The diagnosis and treatment of Canine diabetes mellitus

Definition and signalment
Diabetes mellitus (DM) is a common endocrine disease characterized by absolute or relative insulin deficiency in cats and dogs. There are three types of diabetes:
1) Type I: Insulin-dependent diabetes mellitus (IDDM): insufficient insulin secretion leads to an absolute lack of insulin and relies on external insulin supplementation. Type I diabetes, the most common form in dogs, may be caused by autoimmune destruction of the beta cells of the pancreas that secrete insulin.
2) Type II: none insulin-dependent diabetes mellitus(NIDDM) is characterized by beta cell dysfunction, which leads to impaired insulin secretion, and peripheral insulin resistance. Insulin production may be normal or increased; However, insulin is not enough to prevent high blood sugar. Abnormal insulin secretion combined with insulin resistance leads to stable re-regulation of blood glucose levels at higher concentrations. Type 2 diabetes is sometimes reversible, meaning the disease can go into remission. Type 2 diabetes occurs in cats, not dogs.
3) Type III: gestational hormone-induced diabetes, which occurs when insulin resistance is associated with high concentrations of progesterone or other prediabetic hormones (such as cortisol, adrenaline, growth hormone, and glucagon). Both cats and dogs are reported to have Type III diabetes.

Physiology of pathology
The role of insulin: The existence of insulin is mainly in the liver, muscle, and fat cells. Its primary function is to promote the storage of glucose to be glycogen, amino acids to be protein, and fatty acids to be overweight. Insulin also promotes glycogen synthesis and gluconeogenesis, reducing liver enzymes that convert amino acids into glucose. Insulin promotes lipid synthesis and inhibits lipid degradation. Insulin promotes positive nitrogen balance by stimulating protein synthesis and inhibiting protein degradation.

The effects of insulin deficiency: In the case of absolute or relative insulin deficiency, the flow of glucose into the liver, muscle, and adipose tissue is reduced. The liver also produces more glucose through increased gluconeogenesis and glycogen breakdown, which leads to high blood sugar. Once the kidney’s ability to reabsorb glucose is exceeded, glucose is lost through the urine, resulting in osmotic diuresis. When insulin is deficient, protein synthesis decreases, and protein catabolism increases. These effects can lead to loss of muscle mass and negative nitrogen balance, a lipid metabolism disorder. The Increasing non-esterified fatty acids are transported to the liver, leading to hepatic steatosis and hyperlipidemia. The increase in ketone bodies eventually leads to ketoacidosis.

The cause of Immune-mediated disease: Diabetes is considered to be a multi-factorial disease. In most dogs, it is believed that the immune-mediated process leads to the destruction of insulin-secreting pancreatic beta cells, resulting in absolute insulin deficiency. Various beta-cell antibodies have been found in people with type 1 diabetes; However, no large-scale anti-cellular antibody studies have been conducted in dogs. One report found anti-beta cell antibodies in 9 out of 23 newly diagnosed diabetic dogs. Another report found the anti-beta cell antibody GAD65 in 4 out of 30(13%) newly diagnosed diabetic dogs. In contrast, about 85 percent of newly diagnosed type 1 diabetes patients have antibodies to GAD65.Pancreatitis.Chronic pancreatitis leads to the progressive destruction of insulin-secreting cells, as well as glucagon-secreting cells. Chronic pancreatitis is secondary to about 30% of canine cases. Lipemia, a high-fat diet, and obesity are associated with the origin of pancreatitis and may contribute to the development of diabetes.

Genetics
Genetics also plays a role in canine diabetes mellitus. Some breeds of dogs have a genetic predisposition, while others have a lower risk of diabetes. Breed susceptibility varies geographically and may be related to genetic influences. The specific genetic determinants of canine diabetes are not well defined. Associations between diabetes risk and single nucleotide polymorphisms were found in the insulin gene region of the Jack Russell terrier and Cocker Spaniel and cytotoxic t lymphocyte-associated protein 4 in several breeds. A pattern of polygenic inheritance has been found in American Eskimo dogs. The genetic determinants of dogs may be related to the canine leukocyte antigen (DLA) gene encoding major histocompatibility complex Class II (MHC-II). MHC-II is responsible for presenting antigens to T lymphocytes. In theory, MHC genes benefit the positive selection of anti-pancreatic t cells in high-risk patients.

Other Causes
Exposure to elevated levels of progesterone during pregnancy can lead to glucose intolerance and gestational diabetes in dogs. Exposure to excessive amounts of other diabetes hormones (growth hormone, cortisol) can also lead to diabetes. Hyperadrenocorticosis is a common diagnosis in diabetic dogs. In a study of 35 dogs with multiple endocrine disorders, 20/35(57.1%) had both diabetes and hyperadrenocorticism activity. Another study of 221 dogs with diabetes reported that 51 (23%) also had hyperadrenocorticism training. Streptozotocin use can cause diabetes in dogs. While obesity may indirectly influence the development of diabetes, no direct link has been found between the two.

The prognosis
Except for the brief periods of type III diabetes (such as pregnancy), diabetes in dogs does not go into remission, and treatment is usually life-long. In a study of 439 dogs, the median survival time (MST) after diagnosis was 17.3 months. In another study of 860 dogs, MST was two years (excluding patients who died within a day of diagnosis). Another study of 68 dogs reported an MST of 964 days. However, many diabetic dogs are euthanized because owners are frustrated with the cost of treatment and the time commitment of managing the disease. Therefore, educating the owners; Setting reasonable expectations; Constant communication is essential. In some cases, it may be helpful to use a quality-of-life questionnaire.