Effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses

Heather A. Tiley Departments of Biomedical Sciences and Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada

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Ray J. Geor Departments of Biomedical Sciences and Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada

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L. Jill McCutcheon Departments of Biomedical Sciences and Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada

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 DVM, PhD

Abstract

Objective—To determine effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses.

Animals—6 adult Standardbreds.

Procedures—In a balanced crossover study, horses received dexamethasone (0.08 mg/ kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution (control treatment) during a 21-day period. Horses underwent a 3-hour frequently sampled IV glucose tolerance test (FSIGT) 2 days after treatment. Minimal model analysis of glucose and insulin data from FSIGTs were used to estimate insulin sensitivity (Si), glucose effectiveness (Sg), acute insulin response to glucose (AIRg), and disposition index. Proxies for Si (reciprocal of the inverse square of basal insulin concentration [RISQI]) and beta-cell responsiveness (modified insulin-to-glucose ratio [MIRG]) were calculated from basal plasma glucose and serum insulin concentrations.

Results—Mean serum insulin concentration was significantly higher in dexamethasone-treated horses than control horses on days 7, 14, and 21. Similarly, mean plasma glucose concentration was higher in dexamethasone-treated horses on days 7, 14, and 21; this value differed significantly on day 14 but not on days 7 or 21. Minimal model analysis of FSIGT data revealed a significant decrease in Si and a significant increase in AIRg after dexamethasone treatment, with no change in Sg or disposition index. Mean RISQI was significantly lower, whereas MIRG was higher, in dexamethasone-treated horses than control horses on days 7, 14, and 21.

Conclusions and Clinical Relevance—The study revealed marked insulin resistance in healthy horses after 21 days of dexamethasone administration. Because insulin resistance has been associated with a predisposition to laminitis, a glucocorticoid-induced decrease in insulin sensitivity may increase risk for development of laminitis in some horses and ponies.

Abstract

Objective—To determine effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses.

Animals—6 adult Standardbreds.

Procedures—In a balanced crossover study, horses received dexamethasone (0.08 mg/ kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution (control treatment) during a 21-day period. Horses underwent a 3-hour frequently sampled IV glucose tolerance test (FSIGT) 2 days after treatment. Minimal model analysis of glucose and insulin data from FSIGTs were used to estimate insulin sensitivity (Si), glucose effectiveness (Sg), acute insulin response to glucose (AIRg), and disposition index. Proxies for Si (reciprocal of the inverse square of basal insulin concentration [RISQI]) and beta-cell responsiveness (modified insulin-to-glucose ratio [MIRG]) were calculated from basal plasma glucose and serum insulin concentrations.

Results—Mean serum insulin concentration was significantly higher in dexamethasone-treated horses than control horses on days 7, 14, and 21. Similarly, mean plasma glucose concentration was higher in dexamethasone-treated horses on days 7, 14, and 21; this value differed significantly on day 14 but not on days 7 or 21. Minimal model analysis of FSIGT data revealed a significant decrease in Si and a significant increase in AIRg after dexamethasone treatment, with no change in Sg or disposition index. Mean RISQI was significantly lower, whereas MIRG was higher, in dexamethasone-treated horses than control horses on days 7, 14, and 21.

Conclusions and Clinical Relevance—The study revealed marked insulin resistance in healthy horses after 21 days of dexamethasone administration. Because insulin resistance has been associated with a predisposition to laminitis, a glucocorticoid-induced decrease in insulin sensitivity may increase risk for development of laminitis in some horses and ponies.

Contributor Notes

Dr. Geor's present address is Department of Animal and Poultry Science, College of Agriculture and Life Sciences, Virginia Tech, Middleburg Agricultural Research and Extension Center, 5527 Sullivan's Mill Rd, Middleburg, VA 20117.

Dr. McCutcheon's present address is Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Marion duPont Scott Equine Medical Center, Leesburg, VA 20177.

Supported by the Ontario Ministry of Agriculture, Food and Rural Affairs and Natural Science and Engineering Research Council of Canada.

Address correspondence to Dr. Geor.
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