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The
basic argument: Stress and aging make cells less responsive in
many ways by damaging their ability to produce energy and to adapt.
The polyunsaturated fats are universally toxic to the energy producing
system, and act as a "misleading signal" channeling cellular
adaptation down certain self-defeating pathways. Diabetes is just
one of the "terminal" diseases that can be caused by the polyunsaturated
vegetable oils. Coconut oil, in diabetes as in other degenerative
diseases, is highly protective.
When
the oral contraceptive pill was new (Enovid), it was found to produce
signs of diabetes, including decreased glucose tolerance. Spellacy
and Carlson (1966) suggested that an elevation of circulating free fatty
acids might be responsible, and remarked that "Free fatty acids
can block the Krebs cycle, with relative insulin action resistance resulting."
"The potential danger of the oral contraceptives is one of prolonged
pancreatic stimulation." Recent papers are reporting that
the estrogen used to "treat menopause" causes an increase
in free fatty acids. Spellacy and Carlson suggested that estrogen's
effect was mediated by growth hormone, and that is now the consensus.
Women are much more likely than men to develop diabetes.
Ephraim
Racker observed that free unsaturated fatty acids inhibit mitochondrial
respiration, and recent studies are finding that free linoleic and linolenic
acids act as intracellular regulators, stimulating the protein kinase
C (PKC) system, which is also stimulated by estrogen and the (cancer
promoting) phorbol esters. They stimulate the cell while blocking
the energy it needs to respond.
Scleroderma,
or systemic sclerosis, is a supposedly mysterious condition in which
tissues harden, with an excessive deposition of fibrous material.
Besides hardening the skin, it can involve fibrosis of the heart and
other organs, and can cause changes in blood vessels of the kidneys
like those seen in some types of hypertension, and often involves Raynaud's
phenomenon and osteoporosis of the fingers. (Silicone functions
as an adjuvant, making exposure to irritants, solvents or infections
more harmful. This seems to be the reason for the association
between breast implants and scleroderma.) Another type of disease
that involves hardening of the skin is scleredema, in which the skin
thickens with an accumulation of "mucin" between collagen
bundles, and in which fibroblasts are overactive in producing collagen.
(Varga, et al.) This condition is believed to often follow a "febrile
illness" and is associated with diabetes. My interest in
these conditions comes from my awareness that estrogen promotes collagen
formation, and that changes in the connective tissue are deeply associated
with the processes of stress and aging, following the ideas of Metchnikov
and Selye.
Many
people are still committed to the various old theories of diabetes,
though a few are showing ways in which multiple causes can lead to diabetes.
Increasingly, old age itself is seen to be "like diabetes (Meneilly,
et al.; Smith, et al.), and the situation is ripe for a recentering
of our understanding of diabetes around some of the general facts about
aging and stress.
Diabetes
mellitus, as named, refers to excessive urination and sugary urine,
but it is now often diagnosed in people who neither urinate excessively
nor pass glucose in the urine, on the basis of a high level of glucose
in the blood. Many other signs (abnormal mucopolysaccharide metabolism
with thickening of basement membranes, leakage of albumin through capillary
walls and into the urine, a high level of free fatty acids in the blood,
insensitivity of tissues to insulin, or reduced sensitivity of the beta
cells to glucose) are considered diagnostic by some people, who believe
that the worst aspects of the disease can be prevented if they can diagnose
early and take preventive measures. This attitude derives largely
from the genetic theory of causation, though it incorporates a belief
that (environmental) intervention can ameliorate the course of the disease.
When I wrote Nutrition for Women, I mentioned that the sudden appearance
of diabetes in non-European Jews when they moved to Isreal made the
genetic theory of diabetes untenable, and since then other studies have
made the similar point that environmental factors seem crucial. (Shaltout,
et al.) Many people are arguing for the racial/genetic theory
of diabetes, but they are failing to consider some simple dietary factors,
especially the high consumption of unsaturated seed oils and the combination
of nutritional deficiencies and environmental stress.
I
have known adults and children who were diagnosed as diabetic, and given
insulin (and indoctrinated with the idea that they had a terminal degenerative
disease) on the strength of a single test showing excessive glucose.
When I taught at the naturopathic medical school in Portland, I tried
to make it clear that "diabetes" (a term referring to excessive
urination) is a function, and that a high level of glucose in the blood
or urine is also a function, and that the use of insulin should require
a greater diagnostic justification than the use of aspirin for a headache
does, because insulin use itself constitutes a serious health problem.
(And we seldom hear the idea that "diabetes" might have a
positive side [Robinson and Johnston], for example that it reduces the
symptoms of asthma [Vianna and Garcialeme], which get worse when insulin
is given. Normal pregnancy can be considered "diabetic"
by some definitions based on blood sugar. I got interested in
this when I talked to a healthy "diabetic" woman who had a
two year old child whose IQ must have been over 200, judging by his
spontaneous precocious hobbies. Old gynecologists told me that
it was common knowledge that "diabetic" women had intellectually
precocious children.)
When
non-diabetic apes were given insulin treatments, they developed some
of the same "complications of diabetes" that are seen in humans,
and antibodies to insulin were found in their retinas, suggesting that
some "complications of diabetes" were complications of insulin
treatment. Patients were seldom well informed of the arguments
against the use of insulin, but the justification for the new genetically
engineered human insulin is precisely that it avoids immunological damage.
Insulin was introduced into medicine in the 1920s. According to the Britannica Book of the Year for 1947, page 265, "Mortality from diabetes in 1920 in the United States was 16.0 per 100,000, 14,062 deaths, but in 1944, it was 26.4 per 100,000, 34,948 deaths."
One of the theories of the cause
of diabetes is that a virus damages the beta cells in the pancreas,
and the main argument for that in the 1970s was that the onset of diabetes
in children can often be dated to a time shortly after a severe viral
infection. It is true that intense sickness and a high fever (and
high doses of drugs given to treat the sickness) can cause very high
levels of glucose in the blood, and even glucose in the urine, but this
is a fairly well recognized consequence of stress. High doses
of cortisone (prednisone, etc.) typically cause elevated glucose levels.
Cushing's syndrome usually involves hyperglycemia. Normally, this
is just a functional response to an excess of glucocorticoids, but studies
in dogs suggested that intense and/or prolonged stress can damage the
insulin-secreting cells in the pancreas. Dogs had half of their
pancreas removed, to increase the burden put on the remaining tissue,
and after a large dose of cortisone the dogs became (and remained) diabetic.
One
of the problems associated with diabetes is the calcification of blood
vessels, though now there is more emphasis on fatty degeneration.
Other blood vessel problems include hypertension, and poor circulation
in general, leading to gangrene of the feet, impotence, and degeneration
of the retina. In muscles, and probably in other tissues of diabetics,
capillaries are more widely spaced, as if the basal oxidative requirement
were lower than normal. However, mitochondria contain more respiratory
enzymes, as if to partly compensate for the poor delivery of oxygen
to the cells. Osteoporosis or osteopenia is a common complication of
diabetes, and seems to be associated with the calcification of soft
tissues.
F. Z. Meerson's description of the stress-injured heart is very similar to the general changes that occur in chronic diabetes. He found that the stressed heart becomes rigid and unable to contract completely, or to relax completely. Excess calcium enters cells, and fatty acids are mobilized both locally and systemically, and both of these tend to damage the mitochondria. In diabetes, fatty acids are mobilized and oxidized instead of glucose, and calcium enters cells, increasing their rigidity and preventing relaxation of muscles in blood vessels. (I'm not sure whether it is relevant to cell physiology, but the presence of an excess of free unsaturated fatty acids, and of calcium, in cells makes me think of the insoluble soap that these substances form in other situations, including the intestine. It seems that this could form a harmful deposit in cells, blocking many metabolic processes.)
For
many years, histologists have observed that calcium and iron tend to
be deposited together in "devitalized" tissues. Now
we know that cell death from a great variety of causes involves the
cell's absorption of increased amounts of calcium. Simply the
lack of energy increases the amount of calcium in a cell, and stimulation
or excitation does the same, creating or exaggerating a deficiency of
energy. In low thyroid people, many (if not all) tissues are very
easily damaged. Since glucose is needed by liver cells to produce
the active (T3) form of thyroid, diabetes almost by definition will
produce hypothyroidism, since in diabetes glucose can't be absorbed
efficiently by cells.
In
the form of cell damage caused by the "excitotoxins," glutamic
and aspartic acids, the damage seems to require both stimulation, and
difficulty in maintaining adequate energy production. This combination
leads to both calcium uptake and lipid peroxidation. When cells
are de-energized, they tend to activate iron by chemical reduction,
producing lipid peroxidation. This could explain the presence
of chemically active iron, but an actual increase in the iron concentration
suggests that there has been prolonged injury (oxidative stress) to
the cell, with increased production of the heme group, which binds iron.
Hans
Selye found that he could produce scleroderma (hardening and calcification
of the skin) in rats by giving them a toxic dose of a heavy metal, and
then irritating the skin a little by plucking hair. Iron is now tending
to be recognized as a factor in inflammation. Vitamin E was able
to prevent the development of scleroderma under Selye's experimental
conditions, suggesting that the irritation allowed the heavy metal to
cause oxidative damage to the skin. Selye found other ways to
cause calcification of tissues, including the walls of arteries, but
he directed most of his attention to the role of "pro-inflammatory"
hormones. A decreased blood supply was often used to predispose
an organ to calcification. In diabetes, a characteristic feature
is that the blood supply is relatively remote from cells in muscle and
skin, so the oxygen and nutrients have to diffuse farther than in normal
individuals, and the ATP level of cells is characteristically lower
than normal. In blood cells, both red (Garnier, et al.) and white
cells are probably more rigid in diabetes, because of lower ATP production,
and higher intracellular calcium and sodium.
Magnesium in the cell is largely associated with ATP, as the complex Mg-ATP. When ATP is "used" or converted to ADP, this lower-energy substance associates with calcium, as Ca-ADP. In a hypothyroid state, the energy charge can be depleted by stress, causing cells to lose magnesium. ATP is less stable when it isn't complexed with magnesium, so the stress-induced loss of magnesium makes the cell more susceptible to stress, by acting as a chronic background stimulation, forcing the cell to replace the ATP which is lost because of its instability. In this state, the cell takes up an excess of calcium.
The picture that I think explains
many of the features of diabetes is that an energy deficit produces
an alarm state, causing increased production of adrenalin and cortisol.
Adrenalin mobilizes fat from storage, and the free fatty acids create
a chronic problem involving 1) blocked ATP production, 2) activation
of the protein kinase C system (increasing tension in blood vessels),
3) inhibition of thyroid function with its energetic, hormonal, and
tissue-structure consequences, 4) availability of fats for prostaglandin
synthesis, and 5) possibly a direct effect on clot dissolving, besides
the PAI-1 (plasminogen activator inhibitor) effect seen in diabetes
(Ceriello, et al., Udvardy, et al., Vague, et al.). (Estrogen
has many pro-clotting effects, and one of them is a decreased activity
of vascular plasminogen activator. K. E. Miller and S. V. Pizzo,
"Venous and arterial thromboembolic disease in women using oral
contraceptives," Am. J. Obst. Gyn. 144, 824, 1982. In 1968,
D. G. Daniel et al., reported that estrogen promotes thromboembolism
by increasing clotting factor IX in the blood.)
Increased
entry of calcium into cells is complexly related to increased exposure
to unsaturated fatty acids, decreased energy, and lipid peroxidation.
Osteoporosis, calcification of soft tissues and high blood pressure
are promoted by multiple stresses, hypothyroidism, and magnesium deficiency.
The particular direction a disease takes--diabetes, scleroderma, lupus,
Alzheimer's, stroke, etc.--probably results from the balance between
resources and demands within a particular organ or system. Calcium
overload of cells can't be avoided by avoiding dietary calcium, because
the bones provide a reservoir from which calcium is easily drawn during
stress. (In fact, the reason calcium can temporarily help prevent
muscle cramps seems to be that it makes magnesium more available to
the muscles.)
If
we want to stop a disease that involves abnormal calcification or contraction
of muscle (see Zenere, et al.), we can increase our consumption of magnesium,
and to cause cells to absorb and retain the magnesium, we can increase
our thyroid function. The use of coconut oil provides energy to
stabilize blood sugar while protecting mitochondria and the thyroid
system from the harmful effects of unsaturated fats.
In
1947, B. A. Houssay found that a diet based on sugar as a source of
energy was more protective against diabetes than a diet based on lard,
while the most protective diet was based on coconut oil. Lard
reflects the pigs' diet, and is usually extremely unsaturated, especially
since it became standard to fatten them on soybeans and corn.
Essentially, his study seems to show that unsaturated (pork) fat permits
diabetes to develop, sugar is slightly protective, and coconut oil is
very protective against the form of diabetes caused by a poison.
At
the same time, A. Lazarow was demonstrating that a low protein diet
made animals more sensitive to diabetes, and that cysteine, glutathione,
and thioglycolic acid (antioxidants) are protective against diabetes.
The chelator of metals, BAL (British anti-lewisite), was also found
to protect against diabetes.
Taken together, those studies suggest that the oxidizable unsaturated fats are involved in the process of producing diabetes. At the same time, other studies were showing that the unsaturated oils suppress the thyroid, and that coconut oil increases the metabolic rate, apparently by normalizing thyroid function. Hypothyroidism is known to include deposition of mucopolysaccharides in tissues, increased permeability of capillaries with leakage of albumin out of the blood, elevated adrenalin which can lead to increased production of cortisol, decreased testosterone production, high risk of heart and circulatory disease, including a tendency to ulceration of the extremities, and osteoporosis, all of which are recognized "complications of diabetes." Broda Barnes gave all of his diabetic patients a thyroid supplement, and found that none of them developed the expected complications of diabetes.
Recently, a high safflower oil
diet was found to cause diabetes (Ikemoto, et al.), and obesity itself
is thought to be a factor in developing diabetes. The hormone
patterns associated with obesity can be seen as either cause or effect
of the obesity (or both cause and effect), since, for example, low thyroid
can increase both estrogen and cortisol, which support the formation
of fat, and the fat cells can become a chronic source of estrogen synthesis.
On a diet lacking the "essential" unsaturated fatty acids, Benhamou (1995) found that nonobese diabetic mice didn't develop diabetes, that is, the unsaturated fats themselves, without obesity, are sufficient to cause diabetes. (Also see Girard; Golay, et al., and Kusunoki, et al.)
Estrogen and the polyunsaturated
fatty acids (PUFA), linoleic and linolenic acid, alike activate the
protein kinase C (PKC) system of cellular activation. Many of
the functions of PUFA are similar to the functions of estrogen (e.g.,
antagonism to thyroid function, promotion of age pigment/lipofuscin),
so this information showing that they both act similarly on the same
basic regulatory pathway is important. Estrogen increases secretion
of growth hormone (GH; it's closely associated with prolactin, also
increased by estrogen), and GH causes an increase in free fatty acids
in the blood. Estrogen promotes iron retention, so it sets the
stage for oxidative stress. At least in some systems, both estrogen
and PUFA promote the entry of calcium into the cell.
In
diabetes, there is a generalized excess activation of the PKC system.
The starch-based diet, emphasizing grains, beans, nuts, and vegetables,
has been promoted with a variety of justifications. When people are
urged to reduce their fat and sugar consumption, they are told to eat
more starch. Starch stimulates the appetite, promotes fat synthesis
by stimulating insulin secretion, and sometimes increases the growth
of bacteria that produce toxins. It is often associated with allergens,
and according to Gerhard Volkheimer, whole starch grains can be "persorbed"
from the intestine directly into the blood stream where they may block
arterioles, causing widely distributed nests of cell-death. I
have heard dietitians urge the use of "complex carbohydrates"
(starch) instead of sugar. In the first physiology lab I took,
we fed rats a large blob of moist cornstarch with a stomach tube, and
then after waiting a few minutes, were told to dissect the rat to find
out "how far the starch had gone." In such a short time,
we were surprised to find that not a trace of the starch could be found.
The professor's purpose was to impress us with the rapidity with which
starch is digested and absorbed. Various studies have demonstrated
that starch (composed of pure glucose) raises blood glucose more quickly
than sucrose (half fructose, half glucose) does. The sudden increase
of blood glucose is sometimes thought to contribute to the development
of diabetes, but if it does, it is probably mediated by fat metabolism
and the hormones other than just insulin.
Brewer's
yeast has been used successfully to treat diabetes. In the l930s,
my father had severe diabetes, but after a few weeks of living on brewer's
yeast, he recovered and never had any further evidence of diabetes.
Besides its high B-vitamin and protein content, yeast is an unusual
food that should be sparingly used, because of its high phosphorous/calcium
ratio, high potassium to sodium ratio, and high estrogen content.
The insulin-producing beta cells of the pancreas have estrogen receptors,
but I don't know of any new research investigating this aspect of yeast
therapy. In rabbit studies, diabetes produced by alloxan poisoning,
which kills the beta cells, was cured by DHEA treatment, and beta cells
were found to have regenerated in the pancreatic islets.
I
think the basic anti-aging diet is also the best diet for prevention
and treatment of diabetes, scleroderma, and the various "connective
tissue diseases." This would emphasize high protein, low
unsaturated fats, low iron, and high antioxidant consumption, with a
moderate or low starch consumption. In practice, this means that
a major part of the diet should be milk, cheese, eggs, shellfish, fruits
and coconut oil, with vitamin E and salt as the safest supplements.
It should be remembered that amino acids, especially in eggs, stimulate
insulin secretion, and that this can cause hypoglycemia, which in turn
causes cortisol secretion. Eating fruit (or other carbohydrate),
coconut oil, and salt at the same meal will decrease this effect of
the protein. Magnesium carbonate and epsom salts can also be useful
and safe supplements, except when the synthetic material causes an allergic
bowel reaction..
Although
I started this newsletter with the thought of discussing the Mead acids--the
unsaturated (n-9) fats that are formed under certain conditions, especially
when the dietary polyunsaturated fatty acids are "deficient"--and
their prostaglandin derivatives as a distinct anti-stress, anti-aging
system, the loss of which makes us highly susceptible to injury, I will
save that argument for a future time, leaving this newsletter as an
addition to the view that an excess of the polyunsaturated fats is central
to the development of degenerative diseases: Cancer, heart disease,
arthritis, immunodeficiency, diabetes, hypertension, osteoporosis, connective
tissue disease, and calcification.
REFERENCES WITH EXCERPTS AND
COMMENTS
A. A. Alzaid, et al., "Effects of insulin on plasma magnesium in noninsulin-dependent diabetes mellitus: Evidence for insulin resistance," J. of Clin. Endocr. and Metab. 80(4), 1376-1381, 1995. "...insulin resistance in subjects with NIDDM impairs the ability of insulin to stimulate magnesium as well as glucose uptake."
A. B. Akella, et al., "Diminished
Ca++ sensitivity of skinned cardiac muscle contractility coincident
with troponin T-band shifts in the diabetic rat," Circulation Research
76(4), 600-606, 1995.D. A. Antonetti, et al., "Increased expression
of mitochondrial-encoded genes in skeletal muscle of humans with diabetes
mellitus--Rapid publication," J. of Clinical Investigation 95(3),
1383-1388, 1995. "The increased mitochondrial gene expression
may contribute to the increase in mitochondrial respiration observed
in uncontrolled diabetes." (Low ATP with high respiration
would suggest uncoupling; unsaturated fatty acids are known uncouplers
of respiration from energy production.)
S. Asakuma, et al., "The effects of antianginal drugs on energy expernditure during exercise in normal subjects," Japanese Circulation Journal--English Edition 59(3), 137-145, 1995. "RQ (carbohydrate consumption relative to fat consumption) during exercise was significantly increased and VO2 was decreased after propranolol, metoprolol and amosulalol." "These data suggest that propranolol, metoprolol and amosulalol [beta-blockers] increase the efficiency of energy expenditure during ordinary physical activity by increasing the utilization of carbohydrate and by decreasing the utilization of fat."
M. Bardicef, et al., "Extracellular
and intracellular magnesium depletion in pregnancy and gestational diabetes,"
Amer. J. of Obst. and Gyn. 172(3), 1009-1013, 1995.
P. E. Beales, et al., "Baclofen,
a gamma-aminobutyric acid-b receptor agonist, delays diabetes onset
in the non-obese diabetic mouse," Acta Diabetologica 32(1), 53-56,
1995.
P. Y. Benhamou, et al., :"Essential
fatty acid deficiency prevents autoimmune diabetes in nonobese diabetic
mice through a positive impact on antigen-presenting cells and Th2 lymphocytes,"
Pancreas 11(1), 26-37, 1995.
C. D. Berdanier, "Diet, autoimmunity,
and insulin-dependent diabetes mellitus: A controversy," Proc.
Soc. Exp. Biol. Med. 209(3), 223-230, 1995. "The majority
of the genetic mutations that result in the phenotypic expression of
the insulin-dependent diabetes mellitus genotype are in the immune system."
Antibodies to milk protein can be found in the patient, but these probably
represent antigen mimicry, resulting from the loss of antibody specificity
which is a feature of autoimmune disease.
G. Bianchi, et al., "Thyroid
volume in type 1 diabetes patients without overt thyroid disease,"
Acta Diabetologica 32(1), 49-52, 1995. "An association between
insulin-dependent diabetes mellitus (type 1) and thyroid diseases has
long been reported...."
P. Bjorntorp, "Insulin resistance:
The consequence of a neuroendocrine disturbance?" Int. J. Obes.
19(Suppl. 1), S6-S10, 1995. "The decreased capillary density
may...be of importance for the apparent insulin resistance."
R. Bouillon, et al., "Influence
of age, sex, and insulin on osteoblast function: Osteoblast dysfunction
in diabetes mellitus," J. of Clin. Endocr. and Metab. 80(4), 1194-1202,
1995. "...the osteoblast function is significantly decreased in
diabetic patients...."
A. Ceriello, et al., "The
defence against free radicals protects endothelial cells from hyperglycaemia-induced
plasminogen activator inhibitor 1 over-production," Blood Coagulation
& Fibrinolysis 6(2), 133-137, 1995. "The hypothesis that
oxidative stress may play an important role in the pathogenesis of diabetic
complications is ... supported by this study." [GSH reduced
PAI-1.]
V. Coiro, et al., "Low-dose
ovine corticotropin-releasing hormone stimulation test in diabetes mellitus
with or without neuropathy," Metabolism--Clinical and Experimental
44(4), 538-542, 1995. "...basal and CRH-induced cortisol
levels were significantly higher in diabetics than in normal controls."
"...even uncomplicated diabetes mellitus is associated with adrenal
hyperfunction."
S. R. Colberg, et al., "Skeletal
muscle utilization of free fatty acids in women with visceral obesity,"
J. Clin. Invest. 95(4), 1846-1853, 1995. "Visceral obesity
is strongly associated with insulin resistance." "...visceral
adiposity is clearly associated with skeletal muscle insulin resistance
but this is not due to glucose-FFA [free fatty acid] substrate competition.
Instead, women with visceral obesity have reduced postabsorptive FFA
utilization by muscle."
G. A. Colditz, et al., "Weight gain as a risk factor for clinical diabetes mellitus in women," Annals of Internal Medicine 122(7), 481-486, 1995.
C. Douillet and M. Ciavatti, "Effect
of vitamin E treatment on tissue fatty acids and cholesterol content
in experimental diabetes," J. Nutr. Biochem. 6(6), 319-326, 1995.
"Diabetes induced a decrease of monounsaturated fatty acids and
particularly palmitoleic acid in all studied tissues: liver, aorta,
plasma." C18:3 n-6 and C20:4 n-6 were increased by diabetes.
M. Garnier, et al., "Red
blood cell sodium conent in NID diabetic patients with hemorheological
abnormalities," Clinical Hemorheology 15(3), 325-333, 1995.
K. D. Gerbitz, et al., "Mitochondrial
diabetes mellitus: A review," BBA--Mol. Basis Dis. 1271(1), 253-260,
1995. This particular kind of diabetes, which is combined with
deafness in 60% of the patients, involves a variant mitochondrial gene
and occurs in about 1.5% of diabetics. "The underlying pathomechanism
is probably a delayed insulin secretion due to an impaired mitochondrial
ATP production in consequence of the mtDNA defect." To know
the "causal" value of this gene we have to know how often
it occurs in people who never develop diabetes. It is interesting
that it is suggested to operate by way of impaired ATP production, which
can be the result of so many factors, such as excess unsaturated fats,
low thyroid, low magnesium, low copper, etc. Pages 141-151 of
the same journal as an article by D. C. Wallace, et al., "Mitochondrial
DNA mutations in human degenerative diseases and aging," which
makes the point that "Generally, individuals inheriting these mitochondrial
diseases are relatively normal in early life, develop symptoms during
childhood, mid-life, or old age depending on the severity of the ...
mutation; and then undergo a progressive decline." Their
energy-producing systems are supposedly more susceptible to the effects
of aging.
J. Girard, "Role of free fatty acids in insulin resistance of subjects with non-insulin-dependent diabetes," Diabetes Metab. 21(2), 79-88, 1995. "Studies performed in the rat suggest that impaired glucose-induced insulin secretion could also be related to chronic exposure of pancreatic beta cells to elevated plasma free fatty acid levels." [This direct effect of free fatty acids on the beta cells is extremely important. Estrogen--probably via GH--increases free fatty acids, and adrenalin--which is elevated in hypothyroidism--increases the release of free fatty acids from storage. Free fatty acids impair mitochondrail energy production.]
A. Golay, et al., "Effect
of lipid oxidation on the regulation of glucose utilization in obese
patients," Acta Diabetologica 32(1), 44-48, 1995. [Free fatty
acids strongly and quickly depress the ability to oxidize or store glucose.]
A. Gomes, et al., "Anti-hyperglycemic
effect of black tea (Camellia sinensis) in rat," J. of Ethnopharmacology
45(3), 223-226, 1995. It "was found to possess both preventive
and curative effects on experimentally produced diabetes in rats."
Y. Hattori, et al., "Phorbol
esters elicit Ca++-dependent delayed contractions in diabetic rat aorta,"
Eur. J. Pharmacol. 279(1), 51-58, 1995. [Diabetic tissue is more
responsive to activation of protein kinase C by phorbol esters.]
B. A. Houssay and C. Martinez,
"Experimental diabetes and diet," Science 105, 548-549, 1947.
[Mortality was zero on the high coconut oil diet, 100% on the high lard
diet. It was 90% on the low protein diet, and 33% on the high
protein diet. With a combination of coconut oil and lard, 20%.]
B. A. Houssay, et al., "Accion
de la administracion prolongada de glucosa sobre la diabetes de la rata,"
Rev. Soc. argent. de biol. 23, 288-293, 1947.
S. Ikemoto, et al., "High
fat diet-induced hyperglycemia: Prevention by low level expression
of a glucose transporter (GLUT4) minigene in transgenic mice,"
Proc. Nat. Acad. Sci. USA 92(8), 3096-3099, 1995. "...mice
fed a high-fat (safflower oil) diet develop defective glycemic control,
hyperglycemia, and obesity."
M. Inaba, et al., "Influence
of high glucose on 1,25-dihydroxyvitamin D-3-induced effect on human
osteoblast-like MG-63 cells," J. Bone Miner. Res. 10(7), 1050-1056,
1995.
J. S. Jensen, et al., "Microalbuminuria
reflects a generalized transvascular albumin leakiness in clinically
healthy subjects," Clin. Sci. 88(6), 629-633, 1995.
G. Jorneskog, et al., "Skin
capillary circulation severely impaired in toes of patients with IDDM,
with and without late diabetic complications," Diabetologia 38(4),
474-480, 1995.
A. M. Kahn and T. Song, "Insulin
inhibits dog vascular smooth muscle contraction and lowers Ca++[i] by
inhibiting Ca++ influx," J. of Nutrition 125(6 Suppl.), S1732-S1737,
1995.
F. Kuhlencordt, et al., "Examination
of the skeleton in diabetic patients up to age 45," Deutsche med.
Wchnschr. 91, 1913-1917, 1966. "Some patients have a generalized
osteoporosis-like process, and some have localized bone lesions...."
M. Kusunoki, et al., "Amelioration
of high fat feeding-induced insulin resistance in skeletal muscle with
the antiglucocorticoid RU486," Diabetes 44(6), 718-720, 1995.
"These results suggest that glucocorticoids play, in a tissue-specific
manner, a role in the maintenance and/or production of insulin resistance
produced by high-fat feeding."
A. Lazarow, "Protection against
alloxan diabetes," Anat. Rec. 97, 353, 1947.
A. Lazarow, "Protective effect
of glutathione and cysteine against alloxan diabetes in the rat,"
Proc. Soc. Exp. Biol. & Med. 61, 441-447, 1946. [While certain doses
of cysteine, glutathione, and thioglycolic acid completely prevented
alloxan diabetes, it was interesting that all of the rats receiving
ascorbic acid became diabetic. To me, this argues for the free
radical cause of diabetes, rather than just the sulfhydryl oxidation.
Lazarow suggested that succinic dehydrogenase, and various other sulfhydryl
enzymes, including those involved in fatty acid oxidation, might be
involved.]
R. B. Lipton and J. A. Fivecoate,
"High risk of IDDM in African-American and Hispanic children in
Chicago, 1985-1990," Diabetes Care 18(4), 476-482, 1995.
"The relatively early age at onset may point to an environmental
factor associated with this high incidence of the disease."
G. S. Meneilly, et al., "Insulin-mediated
increase in blood flow is impaired in the elderly," J. Clin. Endocrinol.
Metab. 80(6), 1899-1903, 1995. "Normal aging is characterized
by resistance to insulin-mediated glucose uptake."
J. Ma, et al., "Associations
of serum and dietary magnesium with cardiovascular disease, hypertension,
diabetes, insulin, and carotid arterial wall thickness: The ARIC
study," J. Clin. Epidemiol. 48(7), 927-940, 1995. [Carotid
wall thickness increased in women as serum Mg level decreased.]
Y. Matsumoto, et al., "Creatine
kinase kinetics in diabetic cardiomyopathy," Amer. J. Physiol.-Endocrinol.
Met. 31(5), E1070-E1076, 1995.
F. Mercure and G. Vanderkraak,
"Inhibition of gonadotropin-stimulated ovarian steroid production
by polyunsaturated fatty acids in teleost fish," Lipids 30(6),
547-554, 1995. "The inhibitory actions by PUFAs were not
restricted to long-chain PUFAs, as linoleic and linolenic acids had
similar actions in the goldfish. The inhibitory action of EPA
on testosterone production was reversible upon removal of the PUFA from
medium." "[Stimulated] ...testosterone production ...
was attenuated by PUFAs...."
H. Mulder, et al., "Non-parallelism
of islet amyloid polypeptide (amylin) and insulin gene expression in
rat islets following dexamethasone treatment," Diabetologia 38(4),
395-402, 1995.
S. Nagasaka, et al., "Effect
of glycemic control on calcium and phosphorus handling and parathyroid
hormone level in patients with non-insulin-dependent diabetes mellitus,"
Endocr. J. 42(3), 377-383, 1995. "...hyperglycemia causes
excess urinary calcium and phosphorus excretion in patients with NIDDM.
In response to urinary calcium loss, PTH secretion is mildly stimulated.
Bone formation seems to be suppressed in the hyperglycemic state in
spite of increased PTH secretion." [These are the changes
I would expect to see in hypothyroid people with high cortisol.]
B. Oztas and M. Kucuk, "Influence
of acute arterial hypertension on blood-brain barrier permeability in
streptozocin-induced diabetic rats," Neuroscience Letters 188(1),
53-56, 1995.
S. Phillips, et al., "Neuropathic
arthropathy of the spine in diabetes," Diabetes Care 18(6), 876-869,
1995.
J. F. Pouliot and R. Beliveau,
"Palmitoylation of the glucose transporter in blood-brain barrier
capillaries," Bioch. et Bioph. Acta--Biomembranes 1234(2), 191-196,
1995. "Palmitoylation may be involved in the regulation of
glucose transport activity in hyperglycemia."
R. Ramakrishnan and A. Namasivayam,
"Norepinephrine and epinephrine levels in the brain of alloxan
diabetic rats," Neuroscience Letters 186(2-3), 200-202, 1995.
[Epinephrine increased in striatum, hippocampus and hypothalamus, Norepinephrine
increased in hypothalamus and decreased in pons and medulla.]
J. G. Regensteiner, et al., "Effects
of non-insulin-dependent diabetes on oxygen consumption during treadmill
exercise," Med. Sci. Sports Exerc. 27(6), 874-881, 1995.
"The reduced rate of increase in oxygen consumption during increasing
submaximal work loads in NIDDM suggests that limitations in oxygen delivery
may impair exercise performance in otherwise healthy persons with diabetes."
A. A. Shaltout, et al., "High
incidence of childhood-onset IDDM in Kuwait," Diabetes Care 18(7),
923-927, 1995. The incidence of IDDM in children is high in the
region and has apparently increased nearly fourfold in the last decade.
This is especially significant, since diabetes that appears in childhood
is especially important for the theory of genetic causation. This
study should give the gene people real trouble. They might have
to call in the "gene for bed-wetting" people to help with
their case.
M. A. Smith, et al., "Radical
AGEing in Alzheimer's disease," Trends in Neurosciences 18(4),
172-176, 1995.
A. Tchernof, et al., "Relation
of steroid hormones to glucose tolerance and plasma insulin levels in
men: Importance of visceral adipose tissue," Diabetes Care
28(3), 292-299, 1995.
A. Tchernof, et al., "Reduced
testosterone and adrenal C-19 steroid levels in obese men," Metabolism--Clin.
and Exp. 44(4), 513-519, 1995. "...reduced concentrations
of testosterone and adrenal C-19 steroid precursors are associated with
increased body fatness rather than with excess visceral fat accumulation."
[These results] "...emphasize the importance of adrenal steroids
as correlates of body composition in men."
B. G. Trumper, et al., "Circadian
variation of insulin requirement in insulin dependent diabetes mellitus--The
relationship between circadian change in insulin demand and diurnal
patterns of growth hormone, cortisol and glucagon during euglycemia,"
Hormone and Metabolic Research 27(3), 141-147, 1995. "The
results of the study showed that the early morning rise in the insulin
demand is related to the increased early morning cortisol secretion
and to the nocturnal peaks of growth hormone concentration."
M. Udvardy, et al., "Altered
lysis resistance of platelet-rich clots in patients with insulin-dependent
diabetes mellitus," Thromb. Res. 79(1), 57-63, 1995. Suppression
of clot-dissolving "...was remarkably stronger in IDDM, along with
the highest PAI-1 activity concentration ratio of the platelet lysates,
compared to plasmatic levels."
P. Vague, et al., "Hypofibrinolysis
and the insulin resistance syndrome," Int. J. Obes. 19(Suppl. 1),
S11-S15, 1995. Hypofibrinolysis is observed among obese subjects
and it has been shown that an excess of plasminogen activator inhibitor
1 (PAI 1) the main regulator of the fibrinolytic system, is closely
associated to other components of the insulin resistance syndrome, namely,
excessive body weight, high waist to hip ratio, elevated blood pressure,
hyperinsulinemia and hypertriglyceridemia."
E. O. Vianna and J. Garcialeme, "Allergen-induced airway inflammation in rats: Role of insulin," American J. of Respiratory and Critical Care Med. 151(3), 809-814, 1995. "Clinical asthma appears to be less severe when diabetes mellitus is superimposed."
A. Warley, et al., "Capillary surface area is reduced and tissue thickness from capillaries to myocytes is increased in the left ventricle of streptozotocin-diabetic rats," Diabetologia 38(4), 413-421, 1995.
G. C. Weir, "Which comes
first in non-insulin-dependent diabetes mellitus: Insulin resistance
or beta-cell failure? Both come first," JAMA 273(23), 1878-1879,
1995.
N. R. Williams, et al., "Plasma,
granulocyte and mononuclear cell copper and zinc in patients with diabetes
mellitus," Analyst 120(3), 887-890, 1995. "...the copper
and zinc status of these diabetic patients was reduced, providing further
evidence of a role for these antioxidant" trace elements in this
disease.
T. Yamakawa, et al., "Augmented
production of tumor necrosis factor-alpha in obese mice," Clinical
Immunology and Immunopathology 75(1), 51-56, 1995. "...the
TNF-alpha derived from adipose tissues might be involved in the induction
of peripheral insulin resistance..."
T. Yamashita, et al., "Increased
transendothelial permeation of albumin by high glucose concentration,"
Metabolism 44(6), 739-744, 1995.
M. B. Zemel, "Insulin resistance
vs. hyperinsulinemia in hypertension: Insulin regulation of Ca++
transport and Ca++-regulation of insulin sensitivity," Journal
of Nutrition 125(6 Suppl.), S1738-S1743, 1995.
B. M. Zenere, et al., "Noninvasive
detection of functional alterations of the arterial wall in IDDM patients
with and without microalbuminuria," Diabetes Care 18(7), 975-982,
1995. [There is a reduced vasodilatory capacity in diabetes, and
especially in patients who are leaking albumin.]
D. B. Zilvermit, et al., "Oxidation
of glucose labelled with radioactive carbon by normal and alloxandiabetic
rats," J. Biol. Chem. 176, 389-400, 1948. [Diabetic rats
had the same rate of glucose oxidation as normal rats, in this experiment.
This is an artificial form of diabetes that doesn't immediately involve
an excess of unsaturated fatty acids, as occurs during stress, estrogen
excess, hypothyroidism, or diets high in polyunsaturated fats which
can cause a more "natural" kind of diabetes. The artificial
alloxandiabetes forces the animal to oxidize an excess of fatty acids,
and eventually should lead to the same kind of mitochondrial damage
seen in natural diabetes.]
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