Natural treatment research for type I and type II diabetes

For poorly controlled Type I diabetes, and resistant Type II diabetes, long-term consequences can be ameliorated by a number of natural treatments.

Type I and II diabetes share the same long-term consequences in dogs and cats. These consequences involve glycation and inflammation, which can lead to cataracts, neuropathy, retinopathy, kidney disease, liver disease, and other organ and tissue malfunction. Type I in dogs is an endocrine disease. Type II in cats is a metabolic disease associated with obesity and a high carbohydrate diet, so a big part of its treatment includes dietary and lifestyle changes. With those alone, a cat may return to normal metabolism. For poorly controlled Type I diabetes, and resistant Type II diabetes, long-term consequences can be ameliorated by a number of natural treatments.

Glucose processing
In the wild, most carbohydrates are associated with fiber, which slows their digestion and absorption. Blood sugar may rise slightly, but there are no big spikes. Since there are no sugar spikes, there is no insulin spike and the processing of blood glucose is a slow and gradual affair. Most dry cat food does not have high fiber, so glucose increases in the form of spikes in the bloodstream, instead of being gradually raised. Carbohydrates from dry food are rapidly absorbed, rapidly processed, and stored as fat. Cells become resistant to normal amounts of insulin, and higher and higher amounts are necessary for a cell to be able to process glucose.
As glucose increases, it causes side effects:

Glycoslation – Enzymes add sugars to fat or protein molecules, a normal bodily function.
Glycation – When excess sugar is available in the presence of proteins or lipids, sugar molecules are added to fats or proteins in a haphazard manner.
Maillard reaction – the same thing happens when foods high in protein and/or fat are cooked with sugars or simple carbohydrates at high temperatures or for long periods. In humans, up to 10% of the diet is formed from these substances.1 This process is responsible for the brown crust on roasts and breads, which though tasty, are not good for people or pets.
AGEs – Advanced Glycation End Products is the term for these abnormal proteins and fats. They form gradually in healthy bodies where some are processed while others gradually accumulate, but they form rapidly and in large amounts in a diabetic animal or person.2 This has a toxic effect on the body, since glycated products cannot function normally, and promote inflammation

Age effects
In human medicine, some believe the deleterious action of AGEs starts before diabetes develops. An increase in AGE levels increases the appetite, thus promoting obesity. AGEs are pro-oxidant and promote inflammation. Decreasing oxidative stress in mice by decreasing AGEs in the diet decreases inflammation and prevents diabetes mellitus.3
Excess body fat can change metabolism. We used to think mammalian body fat was inert. Now we know that it makes dozens of proteins. One is the enzyme leptin, which normally signals satiety. Obese animals have higher levels, but are less responsive to them.4 Inducing weight loss (carefully) in an obese animal can decrease this problem, and increase insulin sensitivity. Best is a low-carbohydrate diet, either canned or homemade. A low glycemic index diet can improve the levels of AGEs and hyperglycemia.5,6
AGEs can develop in many cell types, adversely affecting their structure and function. Almost all diabetic complications result from the action of AGEs. They form cross-links in the cells of basement membranes. They activate receptors for AGEs (RAGES). RAGES activate transcription factor nuclear kappa B and its targets. Monocytes are activated but are prevented by AGEs from passing basement membranes. The biggest effect of these actions is on the endothelium of blood vessels.7 This affects circulation to vital organs such as the retina and kidneys.8
Given the increased number of diabetic dogs and cats, it is encouraging to see studies indicating natural approaches that may even prevent the need for drug therapy. In addition to the above-mentioned studies, clinical anecdotal experience shows that both Type I and II diabetes, in some dogs and cats, can be eased with constitutional homeopathy or TCVM (Traditional Chinese Veterinary Medicine). Type II may even be resolved with this approach, especially when obesity is corrected. Three good books with overviews of this approach to health include Manual of Natural Veterinary Medicine: Science and Tradition edited by Wynn and Marsden; Complementary and Alternative Veterinary Medicine edited by Wynn and Schoen; and Integrating Complementary Treatment Options with Traditional Veterinary Medicine edited by Goldstein

Studies on natural treatments

A number of natural substances can decrease or reverse the effect of problems caused by high levels of glucose, which leads to glycation. Although they will not cure diabetes, they can slow its advance, and mild Type II diabetes may respond well enough to not need drugs.
Studies of the effects of natural products on diabetes and its complications include human, rat, mouse, and in vitro. Of these, the human studies are likely to be most pertinent. Human studies impacting the liver cannot extrapolate to cats. Since we know that cat metabolism does not have as close a correlation to human metabolism as dog metabolism does, we must take care to use only those substances that have been shown to be non-harmful to cats.
Increased vitamin C lowers A1c, the form of hemoglobin created by AGEs.9 Still to be determined is if oral vitamin C can create high enough blood levels to drive this reaction.
An in vitro study of erythrocytes showed that curcumin prevented AGEs and lipid peroxidation.10 This is supported by studies in lab animals and humans. One study identified a specific AGE that curcumin can prevent.
An in vitro study of berberine showed a significant increase of nitrous oxide, and decreased AGE formation.11 Like the vitamin C study, it holds promise but does not give us doses for cats and dogs.
Curcumin and turmeric decreased blood sugar levels, oxidative stress, and AGEs in diabetic rats, which helps validate the in vitro study. Curcumin works better than turmeric to achieve this effect.12,13 Curcumin has a high margin of safety and a wide range of uses, especially for diseases related to inflammation (such as arthritis and cancer). The biggest problem with turmeric and curcumin is that they are excellent dyes, and can permanently discolor a rug if a patient vomits or defecates on it.
A number of other traditional herbs, including Embelia ribes (an Ayurvedic herb named Vidanga), Cinnamomi cassiae and Rhodiola rosea,14,15 have been shown to be useful in rats and mice. Before trying these or other herbs in the literature on cats, I would recommend further testing to be sure they are not toxic to the feline liver.
In contrast, histidine, carnosine and l-arginine are amino acids, and l-arginine is already being used for feline herpes. Histidine and carnosine given at the rate of 1 gram per liter of drinking water increased insulin levels and decreased lipid oxidation levels in mice. It also suppressed increase of interleukin 6 and tumor necrosis factor Alpha in diabetic mice.16 L-arginine (1.51%) in the drinking water of diabetic obese rats decreased fat.17 It would be worth trying these in diabetic cats who need more help, and possibly in dogs as well.
Pyridoxamine, a B vitamin, inhibits diabetic retinopathy and neuropathy in rats.18
Curcumin administered at 500 mg/day to Type II diabetic humans decreased urinary excretion of albumin. It also regulated several bacteria in the gut important for maintenance of gut barrier integrity and function.19
Sesame oil used in humans lowers blood pressure and improves antioxidant status in hypertensive and diabetic-hypertensive patients.20 (It might be the easiest supplement to administer to cats.)
The form of CoQ10 known as ubiquinol improves insulin secretion in humans with Type II diabetes.21
Pyridoxamine has support for its anti-AGE action, and glucosamine helps support basement membrane function.22
Ginger has more research supporting its benefits in humans than many other herbs. Three grams of powdered ginger in capsules given daily for three months improved glycemic indices and total antioxidant capacity in humans. It also decreased C-reactive protein,23 AGEs and insulin resistance.23
Fenugreek has been shown to improve glycemic control, and decrease insulin resistance and hyperlipidemia, although the research used an alcoholic extract.24

References

1Uribarri J, et al. “Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet”. J Am Diet Assoc. 2010 June ; 110(6): 911–16.
2Peppa M, et al. “Glucose, Advanced Glycation End Products, and Diabetes Complications: What Is New and What Works”. CLINICAL DIABETES, Volume 21, Number 4, 2003
3Vlassara H, Gary E, Striker GE. “AGE restriction in diabetes mellitus: a paradigm shift”. Nat Rev Endocrinol. 2011 Sep ;7(9):526-39. Epub 2011 May 24.
4Oswal A, Yeo G. “Leptin and the control of body weight: a review of its diverse central targets, signalling mechanisms, and role in the pathogenesis of obesity”. Obesity (Silver Spring), vol. 18, no. 2, pp. 221–229, 2010.
5Nisak M, et al. “Improvement of dietary quality with the aid of a low glycemic index diet in Asian patients with type 2 diabetes mellitus”. J Am Coll Nutr. 2010 Jun;29(3):161-70.
6Haimoto H, et al. “Effects of a low-carbohydrate diet on glycemic control in outpatients with severe type 2 diabetes”. Nutr Metab (Lond). 2009;6:21. Epub 2009 May 6.
7Goldin A, et al. “Advanced Glycation End Products, Sparking the Development of Diabetic Vascular Injury”. Circulation. 2006;114:597-605.
8Koschinsky T, et al. “Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy”. Proc. Natl. Acad. Sci. U.S.A. 94 (12): 6474–9, June 1997.
9Kositsawat, J, Freeman, VL. “Vitamin C and A1c Relationship in the National Health and Nutrition Examination Survey” (NHANES) 2003-2006. J Am Coll Nutr. 2011 Dec ;30(6):477-83.
10Jain SK, Rains J, Jones K. “Effect of curcumin on protein glycosylation, lipid peroxidation, and oxygen radical generation in human red blood cells exposed to high glucose levels”. Free Radic Biol Med. 2006 Jul 1;41(1):92-6. Epub 2006 Mar 30.
11Hao M, et al. “Amelioration effects of berberine on diabetic microendothelial injury model by the combination of high glucose and advanced glycation end products in vitro”. Eur J Pharmacol. 2011 Jan 13. Epub 2011 Jan 13.
12Arun N, Nalini N. “Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats”. Plant Foods Hum Nutr. 2002;57(1):41-52.
13Jagtap AG, Patil PB. “Antihyperglycemic activity and inhibition of advanced glycation end product formation by Cuminum cyminum in streptozotocin induced diabetic rats”. Food Chem Toxicol. 2010 Aug-Sep;48(8-9):2030-6. Epub 2010 May 6.
14Bhandari U, et al. “Beneficial effect of Embelia ribes ethanolic extract on blood pressure and glycosylated hemoglobin in streptozotocin-induced diabetes in rats”. Biofactors. 2008;33(1):49-60.
15Kim SH, et al. “Antioxidative effects of Cinnamomi cassiae and Rhodiola rosea extracts in liver of diabetic mice”. Biofactors. 2006;26(3):209-19. PMID: 16971752
16Lee Y, et al. “Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation”. Cont Lens Anterior Eye. 2008 Jun;31(3):141-6; quiz 170. Epub 2008 Mar 4.
17Fu WJ, et al. “Dietary L-arginine supplementation reduces fat mass in Zucker diabetic fatty rats”. J Nutr. 2005 Apr;135(4):714-21. PMID: 15795423
18Miyazawa T, et al. “Amino Acids. Lipid glycation and protein glycation in diabetes and atherosclerosis”. 2012 Apr;42(4):1163-70. doi: 10.1007/s00726-010-0772-3. Epub 2010 Oct 19.
19Yang H, et al. “Curcumin attenuates urinary excretion of albumin in type II diabetic patients with enhancing nuclear factor erythroid-derived 2-like 2 (Nrf2) system and repressing inflammatory signaling efficacies”. Exp Clin Endocrinol Diabetes. 2015 Jun ;123(6):360-7. Epub 2015 Apr 14. PMID: 25875220
20Sankar D, et al. “Sesame oil exhibits synergistic effect with anti-diabetic medication in patients with type 2 diabetes mellitus”. Clin Nutr. 2011 Jun ;30(3):351-8. Epub 2010 Dec 16.
21Mezawa M, et al. “The reduced form of coenzyme Q10 improves glycemic control in patients with type 2 diabetes: An open label pilot study”. Biofactors. 2012 Aug 8. Epub 2012 Aug 8.
22Williams ME1. New potential agents in treating diabetic kidney disease: the fourth act. Drugs. 2006;66(18):2287-98
23Shidfar, F et al. The effect of ginger (Zingiber officinale) on glycemic markers in patients with type 2 diabetes. J Complement Integr Med. 2015 Feb 10. Epub 2015 Feb 10.
24Mozaffari-Khosravi, H et al. The effect of ginger powder supplementation on insulin resistance and glycemic indices in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial. Complement Ther Med. 2014 Feb ;22(1):9-16. Epub 2014 Jan 8.

Etiquetas: diabetes