What happened to the valid POEMs? A survey of review articles on the treatment of type 2 diabetes
BMJ 2003; 327 doi: https://doi.org/10.1136/bmj.327.7409.266 (Published 31 July 2003) Cite this as: BMJ 2003;327:266All rapid responses
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Evidence based medicine is subject to bias. This study (1) takes the
example of UKPDS and shows that the dissemination of evidence can be
flawed and lopsided. The authors have to be congratulated for their
frank comments . However I would like to make the following points.
1) The researchers of UKPDS presented their results much more
favourably. It was McCormack and Greenhalgh who called this optimism into
question (2) and offered a different interpretation of UKPDS data. These
alternatives feature mainly in the POEM table of the article. Courtesy and
completeness would have demanded that the authors relate to this seminal
work.
2) The distinction of POEM and DOE is somewhat arbitrary and not
always consistant. Although Digoxin does not increase survival in patients
with CHF it gives symptomatic relief. - this matters to patients at least
as much.
3) POEM and DOE are yet another annoying acronyms. Could the
authors please open a debate about more suitable alternatives.
4) Only unbiased discussion will turn 'evidence based medicine'
into evidence based medicine . This article certainly is a good start...
1) Shaugnessy A F,Slawson D C. What happend to the valid POEMs. A
survey of review articles on the treatment of type II diabetes. BMJ 2003,
327: 266
2) McCormack Greenhalgh T.Seeing what you want to see in Randomised
Controlled Trials - versions and perversions of UKPDS data.BMJ 2000, 320 ;
1720 - 1723
Competing interests:
interested in real evidence based medicine
Competing interests: No competing interests
Might type 2 diabetes, or the metabolic syndrome, be the product of a
shift towards dependence upon ATP resynthesis by anaerobic rather than
arobic means?
In inducing a tissue acidosis and, if severe enough, would inhibit
phosphofructokinase and enhance activity within the pentose phosphate
shunt. The shunt generates NADPH which catalyses the reductive
biosynthesis of fatty acids, cholestrol, and steroid hormones. Synthesis
of nitric oxide, cytochrome P450, tetrahydrofolate and reduced
glutathione is also induced. The inhibition of phosphofructokinase is
accompanied by the stimulation of fructose-6-phospharylase and
gluconeogenesis. Glycolysis is inhibited so the rise in blood sugar is a
product of gluconeogenesis rather than glycolysis(1).
If so what might induce the anaerobic shift? A disproportionate
increase in glucose consumption relative of fructose consumption, fructose
not generating NADPH or promotion reductive biosynthesis. The stress
hormones, epinephrine, cortisol and glucagon? Chemicals that impair
mitochondrial oxidative phosphorylation?
What of therapy? Might increasing fructose consumption, relative to
glucose consumption, restore the metabolic balance?
1. Biochemistry Fifth edition. Berg JM, Tymoczko JL, Streyer L, Eds.
WH Freeman and Company, New York, 1999.
Competing interests:
None declared
Competing interests: No competing interests
Sir,
Type 2 diabetes mellitus is becoming extremely common; its prevalence
worldwide is expected to reach 5-7,6% by 2025 (1). In addition,
atherosclerotic cardiovascular disease is the principal cause of death,
disability, and excess healthcare costs in diabetes. Cardiovascular
disease may already be present at the time when diabetes is diagnosed, as
well as a lot of years before, and patients with diabetes are more likely
than their non-diabetic counterparts to die from a first event of
cardiovascular disease (1). The close association of type 2 diabetes with
cardiovascular disease led to the hypothesis that the two arise from a
common antecedent; this concept has been codified by the World Health
Organization and others as "the metabolic syndrome" (2).
Fortunately, at
the beginn of third millennium, the researchers into type 2 Diabetes
Mellitus initiate to find new interesting ways in the prevention,
diagnosis, therapy of diabetes, and, then, in the full understanding of
such as disorder and its vascular complications, in a direction, we
indicated 20 years ago, at least (3, 4). What occurs before the
metabolic syndrome?
As a matter of fact, with the aid of Biophysical Semeiotics (HONCode
233736, http://digilander.libero.it/semeioticabiofisica), doctor can today
realize “clinically” the essence of a particular condition of the
biological systems, real locus (site) of the primary prevention of the
most common and severe human disorders, by bed-side evaluating
microcirculatory actual coditions under absorptive state and post-
absorptive state conditions, in pancreas, liver, skeletal muscle and
adipose tissues (central and peripheral), which are more or less abnormal,
when, in presence of the singular mitochondrial cytopathology, I named as
Congenital Acidosic Enzyme-Metabolic Histangiopathy (1) (See in above-
cited site, URL
http://digilander.libero.it/semeioticabiofisica/Documenti/Eng/istangiopa...
-) the slow transition initiates from the “pre-metabolic syndrome”
(http://digilander.libero.it/microangiologia/Documenti/Eng/A%20Zona%20Gri...),
to metabolic (Reaven’s) syndrome, classic and “variant”, and ultimately
to the diseases themselves, e.g., type 2 diabetes (4, 5, 6). Really, the
“pre-metabolic syndrome” take a part of biophysical semeiotic
constitutions – for instance, diabetic as well as dyslipidemic
constitutions, conditio sine qua non of type 2 diabetes mellitus – fully
described in above cited site,
http://digilander.libero.it/semeioticabiofisica/constitutions.htm).
In
conclusion, biophysical-semeiotic microangiological study (See
http://digilander.libero.it/microangiologia) permits doctor to collect
clinically essential information, which allows doctor bed-side
recognizing and interpreting the real nature of slow changing from
health stage – white zone – to disease stage, including the metabolic
syndrome – black zone – through the grew zone or “pre-metabolic” stage,
explaining, although incompletely at the moment, its clinical and
biological significance, and suggesting, thus, nosological definition of
the term pre-metabolic state, pre-metabolic syndrome, Grew Zone, which
is the proper site of the “primary” prevention of most severe and
numerous human disorders, in rationally select individuals and on very
large scale.
Sergio Stagnaro MD., Member NYAS.
1) Meigs JB. Pre-metabolic Syndrome. BMJ 2003;327:61-62 (12 July)
2) Alberti KG, Zimmet PZ. Definition, diagnosis and classification of
diabetes mellitus and its complications. Part 1: diagnosis and
classification of diabetes mellitus provisional report of a WHO
consultation. Diabet Med 1998;15: 539-53.[CrossRef][ISI][Medline]
3) Stagnaro S., Stagnaro-Neri M. Valutazione percusso-ascoltatoria del
Diabete Mellito. Aspetti teorici e pratici. Epat. 32, 131, 1986.
4) Stagnaro S. Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan
24;346(4):297-298. [PubMed indexed for Medline]
5) Stagnaro S.-Neri M., Stagnaro S., Sindrome di Reaven, classica e
variante, in evoluzione diabetica. Il ruolo della Carnitina nella
prevenzione del diabete mellito. Il Cuore. 6, 617, 1993. [PubMed indexed
for Medline]
6) Stagnaro-Neri M., Stagnaro S., La “Costituzione Colelitiasica”: ICAEM-
a, Sindrome di Reaven variante e Ipotonia-Ipocinesia delle vie biliari.
Atti. XII Settim. It. Dietol. ed Epatol. 20, 239, 1993.
Competing interests:
None declared
Competing interests: No competing interests
UKPDS - Emperors New Clothes
Dear Dr,
I read with great interest your comentary on how UKPDS 33/34 is being
interpreted. It seems just like the tale of the Emperors New Clothes.
As a busy family GP of 17 years , I have many NIDDM patients and get to
know them all quite well. I have looked at the actual evidence ie UKPDS
to see if I can decide for myself how to advise the diabetic who is
torturing themselves physically and psychologically to seek the supposed
targets promoted in Diabetic Education Brochures.
I have read UKPDS 33 over and over and over and am just astounded at
the rampant interpretative bias.
2 major flaws -
(1) If injury from major hypoglycemia was included (if it was measured) as
a diabetes endpoint, I suspect the whole trial would show some very
statitically significant higher number of adverse outcomes in the
Intensive group ( therefore it was not included as an endpoint)
(2) Retinal photocoagulation - This is just simply not a clinical outcome.
It is a set of physical signs that indicate a potential to lose vision.
What % of those with vision threatening retinopathy actually lose
significant vision if untreated ? Similarly what percentage of those who
do get laser actually still go blind anyway ? Both of these realities
would significantly dilute the supposed major substantial reduction in
retinopathy from 11% to 8 % in 10 years.
In reality if 10 years of intensive treatment of 100 patients casued 3
fractured hips due to hypoglycemia, thus negating 3 retinas not
subjected to laser, UKPDS 33 would be out the door cold.
An Endocrinologist colleague was recently asked for independent
advice in a medico legal case where a patient wanted to sue because he had
developed retinopathy and his HBA1C was 9%. A review of the actual
evidence, rather than the zealots interpretations, was very revealing, and
encouraging for the defendant. To my mind every patient injured in a hypo
seeking a BGL of 6 would have a better chance of succesful litigation.
On a final cynical note I wonder how the BMJ/Lancet could have ever
allowed the abstract for UKPDS33 to include the comment , "SUBSTANTIALLY
reduces the risk of diabetic complications". It is the abstract that is
quoted and requoted, and there is the origin of the mythology.
Competing interests:
None declared
Competing interests: No competing interests