More details about the DCCT

The study placed subjects into two cohorts, primary prevention or
secondary intervention, depending on duration of diabetes and existing
complications -- the primary prevention cohort were those with
essentially no complications.

Specifically: all subjects met these criteria:

    Insulin dependent as evidenced by deficient C-peptide secretion
    Age 13 to 39 years at entry to the study
    No hypertension, hypercholesterolemia, severe diabetic complications,
        or other severe medical conditions
    Meet the criteria for one of the cohorts

and were separated into the two cohorts by these criteria:

                              Primary          Secondary
                             Prevention       Intervention
                              Cohort            Cohort

    Duration of IDDM        1-5 yrs           1-15 yrs
    Retinopathy             none detectable   very mild to moderate
                                                  nonproliferative
    Urinary albumin         < 40 mg / 24 hr   < 200 mg / 24 hr

Within each cohort, the subjects were randomly assigned to either
conventional therapy or intensive therapy. Thus the study compared
intensive to conventional therapy in two different cohorts. The two
questions the study was mainly designed to answer were

  1) Will intensive therapy prevent the development of diabetic
     retinopathy in patients with no retinopathy (primary
     prevention), and
  2) Will intensive therapy affect the progression of early
     retinopathy (secondary intervention)?

Conventional therapy included one or two injections per day, daily self
monitoring of blood or urine glucose, education, quarterly
consultations, and intensive therapy during pregnancy. Intensive
therapy included three or more daily injections or an insulin pump, bG
monitoring at least 4x/day, adjustment of insulin dosage for bG level
and food and exercise, monthly personal consultations and more frequent
phone consultations.

To simplify a lot, the DCCT showed the following changes in the
intensive therapy groups compared to the conventional therapy groups.
Note that '-' shows a decrease, '+' shows an increase, in the number of
patients affected. Patients were judged as affected or not based on
binary criteria, so the results only say how many subjects were
affected, not how severely those subjects were affected.

Intensive therapy compared to conventional therapy:

                                Primary                    Secondary
  Complication                 Prevention    Combined     Intervention
  ------------                 ----------    --------     ------------
  Retinopathy(*)                 - 75%                       - 55%
  Nephropathy(*)                 - 35%                       - 45%
  Neuropathy(*)                  - 70%                       - 55%
  Hypoglycemia(*)                              +200%
  Weight gain(*)                               + 33%
  Hypercholesterolemia(*)                      - 35%

(*) This brief table begs many questions about what exactly was
measured and how. For more details, read the paper.

There were no detectable differences on several measures:

  Macrovascular disease
  Mortality
  Changes in neuropsychological function
    (a feared result of severe hypoglycemia)
  Quality of life (based on a questionnaire)

Some limitations of the study: type 1 only, patients young and with
short duration (under 15 years) of diabetes, and short duration of the
study (5-9 years). Measured only number of subjects affected according
to binary criteria, not by measurement of severity of complications.
Excluded patients who already had severe complications and who thus
might benefit the most. The difference between the groups increased
during the study, but there is no proof that the difference would
continue to increase with time.

It is tempting to extrapolate the results to all diabetic patients --
all types, ages, and durations -- and there is at least some support
for doing so. However, the DCCT by itself does not show results for
type 2 patients, older patients, patients who have had diabetes for
many years, or those who already have severe complications. On the
other hand, a different group of subjects might shows differences in
areas such as mortality and macrovascular disease, where the young DCCT
cohorts simply did not have significantly measurable incidence. The
DCCT subjects are being tracked in a followup study which may shed
light on some of the unanswered questions.

Secondary analysis of the data indicates that retinopathy decreases with
decreasing HbA1c. This measure was not part of the study design and is
more difficult to interpret, but still shows clearly a correlation
between HbA1c and retinopathy.