Diabetes mellitus is a common endocrinopathy in dogs, with reported prevalence ranging from 1 in 100 to 1 in 500 dogs affected.1 The cause of DM in dogs is multifactorial, and studies2–5 suggest that genetics, environmental factors, and immune-mediated components contribute to the development of the disease. Epidemiological studies1,4,6 show that age of onset for most affected dogs is between 4 and 15 years and that female dogs have an increased risk of developing DM. Genetic predispositions have been suggested, but the mode of inheritance or specific genes involved have not been identified in most breeds. In addition, most dogs with DM are insulin dependent, resembling type 1 diabetes in humans.6
Cataract formation is the most frequently occurring and important ocular complication associated with DM in dogs, and such cataracts often have an acute onset, are bilaterally symmetric, and rapidly progress. A retrospective cohort study7 of dogs with DM shows that most (89/200 [44.5%]) dogs develop cataracts within 5 to 6 months after DM is diagnosed. Serum glucose and sorbitol concentrations, duration of hyperglycemia, and aldose reductase activity are thought to contribute to the development of cataracts in patients with diabetes.6,8-10
Leakage of soluble lens proteins through the intact capsule of a cataractous lens triggers LIU.11–13 The pathogenesis of LIU is not completely understood but is believed to be the result of a breakdown in the normal T-cell tolerance of lens proteins and other lens components.14 In a healthy eye, small amounts of lens protein leak across the intact lens capsule, which leads to low-dose immunologic T-cell tolerance.15,16 However, increased immune system exposure to lens proteins, either by leakage through the more permeable capsule of a cataractous lens or through a lens capsule rupture, may overwhelm this tolerance and incite a cell-mediated or humoral immune response, alone or in combination, and breakdown of the blood-aqueous barrier has been demonstrated and quantified by fluorophotometry in the eyes of dogs with all stages of cataract.17 In a retrospective study18 of dogs that were cataract surgery candidates, 82 of 116 (71%) dogs overall had LIU, whereas 23 of 25 (92%) dogs with DM had LIU. Furthermore, eyes with LIU may have lower long-term success rates following cataract surgery.11,18,19
Topical ophthalmic preparations of glucocorticoids and NSAIDs are most commonly used to control inflammation in the anterior segment of the eye.13 Such use includes treatment of LIU (clinical or subclinical) in dogs with DM and cataracts and preparing the eyes for cataract surgery. In our experience, patients with moderate to severe LIU are more likely prescribed a topical ophthalmic product containing a glucocorticoid, rather than an NSAID. In addition, most patients undergoing cataract surgery receive a topically administered anti-inflammatory medication for a minimum of 2 months after cataract surgery,20 with some patients receiving the medication indefinitely.
Glucocorticoids impair glucose homeostasis through several complex physiologic mechanisms and negatively impact glycemic control. For instance, glucocorticoids induce the gluconeogenic enzymes fructose-1,6-biphosphatase, glucose-6-phosphatase, and phosphoenopyruvate carboxykinase.21,22 Glucocorticoids also increase substrates for gluconeogenesis by stimulating proteolysis in skeletal muscle and lipolysis in adipose tissue, thereby increasing concentrations of blood glucose.23–25 Endogenous and exogenous systemic glucocorticoids can induce insulin resistance in animals with and without DM and can reduce glycogen synthesis by affecting glycogen synthase kinase-3 phosphorylation.26
A study27 of 130 dogs that underwent surgical treatment for cataracts shows that 66 (50.8%) dogs also had DM. Thus, if topically applied ophthalmic preparations of glucocorticoids could alter glycemic control in treated dogs, then the use of such medication after cataract surgery in dogs with DM may contribute to difficulty in regulating DM. Although it has been suggested that topical ophthalmic preparations of glucocorticoids might cause insulin antagonism and interfere with glycemic control in dogs with DM, especially in toy and miniature breeds,6 there are currently no published reports of investigations that have evaluated the effects of topically applied ophthalmic preparations of glucocorticoids on DM regulation in dogs.
The purpose of the prospective, randomized, double-masked study reported here was to evaluate and compare DM regulation in dogs with cataracts and well-controlled DM that received a topical ophthalmic preparation of prednisolone acetate 1.0% versus diclofenac sodium 0.1%. We hypothesized that regulation of DM in dogs would not meaningfully differ between dogs treated with an ophthalmic preparation of prednisolone and dogs treated with an ophthalmic preparation of diclofenac.
The present study represents the continuation of a project reported in a thesisa and included data on 12 dogs from that thesis.
Supported by Morris Animal Foundation Grant D14CA-321, Kansas State University College of Veterinary Medicine Mark Derrick Canine Research Grant, and a Kansas State University Mentored Clinical, Applied, or Translational Research Grant. This publication has not been reviewed or endorsed by the Morris Animal Foundation, and the views expressed do not necessarily reflect the views of the Morris Animal Foundation or its officers, directors, affiliates, or agents.
The authors declare that there were no conflicts of interest.
Presented in abstract form at the 48th Annual American College of Veterinary Ophthalmologists Meeting, Baltimore, October 2017.
Continuous glucose monitoring system
Least squares mean
Serum fructosamine concentration
Stuckey JA. Preliminary analysis of ophthalmic prednisolone acetate and diclofenac on diabetes mellitus regulation in 12 of 40 dogs. MS thesis, Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, Kan, 2014.
Merck Animal Health, Madison, NJ.
Bio-Glo fluorescein sodium ophthalmic strips, HUB Pharmaceuticals LLC, Rancho Cucamonga, Calif.
TonoVet, Tiolat Ltd, Helsinki, Finland.
SL-14, Kowa Co Ltd, Tokyo, Japan.
Binocular indirect ophthalmoscope, Keeler LTD, Malvern, Pa.
Guardian REAL-Time CGMS, Medtronic MiniMed Inc, Northridge, Calif.
Pred Forte, Allergan, Irvine, Calif.
Voltaren, Akorn, Lake Forest, Ill.
PROC GLIMMIX, SAS, version 9.4, SAS Institute Inc, Cary, NC.
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Variables assessed to determine individual clinical scores as an evaluation of DM control in 22 dogs with cataracts and well-controlled DM that received a topical ophthalmic preparation of either prednisolone acetate 1% (prednisolone group; n = 10) or diclofenac sodium 0.1% (diclofenac group; 12) administered in each eye 4 times daily for 28 days.
|Variables||Point values assigned|
|Need for insulin adjustment in previous 4 weeks||Yes (1 point) or no (0 points)|
|Increased water consumption||Yes (1 point) or no (0 points)|
|Change in urine frequency, amount, or both||Yes (1 point) or no (0 points)|
|Increased appetite or food intake||Yes (1 point) or no (0 points)|
|Decreased activity level||Yes (1 point) or no (0 points)|
|Signs of hypoglycemia noticed||Yes (1 point) or no (0 points)|
|Required treatment for hypoglycemia||Yes (1 point) or no (0 points)|
|Noncompliant with insulin, ocular medications, or both||Yes (1 point) or no (0 points)|
|≥ 5% change in body weight from last examination||Yes (1 point) or no (0 points)|
|Body condition score||Unacceptable (1/5 or 5/5; 1 point) or acceptable (2/5–4/5; 0 points)|
|Hydration status||Dehydrated (1 point) or clinically normal hydration (0 points)|
|Cataract progression||Yes (1 point) or no (0 points)|
|Uveitis present||Yes (1 point) or no (0 points)|
|SFC||Unacceptable (> 450 μmol/L; 1 point) or acceptable (≤ 450 μmol/L; 0 points)|
|Insulin adjustment recommended after glucose curve||Yes (1 point) or no (0 points)|
The total clinical scores recorded for each dog on days 0 and 32 were log transformed for generalized linear mixed-model analysis to assess potential differences between treatment groups throughout the period of observation.