 (6.9) 51.4 (6.9)†
Female (%) 48.5 45.9 49.0 46.0 48.7 45.7
Diabetes duration (years) 5.8 (4.2) 5.5 (4.1) 12.3 (4.9) 11.9 (4.8) 30.7 (5.0) 30.2 (4.9)
DCCT primary prevention cohort (%) 49.0 51.8 49.1 51.7 47.7 50.6
Hypertension (%)|| 3.1 2.1 4.4 3.9 66.6 68.8
Hyperlipidemia (%)** 22.8 23.4 25.6 29.7 68.6 68.2
Current cigarette smoking (%) 18.6 18.4 20.2 19.8 11.5 10.7
Medical treatment
Glucose management
Pump or multiple daily injections ($3) (%) 0 0 97.4 5.0‡ 97.6 97.7
Glucose monitoring $4 times a day (%) 0 0 52.7 3.8‡ 67.7 70.7
Use of antihypertensive medication (%)§
Any d d d d 60.3 62.7
ACE inhibitor or ARB 0 0 d d 56.8 59.8
Physical examination
BMI (kg/m2) 23.4 (2.7) 23.5 (2.9) 26.6 (4.2) 25.0 (3.1)‡ 29.1 (5.7) 28.5 (5.1)
Obese (BMI $30 kg/m2) (%) 1.3 1.9 18.6 5.6‡ 36.1 33.0
Systolic blood pressure (mmHg) 114.5 (11.3) 114.6 (11.4) 116.3 (11.7) 115.3 (12.0) 122.4 (15.4) 121.8 (15.1)
Diastolic blood pressure (mmHg) 73.1 (8.2) 72.9 (8.7) 74.4 (8.8) 74.3 (8.8) 71.4 (9.0) 71.3 (8.8)
Mean arterial pressure (mmHg) 86.9 (8.2) 86.8 (8.6) 88.3 (8.9) 88.0 (8.9) 88.4 (9.8) 88.2 (9.6)
Laboratory values
HbA1c (%)†† 9.1 (1.6) 9.1 (1.6) 7.2 (0.9) 9.1 (1.3)‡ 8.0 (1.0) 8.0 (1.0)
Plasma lipids (mg/dL)
Total cholesterol 177.1 (32.8) 175.7 (33.6) 178.8 (31.2) 183.4 (36.6) 174.8 (35.4) 172.1 (36.4)
HDL cholesterol 50.8 (12.3) 50.3 (12.3) 50.8 (12.8) 51.5 (12.9) 61.9 (19.4) 61.5 (17.7)
LDL cholesterol 110.3 (28.7) 109.1 (29.4) 111.6 (27.2) 114.3 (31.4) 96.7 (29.2) 94.7 (29.5)
Triglycerides 80.8 (43.3) 81.8 (51.3) 82.0 (51.6) 87.8 (54.0)† 81.1 (50.6) 80.6 (71.5)
Complications
Eye
Retinopathy levels (%) ‡ ‡
No retinopathy (10/10) 49.0 51.8 28.3 17.3 10.7 4.7
Microaneurysm only (20/#20) 35.0 27.8 39.7 32.1 36.9 26.8
Mild NPDR (35/#35) 11.6 15.2 21.2 28.5 21.3 18.3
Moderate NPDR (43/#43–53/53) 4.5 5.1 8.2 14.3 16.5 19.6
Severe PDR or worse (53/,53+) 0 0.1 2.6 7.8 14.7 30.7
Renal*
AER (%) ‡ ‡
0 to ,30 mg/24 h 88.3 90.0 89.8 82.2 81.5 75.1
30 to ,300 mg/24 h 11.7 10.1 8.8 14.6 14.2 17.0
$300 mg/24 h or ESRD 0 0 1.4 3.2 4.3 7.9
eGFR (mL/min/1.73 m2) 126.0 (13.9) 126.2 (14.6) 116.0 (13.0) 117.8 (13.7)‡ 93.3 (18.1) 91.7 (20.1)
Sustained eGFR ,60 mL/min/1.73 m2 (%) 0 0 0.1 0.4 3.2 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 1,415 subjects at DCCT closeout and 1,217
subjects at EDIC year 17 or 18 (1,194 with AER at year 17 or 18 and 1,187 with eGFR at year 18). For EDIC year 18, clinical characteristic values were
carried from measurements from the most recent visit if not measured at year 18. AER and lipid data were collected at year 17 or 18. †P , 0.05 by the
Wilcoxon rank sum test or the x2 test comparing CON and INT. ‡P , 0.01 by the Wilcoxon rank sum test or the x2 test comparing CON and INT for all
categories. ||Hypertension was defined by a systolic blood pressure $140 mmHg, diastolic blood pressure $90 mmHg, or use of antihypertensive
medications. ** Hyperlipidemia was defined by an LDL cholesterol level $130 mg/dL (3.4 mmol/L) or the use of lipid-lowering agents. ††End of DCCT
HbA1c values are time-averaged mean HbA1c throughout the DCCT; EDIC year 17/18 HbA1c values are time-averaged mean EDIC HbA1c. Mean (SD)
HbA1c levels time-averaged through DCCT/EDIC were 7.8% (0.9%) and 8.3% (1.0%) among participants assigned to INT and CON, respectively.
§Medication data were not collected during the DCCT. ACE inhibitors were prohibited during the DCCT. At EDIC year 1, ACE inhibitor use was 5.6% in
the INT and 6.9% in the CON groups. ARBs were not available until later during EDIC. Antihypertensive use at EDIC year 1 was 8.7% in the INT and
10.1% in the CON groups. Primary prevention cohort = 1–5 years duration, ,30 mg albuminuria per 24 h, and no retinopathy in either eye at
baseline. ARB, angiotensin II receptor blocker; eGFR, estimated GFR; ESRD, end-stage renal disease; NPDR, nonproliferative diabetic retinopathy;
PDR, proliferative diabetic retinopathy.
care.diabetesjournals.org Nathan 13

provider, some of whom were DCCT/ than 99% (1,422 of 1,441) completed to include episodes that were
EDIC investigators. the study. After another 20 years of recognized and treated by the patients.
Whereas the DCCT was a controlled follow-up in EDIC, 88% of the original To qualify as severe hypoglycemia, an
clinical trial, EDIC was observational. cohort (95% of the survivors) is being episode had to require assistance from
The frequency of interactions with the actively followed in DCCT/EDIC clinical another and included coma or seizures
subjects and of the outcome centers. or episodes requiring glucagon, IV
measurements decreased substantially dextrose, or oral carbohydrate
Glycemia administered by another person.
(Table 1); however, the methods of The DCCT INT did not uniformly achieve
measuring glycemia, other metabolic Although the intent was to limit bias of
the goal HbA1c of ,6.05%; however, ascertainment by collecting the
outcomes, and complications 44% reached that level at least once
remained identical to those used hypoglycemia events at quarterly visits
during the trial (10). The median of the for both INT and CON subjects, INT
during DCCT. Several procedures were quarterly measured HbA1c levels in INT
added to measure atherosclerosis subjects were seen and contacted
was 7% compared with 9% in CON more frequently than those in the
(Table 1). (Fig. 1). There was almost no crossover CON group, and some of the
between INT and CON during the DCCT, differences in hypoglycemia may be
RESULTS other than the protocol-dictated change attributable to differences in the
Subjects to INT for women assigned to CON who frequency of ascertainment. The
The characteristics of the DCCT cohort were planning pregnancy and during frequency of severe hypoglycemia
at baseline and at study end, which pregnancy (14). 97% of study time was (62/100 patient-years) and the subset
represents the EDIC baseline, and at spent on assigned therapy. During EDIC, of episodes involving coma or seizure
the most recent EDIC annual the adoption of INT by the original CON (16/100 patient-years) were both
examination in 2012 are shown in group and the transition for all subjects threefold higher than in the CON group.
Table 2. The baseline characteristics to their own health care providers Despite the increased frequency of
were well matched between the INT resulted in a narrowing and then hypoglycemia, there were no adverse
and CON for the primary prevention disappearance of the differences in effects of INT or of repeated severe
and secondary intervention cohorts. HbA1c maintained during DCCT (Fig. 1). episodes, on rigorously and repeatedly
The changes over time largely reflect measured cognitive function in adults
the effects of INT versus CON. Although Adverse Effects or adolescents, either during the DCCT
in most long-term studies loss to The two major adverse events or after even longer-term follow-up
follow-up may compromise the experienced by INT subjects were (18–20). Weight gain with INT resulted
integrity and interpretation of study hypoglycemia and weight gain (15–17). in significantly more subjects becoming
results, the follow-up in DCCT and The definition established for severe overweight or obese compared with
subsequently in EDIC has been virtually hypoglycemia, which has subsequently CON (17). The 4.6 kg difference in
complete. At the end of DCCT, after an been adopted by many studies, was weight during the DCCT largely
average of 6.5 years (range 3–9), more meant to be relatively inclusive but not dissipated during the EDIC.

Outcomes
More detailed descriptions of the
individual outcomes are presented in
the subsequent articles in this series
(21–25). In brief, DCCT INT reduced the
early stages of microvascular
complications by 35–76% compared
with CON (Fig. 2) (10). The magnitude
and consistent direction of the effects
on retinopathy, neuropathy, and
nephropathy led to the termination
of the study 1 year ahead of schedule
by the independent oversight group.
Analyses of the relationship
between metabolic control, measured
by the “updated mean” HbA1c and
including approximately 18,000 HbA 1c
measurements for each therapy
Figure 1—Median HbA1c concentrations during DCCT, the “training” period between DCCT and group, revealed a strong association
EDIC, and EDIC. P , 0.001 for INT vs. CON during entire DCCT and for the first 3 years during EDIC.
Reprinted and modified with permission from Nathan et al. Diabetes Control and Complications with each of the three complications
Trial/Epidemiology of Diabetes Interventions and Complications study at 30 years: advances and (26,27). The difference in updated
contributions. Diabetes 2013;62:3976–3986. mean HbA1c levels between the
14 DCCT/EDIC at 30 Years: Overview Diabetes Care Volume 37, January 2014

could be ameliorated by intensive

glycemic therapy. The DCCT/EDIC
convincingly demonstrated that the
glucose hypothesis was correct and that
an intervention that aimed to achieve
glycemia as close to the nondiabetic
range as safely possible reduced all of
the microvascular and cardiovascular
complications of diabetes. Translating
the findings of the DCCT/EDIC into
clinical care has substantially improved
the long-term health of people with
type 1 diabetes.

Funding. The DCCT/EDIC has been supported

by U01 Cooperative Agreement Grants
(1982–1993, 2011–2016) and contracts
Figure 2—Summary of reduction in major complications with INT compared with CON during (1982–2011) with the Division of Diabetes
DCCT, EDIC, and combined study periods. 3+step devel, Prim: three-step or more development Endocrinology and Metabolic Diseases of the
of retinopathy based on Early Treatment of Diabetic Retinopathy scale (ref. 13) in the primary National Institute of Diabetes and Digestive
prevention group. Scnd: secondary intervention group. Microalb: microalbuminuria defined as and Kidney Diseases (current grant numbers
albumin excretion $40 mg/24 h. Macroalb: macroalbuminuria defined as albumin excretion U01 DK094176 and U01 DK094157), and
.300 mg/24 h. Reduced GFR: estimated GFR ,60 mL/min/1.73 m2. CVD events: CVD including through support by the National Eye
myocardial infarctions, stroke, and CVD death. Reprinted with permission from Nathan et al. Institute, the National Institute of
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Neurological Disorders and Stroke, the
Complications study at 30 years: advances and contributions. Diabetes 2013;62:3976–3986. Genetic Clinical Research Centers Program
(1993–2007), and the Clinical Translational
Science Center Program (2006–present),
Bethesda, MD.
therapy groups explained the vast mechanism, metabolic memory has lasted The following industry contributors have had no
majority (.98%) of the difference in for at least 10 years. role in the DCCT/EDIC study but have provided
complications between the groups free or discounted supplies or equipment to
The long-term EDIC follow-up has support participants’ adherence to the study:
(26), leaving little room for other allowed the study of the impact of INT Abbott Diabetes Care (Alameda, CA); Animas
established or putative risk factors to versus CON on more advanced (Westchester, PA); Bayer Diabetes Care (North
play a role in the trial’s differential complications than were studied during America Headquarters, Tarrytown, NY); Becton,
outcomes. Dickinson and Company (Franklin Lakes, NJ);
the DCCT. Major beneficial effects of INT
CanAm (Atlanta, GA); Eli Lilly (Indianapolis, IN);
on advanced complications (34), LifeScan (Milpitas, CA); Medtronic Diabetes
including retinopathy (35), nephropathy (Minneapolis, MI); Nova Diabetes Care
EDIC/Metabolic Memory
(reduced glomerular filtration rate (Billerica, MA); Omron (Shelton, CT); OmniPod
Considering the powerful effect that Insulin Management System (Bedford, MA);
[GFR]) (36), and autonomic mani-
glycemic separation had on the outcomes Roche Diabetes Care (Indianapolis, IN); and
festations of neuropathy (37), have
during DCCT, the subsequent narrowing Sanofi (Bridgewater, NJ).
been demonstrated (Fig. 2). Finally,
and then disappearance of the difference Duality of Interest. No potential conflicts of
measurements of atherosclerosis in interest relevant to this article were reported.
in HbA1c levels between the two original
several macrovascular beds, including Author Contributions. D.M.N. researched the
therapy groups during EDIC could
carotid intima media thickness (38) and data and wrote the manuscript. D.M.N. is the
logically have been expected to result in computed tomography–measured guarantor of this work and, as such, had full
the subsequent parallel development of coronary artery calcification (39), have access to all the data in the study and takes
complications. However, the first 4 years revealed less atherosclerosis in the INT responsibility for the integrity of the data and
of the EDIC follow-up demonstrated a the accuracy of the data analysis.
group. The clinical expression of these
further widening of the differences in changes, fatal and nonfatal myocardial
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