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©February
28, 2001®-- Hoadleygold, Inc. Brent Hoadley, Ph.D.
Brent Hoadley's Lilly, Novo, Genentech
and
other Insulin Patent Research and Findings
The 4 million insulin-using diabetics in the
United States are becoming nothing more than a
human population
of guinea pigs. They represent the money tree for ‘Diabusiness.’
In his book 1984, George Orwell wrote
about “newspeak.’ This is now the language used by
the
pharmaceuticals to create billions of dollars in profit from
genetically engineering insulin-like
molecules.
When is an insulin molecule a ‘foreign’
protein? Pharmaceuticals will tell you the foreign
protein
insulin source is the pancreas of a pig or cow. When given names
such as Humalog,
Lantus or NovoRapid by giant corporations, a
foreign protein becomes a wonderful ‘analog’ of
human
insulin. The truth is all three of these substances are foreign
proteins—in some cases
not even an insulin molecule. All could
be considered new growth hormones with very little
being known
about long term effects. Diabetics need to apply for long-term
guinea pig status.
Over the last 30 years, there have been over
2000 patents approved for
various chemical compounds or
processes used to normalize blood sugar metabolism. This
enormous interest is a 30-year ride on the money train called
diabetes. It’s also a good
insight into the lack of progress
in the treatment of diabetes over the last 70-plus years. We
have replaced proven insulin protocols with less effective
insulins.
In a 1999 U.S. Pat. #5,922,675, related to a “better”
basal insulin, Eli Lilly Corporation
researchers state:
“in order to achieve normal glycemia, therapy
must be designed to parallel as closely as
possible the pattern
of endogenous insulin secretion in normal individuals. The daily
physiological
demand for insulin fluctuates and can be separated
into two phases: (a) the absorptive phase
requiring a pulse of
insulin to dispose of the meal-related blood glucose surge, and
(b) the
post-absorptive phase requiring a sustained amount of
insulin to regulate hepatic glucose
output for maintaining
optimal fasting blood glucose. Accordingly, effective therapy
involves the
combined use of two types of exogenous insulin: a
fast-acting meal time insulin and a long-acting
basal insulin.”
The ‘(b)’ phase of the above statement is a
widely accepted necessary component to
normalize blood glucose
metabolism. However, earlier (1996), Hoffmann wrote in Lilly
patent #5,534,488:
The ideal insulin formulation to deal with this
basal glucose output would be one that resulted
in a slow,
steady infusion of insulin into the bloodstream that matched the
low level of glucose
output from the liver. In terms of this
ideal basal time action, the best parenteral product
that
fits this description is commercially available beef
Ultralente insulin. Injected just once per
day, it
gives a low, steady release of insulin into the bloodstream
without any noticeable insulin
peak.
Beef Ultralente is no longer available in the
marketplace because Lilly and NovoNordisk
arbitrarily decided
this only-known ideal basal insulin was an
immunogenic foreign protein
for some diabetic patients. They
said this could lead to alteration in insulin time action
(their
words). Even noted diabetes researcher Irl Hirsch, in a 1993
review of diabetes insulin
treatment called Beef Ultralente the
only true basal insulin, with no peak. He also made
reference to Human UL Ultralente as being something less than
ideal (my words).
U.S. Patent #5,534,488, in discussing Human
Ultralente and Beef Ultralente, states (1996):
“However, several years of clinical experience
led to definite indications that these products
were not
identical. In fact, clinical reports indicated that human
Ultralente was faster acting than
the beef Ultralente
formulation while pork Ultralente was shown to be intermediate
in time action
between the other two species. In clinical
practice this has led many physicians and
diabetologists to
recommend a twice a day injection protocol for human Ultralente.
In addition,
a significant peak of insulin absorption
into the bloodstream is observed about
12 hours after
subcutaneous administration. This phenomena not only
diminishes the
ability of this product to counteract the steady
basal glucose output of the liver, it also results in
hyperinsulinemia
which itself may lead to macrovascular complications.
The reasons for the differences in time action
between human and beef Ultralente products
are not completely
understood.”
The above patent is for new analogue
formulations of human insulin which more closely
mimic basal
levels of insulin found in the normal human body. Beef insulin
is also a naturally
occurring analogue of human insulin. Lilly
admits that they do not know whether it is the
actual amino acid
arrangement of beef insulin or the resulting manipulated beef
crystalline
structure that provides the ‘ideal basal insulin.’
In order to speed up approval and acceptance of
Human UL Ultralente, the product was
placed before the FDA, the
American Diabetes Association (financed by diabusinesses),
and
pushed by the pharmaceutical representatives to doctors because
it was just like
beef Ultralente without antibody response. The
ADA even made a statement in the Wall
Street Journal in
1992, claiming that all human insulin was just like animal
insulin in activity curves.
Recently, the ADA has been forced to
recognize activity curve differences.
Eli Lilly’s Ultralente Human Insulin insert (PA6364AMP) states: this product has a longer
and
less intense duration of activity up to 28 hours. This does
not imply a peak at 12 hours or
the fact that, as stated in
their patent, the product is found to last only 18 hours.
Diabetic patients
are warned to be aware of individual patient
differences.
A significant peak at 12 hours and a greater
risk of macro blood vessel damage could put the
diabetic patient
in harm’s way if the UL Human is split into two doses. That is
NOT just like
Beef Ultralente.
Novo Nordisk stated in 1995 U.S. Pat.
#5,157,021:
“In the case of Insulin-Dependent Diabetes a
frequently used therapy consists in two daily
injections of a
protracted insulin preparation, one in the morning and one in
the evening just
before bedtime, in order to create a basal
insulin level. Additionally, three injections of a fast
acting
insulin preparation are given prior to the principal meals. The
disadvantage of this
therapy is that the late injection of the
protracted preparation may result in a dangerously
low
blood glucose level in the course of the night.”
Does this also point the finger at Human (UL)
Ultralente or does it mean that intermediate
duration insulins
like NPH and Lente, used as split doses, are dangerous
preparations in the
course of sleep hours.
A fact not widely known is that Human R insulin
does not cover the post-prandial (after meal)
rise in blood
glucose in the expected manner for many diabetics. In U.S. Pat.
#5,474,978
(1995) Lilly researchers wrote:
“However, this
therapy has not yet been optimized. The most rapid-acting
insulin
commercially available peaks TOO LATE AFTER
INJECTION AND LASTS TOO LONG
to optimally control
glucose levels.”
This admission is made
in several patents: “Human regular when deposited under
the skin
in a depot reacts too slow to cover post prandial blood
sugar rise in some patients. Secondly
and just as important it
may last too long.” “LAST
TOO LONG” from personal experiences
can mean a
plateau (or peak) in the middle of the night. Combine this with
an “unawareness”,
and you have a recipe for disaster.
Perhaps this is the reason for an increase of the
“dead in bed”
syndrome, especially among the younger and older diabetics.
Even as early as 1986,
NovoNordisk recognized a need for a better rapid-acting insulin
solution. In U.S. Pat. #5,504,188, it is again stated that “commercially
available rapid acting
insulins peak too late.”
In the past few years
a new rapid acting insulin has been marketed by Lilly—Humalog.
NovoRapid has been approved for sale by NovoNordisk in Europe.
Lantus has been approved
for sale as a basal insulin. The only
natural basal insulin is beef ultralente.
Aventis
Pharmaceuticals, in a press release for the new product Lantus,
stated:
“Safety
Information:
Human insulin therapy
may be associated with hypoglycemia, worsening of diabetic
retinopathy, lipodystrophy, skin reactions (such as injection
site reaction, pruitus, and rash)
allergic reactions, sodium
retention, and edema.”
NovoNordisk, in the
announcement regarding NovoRapid®:
“In long-term,
large-scale clinical trials, NovoRapid® significantly improved
glycemic
control compared to that of soluble human insulin and
significantly reduced the risk
of major nocturnal hypoglycemia.
Historically,
improving glycemic control with soluble human insulin has been
associated with an increase of hypoglycemia.”
rDNA Human insulin was
pushed through the FDA in the early 1980s in a period of about
5
months. Lilly was a well-known pharmaceutical, with the only
U.S. expertise in insulin
production. This product was
fast-tracked through the approval process with the false premise
that there were many diabetics dying from allergic reactions to
animal insulins and the possibility
that future supplies of
animal insulins would be in decline.
We now see from the
above rush to patent new insulins that the human insulin product
so
quickly approved was not even equal to the beef and pork
insulin products which have proven
safe over a period of 70
years of use. The only advantage of human insulin is the fact
that the
product is considerably less expensive to produce than
animal insulins and results in
greater profitability for
diabusiness.
The pieces of the
human-insulin puzzle slowly being put together as the truth
includes the
following:
a) After 17-18 years
of human insulin usage, the truth is beginning to emerge. Human
R is
NOT fast acting and may have a delayed peak. Human
UL basal is NOT REALLY basal, and
two shots to cover 24
hours could lead to nighttime hypoglycemia and macro blood
vessel
disease. Intermediate formulations given as two more
shots cause unexpected night-time
lows in some patients. Where’s
the advantage?—PROFIT!
b) Then we note in a
press release the occurrence of rashes, worsening of diabetic
retinopathy,
allergic reactions, sodium retention, and improved
glycemic control with soluble human insulin
is associated with
increased incidence of hypoglycemia.
In a 1995 Patent
#5,422,339, Joslin Diabetes Ctr. States that immune systems of
the patient
produce antibodies which interfere with insulin
related function. Human insulin and animal insulin
antibodies
are an immunological response to insulin treatment.
Animal insulins were
replaced because they were immunogenic to a small percentage of
the insulin-taking diabetic population. Now, it is admitted that
human insulin causes the same
problem. Where’s the advantage?
PROFIT!
c) The naming of
Humalog was meant to indicate it is a human insulin analogue,
and somehow
better than pork or beef. Considering the A and B
chains of human insulin have 51 amino acids,
there are millions
of analogues of this growth hormone that could be considered
using
natural amino acids. Remember beef and pork are just
analogues of human insulin.
Where’s the advantage? PROFITABLE
new insulins with no proven record of better control.
d) An Aventis product—Lantus--has
added 2 additional amino acid molecules (glargine),
for a total
of 53 amino acids, and essentially have created a foreign growth
hormone
structure. ATTENTION DIABETICS1 Step right up. Be a
human guinea pig for determining long
term results.
There is no proof it
is better than Beef UL. Even
plant scientists worry about the impact of
creating new
hormones.
e) The patent
examiners sit on one side of government, knowing the truth about
new and
“old” insulin products. The FDA is lied to about the
efficacy of new insulins while the diabetic
patient is put in
harm’s way. Meanwhile, profits for diabusinesses increase.
f) Once a ‘wonderful
new insulin’ hits the marketplace, the pharmaceutical
companies—
with high-priced public relation campaigns—convince
the ADA, doctors, hospitals, noted clinics
and patients that the
diabetic life will now be “much better.” All of these,
except the diabetic patient,
often benefit from an inflow of
corporate dollars in the form of contributions, advertising,
research grants, sponsorship, and other unqualified perks.
Therefore, their promotion and/or
endorsement of a ‘wonderful
new insulin.’ is not necessarily unbiased or fact-based, but
is
certainly profit-driven.
Lilly’s answer to
problems has always been to blame the patient and/or blame the
disease.
The perfect insulin has not been invented. Any problems
suffered by a diabetic on human
insulin protocols will be
attributed to the patient’s noncompliance and/or negligence.
Proven protocols for
some diabetic patients were destroyed when animal insulins—
PARTICULARLY
BEEF IN ALL FORMS—were taken off the market.
It is not just
coincidence that there has been an increase in diabetic deaths,
increased
emergency room visits, increased automobile accidents
due to hypoglycemia, and
increased “dead in bed” syndrome. A
large percentage of the diabetic population
could maintain lower
glycohemoglobin levels (A1c’s), have less incidence of
hypoglycemia
and have lower maintenance costs using animal
insulin protocols.
Let us have all the
tools available, including the analogues of beef and pork
insulin.
Let the doctor-patient relationship work out the best
protocols for each individual to obtain an
acceptable A1c.
Brent Hoadley, Ph.D.
Plant Scientist and
Inventor
Diabetes Survivor, 45
years
Author’s note: Now the FDA and the pharmaceuticals use the
threat of BSE-infected cattle to
scare patients away from adding
beef insulin to their protocols.
In an article related
to Bovine Vaccines Currently Safe, the FDA stated they could not
infect
susceptible mice with BSE after exposure to pancreas and
skeletal muscle tissue of infected
cattle. BSE is found in
central nervous system tissue.
If you really want to
consider risk, think about gelatin, which is a component of many
foods
and drugs we consume daily. This is a polygelic product of
ground up cattle remnants, some
of which may even be used
in the broth of bacterial or yeast brew which produces “human
insulin.”
During any process
involving high pressure liquid chromatography, all insulins
should be
totally safe.
Ask any diabetic
whether he would rather die tomorrow because he can’t take
human insulin
or face the “fake risk” of BSE and the
educated answer would always be free choice of protocols.
Profit
again drives diabetic patients to stay away from the proven
product. |
