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Diabetes - Unrecognized Pandemic Subclinical Diabetes of the Affluent Nations: Causes, Cost and Prev
Unrecognized Pandemic Subclinical Diabetes of
the Affluent Nations: Causes, Cost and Prevention
John T. A. Ely,
Ph.D
Journal of Orthomolecular Medicine Vol. 11, Number 2, 1996
Abstract
Regarding populations on the industrialized "western
affluent"diet, arguments are made that: (1) plasma glucose values commonly seen
and accepted as normal are abnormal; (2) their glucose tolerance is innately
unstable; (3) most of their morbidity and mortality is produced by hyperglycemia
far below glycosuria and or arteriosclerosis which can occur independently or
together; (4) simple low cost methods for preventing and treating both have been
in the literature for decades (correction of the sugar, fat and protein
excesses; and controlled supplementation of pyridoxine (vitamin B6). Mg, Cr and
coenzyme Q10); and (5) these lessons were missed by main stream medicine because
of the vast size of the literature, enforcement of "treatment of choice", and
lack of computer aided diagnosis. Cited as striking evidence of this tragic
situation is the failure of mainstream clinical medicine to understand the cause
of the remarkable decline in CVD in the 1960s and 1970s that followed U.S.
enrichment of cereals with pyridoxine (vitamin B6). Recommendations are made for
correction of unnecessary costly delays between publication and implementation
of such research findings.
Brief Overview of the Pathology
Ascribed to Low Ratio of B6 to Protein Intakes
Over 40 years ago Kotake
et al reported1 they had confirmed that xanthurenic acid (XA) appeared copiously
in urine of B6 deficient animals when fed high protein (i.e., high tryptophan)
diets and disappeared quickly when B6 was given; and they had discovered that:
(1) adding fatty acids to the diet greatly increased the excretion of XA and the
amount of B6 needed to eliminate it; (2) both natural and synthetic XA damaged
pancreatic beta cells and produced diabetes in the animals; and (3) XA was found
in the urine of each of the eight diabetic humans tested. They pointed out that
diabetes incidence is much higher in countries where much fat and tryptophan
(from animal protein) is consumed. Because of this simply testable response of
XA rapidly disappearing from urine of diabetics or heart patients (or anyone
given a high dietary ratio of fat or tryptophan to B6), awareness of this
striking and important effect should have spread rapidly like an information
avalanche through clinical medicine world wide.
A second important discovery
was announced 27 years ago when McCully published his theory2 that made a number
of predictions including: (1) a low ratio of B6 to protein causes a toxic
metabolite called homocysteine (HO) to be formed (from the amino acid
methionine); and (2) HO would collect in the blood and result in lesions of the
intimal surface. In the following year (1970), he reported a study on rabbits
supporting his theory (this and essentially all work on HO up to 1983 are
described in his review3 with 201 references). In 1974, more support came from
extensive studies on baboons.4 In the 1970s, all of the theory's predictions
were borne out. HO appears to be more toxic than XA in the sense that vascular
damage occurs rapidly when blood HO is below the level that can be detected in
urine; but XA can be detectable for years while pancreatic damage slowly
accumulates. Yet, paradoxically, only 10 mg of B6 per day is believed to provide
ample margin of protection against HO formation whereas over 100 mg of B6
appeared necessary to eliminate XA in many subjects. It was found that normal
humans on a B6 deficient diet for only three weeks (or anyone deficient in B6)
would excrete HO in the urine when fed methionine; this has extremely important
implications because virtually all Americans above age 60 are reported to be B6
deficient. In addition, compared to controls, women using the oral contraceptive
formulations in the 1970s:
(1) had lower blood B6;
(2) would excrete
urinary HO after methionine challenge;
(3) had ten times the death rate due
to vascular disease.3
Karl Folkers at Merck was a leading figure in
determining the molecular structure of both B6 in 1939 and CoQ10 in 1958, two
molecules that will revolutionize all medicine (if we can get medicine's
attention), not only cardiovascular disease. He is still a driving force in the
endless applications of CoQ10 that include cancer, AIDS and aging itself.5
John M. Ellis, a giant in his own right, was well aware of the work of these
people including the 1953 findings of Kotake. As a result, Ellis6 had already
done extensive clinical trials with B6 in the 100 mg per day range by the time
Mc Cully's theory had (quite rapidly) deduced that HO might be lethal to 40,000
times more people in North America than die of genetic homocystinuria (i.e.,
~50% vs 0.001%). So, it was essentially known in the early 1970s that CVD and
diabetes were preventable by a diet low in fat, sugar, and animal protein but
high in complex carbohydrate and vegetable protein (when supplemented as
necessary daily to absorb: B6, ca 100 mg with half in B complex; Mg 400 mg; 200
mcg tri-valent chromium (as in certain yeasts); CoQ10 at doses not yet known but
empirically adjusted for age and severity of CVD5). Space does not permit
coverage of the important 1960s work on chromium by Mertz, Schwarz and Henry A.
Schroeder who, prior to 1973 had written "B6 is necessary for the smooth
integrity of arterial walls" and performed cadaver analyses world-wide related
to the role of Cr in diabetes and atherosclerosis. Some reviews with extensive
reference lists cover various aspects of the pathology and the successful
research. 3-9
The Literature Problem (again)
According to the easily testable
findings cited above, vascular disease and diabetes, the principle causes of
morbidity and mortality and ruinous health care costs, are both preventable by
extremely simple and very low cost measures that were demonstrated 30 to 40
years ago. In a recent mini-survey of 20 diabetics including three Type 1, not
one was found whose physician had ever prescribed or even discussed B6 or
magnesium. One wonders how this can be possible. The vast size and growth rate
of the medical science literature (over 4 million new pages per year of indexed
journals)10 is the major physically insurmountable problem. What else can solve
this except Computer Aided Diagnosis (with monthly updates as is done now for
Medline) from the National Library of Medicine. Related to the literature size
problem, is the understandable tendency for the pressured clinician to seize
upon a convenient and fashionable dictum, especially if it bears the authority
of the journal with the largest circulation. In the case of B6, exactly this
occurred. In the August 25, 1983, NEJM, two featured articles focused on the
important problems of neuropathy from B6 abuse. The articles correctly commented
on specific cases of abuse, but included the application of B6 in carpal tunnel
syndrome, along with obvious abuses, in a manner that (in this author's opinion)
could only impugn in the reader's mind that application and all of the B6
findings cited here. Both papers failed to point out the dosing methods, the
size of the Texas trials and the types of benefit that have been
demonstrated.11
Gross Glycemic Abnormality of Western
Society
During the Calcutta Diabetes Study, the 2-hour postprandial blood
glucose values for non-diabetic humans aged 40 to 70 in India were reported to
range from 50 to 90 mg/dl.12 However, in a long term investigation of 1400
people in the U.S.A., decadal age group medians for the same 2-hour values were
reported to range from 105 to 122 mg/dl in nondiabetic 40 to 70 year olds;13
this distribution is completely disjoint from the Indian median values (which
clearly must fall inside the 50 to 90 range reported above). In addition, the
2-hour GTT values are observed to rise circa 10% per decade of age in the
U.S.A.14 With regard to the U.S.A. and similarly fed nations, we argue from data
published in leading journals that: (1) these results have a dietary basis; and
(2) these populations should be recognized as hyperglycemic, and are in
subclinical diabetes (i.e., have depressed insulin sensitivity) the leading
contributor to U.S.A. morbidity, mortality, and health care costs.15 We cite the
findings that arteriosclerosis is prevented and treated by the same simple
corrections that apply to most cases of hyperglycemia.
The Affluent
Diet: Toxic Factors
Several long known but ignored factors elucidate both
the causes and cures of this human and fiscal tragedy. These factors are the
following listed departures of the 20th century affluent diet from that
prevalent in 19th century agrarian cultures: (1) high glycemic index meals due
to greatly increased content of sugars and rapidly hydrolyzable carbohydrate in
general; (2 and 3) excesses of protein and fat with respect to intakes of
pyridoxine (vitamin B6) and magnesium; (4) insufficient "glucose-tolerance
factor" (widely believed to be some form of tri-valent chromium); and (5)
insufficient nutrient content to support synthesis of endogenous ubiquinone
(CoQ10). The physical injuries reported to be associated with hyperglycemia
occur even at "modest" levels below 150 mg% that do not produce glycosuria or
elicit a diagnosis of diabetes. These include: (1) accelerated aging; (2) birth
defects; (3) cancer; (4) diabetes; (5) infectious diseases; (6) neurological and
psychiatric disorders (due to micromercurialism) and (7) vascular disease
producing damage in all organs.10,16-21 Various mechanisms include low
intracellular ascorbate which slows mitosis,19 and reduces phagocytic clearance
of thrombi by neutrophils.18
In essence, we impugn four characteristics of
the affluent diet as outweighing all other factors in producing a progressive
hyperglycemia that is widely regarded as normal. This clinical oversight
persists even though it has been known for some decades that the relatively mild
symptomless hyperglycemia discussed here is accompanied by increased risks of
all vascular diseases,12,13 cancer,10,21 and birth defects.16,17,20 The relevant
dietary defects associated with affluence are: (1) a major increase in sugar
(the U.S.A./India ratio of per capita sugar consumptions circa 1975 was over ten
fold, 65 kg vs 5 kg) [WHO data]; (2 and 3) an excessive intake of fat and
(cooked)
protein compared to that of pyridoxine (vitamin B6) and
magnesium,1,3 and (4) low intake of an insulin cofactor called "glucose
tolerance factor" or GTF (believed to be tri-valent Cr that is low in the soil
of some areas such as North America and removed in much food processing).22
Another factor is age dependent and may become dominant in many people as they
grow older; this is CoQ10 for which human synthesis falls off after age 20
although its continuous replacement is always needed in all
cells.5
Innate Instability of Hyperglycemia and Other Features of
Sugar and Fat
Because the natural or primitive diet had very low sugar
content and persisted to this century, there was not time for evolutionary
pressure to select for uniformity in human pancreatic response to sugar load.
Thus many people who would do well on the 19th century or agrarian (unrefined)
diet become reactive hypoglycemics and or simply hyper-glycemic on the affluent
fare. Foods that are high in both sugar and fat are predicted to accelerate
atherosclerosis since fat agonizes platelet aggregation and sugar impairs
phagocytic removal of the thrombi.18 Numerous papers prior to 196023 established
the basis for the following model (Ely unpub.): The first of the affluent
dietary insults above refers to habitual postprandial hyperglycemia initially
due to "high glycemic index" meals. Hyperglycemia rapidly induces a persistent
(but easily reversible) insulin resistance (simple and convenient for studies in
mice) by causing internalization of insulin receptors (to protect the cellular
cytoplasm from glucose excess). Hyperglycemia demands more insulin which forces
more receptor internalization. This further increases insulin resistance,
raising blood glucose and insulin further, eventually exhausting beta
cells.
Early success suggested that most cases of diabetes, both types 1 and
2, can be reversed by using exogenous insulin to carefully lower blood glucose
to the range circa 70 mg % for a few months until the dose becomes zero (due to
reductions necessary to prevent hypoglycemia); this regimen which allowed the
beta cells and insulin sensitivity to recover would seem vastly more assured of
success now (by B6, Mg Cr, and CoQ10). The arginine test can be used to test
insulin secretion (in cases of paradoxical suppression). Was most of the vast
human and financial cost of diabetes in recent decades avoidable?
A
Closing Overview
The primate line, as evolving omnivores, up to the
present day adapted to a diet that included much plant bulk and little animal
protein. Hence the ratio of pyridoxine (vitamin B6) to protein intakes has been
much larger than that found in the diets of affluent peoples today. In
particular, the ratios of B6 to the essential amino acids tryptophan and
methionine are greatly reduced in those with high meat consumption, more so if
the meat is cooked. As serious consequences, the toxic metabolite xanthurenic
acid (XA) is produced from tryptophan, and HO is produced from methionine. The
role of HO in vascular lesions even in the young and normoglycemic has been
discussed in this and other journals over the last two decades. A decline in
vascular disease and related deaths became clearly evident in the 1970s among
populations with moderate methionine intake and was attributed to an increase in
average B6 intake due to large increases in imported synthetic B6 used to
fortify cereals. Here we have concerned ourselves more with certain aspects of
XA and diabetes because: (1) the B6 requirement to protect against HO is so much
smaller than that needed for XA; and (2) in spite of much attention from the
medical sciences, diabetes has not been placed in proper perspective or given
adequate attention by clinicians. As a result, it appears that diabetes which
should be preventable in most cases is so pandemic that a
major fraction of
the developed nations' populations is in subclinical diabetes and progressing to
clinical. This is especially tragic in view of long reported findings that
modest supplementaion of B6 and Mg has been shown decades ago in both human and
animals to prevent the formation of XA and the related pancreatic lesions.
In
addition to the costly and terrible morbidity and mortality of diabetes itself,
it has long been known24,25 that the incidences of the same vascular injuries
and of numerous other diseases are increased by the effects of "modest"
hyperglycemia. Yet such hyperglycemia is accepted by most clinicians as normal
among those patients who have not yet developed clinical diabetes in any of its
forms (by present definitions).
Conclusion
Researchers appear
to have efficiently produced solutions for our most costly health problems. But
these seem ignored by the clinical community. Although clinicians appear to be
(innately) much more efficient people, even they cannot cope with the literature
due both to its size (Problem 1) and to their time burdens that result in large
part from the very inefficient and ineffectual modalities that are enforced as
"treatment of choice" (Problem 2).
It is concluded that even a relatively
primitive and low cost Computer Aided Diagnostic system (CAD) should be
evaluated. [Such a scheme might use simple algorithms such as linking
manuscripts (that might discuss either a disorder or a therapy) via symptom key
words that are provided by the authors (or NLM data processing technician) at
the source and the real symptoms provided by the patient to the diagnostician at
the user end.] Before the present clinicians would feel free to use such a
system, it might be necessary that the orientation of medical disciplinary
boards must be reversed to require use of published knowledge (rather than
essentially forbid it, as at present). This could best be done by changing the
composition of boards to include a major fraction of medical science
researchers. It is concluded that the billions that could be saved on the
diseases considered here might dwarf the tens of millions necessary for the
CAD.
Acknowledgements
We again thank: the Wallace Genetic
Foundation and the Northwest Oncology Foundation for support; Glenn A. Warner,
MD, for advice, encouragement and patience; Dr Cheryl A. Krone of NOAA for
consults on methods in chemistry; and our biologist, John Thoreson, for skilled
efforts in research studies.