Diabetes in Pets
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'''Glucose toxicity''' refers to the [[Wikipedia:oxidizing agent|oxidizing]] and [[Wikipedia:Osmosis|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''' refers to the [[Wikipedia:oxidizing agent|oxidizing]] and [[Wikipedia:Osmosis|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, 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 that there is [[hyperglycemia]] which may have been occuring for some time without much symptomatic [http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2003&PID=pr06704&O=Generic notice].
+
Glucose toxicity does occur in people<ref>[http://www.endotext.org/diabetes/diabetes12new/diabetesframe12.htm Endotext.com--Glucose Toxicity]</ref>, 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<ref> [http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2003&PID=pr06704&O=Generic WSAVA 2003-Canine & Feline Diabetes Mellitus]</ref>.
   
 
==Raises blood glucose -- temporary insulin resistance==
 
==Raises blood glucose -- temporary insulin resistance==
When a diabetic animal is [[hyperglycemia|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.
+
When a diabetic animal is [[hyperglycemia|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 diet|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.
+
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 diet|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 level]]s or a [[rebound]] event on a previously "safe" insulin dosage, and be prepared to immediately lower the dosage.
+
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 level]]s 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]].
 
See also the article on [[obstacles to regulation]].
  +
==Suppresses insulin secretion (in cats)==
  +
  +
According to Dr. E. Hodgkins and also Dr. J. Rand<ref>[http://www.uq.edu.au/vetschool/centrecah/index.html?page=43391&pid=0 Rand & Marshall 2005, see P.7, Glucose Toxicity]</ref><ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=3888754&query_hl=1&itool=pubmed_docsum 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.]</ref>, [[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 requirements==
 
==Raises insulin requirements==
   
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.
+
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<ref>[http://www.uq.edu.au/vetschool/centrecah/index.html?page=43391&pid=0 Understanding Feline Diabetes Mellitus: Pathogenesis and Management U-Queensland-Rand/Marshall-2005]</ref>. However, healing can take place only when blood glucose & fatty acid concentrations are reduced.
As the damage from glucose toxicity is repaired, the tissues will heal. As the tissues heal, the animal's insulin requirements (which had been raised by the toxicity) may gradually fall. This mechanism may be an explanation for the increased insulin sensitivity observed with better regulation, in [http://www.acvim.org/wwwpf/Forum/abstracts/AbstractWeb.pdf this study (#68)]. This reduction in insulin requirements may or may not eventually lead to [[remission]].
 
   
==Damages pancreas==
+
==Damages pancreas (in cats)==
   
Unfortunately, the [[pancreas]], particularly the insulin-producing [[Wikipedia:beta cells|beta cells]] can be profoundly damaged by glucose toxicity. Injecting a large glucose load into a cat can make it temporarily diabetic, and not all animals will recover. 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 [[Wikipedia:Redox|oxidation]] mechanisms like glucose autoxidation, protein kinase C activation, methylglyoxal formation and glycation, hexosamine metabolism, sorbitol formation, and oxidative phosphorylation. (See [http://www.jbc.org/cgi/content/full/279/41/42351 this journal article]). [[Antioxidants]] may be helpful to breaking this [[:Category:vicious circles|vicious circle]].
+
Unfortunately, the [[pancreas]], particularly the insulin-producing [[Wikipedia:beta cells|beta cells]] can be profoundly damaged by glucose toxicity<ref>[http://web.archive.org/web/20070208103248/http://bettermedicine.intervetusa.com/june2006/managing_diabetes.html Better Medicine-E-Newsletter-June 2006]</ref>. 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 [[Wikipedia:Redox|oxidation]] mechanisms like glucose autoxidation, protein kinase C activation, methylglyoxal formation and glycation, hexosamine metabolism, sorbitol formation, and oxidative phosphorylation. (See JBC article<ref>[http://www.jbc.org/cgi/content/full/279/41/42351 JBC- Chronic Oxidative Stress & Beta Cell Glucose Toxicity]</ref> re: Oxidative Stress & Glucose Toxicity). [[Antioxidants]] may be helpful to breaking this [[:Category:vicious circles|vicious circle]].
   
 
==Damages tissues==
 
==Damages tissues==
   
Glucose toxicity also damages other tissues of the body, particularly [[Wikipedia:capillaries|capillaries]] and [[Wikipedia:neuron|nerve cells]], which leads to [[neuropathy]] and in dogs, [[retinopathy]]. Damage to other tissues leads to other well known [[:Category:Complications|complications of diabetes]] including kidney malfunctions and (in dogs) [[cataracts]].
+
Glucose toxicity also damages other tissues of the body, particularly [[Wikipedia:capillaries|capillaries]] and [[Wikipedia:neuron|nerve cells]], which leads to [[neuropathy]] and in dogs, [[retinopathy]]. Damage to other tissues leads to other well known [[:Category:Complications|complications of diabetes]] including kidney malfunctions and (in dogs) [[cataracts]].
   
 
==Possible treatments==
 
==Possible treatments==
Obviously, anything that helps [[regulation|regulate]] [[blood glucose level]]s will reduce the stress of glucose toxicity. In addition, the PNRI Journal article below speculates that [[Wikipedia:antioxidant|anti-oxidants]] including [http://www.nzymes.com/Articles/antioxidants.htm Vitamin E and Selenium] will act to reduce most of the mechanisms and help reduce and heal glucose toxicity damage.
+
Obviously, anything that helps [[regulation|regulate]] [[blood glucose level]]s will reduce the stress of glucose toxicity and in some cases lead to remission<ref>[http://www.jvetintmed.org/perlserv/?request=get-abstract&doi=10.1892%2F0891-6640%281999%29013%3C0028%3ATCDMIC%3E2.3.CO%3B2 Nelson et. al, 1999, transient feline diabetes]</ref>. In addition, the PNRI Journal article below speculates that [[Wikipedia:antioxidant|anti-oxidants]] including Vitamin E and Selenium<ref>[http://www.nzymes.com/Articles/antioxidants.htm Nzymes.com-Vitamin E and Selenium]</ref> will act to reduce most of the mechanisms and help reduce and heal glucose toxicity damage.
  +
  +
==Reversal and Remission (in cats)==
 
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)<ref> [http://images2.wikia.nocookie.net/petdiabetes/images/e/e2/Acvim_2004_abstracts.pdf ACVIM Abstract #68--Glucose Toxicity]</ref>. 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 Reading==
 
==Further Reading==
  +
  +
[[Image:Wikicat3.jpg|100px]]
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  +
*[[:Category:Feline glucose toxicity cases|Wiki cases--Glucose Toxicity]]
 
*[http://www.jbc.org/cgi/content/full/279/41/42351 PNRI Journal Article on glucose toxicity including damage to pancreatic beta cells.]
 
*[http://www.jbc.org/cgi/content/full/279/41/42351 PNRI Journal Article on glucose toxicity including damage to pancreatic beta cells.]
*[http://66.249.93.104/search?q=cache:elp44c4qO2QJ:www.joplink.net/prev/200209/200209_02.pdf Amyloidosis and progression of Type-2 diabetes (pdf)]
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*[http://www.joplink.net/prev/200209/200209_02.pdf Amyloidosis and progression of Type-2 diabetes (pdf)]
  +
*[http://www.servier.com/pro/diabetologie/diabetographia/ud/06.asp Excellent article from Japan: Blood glucose toxicity and β-cell dysfunction]
  +
*[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=16356119 Proposed mechanisms for the induction of insulin resistance by oxidative stress.]
  +
*[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=11375349 The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake...]
 
*[http://www.felinediabetes.com/phorum5/read.php?15,180387 Discussion of glucose toxicity on the FDMB]
 
*[http://www.felinediabetes.com/phorum5/read.php?15,180387 Discussion of glucose toxicity on the FDMB]
 
*[http://www.felinediabetes.com/phorum5/read.php?15,222507 More Discussion of glucose toxicity on the FDMB]
 
*[http://www.felinediabetes.com/phorum5/read.php?15,222507 More Discussion of glucose toxicity on the FDMB]
   
  +
[[Category:Conditions]][[Category:Complications]][[Category:Regulation]][[Category:Terms]][[Category:Vicious circles]]
 
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  +
[[Image:Wikidog3.jpg|100px]]
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  +
*[[:Category:Canine glucose toxicity cases|Wiki cases--Glucose Toxicity]]
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  +
==References==
  +
<references/>
  +
[[Category:Conditions]]
  +
[[Category:Complications]]
  +
[[Category:Regulation]]
  +
[[Category:Terms]]
  +
[[Category:Vicious circles]]

Latest revision as of 07:53, 14 October 2011

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 resistance

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)

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 requirements

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)

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 tissues

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 treatments

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)

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 Reading

Wikicat3


Wikidog3

References