Archive-name: diabetes/faq/part5
Posting-Frequency: biweekly
Last-modified: 18 Dec 1995

Changes: none

Subject: READ THIS FIRST
========================

Copyright 1993-1995 by Edward Reid. Re-use beyond the fair use provisions
of copyright law and convention requires the author's permission.

Advice given in m.h.d is *never* medical advice. That includes this FAQ.
Never substitute advice from the net for a physician's care. Diabetes is a
critical health topic and you should always consult your physician or
personally understand the ramifications before taking any therapeutic action
based on advice found here or elsewhere on the net.

Subject: Table of Contents
==========================

INTRODUCTION (found in all parts)
  READ THIS FIRST
  Table of Contents
GENERAL (found in part 1)
  Where's the FAQ?
  What's this newsgroup like?
  Abuse of the newsgroup
  The newsgroup charter
  Newsgroup posting guidelines
  What is glucose? What does "bG" mean?
  What are mmol/L? How do I convert between mmol/L and mg/dl?
  What is c-peptide? What do c-peptide levels mean?
  What's type 1 and type 2 diabetes?
  Is it OK to discuss diabetes insipidus here? What is it?
  How about discussing hypoglycemia?
BLOOD GLUCOSE MONITORING (found in part 2)
  How accurate is my meter?
  Ouch! The cost of blood glucose measurement strips hurts my wallet!
  What do meters cost?
  Comparing blood glucose meters
  How can I download data from my One Touch II?
  How can I download data from my Glucometer (tm)?
  Other recordkeeping software
  I've heard of a non-invasive bG meter -- the Dream Beam?
  What's HbA1c and what's it mean?
  Why is my morning bg high? What are dawn phenomenon, rebound,
    and Somogyi effect?
TREATMENT (found in part 3)
  My diabetic father isn't taking care of himself. What can I do?
  Managing adolescence, including the adult forms
  So-and-so eats sugar! Isn't that poison for diabetics?
  Insulin nomenclature
  What is Humalog / LysPro / lispro / ultrafast insulin?
  Travelling with insulin
  Injectors: Syringe and lancet reuse and disposal
  Injectors: Pens
  Injectors: Jets
  Insulin pumps
  Type 1 cures -- beta cell implants
  Type 1 cures -- pancreas transplants
  Type 2 cures -- not even a dream
  What's a glycemic index? How can I get a GI table for foods?
  Should I take a chromium supplement?
  I beat my wife! (and other aspects of hypoglycemia) (not yet written)
  Does falling blood glucose feel like hypoglycemia?
  Alcohol and diabetes
  Necrobiosis lipoidica diabeticorum
  Has anybody heard of frozen shoulder (adhesive capsulitis)?
  What is pycnogenol? Where and how is it sold?
  What claims do the sales pitches make for pycnogenol?
  What's the real published scientific knowledge about pycnogenol?
  How reliable is the literature cited by the pycnogenol ads?
  What's the bottom line on pycnogenol?
  Pycnogenol references
SOURCES (found in part 4)
  Online resources: diabetes-related newsgroups
  Online resources: diabetes-related mailing lists
  Online resources: commercial services
  Online resources: FTP
  Online resources: World Wide Web
  Online resources: other
  Where can I mail order XYZ?
  How can I contact the American Diabetes Association (ADA) ?
  How can I contact the Juvenile Diabetes Foundation (JDF) ?
  How can I contact the British Diabetic Association (BDA) ?
  How can I contact the Canadian Diabetes Association (CDA) ?
  What about diabetes organizations outside North America?
  How can I contact the United Network for Organ Sharing (UNOS)?
  Could you recommend some good reading?
RESEARCH (found in part 5)
  What is the DCCT? What are the results?
  More details about the DCCT
  DCCT philosophy: what did it really show?
IN CLOSING  (found in all parts)
  Who did this?

Subject: What is the DCCT? What are the results?
================================================

The DCCT was a large multi-center trial involving over 1400 volunteer
patients with type 1 diabetes. It began in 1983, ramped up to full speed by
1989, and ended early in 1993 when the investigators felt the results were
clear. The volunteers were all undergoing "standard" treatment when they were
recruited, meaning one or two injections per day. They were randomly assigned
to two groups. One group continued as before. The other group received
intensive treatment aimed at achieving blood glucose (bG) profiles as close
as possible to normal. The intensive treatment involved multiple bG checks
per day, multiple injections and/or an insulin pump, and access to and
regular consultation with a team of treatment experts.

It is particularly important to note that intensive treatment was defined as
a collaborative effort involving the patient and a skilled team of health
care professionals. It was not defined by particular techniques, although
certain techniques were typically used. The frequent consultations and
availability of a professional team were critical components of intensive
therapy.

The results show that the intensive treatment group did indeed achieve bG
levels closer to normal, and that they experienced far fewer diabetic
complications though also more hypoglycemia. In particular, patients who
maintained HbA1c levels around 7% appear to be much better off than those
whose HbA1c hovers around 9%. (See caveats in the section on HbA1c.) Though
it is not possible to separate the effects of all the aspects of the
intensive treatment, it is reasonable to believe that lowering average bG may
be effective even in isolation from the other aspects of the intensive
treatment. In its position statement, the ADA says

   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.

Though type 2 patients were not included in the study, it is generally
believed that the results showing the benefits of tight control apply to
type 2 patients as well.

The entire position statement was published in most of the ADA's publications
(see "could you recommend some good reading") in the summer and fall of 1993.

The formal report detailing the results was published in The New England
Journal of Medicine, aka NEJM, of September 30,1993 (v 329 pp 977-986). The
following discussion is based on that article.

Several DCCT subjects participate in m.h.d and are willing to answer
questions related to the personal aspects of DCCT participation.

Subject: 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.

Subject: DCCT philosophy: what did it really show?
==================================================

It is often stated that the DCCT proved that tight control or lowered HbA1c
reduces complications. This is not the case. The controlled variable in the
DCCT was intensive vs conventional therapy, and intensive therapy was defined
by several factors including a team of skilled health care professionals
acting in partnership with the patient. The results show that intensive
therapy results in both lowered HbA1c and fewer complications, but do not
show that one causes the other. The lead authors provide a good summary of
this point in a followup (NEJM 330:642, March 3, 1994):

    We want to stress that the most valid interpretation of the trial is that
    intensive therapy, with the **goal** of achieving blood glucose
    concentrations as close to the nondiabetic range as possible, delays the
    onset and slows the progression of long-term diabetic complications. The
    secondary analyses support the notion that lower glycosylated hemoglobin
    values are associated with a lower risk of progression of retinopathy,
    but they do not prove that hyperglycemia in itself causes retinopathy.
    [emphasis added]

Many of us believe, and believed before the DCCT, that actually achieving
good control aids our health. The DCCT adds weight to this case but does not
prove the point.

Subject: Who did this?
======================
-- 
Edward Reid          edward@paleo.greensboro.fl.us
PO Box 378
Greensboro FL 32330
