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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.

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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.

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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.

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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

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  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.

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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.

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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