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Diabetologia 1991 34: 171-175 https://link.springer.com/article/10.1007%2FBF00418271?LI=true
Disturbed handling
of ascorbic
acid in diabetic patients with and without
Micro-angiopathy during high dose ascorbate
supplementation
 Summary. Abnormalities of
ascorbic acid metabolism have been
reported
in experimentally-induced diabetes
and in
diabetic patients. Ascorbate
is a powerful antioxidant, a co
factor in collagen biosynthesis, and affects platelet
activation, prostaglandin synthesis and the
polyol
pathway. This suggests a possible close interrelationship between
ascorbic acid metabolism and pathways known to be influenced by diabetes. We determined serum
ascorbic acid and its metabolite,
dehydroascorbic acid,
as indices of antioxidant status,
and the ratio, dehydroascorbate/ascorbate, as an index of
oxidative stress, in 20 matched diabetic patients
with and  without microangiopathy (small vessel bleeding) and in 22 age-matched control subjects. Each study subject
then took ascorbic
acid, 1g daily orally, for
six weeks with repeat measurements taken at
three and six weeks. At baseline, patients
with microangiopathy had lower
ascorbic acid concentrations
than those
without microangiopathy
and
control subjects (42.1 ± 19.3 vs 55.6 ± 20.0, p < 0.01, vs 82.9
± 30.9 )lmol/1,
p < 0.001) and elevated
dehydroascorbate/ascorbate
ratios (0.87 ± 0.46 vs 0.61 ± 0.26, p < 0.01, vs 0.38 ± 0.14, p < 0.001).
At three weeks,
ascorbate concentrations rose in all groups
(p
< 0.0001) and was maintained in control subjects (151.5 ±
56.3 ) lmol/1), but
fell in both diabetic groups
by six weeks (p < 0.01).
Dehydroascorbate/ascorbate
ratios fell
in
all
groups at three
weeks (p <
0.0001) but rose again in the diabetic groups by six weeks (p <
0.001) and was unchanged in the control
subjects. Dehydroascorbate concentrations rose significantly from baseline in all groups by six weeks of
ascorbic acid supplementation (p
< 0.05). No
significant changes were observed
in fructosamine concentrations in any
group during the study. Diabetes mellitus is associated with a major disturbance of ascorbic acid metabolism which is only partially corrected by ascorbate supplementation.
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
http://diabetes.diabetesjournals.org/content/37/3/359.short Diabetes 1988
Mar; 37(3): 359-361.
Deficiency
of Ascorbic Acid in Experimental Diabetes: Relationship With Collagen and
Polyol Pathway Abnormalities
Abstract
The
plasma and tissue concentration of ascorbic acid (AA) is reduced in diabetes.
This study was designed to investigate the mechanism and significance of this
phenomenon. The low plasma AA concentration of diabetic rats can be normalized
by dietary AA supplement (20–40 mg/day), a dosage approximately equal to the
maximal synthetic rate of this substance in the rats. Treatment of diabetic
rats with this regime prevented the decrease in activity of granulation tissue
prolyl hydroxylase (PRLase), an AA-dependent enzyme required for maintaining
the normal properties of collagen. The decreased plasma AA concentration and
granulation tissue PRLase activity in diabetes can also be normalized by the aldose
reductase inhibitor tolrestat. We conclude
that in diabetic animals there is a true deficiency of AA that may be responsible
for some of the changes of
collagen observed in diabetes. Treatment
with AA or an aldose reductase inhibitor may
prevent some of the diabetic complications with underlying
collagen abnormalities.
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
Diabetic angiopathy is
a form of angiopathy associated with diabetes
mellitus.
While not exclusive, the two most common
forms are Diabetic
retinopathy and Diabetic
nephropathy,
whose
pathophysiologies are largely identical.
As typical of pharma in framing
the
discussion of a topic, it has blamed it in high sugar rather than low
ascorbate. As insulin is required
for glucose uptake,
hyperglycemia in diabetes mellitus does not result in a net increase in
intracellular glucose in most cells. However, chronic dysregulated blood
glucose in diabetes is toxic to cells of the vascular endothelium which
passively assimilate glucose. https://en.wikipedia.org/wiki/Diabetic_angiopathy
The putative toxicity of glucose is not established. For example tight management of glucose in
diabetics is strongly associated with a worse outcome, heart attacks and death. One
such trial was using rosiglitazone, Prof.
Ben Goldacre, Bad Pharma p 91-93.
.
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
http://diabetes.diabetesjournals.org/content/38/2/257.hort Diabetes 1989 Feb; 38(2): 257-261.
Ascorbic
Acid Metabolism and Polyol Pathway
in Diabetes
Abstract
It has been
reported previously that the plasma concentration of ascorbic acid (AA) is
reducedin streptozocin-induced diabetic rats and can be normalized by treatment
with the aldose reductase inhibitor tolrestat. This study was designed
to investigate further
the relationship between the polyol pathway and AA metabolism in diabetic rats.
Disturbance of AA metabolism was demonstrable after 1 wk of diabetes. Dietary myo-inositol
supplementation*was effective
in normalizing plasma AA levels, as was treatment with tolrestat. In untreated diabetes, despite
low plasma AA concentration, there was increased urinary excretion of AA that
was reversed by treatment with either tolrestat or myoinositol. In contrast, AA
supplementation normalized plasma AA concentrations while further increasing
urinary AA excretion. The abnormality of AA metabolism was less severe in
galactose-fed rats [milk sugar--lactose is glucose + galactose], which had
normal plasma AA levels and only minor increases in urinary AA excretion. These
studies demonstrated a disturbance in the regulation of plasma and urinary AA
concentration in experimental diabetes and confirmed the relationship of AA
with the polyol pathway. Because AA has many important biological
functions, abnormalities of AA metabolism could be important in the
pathogenesis of some diabetic complications. The interaction of the polyol and AA pathways suggests that this
could be another site of action for aldose reductase inhibitors.
Received February 1, 1988. * Inositol or cyclohexane-1,2,3,4,5,6-hexol is a chemical compound with
formula C6H12O6 or
(-CHOH-)6, a six-fold alcohol (polyol) of cyclohexane. It exists in
nine possible stereoisomers, of which the
most prominent form, widely occurring in nature, is cis-1,2,3,5-trans-4,6-cyclohexanehexol,
or myo-inositol (former names meso-inositol or
i-inositol).[2][3] Inositol is a sugar alcohol. Its taste has
been assayed at half
the sweetness of table sugar (sucrose). myo-Inositol
plays
an important role as the structural basis for a number of secondary messengers in eukaryotic cells, the various inositol phosphates. In addition,
inositol serves as an important component of
the structural lipids phosphatidylinositol (PI) and
its various phosphates, the phosphatidylinositol
phosphate (PIP) lipids. Inositol
or its phosphates and associated lipids are found in many foods, in particular
fruit, especially cantaloupe and oranges.[4] In plants, the hexaphosphate
of inositol, phytic acid or its salts, the phytates,
are found. These serve as phosphate stores in the seed. Phytic acid occurs also
in cereals with high bran content
and also nuts and beans. Yet, inositol, when present as phytate, is not
directly bioavailable to humans in the diet, since it is not digestible. myo-inositol (free of
phosphate) was once considered a member of the vitamin B complex (formerly Vitamin
B8); however, because
it is produced by the human
body from glucose, it is not an essential nutrient.. https://en.wikipedia.org/wiki/Inositol ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ https://www.karger.com/Article/Abstract/213339 Gerontology
1992;38:268–274
An Investigation of the Relationship between
Free Radical Activity and Vitamin C Metabolism in Elderly Diabetic Subjects
with Retinopathy
Abstract
Abnormalities of both free radical activity
and ascorbic acid
metabolism have been documented in diabetes, but their biological basis is
unclear and their relationship unstudied in any detail. This study was designed
to compare changes in antioxidant status and free radical reactions in a group
of elderly diabetic patients (with and without retinopathy) with those in a
group of age-matched control subjects. No significant differences in
thiobarbituric acid (TBA) reactivity, red cell glutathione (GSH) concentrations
or diene conjugates (DC) between patients and controls were seen despite
significant depletion of ascorbic acid in patients with diabetes, especially in
those with retinopathy. The results emphasise the present-day difficulties of
measuring free radical activity and demonstrate a marked abnormality in
ascorbic acid metabolism in diabetes.
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
This misses the main problem, that plasma ascorbate reflects
recent diet, while leucocytes is a measurement of storage. See testing
for levels in https://en.wikipedia.org/wiki/Vitamin_C#Deficiency
DiabeticMedicine, Nov. 1994
http://onlinelibrary.wiley.com/doi/10.1111/j.1464-5491.1994.tb00375.x/full
Low
Plasma Ascorbate Levels in Patients with
Type 2 Diabetes Mellitus Consuming Adequate Dietary Vitamin C
Abstract
Low
ascorbate
concentrations in diabetes may be secondary to inadequate dietary vitamin C
intake or may relate to the varied metabolic roles of the vitamin. To determine
whether inadequate dietary intake is a factor we calculated daily vitamin C
intakes using both a vitamin C questionnaire and a 4-day food diary in a group
of 30 patients with Type 2 diabetes (mean age 68.8 ± 6.9 yr, 17M/13F) and in 30
community controls (mean age 68.0 ± 5.5 yr, 12M/18F)). Measures of plasma
glucose, serum fructosamine, and plasma ascorbic and dehydroascorbic acid were
obtained from 20 subjects in each group. There was no significant difference in
daily vitamin C intake between the two groups using both methods: food diary,
61.4 ± 28.3 (patients) vs 69.5 ± 33.4 (controls) mg; questionnaire, 54.0 ± 28.9
(patients) vs 65.0 ± 30.9 (controls) mg. Vitamin C intake derived from both
methods was significantly correlated (p < 0.001). Plasma ascorbate (30.4 ± 19.1 μol
l−1)
and dehydroascorbate (27.6 ± 6.4 μmol l−1) levels were significantly lower in patients vs in controls
(68.8 ± 36.0 and 31.8 ± 4.8 μmol l−1,
respectively), p < 0.0001 and p <
0.01. Plasma ascorbate levels were significantly correlated
with vitamin C intake derived from the food diary (p < 0.01) and questionnaire
(p <
0.01) methods in the diabetic group only.
Low ascorbate levels in diabetes appears
to be a consequence of the disease itself and not due to inadequate dietary
intake of vitamin C. A short vitamin C questionnaire is a convenient and
reliable estimate of vitamin C intake. Vitamin C supplementation of the
diabetic diet deserves further consideration.
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
The Chinese diet is low in fruit, thus vitamin C, therefore
they should be an ideal group to benefit from a supplement. Again and
again I see a promising therapy is
for a non-patentable drug or supplement it is ignored in the US but not in
China. And if it is reluctantly becomes
used, often it is in too low a dose, or an ineffective analogue. Below is another
example of profits before
patients in the US. This article, though
in English has 7 Chinese authors, and is published in 2016.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0163571
Dietary Vitamin C Intake
Reduces the Risk of
Type 2 Diabetes in Chinese Adults: HOMA-IR and T-AOC as Potential Mediators
- PLOS Published:
September 29, 2016
Abstract
Despite
growing
interest in the protective role that dietary antioxidant vitamins may have in
the development of type 2 diabetes (T2D), little epidemiological evidence is
available in non-Western populations especially about the possible mediators
underlying in this role. The present study aimed to investigate the association
of vitamin C and vitamin E
intakes with T2D risk in Chinese adults and examine the potential
mediators. 178 incident T2D cases among 3483 participants in the Harbin People
Health Study (HPHS), and 522 newly diagnosed T2D among 7595 participants in the
Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases
(HDNNCDS) were studied. In the multivariable-adjusted logistics regression
model, the relative risks (RRs) were 1.00, 0.75, and 0.76 (Ptrend =
0.003) across tertiles of vitamin C
intake in the HDNNCDS, and this association was validated in the HPHS with RRs
of 1.00, 0.47, and 0.46 (Ptrend =
0.002). The RRs were 1.00, 0.72, and
0.76 (Ptrend = 0.039) when T2D
diagnosed by
haemoglobin A1c in the
HDNNCDS. The mediation analysis discovered that insulin resistance (indicated
by homeostasis model assessment) and oxidative stress (indicated by plasma
total antioxidative capacity) partly mediated this association. But no association
was evident between vitamin E intake and T2D. In conclusion, our research adds
further support to the role of vitamin C intake in reducing the development of
T2D in the broader population studied. The results also suggested that this
association was partly mediated by inhibiting or ameliorating oxidative stress
and insulin r
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