A couple of weeks ago i decided to research online to see what exactly is happening inside of the body of a diabetic cat. i was particularly curious about the consequences of high blood sugar.
Some of this is on humans, but it seems that type 2 diabetes is similar in humans and cats. i'm not a scientist and some of this is really complex but, for most of it, you can get the idea they are trying to convey. I won't try to interpret the articles and people will need to do their own research and draw their own conclusions. I'm just sharing what i found for those who are also interested in the question of "how does this all work."
Each of the quotes below is just a glimpse at the information the article contains. The links will give you the entire article.
Diabetes in Pets, Glucose Toxicity http://petdiabetes.wikia.com/wiki/Glucose_toxicity
Glucose toxicity refers to the oxidizing and hypertonic (dehydrating) properties of hyperglycemia, both of which continually stress and damage tissues in the body. But the term is also specifically used to refer to the phenomenon of temporary insulin resistance brought on by this tissue stress.
Glucose toxicity does occur in people[1], but it is of high importance to pets--particularly cats. The difference between pets and people is that many pets are not diagnosed and treated until the symptoms of diabetes are impossible to avoid noticing. This means pets can easily go long periods with severe hyperglycemia without much symptomatic notice[2].
Amyloidosis http://petdiabetes.wikia.com/wiki/Amyloidosis
Amyloidosis is a major cause of diabetes, and is also one of the major forms of damage done to the pancreas by high blood sugar. Diabetic cats may still have a workable pancreas, but if left at high blood sugar levels over time, irreversible damage may be caused to the pancreas, which will continually reduce chances of remission. Amyloidosis from other causes can attack a healthy pancreas causing diabetes, too.
Pancreatic damage is caused by a combination of glucose toxicity and amyloidosis from high blood sugar, such that the insulin-producing Islets of Langerhans[1] of the pancreas become clogged with amyloid deposits. 80-95% of diabetic cats present with type-2 (insulin-resistant) diabetes[2], and it is probably these type-2 diabetic cats who are candidates for remission, but hyperglycemia, left untreated, may damage the pancreas over time, making remission impossible. Diabetic dogs are almost invariably type-1 and so do not usually have remission.
Like diabetes itself, amyloidosis[3], can cause gastroparesis.
Understanding Feline Diabetes Mellitus, Pathogenesis and Management http://www.uq.edu.au/ccah/index.html?page=43391&pid=0
Centre for Companion Animal Health University of Queensland, Australia
Professor Jacquie Rand, BVSc, DVSc, DACVIM
(Who developed the Tight Regulation Protocol)
Rhett Marshall, BVSc, MACVSc
This one won't copy because it's a compressed pdf - perhaps one of you is smarter than me and can copy some of it here for others. This is probably the best and most specific of all of the articles in addressing our questions as caregivers of diabetic cats.
Take a look at the lower right side of page 7, however for a key point. "Glucose toxicity contributes to loss of Beta cell secretion. Initially this toxicity is functional and reversible, but later it leads to permanent loss of Beta cells. Glucose toxicity is defined as impaired insulin secretion from chronic hyperglycemia. At a blood glucose concentration of 540mg insulin secretion is minimal by 3-7 days in previously normal cats."
Pathogenesis of Feline Diabetes Mellitus http://www.ncbi.nlm.nih.gov/pubmed/12431815?dopt=abstractplus
The common form of spontaneous diabetes mellitus that occurs in domestic cats bears close resemblance clinically and pathologically to human type 2 diabetes mellitus (T2DM). For example, the typical diabetic cat is obese and middle-aged, and has low but detectable circulating insulin levels. However, the most striking similarity is the occurrence of islet amyloidosis (IA) in nearly all diabetic cats and in over 90% of humans with T2DM.
IA in both humans and cats is derived from islet amyloid polypeptide (IAPP, or amylin) which is a hormone produced and secreted along with insulin by the pancreatic beta cells. Since all cats and humans normally produce IAPP, additional factors must be invoked in order to explain the development of IA. Several lines of evidence support the concept that IA is caused by chronically increased stimulus for beta cells to secrete IAPP (and insulin). For example, peripheral insulin resistance such as in chronic obesity results in increased IAPP and insulin secretion.
A recent study, in which diabetes mellitus was induced in cats, demonstrated that IAPP hypersecretion was induced by treatment with a sulfonylurea drug and resulted in 4/4 cats in this group developing IA. In contrast, cats treated with insulin had low IAPP secretion and minimal IA developed in 1/4 cats.
Several human-IAPP transgenic mouse models, in which there is IAPP overexpression, also support the notion that prolonged high expression of IAPP leads to IA. In vitro models of IAPP overexpression also support this mechanism for IA formation and by demonstrating an association between IA formation and beta cell toxicity, suggest a linkage between IA formation and loss of beta cells in T2DM.
A recent study has indicated that intermediate-sized IAPP-derived amyloid fibrils can disrupt cell membranes and therefore, may be involved in the destruction of beta cells. Striking parallels between the pathogenesis of IA and beta-amyloid plaque formation in Alzheimer's disease suggest possible parallel pathogenetic mechanisms of cell death and provide potential avenues for future studies into the pathogenesis of IA.
Case Study: Glucose Toxicity, Type 1 or Type 2? http://clinical.diabetesjournals.org/content/23/1/44.full
Clinical Pearls
Glucose toxicity occurs frequently in type 2 diabetes. When profound hyperglycemia (blood glucose > 300 mg/dl) is persistently present, pancreatic β-cell insulin release is downregulated. In the presence of underlying insulin resistance, this contributes to progressly greater hyperglycemia and may lead to ketosis.
Glucose toxicity can be reversed by aggressive treatment of severe hyperglycemia with insulin. The goal is to return blood glucose to near-normal values for several days or weeks to allow restoration of islet-cell insulin production. When this occurs, then diet, exercise, and oral antidiabetic medications may be sufficient to allow the patient to maintain near-normalization of blood glucose for extended periods of time.
Alcohol abuse can contribute to the symptoms of glucose toxicity. Alcoholism prevention and intervention should be as much of an issue for patients such as J.S. as prevention of diabetes complications. Open discussion and appropriate referral should be considered at office visits.
Management of New Onset Type 2 Diabetes http://www.medscape.com/viewarticle/428857
When a patient presents with severe hyperglycemia, glucose toxicity may be a major issue affecting the course of treatment. Often these patients have been hyperglycemic for weeks or months prior to presenting with the usual symptoms of polyuria and polydipsia. During this time, the pancreatic beta cells are desensitized to glucose-stimulated insulin secretion due to the persistently high ambient glucose concentrations,[1] resulting in insufficient insulin production and availability.
However, glucose toxicity is at least partially reversible, and this has major implications in the choice of an initial treatment. Many patients with severe glucose toxicity are best managed by insulin therapy because of their relative lack of endogenous insulin secretion and underlying insulin resistance that is exacerbated by glucose toxicity. As the effects of glucose toxicity are reduced over the first few weeks of treatment, the insulin dose can be tapered and oral medications may be successfully introduced.
Unfortunately, severe hyperglycemia does not provide an accurate estimate of the 2 major underlying factors in type 2 diabetes, which are insulin resistance and beta-cell reserve. In a nondiabetic person, insulin stimulates glucose uptake in skeletal muscle. In type 2 diabetes, skeletal muscle is resistant to the effects of insulin. Therefore, over time, pancreatic beta cells secrete greater and greater amounts of insulin to overcome insulin resistance. Eventually beta-cell exhaustion occurs and hyperglycemia develops.
The amount of insulin resistance and beta-cell reserve is highly variable from patient to patient at presentation. Once glucose toxicity is reduced, patients often have enough residual beta-cell function for oral agents to be effective. Measuring C-peptide levels can help determine the level of beta-cell reserve, as C-peptide is only produced if insulin is secreted by the beta cell.[2] However, this is not always a reliable test because glucose toxicity may suppress C-peptide levels. In addition, tests can be done to determine if the patient develops late-onset type 1 diabetes due to an underlying autoimmune destruction of beta cells.
Chronic Oxidative Stress as a Central Mechanism for Glucose Toxicity in Pancreatic Islet Beta Cells in Diabetes*http://www.jbc.org/content/279/41/42351.full
Journal of Biomedical Chemistry
Glucose in chronic excess causes toxic effects on structure and function of organs, including the pancreatic islet. Multiple biochemical pathways and mechanisms of action for glucose toxicity have been suggested. These include glucose autoxidation, protein kinase C activation, methylglyoxal formation and glycation, hexosamine metabolism, sorbitol formation, and oxidative phosphorylation. There are many potential mechanisms whereby excess glucose metabolites traveling along these pathways might cause beta cell damage. However, all these pathways have in common the formation of reactive oxygen species that, in excess and over time, cause chronic oxidative stress, which in turn causes defective insulin gene expression and insulin secretion as well as increased apoptosis. This minireview provides an overview of these mechanisms, as well as a consideration of whether antioxidant strategies might be used to protect further deterioration of the beta cell after the onset of diabetes and hyperglycemia.
Protection by Antioxidant Drugs against Beta Cell Oxidative Stress—Several antioxidant drugs have been evaluated as protectors against beta cell oxidative stress. N-Acetylcysteine protects against oxidative stress and diabetes in ZDF rats and db/db mice (55, 56). In both instances, this drug provided preserved insulin content and insulin gene expression as well as PDX-1 binding to the insulin promoter. The oral hypoglycemic agents metformin and troglitazone have antioxidant properties and prevent hyperglycemia in the ZDF rat (30, 57). Vitamin E has beneficial effects on glycemic control in GK rats (58). Glicazide, a commonly used sulfonylurea used in the treatment of type 2 diabetes, has been shown to protect pancreatic beta cells from damage by hydrogen peroxide (59). These findings suggest that adjunct therapy with antioxidants may represent a useful ancillary pharmacologic approach to the management of type 2 diabetes.
Conclusion
One potential central mechanism for glucose toxicity is the formation of excess ROS levels, which takes place within multiple mitochondrial and non-mitochondrial pathways. The islet is especially vulnerable to ROS because of its low intrinsic level of antioxidant enzymes. Chronically excessive glucose and ROS levels can cause decreased insulin gene expression via loss of the transcription factors PDX-1 and MafA and can also accelerate rates of apoptosis. This pathophysiologic sequence sets the scene for considering antioxidant therapy as an adjunct in the management of diabetes.
More related articles from the University of Queensland
What Diet Should I Choose and How Should I Manage Problem Cats? (for vets) 2006, modified 2008
http://www.uq.edu.au/ccah/docs/diabetesinfo/article4.pdf
Diabetes Mellitus in Cats (this article seems to be a subset of the link at the top of this post)
http://www.uq.edu.au/ccah/index.html?page=43599&pid=0
Which Insulin Do I Choose and How Do I Adjust the Dose? 2006, modified 2008
http://www.uq.edu.au/ccah/docs/diabetesinfo/article5.pdf
edited to add
Feline Diabetes Mellitus, by David Church World Congress 2006
http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2006&PID=15706&Category=2688&O=Generic
