The Endocrinology of Obesity in Dogs

Kurt Verkest (2011). The Endocrinology of Obesity in Dogs PhD Thesis, School of Veterinary Science, The University of Queensland.

       
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Author Kurt Verkest
Thesis Title The Endocrinology of Obesity in Dogs
School, Centre or Institute School of Veterinary Science
Institution The University of Queensland
Publication date 2011-04
Thesis type PhD Thesis
Supervisor Linda M Fleeman
Jacquie S Rand
Total pages 335
Total colour pages 7
Total black and white pages 328
Language eng
Subjects 07 Agricultural and Veterinary Sciences
Abstract/Summary This thesis presents important new information about the consequences of obesity on the endocrine regulation of energy homeostasis in dogs. Background . Obesity is a risk factor for the development of some types of diabetes mellitus in humans, including type 2 diabetes and diabetes associated with chronic pancreatitis. Dogs, like humans and domestic cats, develop obesity-induced insulin resistance. However, unlike humans and cats, dogs do not appear to progress from obesity-induced insulin resistance to type 2 diabetes mellitus. This implies that either there is a mechanism that protects dogs from type 2 diabetes, or that dogs lack a pathophysiological process crucial to the development of type 2 diabetes. Methods . The insulin secretion patterns in lean and severely obese dogs were described using frequently-sampled glucose tolerance tests with MINMOD analysis. There was a need for simpler methods for assessing insulin sensitivity and beta cell function in dogs that are less expensive, time-consuming, and invasive, and can be applied to large numbers of dogs in clinical settings. Therefore methods to assess fasting insulin sensitivity and beta cell function using homeostasis model assessment (HOMA) were validated, as were simplified glucose tolerance tests with MINMOD analysis that require half as many samples as traditionally used frequently-sampled glucose tolerance tests. The fasting measures of insulin sensitivity and beta cell function were then applied in the first study reported using path analysis in small animal medicine or veterinary endocrinology, in which the hormonal mechanisms involved in the pathophysiology of insulin resistance and insulin secretion were examined in over 100 naturally-occurring lean, overweight, and obese dogs. Further investigation of the role of adiponectin in obesity in dogs was then facilitated by adaptation of the gold-standard sucrose gradient technique with SDS-PAGE and western blotting for use in dogs, which allowed separate measurement of low molecular weight (LMW) trimers and hexamers, and high molecular (HMW) larger multimers. Finally, meal response tests in overweight and obese dogs examined postprandial plasma glucose, insulin, and triglyceride concentrations, and allowed investigation of the association between hypertriglyceridaemia and the risk of having high plasma canine pancreatic lipase concentrations. Results and discussion . Obese, insulin-resistant dogs maintained fasting and first-phase insulin secretion. Loss of first-phase insulin secretion is one of the early markers of the development of type 2 diabetes in humans and cats. Leptin does appear to be involved in the pathophysiology of either insulin resistance or compensatory hyperinsulinaemia in overweight and obese dogs. However, dogs differ from humans and laboratory rodents in that adiponectin, a key hormone mediating obesity-induced insulin resistance, does not appear to be decreased in obesity nor associated with obesity-induced changes in fasting insulin sensitivity or fasting insulin concentrations. Adiponectin is also not decreased in intact male dogs compared with neutered or female dogs, suggesting that adiponectin is not suppressed by testosterone in dogs as it is in humans and laboratory rodents. The biologically active forms of adiponectin, the HMW multimers, are not selectively decreased in severely obese dogs, and are not associated with insulin sensitivity measured using frequently-sampled glucose tolerance tests with MINMOD analysis. A subset of severely obese dogs with increased postprandial glucose concentrations and postprandial insulin concentrations lower than in other obese dogs was identified. Hyperglycaemia paradoxically contributes to impaired insulin secretion through glucose toxicity to pancreatic beta cells and these dogs exhibited glucose concentrations sufficient to cause glucose toxicity in humans, but they did not progress to overt type 2 diabetes during a follow-up period of over two and a half years. Hypertriglyceridaemia was not the cause of impaired insulin secretion in the persistently hyperglycaemic dogs. However, an association between peak postprandial triglyceride concentrations .5 mmol/L and high canine pancreatic lipase concentrations was demonstrated, contributing to the literature that suggests a causal relationship between high triglyceride concentrations and the development of pancreatitis. Obese dogs are at increased risk for both hypertriglyceridaemia and pancreatitis, and chronic or recurrent pancreatitis is the cause of one type of diabetes mellitus in humans. This study might lead to the use of postprandial triglyceride concentrations as early markers of the risk for pancreatitis and evaluation of the value of dietary fat restriction in dogs at risk of pancreatitis. Conclusion . There are important differences between dogs and species that develop type 2 diabetes. Adiponectin and HMW adiponectin are not decreased in obese dogs, insulin resistant dogs, or intact male dogs. These observations might explain why insulin resistant obese dogs maintain adequate fasting and first-phase insulin secretion and do not progress to develop beta cell failure and type 2 diabetes mellitus. Hypertriglyceridaemia is associated with pancreatitis in dogs as it is in humans and, through this association, obesity might play a role in the development of diabetes due to chronic pancreatitis in dogs.
Keyword obesity
insulin resistance
Type 2 diabetes
glucose homeostasis
insulin secretion
canine
Additional Notes Colour figures Document page 137 148 325 326 327 328 329 Landscape pages Document page 104 105 226 227

 
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Created: Thu, 08 Dec 2011, 00:03:22 EST by Mr Kurt Verkest on behalf of Library - Information Access Service