American Diabetes Association

                             Position Statement

                              Implications of
                 The Diabetes Control and Complications Trial

Approved by the Executive Committee of the Board of Directors, June 1993

                             Summary Statement

The Diabetes Control and Complications Trial (DCCT) is a landmark
multicenter trial designed to test the proposition that complications 
of diabetes mellitus are related to elevation of the plasma glucose
concentration. The study design was simple. Two groups of patients were 
followed long-term, one treated conventionally (goal: clinical 
well-being; called standard treatment group) and another more 
intensively (goal: normalization of blood glucose; called intensive 
treatment group). The intensive treatment group was clearly 
distinguished from the control group in terms of glycated hemoglobin 
levels and measured capillary blood glucose values. Normalization of 
glucose values was not achieved in the intensively treated cohort as a 
group since mean glucose values were approximately 40% above normal 
limits. Nevertheless, there was an approximate 60% reduction in risk 
between the intensive treatment group and the standard treatment group 
in diabetic retinopathy, nephropathy, and neuropathy. The benefit of 
intensive therapy resulted in a delay in the onset and a major slowing 
of the progression of these three complications. Finally, the benefits 
of intensive therapy were seen in all categories of subjects regardless 
of age, sex or duration of diabetes.

The American Diabetes Association believes the study has both 
statistical and clinical significance. The DCCT is the longest and 
largest prospective study showing that lowering the blood glucose 
concentration slows or prevents the development of diabetic 
complications. As such, it has therapeutic implications for health-care 
providers and their patients. Many questions remain to be answered but 
the following conclusions appear warranted:

1.  A primary treatment goal in insulin-dependent diabetes mellitus 
should be blood glucose control at least equal to that achieved in the 
intensively treated cohort. This goal may not apply to all patients 
with IDDM (insulin-dependent diabetes mellitus) and must be based on 
clinical judgment. Of importance, intensively treated patients had a 
three-fold greater risk of hypoglycemia than did the patients in the 
control group. Because serious hypoglycemia is dangerous, "tight" 
control goals may have to be sacrificed in people in whom frequent or 
severe hypoglycemia cannot be avoided by treatment modification.

2.  It is not known for certain whether the results obtained in this 
study of people with insulin-dependent diabetes apply to people with
non-insulin-dependent diabetes mellitus (NIDDM). Nonetheless, it seems
reasonable to recommend more intensive therapy in many patients with
non-insulin-dependent disease because it is presumed that the 
mechanisms by which glucose causes complications is the same in both 
forms of diabetes. However, because there may be other medical 
conditions in people with NIDDM, tight control may not be appropriate 
for all people with this type of diabetes.

3.  There is no favored form of treatment to achieve tight control 
blood glucose levels. The decision to use multiple injections of 
insulin versus an insulin pump depends on the preference of the patient 
with IDDM and the ability of the health care team to provide the 
necessary resources and support. In NIDDM,  diet, exercise and oral 
drugs may achieve tight control, but insulin will often be required.

In order to expand on these conclusions, a list of pertinent questions 
and answers is provided in the accompanying pages.

The American Diabetes Association Response to the DCCT

1.  Are the results of the DCCT significant and reliable?

The DCCT was well designed and efficiently carried out. The results are
statistically significant and are of major clinical importance. They
convincingly demonstrate that blood glucose control significantly 
influences development of complications in subjects with IDDM. The 
study does not appear to have major flaws. As in all clinical trials, 
not every variable could be studied. In the DCCT, the age range was 
rather narrow and relatively few minority patients were included, but 
there is no reason to believe that the results do not apply in all 
persons with IDDM.

2.  What level of glucose control should be sought?

It appears that there is a direct relationship between blood glucose 
level and the risk of complications. However, there are other factors, 
such as genetics, that influence complications. Nevertheless, patients 
should aim for the best level of glucose control they can achieve 
without placing themselves at undue risk for hypoglycemia or other 
hazards associated with tight control (see question 3). As has always 
been the case, therapy for diabetes must be individualized in 
consultation between patient and primary health care provider. If the 
IDDM patient is intellectually, emotionally, physically and financially 
able to attempt tight control, and if a health care team is available 
to provide resources, guidance and support, a reasonable goal is the 
mean plasma glucose and hemoglobin A1c levels achieved in the intensive 
treatment group of the trial (i.e., mean blood glucose of 155 mg/dl and 
HbA1c of ~7.2%; normal average blood glucose -- 110 mg/dl and HbA1c 
-- weight gain->more insulin 
is possible. Some investigators believe that the higher insulin 
concentrations required to overcome insulin resistance may be a factor
in development of high blood pressure, abnormal lipid levels and
artherosclerosis. Also, because of an increased prevalance of 
macrovascular disease, older patients with NIDDM may be more vulnerable 
to serious consequences of hypoglycemia including fainting, seizures, 
falls, stroke, ischemia, or sudden death. Thus, as is the case for 
everyone having diabetes, the treatment in NIDDM has to be 
individualized. But the results of the DCCT do suggest that many 
otherwise healthy patients with NIDDM should strive to achieve tight 
control. Advanced age or significant co-morbidity (e.g., 
cerebrovascular or coronary artery disease) should be considered a 
relative contraindication to tight control in NIDDM. Also, other 
factors important in the development of atherosclerosis in these 
patients, including smoking, elevated blood pressure, abnormal lipid 
values and obesity, must be addressed.

5.  Is tight control contraindicated in any group of patients?

Tight control should not be attempted by patients unable or unwilling 
to participate actively in their glucose management. Tight control is
contraindicated in infants under 2 and should be undertaken with 
extreme caution in children between ages of 2 and 7, because 
hypoglycemia may impair normal brain development which is not complete 
until 7 years. The danger of hypoglycemia is greater in infants and 
children because food intake, activity and adherance to treatment 
schedules are less predictable than in adults. Because pre-adolescents 
appear to be relatively protected from micro-vascular complications, 
the need for tight control might be less than in post-pubertal 
subjects. Older patients with significant atherosclerosis may be 
vulnerable to permanent injury from hypoglycemia. Although there are 
few absolute contraindications to tight control, relative 
contraindications will be more frequent. Clinical judgment and common 
sense will be required in decision making under the latter 
circumstance. Given the above caveats, multiple insulin injections and 
frequent blood glucose monitoring from the onset of IDDM should be 
standard therapy.

6.  Should tight control be the goal for patients with established
    complications?

Again, clinical judgment is required. Unless patients have advanced,
severe complications, the answer would often be yes. Tight control may
not be indicated for patients who already have marked visual loss, are
blind, or have end-stage renal disease. Patients with advanced 
complications were not entered in the trial so no direct evidence is
available to indicate that tight control in such patients is 
beneficial.

7.  Should intensive therapy be offered to patients with longstanding
    diabetes and no evidence of microvascular disease?

If a person has had diabetes for 20-25 years without signs of retinal,
nerve or kidney disease, or if complications are minimal (e.g., one or
two microaneurysms in the retina), standard rather than tight control
may be reasonable.

8.  Will tight control prevent macrovascular complications?

Atherosclerosis occurs earlier in subjects with diabetes than it does 
in persons without elevated blood glucose, and it is reasonable to 
suppose that better control might slow macrovascular as in addition to 
microvascular complications.

9.  Is there any way to predict genetic susceptibility to diabetic
    complications?

As mentioned earlier, susceptibility to complications and damage from
elevated blood glucose is influenced by one's genes. Unfortunately, we 
do not have measurable genetic markers of susceptibility.

10.  For those choosing tight control, is life-time treatment required?

In general, tight control for subjects beyond puberty should be 
maintained for life. Alteration of therapy may be required by advanced 
age or other changes in clinical circumstances; e.g., following a 
stroke or heart attack signalling more serious risks from hypoglycemia.

11.  Are the results of the DCCT achievable in the general population 
     of subjects with diabetes?

In theory the answer is yes. However, in the real world, great effort
will be required to reproduce the results of DCCT. Practically it must
be recognized that the study group was young, generally healthy and 
highly motivated. The professional personnel carrying out the study 
were trained endocrinologists and diabetes educators in academic 
centers who were highly motivated and meticulous in management of the 
study subjects. The intensively treated group received far more 
attention and medical services than are routinely available in clinical 
practice. In many cases, participants and professionals became 
"family." Broad implementation of intensive therapy will require 
expanded health care teams (knowledgeable physicians, diabetes 
educators, nutritionists and social workers), major professional and 
patient educational efforts, and an enhanced partnership between 
specialists and primary care providers. The costs of these services and 
reimbursement mechanisms will have to be adressed (see Question 13).

12.  What form of intensive treatment is recommended?

Improved glucose control in IDDM had beneficial effects whether 
delivered by multiple daily injections or programmable insulin infusion 
pumps. The choice of treatment depends on the wishes of the individual 
patient and the comfort/competence of the health care team with a given 
technique.

14.  Will the postulated benefits of better control be worth the 
     increased costs?

It is recognized that there will be increased costs of widely applying 
the recommendations of this study in the United States. There will also 
need to be additional efforts to insure professional education, so that 
health practitioners are able to effectively and safely implement the 
therapy employed in the DCCT. It is hoped that the long term benefits 
of healthier, more productive lives with fewer complications would 
offset the costs of tight control. This issue is being studied. 
Ultimately, this will be a societal decision.

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DEFINITIONS

1.  Insulin-dependent diabetes mellitus (IDDM):  The form of diabetes
commonly developing in persons under the age of 25, which was the study
group in this trial. Insulin is required in all patients and its 
omission results in life-threatening diabetic ketoacidosis ("diabetic 
coma"). It is also called type I diabetes.

2.  Non-insulin-dependent diabetes mellitus (NIDDM):  By far the most
common form of diabetes, NIDDM usually begins in middle age but can 
occur earlier or later. It is called non-insulin-dependent to indicate 
resistance to diabetic ketoacidosis. Patients may be treated by diet or 
oral drugs ("sulfonylureas") but many are best managed by insulin. 
NIDDM is also called type II diabetes.

3.  Complications:  Diabetes of both types may result in tissue 
damaging complications. One set of complications is designated 
microvascular. Microvascular means small blood vessel, but this is 
simply a traditional terminology and does not imply that the 
complications are due to blood vessel disease. The microvascular 
complications affect three organ systems: the eyes ("retinopathy"), the 
kidneys ("nephropathy") and the nerves ("neuropathy"). These 
complications lead to visual loss, kidney failure and multiple 
neurologic symptoms in some patients. The purpose of the DCCT was to 
test the hypothesis that these complications could be prevented or 
their progress slowed by better control of blood glucose. Macrovascular 
means large blood vessel. Macrovascular complications are due to 
atherosclerosis of the blood vessels which results in narrowing or
clotting such that blood flow to tissues is impaired. Complications 
include angina, heart attacks, strokes, and amputations. In addition to
hyperglycemia, other factors are important in the pathogenesis of
atherosclerosis in diabetes. These include known risk factors in 
persons without diabetes such as smoking, high blood pressure and 
abnormal lipids.

4.  Tight control:  This term will be used to indicate blood glucose 
equal to or better than those achieved in the intensively treated group 
in the DCCT.

5.  Hemoglobin A1c, or glycated hemoglobin:  This is a form of 
hemoglobin (the oxygen-carrying molecule of the blood) that reflects 
the average blood glucose concentration over a three month period. A 
high percentage of hemoglobin A1c indicates poor control while a low 
percentage indicates good control.