Diabetes Natural Animal Model
Diabetes mellitus is a metabolic disorder that is increasing in prevalence in people, dogs, and cats. In each species, the disorder results from a defect in insulin secretion or reduced insulin sensitivity. Insulin is an anabolic hormone produced by pancreatic beta cells, and the most famous of its many functions is to allow glucose and lipids to enter cells from the blood stream to be stored or used for energy production. When the body fails to produce insulin, or when the insulin produced does not work properly, sugar and lipids build up in the bloodstream. If not managed properly, hyperglycemia (or excess sugar in the blood) and dyslipidemia (excess free fatty acids) can damage blood vessels and nerve conduction in many parts of the body, including the kidneys and the eyes, leading to nephropathy or retinopathy.
In humans, the two most common forms of diabetes are type 1 and type 2 diabetes. Type 1 diabetes tends to manifest in childhood and is attributed to autoimmune-induced destruction of pancreatic beta cells. However, many in the field believe, at least early on, that the inflammatory environment in the islet leads to beta cell dysfunction and loss of insulin production but that the beta cells may not be dead and have the potential to recover. Currently, type 1 diabetes must be treated with insulin therapy. In contrast, type 2 diabetes is characterized by insulin resistance, which is often associated with obesity. This form of the disorder is most commonly diagnosed in adulthood, but the incidence is rising in children due to an increase in childhood obesity. As type 2 diabetes is often related to the lifestyle of affected individuals, it is generally treated with dieting and exercise.
Similarities in Humans:
Diabetes manifests in many similar ways in humans, dogs, and cats. Patients present with similar symptoms because of the shared etiology of the disease and the actions of insulin in all three species. Type 1 diabetes in humans is most similar to the disease that affects canine patients, so the treatment regimen typically involves insulin therapy for both species. The two diseases may also share a genetic basis, and the cause of beta cell destruction may be similar.
Type 2 diabetes in humans is similar to the disease that manifests in feline patients as both are associated with obesity, inactivity, and older age. For this reason, type 2 diabetes and feline diabetes treatment involve changing the diet and lifestyle to improve the body’s sensitivity to insulin.
Differences in Humans:
One large difference between type 1 diabetes in humans and dogs is the age of onset. Type 1 diabetes is most often diagnosed in early childhood or adolescence, but there is a less common form, adult-onset type 1 diabetes. Diabetes is rare in young dogs and is most often diagnosed in middle-aged or older dogs. Type 2 diabetes is rarely diagnosed in dogs but is quite common in humans. Obese dogs may demonstrate some insulin resistance, but this rarely progresses to overt diabetes.
Type 1 diabetes is not common in cats. Very few diabetic cats have antibodies to beta-cells that would indicate an immune-mediated condition, which is likely why type 1 diabetes is rare in feline patients. Another difference between human and feline diabetes is that feline patients are often treated with insulin injections as soon as they are diagnosed, while lifestyle changes are first attempted and often sufficient for the management of most cases of human diabetes.
Type 1 diabetes is caused by the autoimmune-induced dysfunction and destruction of pancreatic beta cells. The disease has a major genetic component, and certain haplotypes of the major histocompatibility complex (a significant component of the immune system) are associated with development of the disorder. Likewise, a family history of type 1 diabetes increases the risk of developing the condition. Environmental factors have also been implicated in the development of diabetes, and certain viruses may be related, including rubella. This disease etiology is similar to that of canine diabetes, which also has a significant genetic component. Breed differences in susceptibility to the condition exist, and canine diabetes has also been associated with certain major histocompatibility complex genes. The exact cause of beta cell destruction is unknown, but it is believed to be related to pancreatic disease or autoimmunity in dogs.
Type 2 diabetes in humans is more influenced by environmental factors and is highly associated with lifestyle and obesity. Obesity can lead to insulin resistance, forcing beta cells to work harder in an attempt to compensate by producing more insulin. This creates a feedback loop, eventually leading to decreased function of beta cells. Type 2 diabetes may also have a genetic component because there is increased prevalence in first-degree relatives of affected patients. This disease etiology is very similar to that of feline diabetes, which is strongly associated with obesity and inactivity. In addition, older cats, male cats, and neutered cats are at higher risk for developing diabetes.
The clinical presentation of diabetes is similar for dogs, cats, and humans. Because insulin is not produced or does not function correctly in patients with diabetes, glucose builds up in the bloodstream. This leads to hyperglycemia (increased sugar in the blood), and patients often present with excess sugar in their urine. Other symptoms include increased thirst, frequent urination, extreme hunger, unintended weight loss, irritability, fatigue, and weakness.
Since type 1 diabetes and canine diabetes are marked by dysfunction and destruction of the beta cells, patients with these conditions require insulin injections to regulate blood sugar levels. This often involves monitoring of the blood sugar throughout the day to ensure that values remain stable. In humans, islet transplantation with immunosuppressive regimens has been successful in allowing the body to produce its own insulin, eliminating the need for exogenous insulin therapy.
In patients with type 2 diabetes, people are generally encouraged to change their lifestyle by changing their diet and exercising consistently. Drugs used to control high blood sugar and decrease insulin resistance may also be used in conjunction with behavioral changes. Treatment regimens for feline diabetic patients also involve lifestyle changes, and many cats are put on a diet to lose weight in a controlled manner. This often involves wet food and diets that are low in carbohydrates. In addition, most diabetic cats also require exogenous insulin treatments to control blood sugar.
Brito-Casillas Y, Melián C, Wägner AM. Study of the pathogenesis and treatment of diabetes mellitus through animal models. Endocrinología y Nutrición (English Edition). 2016 Aug 1;63(7):345-53.
Catchpole B, Adams JP, Holder AL, Short AD, Ollier WE, Kennedy LJ. Genetics of canine diabetes mellitus: are the diabetes susceptibility genes identified in humans involved in breed susceptibility to diabetes mellitus in dogs?. The veterinary journal. 2013 Feb 1;195(2):139-47.
Nelson RW, Reusch CE. Animal models of disease: classification and etiology of diabetes in dogs and cats. Journal of Endocrinology. 2014 Sep;222(3):T1-9.
Catchpole B, Adams JP, Holder AL, Short AD, Ollier WE, Kennedy LJ. Genetics of canine diabetes mellitus: are the diabetes susceptibility genes identified in humans involved in breed susceptibility to diabetes mellitus in dogs?. Vet J. 2013 Feb 1;195(2):139-47.
Devendra D, Liu E, Eisenbarth GS. Type 1 diabetes: recent developments. BMJ. 2004 Mar 25;328(7442):750-4.
Haak T, Gölz S, Fritsche A, Füchtenbusch M, Siegmund T, Schnellbächer E, Klein HH, Uebel T, Droßel D. Therapy of Type 1 Diabetes. Exp Clin Endocrinol Diabetes. 2019 Dec;127(S 01):S27-38.
Metformin Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing. (n.d.). Retrieved July 13, 2020, from https://www.webmd.com/drugs/2/drug-11285-7061/metformin-oral/metformin-oral/details
Oram RA, Sims EK, Evans-Molina C. Beta cells in type 1 diabetes: mass and function; sleeping or dead. Diabetologia. 2019 Feb;62:567-577.
Rand JS, Fleeman LM, Farrow HA, Appleton DJ, Lederer R. Canine and feline diabetes mellitus: nature or nurture?. The Journal of Nutrition. 2004 Aug 1;134(8):2072S-80S.
Rønningen KS. Environmental trigger (s) of type 1 diabetes: why so difficult to identify?. Biomed Res Int. 2015 Mar 30;2015.
Sparkes AH, Cannon M, Church D, Fleeman L, Harvey A, Hoenig M, Peterson ME, Reusch CE, Taylor S, Rosenberg D. ISFM consensus guidelines on the practical management of diabetes mellitus in cats. JFeline Med Surg. 2015 Mar;17(3):235-50.
Temneanu OR, Trandafir LM, Purcarea MR. Type 2 diabetes mellitus in children and adolescents: a relatively new clinical problem within pediatric practice. J Med Life. 2016 Jul;9(3):235.
Type 1 diabetes. (2017, August 07). Retrieved July 13, 2020, from https://www.mayoclinic.org/diseases-conditions/type-1-diabetes/symptoms-causes/syc-20353011