Diabetes Mellitus (DM) is not a single disease, but a syndrome characterized by hyperglycemia that result from defects in insulin secretion or insulin sensitivity (in target tissues), or both. Several pathogenic processes may lead to development of DM, from autoimmune destruction of beta cells of the pancreas with consequent absolute insulin deficiency to abnormalities that result in resistance to insulin action such as hypersomatotropism (HST). The cause of beta cell dysfunction in cats is currently unknown. Regardless of cause, deficiency in insulin or its action on target tissues leads to a myriad of abnormalities in carbohydrate, fat, and protein metabolism. The presence and magnitude of hyperglycemia may change over time, depending on the extent of the underlying disease process and associated comorbidities. A disease process may cause prediabetes without progressing to overt diabetes. Prediabetes in cats is currently poorly defined, creating a huge hurdle in the study of the natural history of DM and inability to prevent progression to DM, despite available treatment options.
Similarities in humans
- Impaired beta cell function with residual but declining insulin secretion; Cause of impaired beta cell function and destruction is unknown
- Strongly associated with obesity, insulin resistance and decreased physical activity
- Genetic predisposition
- Most commonly diagnosed in middle-age or older individuals
- Patients might be “insulin independent” (NIDDM; i.e. non-ketotic without exogenous insulin supplementation) or “insulin dependent (IDDM; require exogenous insulin supplementation to avoid ketosis) and can revert from IDDM to NIDDM and back depending on a variet of factors
- Amylin (IAPP) is secreted from beta cells and tends to form amyloid in primates and cats. Amyloid deposits in the islet of Langerhans in > 90% of human and feline diabetics but infrequent in non-diabetics. The extent to which amyloid causes DM or contributes to its progression is currently unclear
Differences in humans
In people, fasting glucose, oral glucose tolerance testing and hemoglobin A1c are used for screening of prediabetes. A variety of life-style changes, pharmacological and surgical interventions in prediabetics are effective in slowing progression or even preventing DM. There is currently no clear definition of prediabetes or pre-clinical DM in cats and therefore inability to screen clinically normal patients and treat them with the goal of preventing or delaying an insulin-dependent state.
The cause of impaired beta cell function in type 2 DM is unknown.
About 25% of cats are diagnosed with DM secondary to hypersomatotropism.
Early stages of hyperglycemia: No clinical signs
Late stages of hyperglycemia: Polyuria, polydipsia, polyphagia, weight loss. Some cats progress to having diabetic neuropathy manifested as hind limb weakness, plantigrade stance and ataxia.
Insulin: All insulin formulations that are used in people can be used in cats although the time-action profiles sometimes differ significantly between species.
Because of the inability to diagnose DM in cats early in the course of their disease, there is little data on the role non-insulin interventions in cats. Oral hypoglycemics that are effective in people might be effective in cats if used early in the disease process. GLP-1 analogues and DPP-4 inhibitors potentiate insulin secretion in healthy cats and have some clinical utility in diabetic cats but more studies are needed on their effects in prediabetic and sub-clinical diabetic cats.
University of Florida, College of Veterinary Medicine
The effect of the ghrelin-receptor agonist capromorelin on glucose metabolism in healthy cats. Pires J, Greathouse RL, Quach N, Huising MO, Crakes KR, Miller M, Gilor C. Domest Anim Endocrinol. 2020 Apr 18;74:106484. doi: 10.1016/j.domaniend.2020.106484. Online ahead of print. PMID: 32619812
Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy cats. Gilor C, Culp W, Ghandi S, do Carmo Emidio E Silva JA, Ladhar A, Hulsebosch SE. Domest Anim Endocrinol. 2019 Oct;69:19-29. doi: 10.1016/j.domaniend.2019.04.001. Epub 2019 Apr 16. PMID: 31280022
The effect of diet, adiposity, and weight loss on the secretion of incretin hormones in cats. McCool KE, Rudinsky AJ, Parker VJ, Herbert CO, Gilor C. Domest Anim Endocrinol. 2018 Jan;62:67-75. doi: 10.1016/j.domaniend.2017.10.004. Epub 2017 Oct 20. PMID: 29128557
New Approaches to Feline Diabetes Mellitus: Glucagon-like peptide-1 analogs. Gilor C, Rudinsky AJ, Hall MJ. J Feline Med Surg. 2016 Sep;18(9):733-43. doi: 10.1177/1098612X16660441. PMID: 27562982 Review.
What's in a Name? Classification of Diabetes Mellitus in Veterinary Medicine and Why It Matters. Gilor C, Niessen SJ, Furrow E, DiBartola SP. J Vet Intern Med. 2016 Jul;30(4):927-40. doi: 10.1111/jvim.14357. PMID: 27461721 Free PMC article. Review.
Duration of fasting but not diurnal variation affects the response to glucagon in healthy cats. Gilor C, Glock R, Gilor S. Domest Anim Endocrinol. 2015 Oct;53:103-7. doi: 10.1016/j.domaniend.2015.05.004. Epub 2015 Jun 9. PMID: 26201763
Pharmacokinetics and pharmacodynamics of the glucagon-like peptide-1 analog liraglutide in healthy cats. Hall MJ, Adin CA, Borin-Crivellenti S, Rudinsky AJ, Rajala-Schultz P, Lakritz J, Gilor C. Domest Anim Endocrinol. 2015 Apr;51:114-21. doi: 10.1016/j.domaniend.2014.12.001. Epub 2014 Dec 12. PMID: 25625650
Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats. Rudinsky AJ, Adin CA, Borin-Crivellenti S, Rajala-Schultz P, Hall MJ, Gilor C. Domest Anim Endocrinol. 2015 Apr;51:78-85. doi: 10.1016/j.domaniend.2014.12.003. Epub 2014 Dec 20. PMID: 25594949
Distribution of K and L cells in the feline intestinal tract. Gilor C, Gilor S, Graves TK, Borst LB, Labelle P, Ridge TK, Santoro D, Dossin O. Domest Anim Endocrinol. 2013 Jul;45(1):49-54. doi: 10.1016/j.domaniend.2013.04.004. Epub 2013 May 18. PMID: 23751572
The GLP-1 mimetic exenatide potentiates insulin secretion in healthy cats. Gilor C, Graves TK, Gilor S, Ridge TK, Rick M. Domest Anim Endocrinol. 2011 Jul;41(1):42-9. doi: 10.1016/j.domaniend.2011.03.001. Epub 2011 Apr 6. PMID: 21645806 Clinical Trial.
The incretin effect in cats: comparison between oral glucose, lipids, and amino acids. Gilor C, Graves TK, Gilor S, Ridge TK, Weng HY, Dossin O. Domest Anim Endocrinol. 2011 May;40(4):205-12. doi: 10.1016/j.domaniend.2011.01.002. Epub 2011 Feb 24. PMID: 21397435
Pharmacodynamics of insulin detemir and insulin glargine assessed by an isoglycemic clamp method in healthy cats. Gilor C, Ridge TK, Attermeier KJ, Graves TK. J Vet Intern Med. 2010 Jul-Aug;24(4):870-4. doi: 10.1111/j.1939-1676.2010.0544.x. Epub 2010 Jun 18. PMID: 20561185 Clinical Trial.
The effects of body weight, body condition score, sex, and age on serum fructosamine concentrations in clinically healthy cats. Gilor C, Graves TK, Lascelles BD, Thomson AE, Simpson W, Halpern DS. Vet Clin Pathol. 2010 Sep;39(3):322-8. doi: 10.1111/j.1939-165X.2010.00227.x. PMID: 20412547