THE
STANDARD
Volume 5, No. 1
Diabetes - The Preventable Epidemic
Thomas G. Guilliams Ph.D.
Diabetes is the 7th leading cause of death among Americans and cases of
this disease are growing at an alarming rate. Without exaggeration diabetes is
becoming a modern, albeit silent, epidemic. Currently, over 10 million Americans
are diagnosed with some form of diabetes, while another 5 million are considered
to be diabetic without their knowledge. What makes this information so tragic is
the fact that most of these individuals may have been able to prevent the onset
of the disease with proper awareness, diet and exercise. The modern Western diet
and lifestyle has done much to lead our generation to the threshold of insulin
resistance, and with it, the collection of symptoms known as Syndrome X. This
issue will review some of the basics of preventable diabetes (type II) and the
consequences of poor glycemic control leading to insulin resistance. The major
focus will be on the accumulated research of various nutraceuticals as they have
been used to treat or prevent diabetes and its harmful complications.
Diabetes mellitus is a metabolic disorder characterized by elevation of fasting
blood sugar (glucose). While the cause of the elevated blood glucose may be
associated with either too little or too much insulin, the complications of
chronically high serum glucose is devastating to the individual. Complications
of uncontrolled blood sugar include increased risk of heart disease, stroke,
kidney disease, blindness, and loss of nerve function. Regulating blood sugar
for diabetics is therefore crucial to both the immediate as well as long-term
care of diabetic patients.
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Fig 1 Number of people in the United States with diagnosed diabetes
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Often called insulin dependent diabetes mellitus (IDDM), this form of diabetes is
characterized by the destruction of the pancreatic beta cells that manufacture
insulin. Typically this form is diagnosed while the patient is a child or
adolescent and requires insulin for the management of blood sugar. Many theories
have attempted to account for the damage of these important insulin-producing cells
including autoimmune processes, chemical damages, viral infection, and genetic
disposition. Whatever the cause, the result is very low or no insulin; a protein
that is the primary mediator of glucose transport into cells. This diminished
insulin level leads to elevated levels of glucose in the blood, which then results
in numerous complications. Of the more than 15 million Americans with diabetes,
only about 10% are considered to have type I diabetes.
Almost 90% of diabetics are considered to have non-insulin dependent diabetes
mellitus (NIDDM) or type 2 diabetes. While also characterized by high blood glucose
levels, type II diabetics often have high, rather than low, levels of serum
insulin. Type 2 diabetics are typically insulin resistant, rather than insulin
depleted. A current report in JAMA concludes that nearly one-fifth, or 47 million
Americans are at an increased risk of type 2 diabetes, using the criteria of
abdominal obesity, elevated triglycerides, low HDL cholesterol, high blood pressure
and high normal blood sugar (1). In this report, these symptoms were called
"metabolic syndrome", but many people already know them as "Syndrome X". This
syndrome and the subsequent diabetic condition that follows are preventable.
Through an awareness of the various risk factors, proper diet and exercise; type 2
diabetes could be altered from a national epidemic to a manageable but minor
disease. History tells us, unfortunately, that the Western diet and lifestyle have
a tenacious hold on the American culture and this trend toward obesity, insulin
resistance and diabetes is unlikely to abate anytime soon.he ovulation phase,
typically 2-4 days.
Hyperglycemia (high blood glucose) causes complications in patients with diabetes,
regardless of whether it is type 1 or 2. While some complications can be of an
acute nature (ketoacidosis due to low insulin or hypoglycemic shock due to insulin
overdose), most complications are a result of years of unregulated and high serum
glucose. These complications include increased heart disease, retinopathy,
nephropathy ending in renal failure, neuropathy, foot and leg ulcers, impotence,
and the inhibition of many important metabolic enzymes. Most of these complications
are due to hyperglycemic-induced increase reactive oxygen species (ROS) that cause
glucose-induced activation of protein kinase C, increased formation of glucose-
derived advanced glycation end products (AGEs) and increased glucose flux through
the aldose reductase pathway (2). These vascular complications are cumulative, but
preventable. Maintaining proper blood glucose is vital to preventing these
complications. Additionally, there are a number of natural ingredients that can
prevent and even reverse the progress toward these devastating complications.
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Syndrome X and Insulin Resistance
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Syndrome X is the name given to a collection of metabolic conditions; highlighted
by insulin resistance, but also includes obesity (especially in the abdomen), high
cholesterol, low HDL cholesterol, high triglycerides and hypertension. These
symptoms are often termed pre-diabetic syndrome. Insulin resistance is one of the
key features and dangers of this syndrome. Insulin resistance is a condition where
the pancreas is able to manufacture more than enough insulin, but cells have
become resistant to insulin's effects. This increases blood glucose as well as
stimulates insulin-induced metabolic functions (conversion of carbohydrates to
fats leading to obesity). The constant intake of refined carbohydrates, leading to
dramatic spikes in blood glucose followed by dramatic spikes in insulin secretion,
is the primary cause of insulin resistance and then type 2 diabetes. It is for
this reason that diet is possibly the most important aspect to the treatment and
prevention of type 2 diabetes and its precursor condition, Syndrome X.
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Diet and Lifestyle are vital
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It is difficult to over emphasize the importance of diet as it pertains to
preventing and treating type 2 diabetes (many of the principles discussed here are
applicable to type 1 diabetes as well, the role of therapeutic levels of insulin in
these patients has nuances that are not discussed here). Since diabetes is a
metabolic disorder, food can be considered either a poison or a therapy depending
on its content. Not only can food lead to obesity, food is the primary foundation
for blood sugar control often called glycemic control or balance. The steady
balance or glycemic control is the key to prevent and treat syndrome X and type 2
diabetes. Avoiding foods that destabilize glycemic balance and eating foods that
promote glycemic balance is the key to a healthy diet for everyone, but especially
for those with insulin resistance.
Since this review is primarily focused on therapeutic natural ingredients, so-
called nutraceuticals, this will only provide basic principles for the diet.
More information should be gathered from a resource designed specifically with
that subject in mind, some of which are provided in the general reference
section at the end of this review.
General Guidelines
·Understand that glycemic index and total carbohydrates may differ dramatically
·Avoid most processed foods regardless of their protein:carb ratio
·Avoid trans-fatty acids and increase omega-3 fatty acids and GLA
·Increase dietary fiber
·Avoid or test for commonly allergenic foods (dairy, gluten etc)
·Avoid refined sugar in all its forms
·Avoid alcohol
·Avoid artificial sweeteners like aspartame try stevia or xylitol instead
·Drink plenty of pure water
·Don't assume anything Read the label.
Other lifestyle factors are also important for those with diabetes or syndrome
X. Among them, exercise and stress management are vital. Physical activity and
regular exercise may not only have direct impacts on glucose use and insulin
sensitivity, but also on many risk factors such as obesity, triglycerides, and
hypertension. In a recent study, exercise had significant improvement on the
vascular function in type 2 diabetics (62). It should be noted that patients
taking pharmaceuticals to reduce blood sugar or insulin should be monitored
during exercise to prevent hypoglycemia. Typically, less hypoglycemic medication
is required during physical activity. If the patient is not physically active, a
slow progression into an exercise program with consistent monitoring of blood
sugar is prudent. In a study just published in New England Journal of Medicine,
effective lifestyle changes were compared to a popular oral hypoglycemic in
preventing type 2 diabetes in patients with pre-diabetic hyperglycemia (69). In
this study, 3234 "pre-diabetic" patients were given either metformin
(Glucophage®- 850 mg b.i.d.), put on a lifestyle modification program (goals of
7% reduction in weight and 150 minutes of physical activity per week), or
placebo. Each group was instructed with the same dietary guidelines. After
almost 3 years, there were 31% fewer diabetics in the drug group versus placebo,
but there were 58% fewer diabetics in the lifestyle group than placebo.
Lifestyle modification was significantly more effective than metformin in this
study, not to mention the other benefits gained by weight reduction and
increased physical activity.
Another key factor is stress management. Along with the pancreatic production of
insulin, the adrenal glands are important in the regulation of blood sugar. The
adrenal hormone cortisol is stimulated whenever the body is "under stress".
Whether this stress comes from mental or emotional stress, chronic inflammation,
food allergies, or low blood sugar; cortisol effectively raises blood glucose
levels by stimulating gluconeogenesis. This raised glucose level can exceed
desired levels when stress-induced cortisol levels are extremely high (alarm
reaction). Chronic glycemic imbalance or other stress could then result in both
reduced insulin sensitivity and adrenal exhaustion. Studies have shown that
glycemic control of diabetics with higher measurable stress is worse than those
with lower measurable stress and, additionally, techniques to reduce stress lead
to better glycemic control among diabetic patients (3,4,5).
Reports have also
directly linked the function of the hypothalamic-pituitary-adrenal axis with the
risk of type 2 diabetes (11). An excellent way to determine adrenal stress is by
measuring salivary cortisol throughout a single day (See The Standard vol. 3
no.1 for a complete discussion of diagnosing and treating adrenal stress).
The first goal in therapy is to reach and maintain an optimal fasting blood
glucose level. This can be done in a way that benefits other metabolic outcomes
such as improving lipid profiles and reducing blood pressure. The second goal in
therapy is to prevent and treat the chronic consequences and complications
associated with years of poor blood sugar control.
Supplemental Fiber
Dietary fiber is an important aspect of blood sugar control. The addition of
water-soluble fibers such as gums, pectins, and mucilage are capable of reducing
the speed at which carbohydrates are absorbed and increase tissue sensitivity to
insulin. This has been of benefit for both type 1 and type 2 diabetics (6,7). The use of psyllium husk powder (5 grams twice
daily 20-30 min. before meals) has been shown to reduce fasting and postprandial
blood glucose levels as well as improve lipid profiles in type 2 diabetics, when
compared to placebo in double-blinded studies (8). Other
studies had similar results when giving type 2 diabetics 5 grams of psyllium
before each of three meals daily (9). Long-term favorable
effects on glycemic control and lipid concentrations are also associated with
15g/day of supplemental guar gum (10). Adding supplemental
fiber to the diet, in the form of a psyllium or similar product can be an
excellent way to keep and maintain glycemic control. Increase in soluble dietary
fiber will promote healthy bowel transit times and benefit the gut microflora as
well.
Essential Fatty Acids
The role of essential fatty acids is critical in the overall health of diabetics
as it is with all individuals. For a complete review of essential fatty acids and
their role in diabetic therapies see The Standard Vol. 3 no. 2. In summary, the
decreased conversion of the essential omega-6 fatty acid linoleic acid into
gamma-linolenic acid (GLA) in diabetic patients leads to the therapeutic benefit
of ingesting GLA-rich oils such as borage and evening primrose. The greatest
benefits of GLA supplementation are increasing nerve conduction and the
improvement of skin related disorders. Additionally, omega-3 fatty acids from
flax seed oil or fish oil supplementation should be considered as well. The
benefit of these oils in diabetic patients is primarily in their relationship to
the cardiovascular system, an area which diabetics are vulnerable due to
increased lipid peroxidation, atherosclerosis, cholesterol and other lipid
disorders. The long chain EPA and DHA found in fish oils are also necessary for
the retina in particular, a tissue that is often damaged after years of poor
blood sugar management (diabetic retinopathy See The Standard Vol. 2 no. 1 for
more information about treating diabetic retinopathy). The reduction of oxidized
and trans-fatty acids and the increase of high quality essential fatty acids
should be a goal for everyone, but especially for those who have, or are
susceptible, to type 2 diabetes.
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Micronutrients and Nutraceuticals
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While the role of diet and lifestyle is fundamental to improving outcomes for
diabetic patients, supplemental nutrients and natural therapeutic ingredients can
also play a vital role in patient care. Tissue levels of B-vitamins are
significantly depleted in animal models of diabetes (19) as has also been reported
in humans with diabetes. A high quality multivitamin-mineral product should be the
basis of supplemental therapy, one with adequate levels of B-vitamins, vitamin C
and magnesium. Below are additional micronutrients and nutraceuticals that should
be considered in the treatment of diabetic and syndrome X patients.
Chromium
Chromium is a key constituent in the molecule known as glucose tolerance factor
(GTF). This complex facilitates the uptake of glucose into cells in conjunction
with insulin, somewhat like a cofactor to insulin. A recent study compared the
supplemental intake of 200 mcg of Cr/day, 1000 mcg/day Cr or placebo on the glucose
and insulin variables of 180 men and women with type 2 diabetes. While they noted
some improvement in the 200 mcg/day group, the group taking 1000 mcg/day had
statistical improvements in HbA1c (glycosylated hemoglobin), fasting glucose,
insulin and cholesterol levels when compared to placebo (12). Additionally,
research has concluded that non-insulin dependent diabetic patients have a
compromised chromium status, when compared to healthy controls. The researchers
speculate that this is one of the factors leading to insulin resistance in these
patients (13).
Vanadium
For some time, vanadium has demonstrated an insulin-like property in isolated cells
and tissues and has been considered to have therapeutic potential for diabetic
patients. What has been described as an insulin-mimetic activity by most
researchers may actually be an insulin-enhancing function (14). Regardless of the
mechanism, vanadium has been used clinically to help manage serum glucose levels. A
small study showed that 100 mg/day of vanadyl sulfate (VS) for three weeks was able
to significantly improve hepatic and peripheral insulin sensitivity in insulin-
resistant NIDDM patients. These effects were even sustained for as much as 2 weeks
after discontinuation of vanadyl sulfate (15). This same dose did not alter insulin
sensitivity in non-diabetic individuals, suggesting a corrective role for vanadium
(16). The safety and efficacy of 100 mg/day of VS has been tested and shown to be
quite good (17), and other studies have been successful and safe at even higher
doses (18). It should be noted that chronic use of vanadium at these high doses has
not been validated; and a lower dose may be helpful when used in combination with
other natural remedies.
Biotin
The importance of this vital micronutrient produced by healthy gut microbes has
often been overlooked in the management of diabetics. Biotin has a number of
relevant activities including stimulation of glucose-induced insulin secretion,
enhancing insulin sensitivity, and the acceleration of glycolysis in the liver and
pancreas by its enhancement of the enzyme, glucokinase (24). Biotin supplementation
has been shown in both insulin-dependent and non-insulin dependent diabetic animal
models to improve glucose and insulin tolerances (20,21). In humans, improvements
in oral glucose tolerance tests as well as diabetic related neuropathy symptoms are
associated with increased biotin intake (22,23).
Alpha Lipoic Acid
Also known as thioctic acid, alpha lipoic acid is a natural and versatile
antioxidant with numerous therapeutic uses. As an antioxidant it is able to
"recharge" vitamin C, vitamin E and glutathione because of its three-fold water-
soluble, fat-soluble and sulfhydryl properties. In the case of impaired glucose
metabolism and the complications associated with diabetes, the actions of lipoic
acid are quite helpful. Not only does lipoic acid modulate glucose and insulin
sensitivities but acts as to prevent and treat many of the oxidative damages that
occur with hyperglycemia. One recent study compared insulin sensitivity in type 2
diabetics after one month of placebo, 600 mg/day, 1200 mg/day, or 1800 mg/day oral
lipoic acid (25). They found that the treatment, regardless of dose, was equally
able to improve insulin sensitivity by 27% over placebo. This data confirmed
research they had done previously by intravenous administration (26,27).
As an antioxidant, lipoic acid is capable of decreasing oxidative stress, the main
stimulus for diabetic complications. A cross-sectional study was performed to
assess the oxidative load (by looking at lipid peroxide levels) in diabetic
patients some of which were taking 600 mg lipoic acid per day for 3 months (28).
The lipoic acid group had 36% lower levels of lipid peroxides and a 38% improvement
in the ratio between oxidative stress and oxidative defense (measuring lipid
peroxides vs. alpha-tocopherol/cholesterol levels). These data confirm the
antioxidant role of lipoic acid in these patients with poor glycemic control, a
group prone to oxidative stress and damage.
Perhaps the longest use of lipoic acid in diabetes is in the treatment of diabetic
neuropathy. Lipoic acid has been used in Germany for over 30 years for the
treatment of diabetic-induced neuropathy (29,30). Its mechanism of action seems to
be related to its antioxidant activity leading to improved microcirculation and a
positive influence on impaired neurovascular reflex arc in patients with diabetic
neuropathy (34,35). While most of these studies were performed using intravenous
delivery, recent studies confirm that similar results can be obtained by oral
administration of 800 mg/day
(31) or in other studies 600 mg t.i.d. (32). However, one study showed only
marginal favorable effects when using 600 mg t.i.d. in a multicenter controlled
trial (33). Clearly more data must be gathered in the use of lipoic acid in long-
term studies, but it is clear from the available literature that the use of lipoic
acid is a vital and safe component to nutraceutical therapy in diabetic patients,
as well as those with metabolic insulin disorders like syndrome X. The use of high
oral doses of lipoic acid should be accompanied with biotin to prevent competitive
inhibition of biotin-dependent enzymatic processes (36).
There are many other nutraceuticals that have been used successfully in the
treatment of diabetic patients. Those that have a positive effect on lipid or
carbohydrate metabolism, increase general metabolism or weight-loss, or inhibit the
formation of sorbitol may be beneficial for preventing or treating diabetes. These
may include carnitine, niacin, zinc, quercetin (or similar flavonoids) and
lipotropic agents like inositol and choline to name only a few. These and others
are likely to be the focus of attention in in vitro, animal, and clinical research
in the near future.
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Herbs and Botanical Extracts
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The use of various plants and their extracts for diabetes (sugar in the
urine) has been common since ancient times. Recently, we have been able to
scientifically investigate the use of several botanical extracts for their
hypoglycemic and insulin modifying effects. This review will discuss those with the
most research and potential for therapeutic use as nutraceuticals in the U.S.
Gymnema sylvestre
Gymnema is a woody plant that grows in the central and southern parts of India,
where it has been used for almost two millennia for the treatment of diabetes. Some
preliminary research was conducted on this plant over 70 years ago but most of what
we know of its hypoglycemic properties has been learned in the past 20 years. The
activity is thought to reside primarily in a group of compounds called gymnemic
acids, of which extracts are usually standardized. In animal studies, gymnema leaf
powder was able to control blood sugar levels as well as other insulin-dependent
metabolic pathways (37,38).
One particular extract, known as GS4, has been used in clinical trials with both
insulin-dependent and non-insulin dependent diabetic patients. In IDDM patients
given 400 mg/day GS4, insulin requirements were reduced as well as fasting blood
glucose levels, perhaps by increasing insulin usage or residual beta cell function
(39). This same gymnema extract was able to double the number of pancreatic beta
cells when given to diabetic rats (40). Likewise, this research group also
investigated the use of 400 mg/day GS4 in 22 Type 2 diabetic patients who were
taking conventional oral anti-hyperglycemic medications. After 18-20 months of
Gymnema extract use, the patients showed a significant reduction in blood glucose,
glycosylated hemoglobin and reduction in conventional drug use. Five of the 22
discontinued medication altogether and insulin levels in these patients were
increased after taking GS4 (41).
Several mechanisms are thought to
account for the hypoglycemic activity of gymnema extracts. As mentioned previously,
gymnema extracts are associated with increased pancreatic function and insulin
release. While recent studies have confirmed these results in animals (42), in
vitro tests seem to imply that these extracts may stimulate insulin secretion by
increasing beta cell membrane permeability (43). Other research has also implicated
gymnema in the suppression of blood glucose by inhibiting glucose uptake in the
intestine (44). The current research and safety profile of gymnema extracts make it
a leading botanical in the treatment of type 2 diabetes, and potentially, type I
diabetes.
Bitter Melon
Bitter melon (Momordica charantia) is a tropical fruit that looks like a cross
between a gourd and a cucumber. The fruit is eaten as a vegetable in many cultures,
but has also been used for the treatment of diabetes by these same cultures. A
large body of research now confirms the hypoglycemic effects of bitter melon in
animal models, while only a few clinical trials have been done with diabetic
patients. A trend in the animal research seems to imply the need for some insulin
production, as NIDDM animal models responded to bitter melon treatment while IDDM
models rarely did (45-49). This mechanism seems to be confirmed by in vitro
evidence that shows protection of and increased numbers of pancreatic beta cells,
and in some cases, an insulin-releasing activity (50-52).
Bitter melon extracts were also able to reduce oxidative stress and reverse the
effects of chronic diabetes in an IDDM animal model (53). Additionally, bitter
melon extracts show triglyceride and cholesterol lowering activity in diabetic
animals (54), as well as non-diabetic animals fed cholesterol-rich diets (55). In
an investigation of 4 traditional Indian anti-diabetic herbs (M. charatia, Eugenia
jambolana, Mucuna pruriens and Tinospora cordifolia) in streptozotocin induced
diabetic mice, bitter melon not only reduced plasma glucose levels more than the
other herbs, but also significantly reduced renal hypertrophy compared to untreated
diabetic controls (56).
Unfortunately, there are few published clinical trials using bitter melon in
humans. In one case, 86% of the NIDDM patients experienced a hypoglycemic response
to drinking an aqueous homogenized suspension of the vegetable pulp (57). This was
similar to a report that 73% of type II diabetics responded to 2 oz of bitter melon
juice (58). In both studies, response was measured by reduction in glucose
tolerance after glucose challenge. These were not controlled trials, nor did they
use extracts, making it difficult to assess what dose of the extract would best be
used for diabetic patients. Various powdered extracts are now available and dosing
is estimated at 750-1250 mg per day. More studies need to be conducted to confirm
the efficacy of these extracts in humans, although the years of dietary use
suggests that safety is unlikely to be an issue.
Fenugreek
The seeds of this Mediterranean spice have long been used for treating diabetes. It
has been thought that the primary hypoglycemic mechanism is related to the large
amount of water-soluble fiber content found in these seeds. Recently however, other
hypoglycemic compounds have been isolated from fenugreek seeds and are being
investigated for their role in treating diabetics (59-61). Most of the human
clinical trials have been done with between 5 to 100 grams daily of fenugreek seed
powder. This may be manageable for only a few patients who are willing to ingest
these large amounts of powdered seed. Extracts may soon be used in clinical trials
so that the non-fibrous hypoglycemic portions can be tested for effectiveness,
dosing and safety.
Other Botanicals
It would be impossible to review all the other botanicals that have published
research indicating potential use with diabetics, let alone cover all those for
which traditional information is available. That said there are a few which are
worth mentioning here. One of those is the herb Holy basil (Ocimum sanctum L.). In
animal studies and one human study, the leaves of holy basil had hypoglycemic
activity. Unlike some of the other herbs above, holy basil lowered serum blood
glucose in both normal and diabetic animals (63,64). A single-blinded placebo-
controlled crossover study did show positive benefit in both fasting blood sugar
and postprandial blood sugar in NIDDM patients consuming holy basil leaves (65).
This may be an herb to watch as more research and extracts become available.
Another botanical worth considering is the multi-purpose milk thistle (Silybum
marianum L.), or more specifically the "seed" extract known as silymarin. Most
often used for its liver specific effects, silymarin has shown promise in
protecting chemically induced pancreatic damage (lipid
peroxidation) in animal models of diabetes (66,67). Silymarin (600 mg/day) was also
given to 30 insulin-treated type II diabetics suffering from alcohol induced lever
cirrhosis. Both the treatment and the control group were treated with their
previous standard therapy (68). In the silymarin group, their was a significant
decrease in fasting blood glucose levels, mean daily blood glucose levels,
glycosylated hemoglobin after only 4 months of treatment. At the same time there
was a reduction in fasting insulin levels and stabilization of insulin need. While
the data here is sparse, the overall safety and multiple other benefits gained by
using silymarin may make it a beneficial addition to the natural treatment of
diabetics.
Research from the University of Toronto has shown the potential use of
American ginseng (Panax quinquefolius L.) in glycemic control (70-72). The use of
as little as one gram of ginseng powder administered 40 minutes before a
meal/glucose challenge was able to lower prostprandial glycemia. These effects were
seen in normal as well as type 2 diabetic patients. Taken 40 minutes before a meal,
ginseng may be helpful in the regulation of glycemic balance.
An extract of Lagerstroemia speciosa L., containing trace levels of corosolic acid,
is currently being studied for its ability to lower blood glucose levels. A
mechanism that allows glucose transport into cells, apparently without insulin, is
being postulated. This mechanism seems to lower blood glucose regardless of
diabetic status (at least for rats), and is deemed phyto-insulin by one company
selling the extract.
Other botanicals include Pterocarpus marsupium, Atriplex halimu, and garlic (Allium
sativum), to name only a few that have published data. In the next 5-10 years, the
growing desire to use natural remedies combined with the epidemic growth of
syndrome X and diagnosed diabetes will cause the list of published botanical
research reports to expand, and give the clinician and patient many more options.
Statistical research predicts that regardless of the type of practice, at least one
in five individuals entering clinics in the United States has the metabolic
precursors for insulin resistance and type 2 diabetes. The treatment and prevention
of these disorders is both natural and eminently holistic. It was the intention of
this review to give the clinician information on the many natural options
available, and to act as a guideline for treatment and prevention. As each patient
presents a different and unique history, different approaches may be applicable for
their individual regimen. Balancing lifestyle and diet changes, as well as
introducing nutraceuticals for prevention and treatment will be rewarded by slowing
or even stopping potentially devastating outcomes a reward worth the effort.
GENERAL REFERENCES:
Brownlee M. Biochemistry and molecular cell biology of diabetic complications.
Nature 2001; 414(6865):813-20
Sosin A.E. The Doctor's Guide to Diabetes and your Child.
2000 Kensington Publishing Corp. NY
Challem J et al. Syndrome X -The complete nutritional program to prevent and reverse insulin resistance.
2000 John Wiley and Sons, Inc NY
Pizzorno J and Murray M. Textbook of Natural Medicine 2nd Ed.
Churchhill Livingstone Edinburgh UK pgs 1193-1218
REFERENCES CITED:
- Ford ES, Giles WH, Dietz WH. Prevalence of the Metabolic Syndrome Among US
Adults: Findings From the Third National Health and Nutrition Examination Survey.
JAMA 2002; 287(3):356-9
[PubMed]
- Nishikawa T, Edelstein D, Brownlee M. The missing link: a single unifying
mechanism for diabetic complications.
Kidney Int Suppl 2000;77:S26-30
[PubMed]
- Viner R, McGrath M, Trudinger P. Family stress and metabolic control in
diabetes.
Arch Dis Child 1996; 74(5):418-21
[PubMed]
- Surwit RS et al. Stress management improves long-term glycemic control in type 2
diabetes.
Diabetes Care 2002; 25(1):30-4
[PubMed]
- Surwit RS, Schneider MS. Role of stress in the etiology and treatment of
diabetes mellitus.
Psychosom Med 1993; 55(4):380-93
[PubMed]
- Giacco R et al. Long-term dietary treatment with increased amounts of fiber-rich
low-glycemic index natural foods improves blood glucose control and reduces the number of hypoglycemic events in type 1
diabetic patients.
Diabetes Care 2000; 23(10):1461-6
[PubMed]
- Chandalia M et al. Beneficial effects of high dietary fiber intake in patients
with type 2 diabetes mellitus.
N Engl J Med 2000; 342(19):1392-8
[PubMed]
- Anderson JW, Allgood LD, Turner J, Oeltgen PR, Daggy BP. Effects of psyllium on
glucose and serum lipid responses in men with type 2 diabetes and hypercholesterolemia.
Am J Clin Nutr 1999;70(4):466-73
[PubMed]
- Rodriguez-Moran M, Guerrero-Romero F, Lazcano-Burciaga G. Lipid- and glucose-
lowering efficacy of Plantago Psyllium in type II diabetes.
J Diabetes Complications 1998; 12(5):273-8
[PubMed]
- Groop PH, Aro A, Stenman S, Groop L. Long-term effects of guar gum in subjects
with non-insulin-dependent diabetes mellitus.
Am J Clin Nutr 1993 Oct;58(4):513-8
[PubMed]
- Rosmond R, Bjorntorp P. The hypothalamic-pituitary-adrenal axis activity as a
predictor of cardiovascular disease, type 2 diabetes and stroke.
J Intern Med 2000; 247(2):188-97
[PubMed]
- Anderson RA et al. Elevated intakes of supplemental chromium improve glucose
and insulin variables in individuals with type 2 diabetes.
Diabetes 1997; 46(11): 1786-91
[PubMed]
- Morris BW et al. Chromium homeostasis in patients with type II (NIDDM)
diabetes.
J Trace Elem Med Biol 1999;13(1-2):57-61
[PubMed]
- Cam MC, Brownsey RW, McNeill JH. Mechanisms of vanadium action: insulin-
mimetic or insulin-enhancing agent?
Can J Physiol Pharmacol 2000; 78(10):829-47
[PubMed]
- Cohen N et al. Oral vanadyl sulfate improves hepatic and peripheral insulin
sensitivity in patients with non-insulin-dependent diabetes mellitus.
J Clin Invest 1995; 95(6):2501-9
[PubMed]
- Halberstam M, Cohen N, Shlimovich P, Rossetti L, Shamoon H. Oral vanadyl
sulfate improves insulin sensitivity in NIDDM but not in obese nondiabetic subjects.
Diabetes 1996; 45(5):659-66
[PubMed]
- Boden G, Chen X, Ruiz J, van Rossum GD, Turco S. Effects of vanadyl sulfate on
carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus.
Metabolism 1996; 45(9):1130-5
[PubMed]
- Cusi K et al. Vanadyl sulfate improves hepatic and muscle insulin sensitivity
in type 2 diabetes.
J Clin Endocrinol Metab 2001; 86(3):1410-7
[PubMed]
- Reddi AS et al. Tissue concentrations of water-soluble vitamins in normal and
diabetic rats.
Int J Vitam Nutr Res 1993; 63(2):140-4
[PubMed]
- Reddi A, DeAngelis B, Frank O, Lasker N, Baker H. Biotin supplementation
improves glucose and insulin tolerances in genetically diabetic KK mice.
Life Sci 1988; 42(13):1323-30
[PubMed]
- Zhang H et al. A high biotin diet improves the impaired glucose tolerance of
long-term spontaneously hyperglycemic rats with non-insulin-dependent diabetes mellitus.
J Nutr Sci Vitaminol (Tokyo) 1996; 42(6):517-26
[PubMed]
- Koutsikos D et al. Oral glucose tolerance test after high-dose i.v. biotin
administration in normoglucemic hemodialysis patients.
Ren Fail 1996;18(1): 131-7
[PubMed]
- Koutsikos D, Agroyannis B, Tzanatos-Exarchou H. Biotin for diabetic peripheral
neuropathy.
Biomed Pharmacother 1990; 44(10):511-4
[PubMed]
- Romero-Navarro G et al. Biotin regulation of pancreatic glucokinase and
insulin in primary cultured rat islets and in biotin-deficient rats.
Endocrinology 1999; 140(10): 4595-600
[PubMed]
- Jacob S et al. Oral administration of RAC-alpha-lipoic acid modulates insulin
sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial.
Free Radic Biol Med 1999; 27(3-4):309-14
[PubMed]
- Jacob S et al. Enhancement of glucose disposal in patients with type 2
diabetes by alpha-lipoic acid.
Arzneimittelforschung 1995; 45(8):872-4
[PubMed]
- Jacob S, Henriksen EJ, Tritschler HJ, Augustin HJ, Dietze GJ. Improvement of
insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid.
Exp Clin Endocrinol Diabetes 1996;104(3):284-8
[PubMed]
- Borcea V et al. alpha-Lipoic acid decreases oxidative stress even in diabetic
patients with poor glycemic control and albuminuria.
Free Radic Biol Med 1999; 26(11-12):1495-500
[PubMed]
- Evans JL, Goldfine ID. Alpha-lipoic acid: a multifunctional antioxidant that
improves insulin sensitivity in patients with type 2 diabetes.
Diabetes Technol Ther 2000; 2(3):401-13
[PubMed]
- Ziegler D, Reljanovic M, Mehnert H, Gries FA. Alpha-lipoic acid in the
treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials.
Exp Clin Endocrinol Diabetes 1999;107(7):421-30
[PubMed]
- Ziegler D, Schatz H, Conrad F, Gries FA, Ulrich H, Reichel G. Effects of
treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized
controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie.
Diabetes Care 1997; 20(3): 369-73
[PubMed]
- Ruhnau KJ et al. Effects of 3-week oral treatment with the antioxidant
thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy.
Diabet Med 1999; 16(12):1040-3
[PubMed]
- Ziegler D et al. Treatment of symptomatic diabetic polyneuropathy with the
antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study
Group. Alpha-Lipoic Acid in Diabetic Neuropathy.
Diabetes Care 1999; 22(8):1296-301
[PubMed]
- Haak ES et al. The effect of alpha-lipoic acid on the neurovascular reflex arc
in patients with diabetic neuropathy assessed by capillary microscopy.
Microvasc Res 1999; 58(1):28-34
[PubMed]
- Haak E et al. Effects of alpha-lipoic acid on microcirculation in patients
with peripheral diabetic neuropathy.
Exp Clin Endocrinol Diabetes 2000; 108(3):168-74
[PubMed]
- Zempleni J, Trusty TA, Mock DM. Lipoic acid reduces the activities of biotin-
dependent carboxylases in rat liver.
J Nutr 1997; 127(9):1776-81
[PubMed]
- Shanmugasundaram KR et al. Enzyme changes and glucose utilisation in diabetic
rabbits: the effect of Gymnema sylvestre, R.Br.
J Ethnopharmacol 1983; 7(2):205-34
[PubMed]
- Okabayashi Y et al. Effect of Gymnema sylvestre, R.Br. on glucose homeostasis
in rats.
Diabetes Res Clin Pract 1990; 9(2): 143-8
[PubMed]
- Shanmugasundaram ER et al. Use of Gymnema sylvestre leaf extract in the
control of blood glucose in insulin-dependent diabetes mellitus.
J Ethnopharmacol 1990; 30(3):281-94
[PubMed]
- Shanmugasundaram ER et al. Possible regeneration of the islets of Langerhans
in streptozotocin-diabetic rats given Gymnema sylvestre leaf extracts.
J Ethnopharmacol 1990; 30(3):265-79
[PubMed]
- Baskaran K et al. Antidiabetic effect of a leaf extract from Gymnema sylvestre
in non-insulin-dependent diabetes mellitus patients.
J Ethnopharmacol 1990; 30(3):295-300
[PubMed]
- Sugihara Y, Nojima H et al. Antihyperglycemic effects of gymnemic acid IV, a
compound derived from Gymnema sylvestre leaves in streptozotocin-diabetic mice.
J Asian Nat Prod Res 2000; 2(4):321-7
[PubMed]
- Persaud SJ, Al-Majed H, Raman A, Jones PM. Gymnema sylvestre stimulates
insulin release in vitro by increased membrane permeability.
J Endocrinol 1999; 163(2):207-12
[PubMed]
- Shimizu K et al. Suppression of glucose absorption by some fractions extracted
from Gymnema sylvestre leaves.
J Vet Med Sci 1997; 59(4):245-51
[PubMed]
- Ali L et al. Studies on hypoglycemic effects of fruit pulp, seed, and whole
plant of Momordica charantia on normal and diabetic model rats.
Planta Med 1993; 59(5):408-12
[PubMed]
- Karunanayake EH, Jeevathayaparan S, Tennekoon KH. Effect of Momordica
charantia fruit juice on streptozotocin-induced diabetes in rats.
J Ethnopharmacol 1990; 30(2):199-204
[PubMed]
- Day C, Cartwright T, Provost J, Bailey CJ. Hypoglycaemic effect of Momordica
charantia extracts.
Planta Med 1990; 56(5):426-9
[PubMed]
- Sarkar S, Pranava M, Marita R. Demonstration of the hypoglycemic action of
Momordica charantia in a validated animal model of diabetes.
Pharmacol Res 1996; 33(1):1-4
[PubMed]
- Cakici I, Hurmoglu C, Tunctan B, Abacioglu N, Kanzik I, Sener B. Hypoglycaemic
effect of Momordica charantia extracts in normoglycaemic or cyproheptadine-induced hyperglycaemic mice.
J Ethnopharmacol 1994; 44(2):117-21
[PubMed]
- Welihinda J, Arvidson G, Gylfe E, Hellman B, Karlsson E. The insulin-releasing
activity of the tropical plant momordica charantia.
Acta Biol Med Ger 1982; 41(12):1229-40
[PubMed]
- Sitasawad SL, Shewade Y, Bhonde R. Role of bittergourd fruit juice in stz-
induced diabetic state in vivo and in vitro.
J Ethnopharmacol 2000; 73(1-2):71-9
[PubMed]
- Ahmed I, Adeghate E, Sharma AK, Pallot DJ, Singh J. Effects of Momordica
charantia fruit juice on islet morphology in the pancreas of the streptozotocin-diabetic rat.
Diabetes Res Clin Pract 1998; 40(3):145-51
[PubMed]
- Raza H, Ahmed I, John A, Sharma AK. Modulation of xenobiotic metabolism and
oxidative stress in chronic streptozotocin-induced diabetic rats fed with Momordica charantia fruit extract.
J Biochem Mol Toxicol 2000; 14(3): 131-9
[PubMed]
- Ahmed I, Lakhani MS, Gillett M, John A, Raza H. Hypotriglyceridemic and
hypocholesterolemic effects of anti-diabetic Momordica charantia (karela) fruit extract in streptozotocin-induced diabetic
rats.
Diabetes Res Clin Pract 2001; 51(3):155-61
[PubMed]
- Jayasooriya AP et al. Effects of Momordica charantia powder on serum glucose
levels and various lipid parameters in rats fed with cholesterol-free and cholesterol-enriched diets.
J Ethnopharmacol 2000; 72(1-2):331-6
[PubMed]
- Grover JK, Vats V, Rathi SS, Dawar R. Traditional Indian anti-diabetic plants
attenuate progression of renal damage in streptozotocin induced diabetic mice.
J Ethnopharmacol 2001; 76(3):233-8
[PubMed]
- Ahmad N, Hassan MR, Halder H, Bennoor KS. Effect of Momordica charantia
(Karolla) extracts on fasting and postprandial serum glucose levels in NIDDM patients.
Bangladesh Med Res Counc Bull 1999; 25(1):11-3
[PubMed]
- Welihinda J, Karunanayake EH, Sheriff MH, Jayasinghe KS. Effect of Momordica
charantia on the glucose tolerance in maturity onset diabetes.
J Ethnopharmacol 1986 Sep;17(3):277-82
[PubMed]
- Ravikumar P, Anuradha CV. Effect of fenugreek seeds on blood lipid
peroxidation and antioxidants in diabetic rats.
Phytother Res 1999;13(3):197-201
[PubMed]
- Abdel-Barry JA, Abdel-Hassan IA, Al-Hakiem MH. Hypoglycaemic and
antihyperglycaemic effects of Trigonella foenum-graecum leaf in normal and alloxan induced diabetic rats.
J Ethnopharmacol 1997; 58(3):149-55
[PubMed]
- Sauvaire Y et al. 4-Hydroxyisoleucine: a novel amino acid potentiator of
insulin secretion.
Diabetes 1998; 47(2):206-10
[PubMed]
- Maiorana A et al. The effect of combined aerobic and resistance exercise
training on vascular function in type 2 diabetes.
J Am Coll Cardiol 2001;38(3):860-6
[PubMed]
- Chattopadhyay RR. Hypoglycemic effect of Ocimum sanctum leaf extract in normal
and streptozotocin diabetic rats.
Indian J Exp Biol 1993; 31(11):891-3
[PubMed]
- Rai V, Iyer U, Mani UV. Effect of Tulasi (Ocimum sanctum) leaf powder
supplementation on blood sugar levels, serum lipids and tissue lipids in diabetic rats.
Plant Foods Hum Nutr 1997;50(1):9-16
[PubMed]
- Agrawal P, Rai V, Singh RB. Randomized placebo-controlled, single blind trial
of holy basil leaves in patients with noninsulin-dependent diabetes mellitus.
Int J Clin Pharmacol Ther 1996; 34(9):406-9
[PubMed]
- von Schonfeld J, Weisbrod B, Muller MK. Silibinin, a plant extract with
antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A toxicity.
Cell Mol Life Sci 1997; 53(11-12):917-20
[PubMed]
- Soto CP, Perez BL, Favari LP, Reyes JL. Prevention of alloxan-induced diabetes
mellitus in the rat by silymarin.
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 1998;119(2):125-9
[PubMed]
- Velussi M, Cernigoi AM, De Monte A, Dapas F, Caffau C, Zilli M. Long-term (12
months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and
malondialdehyde levels in cirrhotic diabetic patients.
J Hepatol 1997; 26(4):871-9
[PubMed]
- Knowler WC et al. Reduction in the incidence of type 2 diabetes with lifestyle
intervention or metformin.
N Engl J Med 2002; 346(6):393-403
[PubMed]
- Vuksan V, Sievenpiper JL et al. American ginseng (Panax quinquefolius L)
reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus.
Arch Intern Med 200; 160(7):1009-13
[PubMed]
- Vuksan V, Stavro MP et al. Similar postprandial glycemic reductions with
escalation of dose and administration time of American ginseng in type 2 diabetes.
Diabetes Care 2000; 23(9):1221-6
[PubMed]
- Vuksan V, Sievenpiper JL et al. American ginseng (Panax quinquefolius
L.) attenuates postprandial glycemia in a time-dependent but not dose-dependent manner in healthy individuals.
Am J Clin Nutr 2001; 73(4):753-8
[PubMed]
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