Note from archiver<at>cs.uu.nl:
This page is part of a big collection
of Usenet postings, archived here for your convenience.
For matters concerning the content of this page,
please contact its author(s); use the
source, if all else fails.
For matters concerning the archive as a whole, please refer to the
or contact the archiver.
Subject: diabetes FAQ: research (part 5 of 5)
This article was archived around: Sat, 26 Sep 2015 00:02:43 -0400 (EDT)
Last-modified: 14 July 2005
Changes: see part 1 of the FAQ for a list of changes to all parts.
Subject: READ THIS FIRST
Copyright 1993-2005 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?
Helping with the diagnosis (DM or hypoglycemia) and waiting
Exercise and insulin
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 meter?
I've heard of a non-invasive bG meter -- the Dream Beam?
What's HbA1c and what's it mean?
Why is interpreting HbA1c values tricky?
Who determined the HbA1c reaction rates and the consequences?
HbA1c by mail
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?
What is Humalog / LysPro / lispro / ultrafast insulin?
Travelling with insulin
Injectors: Syringe and lancet reuse and disposal
Type 1 cures -- beta cell implants
Type 1 cures -- pancreas transplants
Type 2 cures -- barely 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)?
Extreme insulin resistance
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?
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?
Could you recommend some good magazines?
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?
Is aspartame dangerous?
IN CLOSING (found in all parts)
Who did this?
Subject: What is the DCCT? What are the results?
The Diabetes Control and Complications Trial 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:
Duration of IDDM 1-5 yrs 1-15 yrs
Retinopathy none detectable very mild to moderate
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
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
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:
Complication Prevention Combined Intervention
------------ ---------- -------- ------------
Retinopathy(*) - 75% - 55%
Nephropathy(*) - 35% - 45%
Neuropathy(*) - 70% - 55%
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:
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: Is aspartame dangerous?
In short, no, except for phenylketonurics.
Aspartame is one of the most intensively studied food additives ever,
and the overwhelming scientific evidence is that it poses no danger.
The many claims of harm are all either anecdotal and not supported by
adequate observation, or are based on serious lack of understanding of
how to demonstrate facts scientifically. One of the most egregious is
the claim that studies with aspartame in capsules are invalid and that
it's only dangerous in solution. But d'oh -- if you administer
aspartame in solution, the patient will know whether he/she is getting
aspartame or not. This unblinds the experiment. Refer to Reid's Third
Law: Never Underestimate the Power of Suggestion.
An good set of links to web pages on aspartame is at
http://urbanlegends.about.com/library/blasp3.htm. (Unfortunately the
links open framed by about.com's heading, an unfair practice eschewed
by the vast majority of web sites. Ten demerits for about.com.)
The well known low-calorie sweeteners are pretty much all safe:
cyclamates, saccharin, aspartame, acesulfame, sucralose. Yes, even
cyclamates and saccharin -- the studies which resulted in their banning
turned out to be non-reproducible. I don't list stevia because it has
not been adequately studied, but I know of no significant indications
If you don't like a given sweetener, try another. If you think you
respond badly in some way to a sweetener, try another. But unless you
have at least a heterozygous gene for phenylketonuria, it's unlikely
that you'll have a verifiable response to aspartame.
Subject: Who did this?
Edward Reid <email@example.com.SPAMNOT>