The World Turned Upside Down: The Second Low-Carbohydrate Revolution (22 page)

The obstinate refusal of
endocrinologists and diabetes
educators to face this is a major hurdle to overcome in dealing with
the
current epidemic. Almost every statement from health agencies and
individual
experts emphasizes weight loss as the prime goal of diabetes treatment.
Endocrinologists to whom these points are presented will generally
follow the
recommendation and target weight loss. It is simply that the scientific
evidence on the subject is just not on their radar. Why not? One reason
is that
when you see how much endocrinologists do know, it is not surprising
that they
don't know about nutrition. As for those who act as if they know
nutrition but
refuse to consider low-carbohydrate diets – not that they have a
refutation but
rather simply ignore it – causes are unknown. For some, it is not that
they
love their patients less but that they love hating Dr. Atkins more.

The quotation about low-GI diets at
the head of this section
is from Eric Westman. In 2008, David Jenkins compared a diet high in
cereal
with a low glycemic index diet
[66]
. 
The glycemic
index is a measure of the actual effect of dietary glucose on blood
glucose. Pioneered by Jenkins and coworkers, a low-GI diet is
based on the
same rationale as a low-carbohydrate diet, that glycemic and insulin
fluctuations pose a metabolic risk. GI emphasizes "the type of
carbohydrate,"
that is, it offers a politically correct form of low-carbohydrate diet
and as
stated in the 2008 study: "We selected a high–cereal fiber diet
treatment for
its
suggested
health
benefit
s for the comparison so that the
potential value
of carbohydrate foods
could
be emphasized equally for both high–cereal fiber and low–glycemic index
interventions." (My emphasis).

The Conclusion of Jenkins's 24-week
study was: "In patients
with type 2 diabetes, 6-month treatment with a low–glycemic index diet
resulted
in moderately lower HbA1c levels compared with a high–cereal fiber
diet." 
Figure 10-4
shows
the results for HbA1c and weight
loss. They are modest enough.

Figure
10-3
. Effect of high–cereal fiber or
low–glycemic index diets on
body weight and hHbA1c. Figure redraw from reference
[66]
.

By coincidence, on almost the same
day, Eric Westman's group
published a study that compared a low GI diet with a true
low-carbohydrate diet
[4]
. The studies
were comparable in duration and
number of subjects and a direct comparison (
Figure
10-4
)
shows the potential of low-carbohydrate diets.

Figures
10-1
,
10-2
and
10-4
, by
themselves constitute the best evidence that a low-carbohydrate diet is
the
"default diet," the one to try first, for diabetes and metabolic
syndrome.
Dietary carbohydrate restriction

• Improves
  glycemic and insulinemic control
  
• Doesn't
  require weight loss (although there
  is nothing better for
  losing weight)
  
• Improves
  the lipid and physiologic markers
  associated with the
  disease
  
• Reduces
  HbA1c, the best predictor of CVD in
  people with diabetes
  

There are hundreds of studies about
all aspects of diabetes
but none contradict the information in these three figures. But there
is one
more. A low-carbohydrate diet reliably reduces the dependence on drugs.
Some people
consider that the results shown in
Figure
10-5
are
the single best reason for going with dietary carbohydrate restriction.
In most
diseases, we consider ability to reduce medication as an advance.

Figure
10-4
. Comparison of low-glycemic index diet
with high cereal
diet, and of low-glycemic index diet with low-carbohydrate diet. Data
from
references
[66]
and
[67]
.

Figure 10-5
.
Reduction of HbA1c and reduction in requirement for drugs. Data from
Yancy, et
al.
[68]

Is that it? That's it. The hundreds
of papers published
provide information about the details of what is a complicated disease
and the
details of the response to the numerous drugs that are used as therapy.
But the
basic principles described here have never been refuted in any
fundamental way.
Diabetes is the necessary battleground in the new low-carb revolution
and it is
likely to provide a major victory. Scientifically, the burden of proof
is on
anybody who would say that it is a good idea for people with diabetes
to have
any significant amount of carbohydrate. Long-term random control (RCT)
studies
are a good thing although the people who insist on them for diabetes
sit on
panels that would never fund such a study if it included
low-carbohydrate
diets. But an RCT is not the best thing for everything. It is one kind
of
experiment. And all possibilities are not up for grabs in science.
Diabetes is
primarily about carbohydrate. For treatment, for however long it is
tested, you
have nothing better than reducing carbohydrate. Harm has not been
demonstrated
and, again, the burden of proof is on showing danger. Harm cannot be
assumed in
science. There is nothing in the outcome of low-carb trials of whatever
length
to suggest harm. Absolute dependence on arbitrary rules and "gold
standards"
causes harm.

What about
Cardiovascular Disease?

The "concerns" about low-carbohydrate
diets still revolve
around the imagined risk of cardiovascular disease from fat in the diet
despite
the continued failure to show any risk. Carbohydrate restriction,
however,
improves the usual markers, notably HDL ("good cholesterol") and
triglycerides.
What about a long term trial to show that it prevents CVD. There is
none but
there are long-term trials of the effect of reducing fat. Many. They
all fail
to show any significant effect. Almost all fail to show any effect at
all.

The problem is exacerbated in
diabetes. There is a strong
association between diabetes and the incidence of CVD. The largely
discredited,
or at least greatly exaggerated, diet-heart hypothesis and its
proscriptions against
dietary fat is what has caused us to ignore the carbohydrate elephant
in the
room. It turns out, however, that the best predictor of microvascular
complications
(blindness, amputations) and, to a lesser extent, macrovascular
complications
(heart attack, stroke) in patients with type 2 diabetes, is hemoglobin
A1c,
which is under the control of chronic dietary carbohydrate consumption.
Data
from the United Kingdom Prevention of Diabetes Study (UKPDS,
[69]
)
shown in
Figure 10-6
provide support for this
idea. In some sense, increased risk of CVD for people with diabetes is
due
simply to the diabetes itself.

Figure
10-6
. Dependence of risk of myocardial
infarction and
microvascular endpoints on HbA1c. Data adjusted for age at diagnosis of
diabetes, sex, ethnic group, smoking etc. Data from reference
[69]
.

Summary

Diabetes is a disease of carbohydrate
intolerance. Type 1 is
characterized by an inability to produce insulin in response to
carbohydrate.
In type 2, there is peripheral insulin resistance along with
deterioration of
the β cells of the pancreas. The most salient symptom (and a major
contributor to the pathology) is high blood sugar which, not
surprisingly, is
most effectively treated by reducing dietary carbohydrates. The
clinical measurements
are 1) fasting blood glucose (sometimes written FBG; medicine is big on
acronyms), 2) an oral glucose tolerance test (sometimes OGTT), the
response in
the blood to a dose of glucose, and 3) the percent of modified
hemoglobin,
hemoglobin A1c (Hob A1c). It is not hard to guess the best treatment
for a
disease where the defect is a poor response to ingested carbohydrates
but you
do need to know if the theory will hold up in practice. A personal
story may
bring this into perspective. Next.

Chapter
11

Wendy's
Story - the
uses of metabolic adversity

Wendy Pogozelski is Professor and
Chairman of Biochemistry
at SUNY Geneseo in upstate New York. One of the people who has used
low-carbohydrate diets to teach metabolism
[1]
,
she
developed type 1 diabetes as an adult. In 2012,
ASBMB Today
,
the house organ of the American
Society of Biochemistry and Molecular Biology, started a series about
challenges to biochemists. Wendy's story was their first publication in
this
series:

Blurred vision was the first sign
that something was wrong.
The front row of the freshman chemistry class I was teaching looked
strangely
fuzzy. Then, over the next few days, I was gripped by an unquenchable
thirst
and was constantly fatigued. Seemingly overnight I lost eight pounds. I
recognized the symptoms of diabetes, but I was young(ish), slim(ish)
and an
avid kick-boxer. Mine was not the typical diabetic profile.

Despite my suspicion that I was
experiencing raging
hyperglycemia, the diagnosis – "You have diabetes" – was devastating.
It marked
the beginning of a lifestyle that is an enormous challenge. However,
the
journey has led me to an increased understanding of biochemistry, has
enhanced
my teaching and ultimately has cast me in a new role of helping others.
It
turned out that I had developed latent autoimmune diabetes in adults,
or LADA,
a subset of type 1 diabetes. LADA is due to an autoimmune reaction to
pancreatic glutamate decarboxylase, or GAD65. While LADA has a slower
onset
than classic type 1, formerly known as juvenile diabetes, the two
diseases
follow a similar course and require injections of insulin.

Fortunately, I felt equipped to
manage my
condition. I teach
metabolism to undergraduates using an approach that emphasizes
insulin-dependent
pathways as a unifying theme and one that offers an everyday context. I
knew
that carbohydrates, whether whole grain or highly processed, could
raise my
blood glucose to dangerous levels, so my response to the diagnosis was
to
reduce greatly carbohydrates in my diet. In addition, I was careful to
monitor
my blood sugar levels and insulin doses. The result was that my
hemoglobin A1c
(glycosylated hemoglobin, a measure of blood sugar control), was 5.4
percent,
higher than the normal 4 percent to 5.5 percent range. My doctor said that I
was his
"best patient ever" and that I was achieving the blood sugars of a
nondiabetic
person.

Despite satisfaction with my glycemic
control, my physician
wanted me to see a dietitian. To my surprise, the dietitian was
appalled by my
diet. She said, "You have to eat a minimum of 130 grams of
carbohydrates a
day." I protested, but she recruited the rest of the medical team to
endorse
her position: "We all say you have to eat more carbs. The American
Diabetes
Association gives us these guidelines." One member of the team said, "I
want
you to eat chocolate. I want you to enjoy life."

As someone raised to be cooperative,
and because I found it
easy to embrace medical advice to eat chocolate, I agreed to eat more
carbohydrates. The result was that my HbA1c rose above 7 percent. My
blood
sugar levels were frequently in the 200 to 300 mg/dl range (far above
the
normal level of about 85 mg/dl), even when I supplemented with extra
insulin.
My former dose of seven units of insulin per day increased to 30 units
per day.
The loss of control was immensely frustrating. My physician attributed
my
initial success to what is called the diabetes honeymoon. Often, when
someone
first begins taking insulin, there is a short-lived period during which
β
cells seem to recover a bit and secrete insulin. Regardless, it was
clear that
the dietitian's approach was not yielding the success I desired. I felt
confused and uncertain as to what to do.

I decided to investigate for myself
what my best diet should
be. I studied the literature, I sought out researchers and physicians,
and I
attended countless metabolism-related talks. In addition, I connected
with
hundreds of people with diabetes. The most important contribution to my
achieving clarity, however, was evaluating literature based on a
molecular
understanding of how metabolism works.

In my quest for answers, I found to
my surprise that many
dietitians and physicians were unable to explain the basis for the
dietary
recommendations they endorsed. Some did, however, express a desire for
a better
understanding or review of what they'd once learned. And in the general
public,
I encountered scores of diabetics and nondiabetics who also wanted
tools to
make sense of conflicting nutritional information.

I began to use what I had learned not
only to expand and
improve my teaching and research but also to step into the role of a
nutrition
explainer. First I was determined to see that none of my students would
lack
understanding of processes such as gluconeogenesis and the many
pathways affected
by insulin. I created new lecture topics and problem sets based on
diabetes and
nutrition applications. My students responded positively and
appreciatively.
There was a palpable increase in attention in class.

Students came to my office to chat
about things that they
had read. My class evaluations praised the use of nutritional context
and often
said, "This material could have been rather dull without all these
great
applications." I even heard (frequently) "I love metabolism!"

Beyond my student population, I
engaged a world of bloggers,
physicians and other people with diabetes, many of whom were eager to
understand more deeply how things work metabolically. I now find myself
being
interviewed, quoted in papers, and invited to speak to groups of
people,
including physicians, who want to deepen their understanding of
metabolic
pathways. I am asked to share my nutrition-based teaching applications
with
other professors and with textbook publishers. In these efforts, I try
to avoid
dispensing nutritional advice; instead, I attempt to show how nutrient
composition affects metabolic pathways so that my audience feels better
able to
evaluate nutritional recommendations.

Five years later, diabetes is still
an immense mental and
physical challenge, but I am grateful for the insight and tools that my
education and training have provided me. Most importantly, if I am able
to
further the use of molecular science to help others find optimal
dietary
strategies, and if I can help the next generation, then my adversity
will have
had a positive outcome.

Wendy Knapp Pogozelski earned
a B.S.from Chatham
University and a Ph.D. in chemistry from Johns Hopkins University under
the
direction of Thomas Tullius. She spent two years as an Office of Naval
Research
postdoctoral fellow working at various sites in radiation biology. She
is a
professor of chemistry at the State University of New York (SUNY)
College at
Geneseo, where she has been since 1996. She teaches biochemistry,
emphasizing
medical and nutrition-based applications. Her current research focuses
on
radiation effects on mitochondrial function and mitochondrial DNA as
well as on
understanding how dietary strategies affect biochemical pathways.

Epilogue by Wendy
Pogozelski

The story in ASBMB Today was written
for a series on how
scientists overcome hard times rather than as a treatise on how to
manage
diabetes. However, the essay was read by many folks who were interested
from a
standpoint of their own health concerns. I received many requests for
an
update, as people wondered if, after my foray into inclusion of
carbohydrates,
I returned to my low-carbohydrate style of eating. The answer is a
resounding
"yes". (With one small
caveat
,
as you'll see below).

As I studied the scientific
literature, I became more and
more convinced that my absolute primary concern should be keeping my
blood
sugar levels as close to normal as possible. I saw that I achieve the
flattest
blood sugars when I keep my carbohydrate low and my insulin low. Dr.
Richard
Bernstein, a type 1 diabetic and engineer-turned physician who
pioneered the
use of glucose meters, calls this principle "the law of small numbers."
Carbohydrate restriction results in minimization of errors.
Hyperglycemia and
hypoglycemia come from mis-estimation of carbohydrate amount, rate of
carbohydrate absorption and insulin absorption and activity. These
factors are
nearly impossible to predict accurately. Many people who use large
amounts of
insulin to cover large amounts of carbohydrate in their diet frequently
find
themselves in dangerous situations (passing out, etc.) when the peak
activity
of the insulin occurs earlier than the peak absorption of the dietary
carbohydrate. I have never passed out and my health care team has been
astounded by my lack of hypoglycemic episodes.
Hyper
glycemia
also needs to be avoided
though. It is these high blood sugars that correlate with the long-term
deleterious effects of diabetes. Observing the diabetic amputees at the
endocrinologist's office and watching people painfully shuffle into the
dialysis
center has been strong motivation to avoid these high blood sugars.

What is the evidence for the
effectiveness of a low-carb
dietary approach with me? I was used as a test subject for "sensor"
technology.
This device consists of a needle, sensor and a transmitter worn on the
body and
it communicates with an insulin pump. When my results were printed out
after
the experiment, my health care team was astonished at how level my
glucose
readings were. I was the last appointment of the day and all the
workers
gathered around to admire the printout of the "beautiful" blood sugars
and ask
me how in the world I did that. (This was at the office where the team
had
insisted that I needed to eat carbohydrate. Yes, it was very
satisfying).

It is worth noting too how well
having level blood sugar
makes me feel. When my blood sugar goes over 200 mg/dl, I start to feel
melodramatic and have an elevated emotional response to even minor
difficulties. Low blood sugar induces glucagon and epinephrine hormone
release,
which result in sweating and a feeling of panic as well as low energy.
Both
high and low blood sugar make my brain sluggish. Also, as a
headache-prone
person for much of my life, I found that my formerly frequent headaches
nearly
disappeared when I began to practice carbohydrate restriction.

When I keep my meal at less than 10 g
of carbohydrate, my
blood sugars rise by no more than 40 mg/dl; sometimes they rise as
little as 10
mg/dl, but regardless, they return to normal within two hours within two hours – like a
non-diabetic. I find that too much protein will elevate my blood sugar
so I
keep that amount moderate but I don't consciously restrict it or my fat.

Despite my knowledge that
carbohydrate restriction is best
for me, I sometimes have deviated from this plan of attack.
Particularly, since
I became a mom, there has been a lot more carbohydrate in the kitchen
tempting
me. Couple that with the chronic exhaustion of motherhood and you've
got a
situation that makes reaching for carbohydrate much more likely. I
rediscovered
that M&Ms (used effectively for potty-training a toddler) are
delicious,
and my plans to eat no more than three have consistently been shown to
be no
match for whatever else is at work. (My theory is that there is an evil
force
activated when one eats M&Ms and he is only appeased when the
bag is
empty). Every time I have indulged, however, I have always concluded
"It wasn't
worth it" when I saw my high blood sugars or had to compensate for my
over-estimation of my insulin.