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BACKGROUND: Type 2 diabetes mellitus in humans is the result of a combination of impaired insulin sensitivity, increased hepatic glucose output, and impaired secretion of insulin. Obesity is a clear risk factor for development of diabetes mellitus in humans and has been found to be a risk factor for diabetes mellitus in cats, presumably by inducing insulin resistance. It is likely that obesity as well as risk factors such as a genetic predisposition or impaired insulin secretion underlie the pathogenesis of diabetes mellitus in many cats as it does in type 2 diabetes mellitus in humans.

SUMMARY: Sixteen healthy cats were evaluated before and after weight gain induced by free choice feeding of a high energy density diet for 9-12 months. Body weight, body mass index, body condition scores and body composition (determined by dual X-ray absorptiometry) were determined before and after weight gain. Glucose tolerance testing, minimal model analysis of the glucose tolerance test, and a meal response test were evaluated before and after weight gain. The minimal model analysis provides an estimate of insulin sensitivity and the insulin-independent uptake of glucose by tissues. The meal response test was performed by obtaining blood samples periodically for 18 hours after a meal for measurement of blood glucose and insulin. The mean body weight of cats before overfeeding was 4.37 kg and that after weight gain was 6.28 kg. Significant increases in body weight, body mass index, and body condition score were found after weight gain. Based on body condition score, 10 cats became obese (score of 5/5) and six became overweight (score of 4/5). All cats were obese based on dual X-ray absorptiometry with a body fat content more than 30%. After weight gain, cats had significantly higher blood glucose concentrations at all time points except the basal fasting glucose. The insulin concentration was significantly higher at most time points after weight gain. The area under the curve for glucose and insulin were higher in cats after weight gain. In addition, the peak insulin response was delayed and did not return to baseline by 120 minutes after glucose administration. Cats with the highest baseline insulin had the most weight gain and the greatest body fat content. Seven obese cats were determined to have glucose intolerance when compared with normal values on glucose tolerance tests that were established in a previous study. There was no difference in weight or body fat between the cats with glucose intolerance and those without. The obese cats with glucose intolerance had a higher half-life of glucose after administration, area under the glucose curve, and mean glucose concentration at the last three times during the glucose tolerance test than obese cats without glucose intolerance. Basal insulin concentrations were higher in cats that were glucose intolerant than before weight gain, while those with normal glucose tolerance were not. Before weight gain, the cats that developed glucose intolerance had a tendency (not statistically significant) to have higher baseline insulin and area under the insulin curve, and had a smaller first phase insulin response compared to cats that failed to develop glucose intolerance. Before weight gain, cats with basal insulin concentrations above the reference range median were significantly (4.7 times) more likely to become glucose intolerant after gaining weight than cats with a baseline insulin concentration below the median of the reference range. When comparing male to female cats, only males had significantly increased baseline insulin concentrations and decreased first phase insulin response after weight gain, while only females had a significantly increased area under the glucose curve. Only two of six males became glucose intolerant while five of 10 females developed glucose intolerance after weight gain. Insulin sensitivity was decreased by about 50% after weight gain. Obese cats with the highest baseline insulin concentrations and those with the highest percentage of body fat had the lowest insulin sensitivities. The ability of glucose to promote its own removal from the plasma (glucose effectiveness) was decreased in cats after weight gain. The measurements of insulin sensitivity based on computer modeling of insulin concentrations and glucose disappearance from the plasma indicated that, after weight gain, cats had altered distribution and binding kinetics of insulin and decreased receptor binding and post-receptor activation of intracellular effects. In cats that developed glucose intolerance after weight gain, insulin sensitivity before weight gain was significantly (35%) less than those that did not develop glucose intolerance. Lean cats with insulin sensitivity below the median of the normal range were 2.9 times more likely to develop glucose intolerance after weight gain. Moreover, cats with both insulin sensitivity and glucose effectiveness below the median of the reference range when lean were four times more likely to develop glucose intolerance after weight gain. Male cats had lower insulin sensitivity than female cats before weight gain, although the difference was not significant. During the meal response test, obese cats with abnormal glucose tolerance had higher fasting glucose and insulin concentrations than obese cats with normal glucose tolerance. The authors concluded that insulin resistance and glucose intolerance occurs in obese cats and that lean cats with low insulin sensitivity are at increased risk for developing glucose intolerance when obese.

CLINICAL IMPACT: This extensive study of glucose tolerance and insulin sensitivity in obese has confirmed that obese cats are probably at increased risk for development of diabetes mellitus. Importantly, they identified that cats with insulin sensitivity, glucose effectiveness, or glucose tolerance below the median of the normal range (not outside the normal range) were more likely to develop insulin resistance and glucose intolerance after weight gain. This implies that some cats have unknown factors that may put them at risk for developing diabetes mellitus. None of the cats studied developed diabetes mellitus during the study. Male cats have been shown to have an increased risk for diabetes mellitus, and possible explanations include an increased incidence of obesity and the lower insulin sensitivity in male cats that was suggested by this study.

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