Risk factors for feline diabetes mellitus

The chapters of Part I of the thesis describe the development of techniques that can be used in the assessment of risk factors for the development of diabetes mellitus (DM) in cats. The hyperglycemic glucose clamp (HGC) was developed for use in conscious cats, equipped with arterial catheters for plasma glucose measurements. The glucose disposal rate measured during HGC was lower in normal glucose-tolerant cats than in normal glucose-tolerant humans, apparently related to the cat’s lower insulin secretion and lower insulin sensitivity. The measures of β-cell function and insulin sensitivity derived from HGCs correlated with their counterparts derived from intravenous glucose tolerance tests (ivGTT) and homeostasis model assessment of fasting plasma glucose and insulin concentrations. It is concluded that the HGC allows for measurement of β-cell function and insulin sensitivity in cats and is to be preferred over the ivGTT whenever possible. The described new technique for arterial catheterisation allows frequent arterial blood sampling and continuous measurement of systemic arterial blood pressure (ABP). Resting cats had lower ABP than inactive but attentive cats, and active cats had higher ABP than resting or inactive but attentive cats. Interaction with a familiar person led to a higher ABP and a longer time to return to resting values than interaction with an unfamiliar person. An attempt was made to develop an easy to perform and inexpensive test to assess pancreatic b-cell function in cats. It is concluded that this calcium-stimulation test is not a valuable tool for the assessment of the β-cell function. The chapters of Part II of the thesis report on studies of potential risk factors for the development of DM in cats. Sixteen diabetic cats were examined for the presence of concurrent pituitary disease. Acromegaly was diagnosed in 5 of the 16 diabetic cats, and pituitary-dependent hypercortisolism was diagnosed in 2 of the 5 acromegalic cats. It is recommended to carry out examinations for concurrent pituitary disease in diabetic cats requiring >1.5 IU lente insulin/kg body weight per injection. In the acromegalic cats the plasma concentrations of growth hormone, adrenocorticotrophic hormone, and cortisol decreased significantly after a single intravenous injection of octreotide. This octreotide-suppression test is suggested as a pre-entry test to select acromegalic cats for treatment with somatostatin analogues. Other risk factors for the development of feline DM were studied in a questionnaire-based retrospective case-control study. Results from this study revealed that physical inactivity and indoor confinement are risk factors, independent of age, body weight or body condition. The percentage of metabolisable energy provided by dry food had no demonstrable effect. In a study on the role of dietary macronutrients the effects of feeding 3 different diets (high-fat, high-carbohydrate, and high-protein) for 9 months on glucose-induced insulin secretion, glucose disposal, insulin sensitivity, ABP, and body composition were studied. The results indicate that diets with a low fat content lower the ABP. The exchange of protein for fat or carbohydrate led to an increase in glucose-induced insulin secretion during the HGC. Glucose disposal increased when protein was exchanged for fat. The macronutrient differences did not influence insulin sensitivity or body composition. It is proposed that the increase in glucose-induced insulin secretion is a primary dietary effect mediated by chronic effects of incretins. It should be emphasised that the results presented here were obtained excluding the influence of the studied parameters on the development of obesity. The findings do not support the concept that high-carbohydrate diets lead to exhaustion and loss of β-cells.