Diagnosis and Possible Reversal of Pre-Diabetes: - Natural ...

Diagnosis and Possible Reversal of Pre-Diabetes:
Featuring commentary from Russ Jaffe, MD, PhD;
Mona Morstein, ND; Cheryl Myers, RN; and Tom Sult, MD
Clinical Challenge
According to the American Diabetes Association, there are nearly 60 million people in the United States
who are pre-diabetic. This poses a huge health threat to a large patient population who, according to recent
research, may already be experiencing the ill health effects of this condition, especially damage related to the
heart and circulatory systems. Four expert panelists were asked to provide key clinical advice that they felt was
significant or often overlooked regarding the diagnosis or treatment of this condition. The panel represents a
diverse group of healthcare professionals. Their commentary is not intended to be comprehensive in nature,
rather it is meant to be concise clinical advice on one or two aspects of this condition.
Comprehensive Supplementation is a Key to
Successful Treatment
Commentary By Russell Jaffe, MD, PhD
At least 92% of diabetes cases can be attributed to lifestyle choices, with
8% attributable to genetics. The fact is, diabetes is extremely expensive,
can be very deadly, and is almost completely avoidable. Pre-diabetes
(PD) is the antecedent to diabetes. The causes of pre-diabetes are
• lack of an essential nutrient,
• environmental toxin exposure,
• distress that impairs stress responsive hormones and neurochemicals,
• autoimmune attack on the insulin production centers or insulin
receptors, and
• being sedentary
The consequences of PD range from obesity to insulin resistance,
also known as metabolic syndrome and syndrome X. The health ramifications
of unmanaged PD that leads to diabetes include heart attacks,
coronary artery atherosclerosis, arteriosclerosis, and stroke.
I will use a recent successful outcome study in pre-diabetes that I
had the opportunity to lead as an example of what can be done using
an innovative comprehensive approach. 1
The goals of our study were to improve sugar insulin performance
and remove obstacles to recovery. This meant that we wanted to reduce
the glucose/insulin ratio to healthier levels. We also wanted to confirm
this by reduction in hemoglobin A1c as an independent risk marker.
Because of the role of stress hormones in PD risk, we also measured
cortisol and DHEA stress hormones to assess how they changed
over the six weeks of the program. We are highly encouraged that all
markers improved and the improvement was statistically significant.
Statistically, we found significance below the 0.001 level. This makes
the outcome highly likely to be real and unlikely to be due to coincidence.
We were also pleased to report that compliance was high and
dropout rates below expectation.
CliniCal Roundtable
In the outcome study, we
• restored tolerance in the immune defense and repair system;
• corrected essential nutrient deficits;
• improved detoxification of environmental toxins;
• reduced excess distress and restored neurohormone balance;
and
• identified deficits in digestion or other systems and improve
function, structure and resilience.
The following supplements proved effective in this program:
1. Novel nutrients and herbs in standardized form in 100% rice bran
oil with phosphatides to improve uptake and components that
improve insulin function:
• Chromium as citrate 250–1,000 mcg/day
• Vanadium ascorbate 250–1,000 mcg/day
• French lilac (Galega) 150–600 mg/day
• Bitter melon (Marah) 150–600 mg/day
• Huckleberry/Bilberry 100–400 mg/day
• Agnus Castus
250–1,000 mg/day
2. L-carnitine as the fumarate, 500–2,500 mg/day; GABA, 200–1,000
mg/day; and alginate, 50–250 mg/day in MCT oil for better
uptake.
3. Fully buffered 100% L-ascorbate with potassium, calcium, magnesium,
and zinc.
4. Polyphenolics as quercetin dihydrate 250–5,000 mg/day and soluble
OPC 5–100 mg/day.
5. Exercise in the form of walking measured with a pedometer with
the goal of 10,000 steps per day.
6. Stress management, mindfulness, and relaxation response practices,
20 minutes twice daily.
7. Good hydration based on drinking at least eight 8-ounce glasses of
water daily, sufficient to stimulate 3 to 6 urinations per day.
Our successful outcome study in people with PD confirms the hope
that people can feel and function better at lower net costs when enough
of the essential protective and repair factors are provided.
©2009 Natural Medicine Journal 1(2), October 2009 | Page 1

Editor’s Note: For a copy of Dr. Jaffe’s study, visit the Clinical Tools
section of the Natural Medicine Journal (www.naturalmedicinejournal.
com) and click on Clinical Insights.
References
1 Jaffe R, Mani J, DeVane J, Mani H. Tolerance loss in diabetics: Association with
foreign antigen exposure. Diabet Med. 2006;23(8):924-5.
Early And Accurate Diagnosis is Critical
Commentary by Mona Morstein, ND
The medical diagnosis of pre-diabetes (PD) includes both standard
evaluations, as well as a unique naturopathic test. The goal of early and
accurate diagnosis is to determine if the patient is in a mild, moderate,
or severe state of pre-diabetes. Early and accurate diagnosis helps
determine how aggressive the treatment needs to be, and how much
damage PD may have already caused the body.
PD is often associated with metabolic syndrome, which is defined similarly
by various organizations. The basic definition based on the American
Heart Association (AHA)/Updated National Cholesterol Education
Program (NCEP) consists of having three or more of the following traits:
• Elevated waist circumference (men >40 inches; women >35
inches; lower for Asian populations)
• Hypertriglyceridemia (>150 mg/dl)
• Reduced HDL (men 100 mg/dl)
Not all pre-diabetic patients have metabolic syndrome; however,
simply having a fasting glucose level of 101–125 mg/dl can identify a
patient as pre-diabetic. When I have a patient with a pre-diabetic glucose
number, I reflex to a more comprehensive analysis of glucose regulation,
which is justified in scientific literature. The Oral Glucose Tolerance
Test is a standard lab test consisting of having a patient fast 12 hours, get
a fasting glucose level, and then drink 75–100 g of a glucose drink, with
repeated glucose blood draws over the next one, two, and three hours.
I have personally adapted this test to a different format. I have patients
fast for 12 hours and then test their fasting glucose and insulin levels.
I then have them eat—preferably at a local fast food restaurant—one
pancake with syrup and one hash brown. This gives the patient 100 g of
refined sugar and grain carbohydrate, as well as saturated fat—the two
top food groups that initiate insulin resistance. I am more interested in
seeing what actual food does to people than just a glucose drink. I then
have the patient return to the clinic 1.5 hours after eating for a second
blood draw of glucose and insulin. Some other naturopaths at my clinic
have patients get postprandial draws of one, two, and three hours, but
I find that is very difficult for many patients, and it is time-consuming.
For my interpretation of the patient’s condition, it also does not seem to
help more than the solo 1.5-hour postprandial reading.
Insulin levels are vital for understanding how much insulin resistance
is occurring. How much insulin that is secreted, analyzed in
combination with glucose levels, gives the clinician a very accurate way
of determining if the patient’s insulin resistance and pre-diabetes status
is mild, moderate, or severe.
Russell Jaffe, MD, PhD, CCN, NACB, FRSM
is a renowned early pioneer of Integrative Medicine.
Starting as a Molecular Biochemist / Pathologist
at Boston U Medical Center and the USPHS/
NIH he was the founding chairman of the Scientific
Committee of the American Holistic Medical Association.
Dr. Jaffe taught one of the first courses on using
Eastern medical strategies in Western medicine. He
has won many awards for his lifetime contributions to clinical medicine,
biochemistry, immunology, methodology, and integrative health policy.
He currently serves on the tasks forces that are modeling evidence
based, affordable, effective, sustainable healthcare. He is chairman and
CEO of PERQUE, LLC, ELISA/ACT Biotechnologies, LLC. He is also a
Senior Fellow of the Health Studies Collegium Foundation.
I also do a comprehensive CMP/CBC, including TSH/FT3/FT4,
vitamin D (25OHVD), ferritin (to check for early liver inflammation
indicating fatty liver), and A1C. It might be wise to also include fibrinogen
to check on blood clotting risk, HS-CRP to analyze inflammation,
and homocysteine to check for L-methylfolate bioavailability.
The initial physical exam should include vitals, heart/lung evaluation,
thyroid exam, search for skin tags or acanthosis nigricans, height,
weight, waist circumference with BMI, body fat percentage (via scale
such as Tanita or Bio-Impedance device), foot exam including edema/
pulses/lesions/neuropathy (using standard monofilament check), and
abdominal exam to check for hepatomegaly.
The patient should be instructed to fill out a week-long diet diary
to track eating habits, accurately recording everything she/he eats and
drinks for all meals/snacks. Bowel movement frequency, symptoms,
and sleeping habits should also be recorded.
Regarding the treatment of pre-diabetes, some clinicians fail to
emphasize the importance of sleep in this patient population. Several
well-designed studies, including a recent one this year from the Journal
of Clinical Endocrinology, 1 have clearly demonstrated that lack of sleep
causes insulin resistance and weight gain. Sleep directly affects the two
main hormones that regulate human appetite: leptin and ghrelin. Leptin
is made in the adipocytes and instructs a person to eat less food. When
a person gets enough sleep, it raises leptin levels, which decreases the
desire to eat. Conversely, low amounts of sleep lower leptin levels and
can thus cause increased appetite. Ghrelin is another appetite hormone
made in the stomach. Opposite to leptin, ghrelin tells the brain to eat
more food. When people don’t get enough sleep, ghrelin levels increase
and people crave high carbohydrate foods.
Less sleep also causes an increase in cortisol output at night, which
can cause hyperglycemia and initiate insulin resistance, another factor
in abdominal weight gain and developing pre-diabetes and diabetes.
Lastly, sleep is also needed for growth hormone (GH) to be fully
secreted. Adult patients with low GH secretion are insulin resistant,
due to several not wholly understood factors.
If a patient presents with PD symptoms and has sleep problems, a sleep
study should be performed. Instituting sleep hygiene is a necessary aspect
of pre-diabetes treatment and includes turning off most lights in the house
so melatonin output can be enhanced; establishing the same bedtime
routine each night; not watching disturbing TV shows or even news at
night before bed, which may cause mental/emotional upset; spending
some time reading before bed to initiate sleep; ensuring the mattress and
room temperature is conducive to the patient’s body; addressing problems
such as partner snoring or restless legs that may be interrupting the
patient’s sleep; urging the use of a continuous positive airway pressure
(CPAP) if apnea is diagnosed; dealing with hormonal imbalances that
©2009 Natural Medicine Journal 1(2), October 2009 | Page 2

may be causing sleeping problems, such as elevated nighttime cortisol, or
menopausal night sweats; using guided relaxation DVDs (or other stress
relaxation techniques) to help induce sleep; and recommending occasional
sleep aids, but avoiding nightly addiction to them.
References
1 Nedeltcheva AV, Kessler L, Imerial J, Penev PD. Exposure to recurrent sleep
restriction in the setting of high caloric intake and physical inactivity results
in increased insulin resistance and reduced glucose tolerance. J Clin Endocrinol
Metab. 2009 Sep; 94(9):3242-51. Epub 2009 Jun 30.
Addressing Chronic Inflammation With Two Key
Dietary Supplements
Commentary by Cheryl Myers, RN
Many of my colleagues no longer support a pre-diabetes diagnoses,
believing instead that any consistent fasting blood sugar (FBS) over 100
should be considered type 2 diabetes (albeit a milder form) and must
be treated. Diabetes is most reversible in the earliest stages, when FBS
is less than 125, which is the general range of the term “pre-diabetes.”
Effective early identification of underlying causes is critical to the
successful treatment of this condition.
While the etiology of pre-diabetes is multifactorial, one consistent
hallmark is chronic inflammation. This potential underlying cause is
often not considered as fully as it should be in clinical practice. In a selfperpetuating,
destructive cycle, hyperglycemia and insulin resistance
beget inflammatory changes. According to one recent study, “insulin
receptor substrates serine phosphorylation is a time-controlled physiological
feedback mechanism in insulin signaling that is hijacked by
metabolic and inflammatory stresses to promote insulin resistance.” 1
FBS consistently above normal and not contributable to non-diabetic
factors is evidence of this process in action. In simpler terms, inflammation
promotes insulin resistance, insulin resistance promotes hyperglycemia,
and hyperglycemia promotes inflammation.
It is important that this cycle be interrupted or pre-diabetes will
evolve to diabetes in the majority of patients thus diagnosed. Two
scientifically substantiated potent anti-inflammatories to consider
clinically are curcumin and omega 3 fatty acids.
Curcumin has been examined for its ability to prevent oxidative
stress, modulate the immune system, and reduce inflammation—all
of which has a positive impact on pre-diabetes. However, one area of
particular interest is curcumin’s ability to inhibit and modulate specific
kinases called c-Jun N-terminal kinases (JNKs, also called “stress-activated
kinases” or SAPKs). JNKs modify the activity of certain proteins
that are especially important in the development of insulin resistance,
which is clinically the earliest stage in the development of type 2
diabetes. 2 Curcumin is a known inhibitor of JNKs and therefore could
be a powerful tool in reversing the metabolic processes that lead to
insulin resistance and subsequent prediabetes. 3
Biochemistry aside, from a treatment perspective, curcumin has been
shown quite efficacious in the prevention of cardiovascular disease, one
of the unfortunate potential sequela of diabetes as well as diabetic retinopathy,
a leading cause of blindness. 4 , 5 Preliminary research indicates
that curcumin may help prevent diabetic neuropathy. 6
Omega 3 fatty acids also have proven anti-inflammatory properties. In
a recent study, 148 men with impaired glucose tolerance and/or impaired
fasting blood glucose were followed for 12 months after counseling in
dietary fat quality. At the end of the study, 92 subjects reverted to normal
Mona Morstein, ND, graduated from National
College of Natural Medicine where she also did a year
residency in Family Practice. She then moved to Great
Falls, Mont., where she had a private practice for 13
years before joining Southwest College of Naturopathic
Medicine (SCNM). She is Chair of the Nutrition
Department, associate professor, and clinical
supervisor at SCNM. Dr. Morstein is a general practitioner
who uses numerous modalities and has focuses on diabetes,
gastroenterology, and women’s health.
glucose levels and 56 remained in prediabetic status. None of the participants
progressed to full diabetes. Additionally, it was noted that subjects in
the highest tertile of omega-3:omega-6 fatty acid ratio showed the highest
chance of improving glucose disturbances (2.51, 1.01-6.37). 7 Therefore,
incorporating more fatty fish into the diet and/or supplementing with
omega 3 fatty acids can have a profound impact on ameliorating blood
sugar changes associated with type 2 diabetes, and studies indicate a higher
omega 3:omega 6 ratio is protective against progression to diabetes.
Given the strong correlation between inflammation and prediabetes,
I feel it is imperative that clinicians address this issue in this
patient population. The scientific literature provides us with enough
substantiation to incorporate curcumin and omega 3 fatty acids into
the dietary supplement program of the pre-diabetic patient, along with
applicable dietary and lifestyle counsel.
References
1 Tanti JF, Jager J. Cellular mechanisms of insulin resistance: role of stressregulated
serine kinases and insulin receptor substrates (IRS) serine phosphorylation.
Curr Opin Pharmacol. 2009 Aug 13.)
2 Kaneto H. The JNK pathway as a therapeutic target for diabetes. Expert Opin
Ther Targets. 2005;9(3):581-92.
3 Moon DO, Jin CY, Lee JD, et al. Curcumin decreases binding of Shiga-like
toxin-1B on human intestinal epithelial cell line HT29 stimulated with TNFalpha
and IL-1beta: suppression of p38, JNK and NF-kappaB p65 as potential
targets. Biol Pharm Bull. 2006;29(7):1470-5.
4 Wongcharoen W, Phrommintikul A. The protective role of curcumin in
cardiovascular diseases. Int J Cardiol. 2009;133(2):145-51.
5 Kowluru RA, Kanwar M. Effects of curcumin on retinal oxidative stress and
inflammation in diabetes. Nutr Metab (Lond). 2007;4:8.
6 Osawa T. Nephroprotective and hepatoprotective effects of curcuminoids.
Adv Exp Med Biol. 2007;595:407-23.
7 Sartorelli DS, Damião R, Chaim R, Hirai A, Gimeno SG, Ferreira SR. Dietary
omega-3 fatty acid and omega-3: omega-6 fatty acid ratio predict improvement
in glucose disturbances in Japanese Brazilians. Nutrition. 2009 Jul 30.
Cheryl Myers, RN, is recognized as an expert in the
health and dietary supplement field. She writes, gives
public appearances, and is in charge of scientific
affairs and education for EuroPharma, Inc. Cheryl
graduated from Purdue University, and also has clinical
certifications in oncology and gerontology, and
has a second degree in psychology. Cheryl’s nationally
published articles have addressed a variety of health
applications for natural products, and Cheryl has been a featured guest
on radio shows, and is frequently interviewed by a variety of periodicals,
including the New York Times, Wall Street Journal, Prevention
Magazine, and Healthy Living.
©2009 Natural Medicine Journal 1(2), October 2009 | Page 3

Addressing Accurate Diagnosis And The
Significance of Patient Compliance
Commentary by Tom Sult, MD
We are surrounded by pre-diabetes (PD), insulin resistance (IR) or
syndrome X—all names for the same thing. While we all may know
what to look for, it can still sometimes be difficult to see. Below are
some of the hallmark symptoms of PD.
• Central obesity. People with elevated insulin will store every extra
calorie they eat as central fat. On days they are trying to be “good”
by skipping meals or starving themselves (a bad idea) they will
burn muscle and not fat. The result is an overweight trunk with
thin legs and arms.
• Constant hunger. When a person with PD eats a high glycemic
index (GI) food, the blood glucose (BG) rises, followed by an
exaggerated insulin release, resulting in reactive hypoglycemia,
which in turn results in hunger. If he “fixes” hunger with another
high GI food, the cycle will start all over again.
• Blurred vision. BG is a major component of the osmotic pressure
in the blood. With swings in BG come swings in osmotic pressure,
causing a distortion of the lens and cornea of the eye, which
results in blurred vision.
• Fatigue. In PD, insulin receptors are insensitive to insulin. This
results in low muscle concentrations of available carbohydrate
and inefficient energy metabolism.
• Depression. The metabolic derangement resulting from PD has
many psychological effects. Depression may arise from the same
type of energy metabolism inefficiencies seen in fatigue.
• Brain fog. The brain is the most prolific consumer of glucose of
any organ. With problems in glucose metabolism and transport,
brain fog seems to arise.
Many clinical tests exist to diagnose PD, but some are more accurate
than others.
• Fasting blood glucose (FBG) . FBG is a late indicator of pre-diabetes.
The metabolic disorders known as PD may exist for 3 to 5 years
prior to diagnosis if done by FBG. A fasting blood sugar level
between 100 and 125 mg/dL is considered pre-diabetes. Optimal
blood sugars are significantly lower—some say as low as 70.
• Postprandial blood glucose (PBG) and glucose/insulin tolerance
testing (GITT). PBG is a better indicator of pre-diabetes because
it is more like a stress test of the glucose metabolism system. I
generally do a GITT with a fasting insulin and FBG, then a 75
gram glucola followed by a 2-hour postprandial insulin level
and BG. I look for fasting insulin less than 10 and FBG less than
95 (some say 85). The postprandial limits are insulin less than 3
times the fasting level and not greater than 30, the BG not greater
than 140 (although I think that is too high).
• Lipids. Lipid levels are another early indicator of PD. We know
that those with PD have elevated triglyceride and low HDL levels.
An ideal triglyceride to HDL ratio (THR) is less than 2. A THR
greater than 4 is worrisome and probably represents PD. A THR
of 6 or more is a significant risk factor for heart disease.
Maintaining a high index of suspicion for pre-diabetes is key to the
diagnosis. Following proper diagnosis, one of the key challenges with
treatment is patient compliance.
The treatment of PD is primarily a lifestyle issue. While there
are pharmacological treatments available, studies have shown them
inferior to lifestyle management. The primary problem with lifestyle
management is compliance. In my early practice I had a “my way or the
highway” type of approach to lifestyle. With age comes some humility,
accompanied by greater empathy for my patents.
Whether the treatment plan features a low glycemic index diet,
increased activity, or various nutrients such as fish oil or lipoic acid, the
nmj oCT09 CR
advice is sound. What fascinates me is how we often do not do what we
know is good for us. I am trained in functional medicine. This means I
assess the biochemical individuality of the patient, consider his current
lifestyle, and then determine whether the two are ideally compatible.
Once this is accomplished I set up a program with follow-up visits. It
is not uncommon for the subsequent visits to reveal a lack of followthrough
with the program. In days gone by I would have been quite
irritated by this. I now see it as the therapeutic moment.
The therapeutic moment is when you have an opportunity to
understand and intervene in noncompliance. Understanding why a
patient was not able to comply with a plan is far more important than
the noncompliance itself. Sometimes it is time, sometimes money, and
sometimes preference. Often it is a deeper issue, like food as comfort
and companion. Creating a therapeutic alliance with the patient and
exploring these issues is often magical, not just for the patient but for
the provider as well.
Tom Sult, MD, is a residency trained and board
certified family doctor. He is boarded in Holistic
medicine and on the faculty of the Institute for Functional
Medicine (IFM). Dr Sult’s practice is in Central
Minnesota were he has a consultative, tertiary care
clinic for Functional Medicine. He primarily sees
autism, Lyme disease, autoimmune disorders, environmental
illness and other chronic complex disease.
Dr Sult teaches GI and Toxicology for IFM. His primary interest is
addressing the underlying causes of illness and addressing the interplay
of genetic predisposition with lifestyle and environmental change.
©2009 Natural Medicine Journal 1(2), October 2009 | Page 4