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Diabetes in Pets

Glucose toxicity

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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].

Raises blood glucose -- temporary insulin resistanceEdit

When a diabetic animal is hyperglycemic for long enough, the animal's damaged tissues may start having trouble using insulin. This in turn means that even a well-dosed animal may continue to have high blood sugar, leading to even more insulin resistance.

Various methods through this "glass floor" have been tried, to varying degrees of success. One way is to continue gradually raising insulin dosage until the tissues pick up the insulin and start absorbing glucose, then quickly back off to a lower dose. Another is to "jumpstart" the process with a fast-acting insulin or a deliberately high dose of the regular insulin, then quickly back off to a lower dose. Another is to reduce the carbohydrate content of the food further, or to eliminate dry food entirely (even low-carb dry food), thereby presenting less of an obstacle for insulin effectiveness and reducing insulin needs. Aggressive attempts to break glucose toxicity are best regarded as dangerous and should be addressed in close partnership with a diabetes-experienced veterinarian.

These methods may provide relief from glucose toxicity suddenly and unexpectedly, risking overdose and hypoglycemia once the "glass floor" is broken. Caregivers should be vigilant about watching for signs that the floor has broken, such as lower than expected blood glucose levels or a rebound event on a previously "safe" insulin dosage, and be prepared to immediately lower the dosage.

See also the article on obstacles to regulation.

Suppresses insulin secretion (in cats)Edit

According to Dr. E. Hodgkins and also Dr. J. Rand[3][4], hyperglycemia also suppresses insulin secretion from the beta cells. After just 3 to 7 days at 30mmol/L (540 mg/dL), Dr. Rand found only "minimal" insulin secretion from the beta cells. Combined with the insulin resistance, this means that once a cat becomes diabetic, it will tend to remain that way until treated with exogenous insulin.

Raises insulin requirementsEdit

Glucose toxicity can continue to raise insulin requirements for some time, even after the "glass floor" is broken and blood glucose is brought under control. This effect may take a long time (weeks) to wear off, due to the gradual healing of formerly glucose-damaged tissue.

As the damage from glucose toxicity is repaired, the tissues will heal; the process can take 1-12 weeks[5]. However, healing can take place only when blood glucose & fatty acid concentrations are reduced.

Damages pancreas (in cats)Edit

Unfortunately, the pancreas, particularly the insulin-producing beta cells can be profoundly damaged by glucose toxicity[6]. The effects of glucose toxicity on insulin secretion and insulin resistance may be temporary as described above, but the ongoing effect of amyloidosis is permanent. So an animal experiencing a lot of hyperglycemia can be permanently damaging its own pancreas, and sliding deeper into insulin-dependence, through amyloidosis as well as oxidation mechanisms like glucose autoxidation, protein kinase C activation, methylglyoxal formation and glycation, hexosamine metabolism, sorbitol formation, and oxidative phosphorylation. (See JBC article[7] re: Oxidative Stress & Glucose Toxicity). Antioxidants may be helpful to breaking this vicious circle.

Damages tissuesEdit

Glucose toxicity also damages other tissues of the body, particularly capillaries and nerve cells, which leads to neuropathy and in dogs, retinopathy. Damage to other tissues leads to other well known complications of diabetes including kidney malfunctions and (in dogs) cataracts.

Possible treatmentsEdit

Obviously, anything that helps regulate blood glucose levels will reduce the stress of glucose toxicity and in some cases lead to remission[8]. In addition, the PNRI Journal article below speculates that anti-oxidants including Vitamin E and Selenium[9] will act to reduce most of the mechanisms and help reduce and heal glucose toxicity damage.

Reversal and Remission (in cats)Edit

When hyperglycemia is brought under control, the tissues begin healing, a process that takes a few weeks. As the tissues heal, the animal's insulin requirements (which had been raised by the toxicity) may gradually fall. The pancreas may begin producing insulin again, freed from the suppression caused by glucose toxicity. Damage caused by amyloidosis will remain. This mechanism may be an explanation for the increased insulin sensitivity observed with better regulation, in this study (Abstract #68)[10]. This reduction in insulin requirements and increased pancreatic production may or may not eventually lead to remission, probably depending on the extent of amyloidosis and other permanent beta cell damage.

Further ReadingEdit

Wikicat3


Wikidog3

ReferencesEdit

  1. Endotext.com--Glucose Toxicity
  2. WSAVA 2003-Canine & Feline Diabetes Mellitus
  3. Rand & Marshall 2005, see P.7, Glucose Toxicity
  4. Unger & Grundy, 1985: Hyperglycaemia as an inducer as well as a consequence of impaired islet cell function and insulin resistance: implications for the management of diabetes.
  5. Understanding Feline Diabetes Mellitus: Pathogenesis and Management U-Queensland-Rand/Marshall-2005
  6. Better Medicine-E-Newsletter-June 2006
  7. JBC- Chronic Oxidative Stress & Beta Cell Glucose Toxicity
  8. Nelson et. al, 1999, transient feline diabetes
  9. Nzymes.com-Vitamin E and Selenium
  10. ACVIM Abstract #68--Glucose Toxicity

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