Pituitary pars intermedia dysfunction does not affect various measures of insulin sensitivity in old horses

Abstract

s / Journal of Equine Veterinary Science 33 (2013) 321-399 358 Production and Management: Graduate Student Competition Pituitary pars intermedia dysfunction does not affect various measures of insulin sensitivity in old horses L.M. Mastro , N.A. Holownia , S.L. Tanner , T. Barnes , M.G. Sanz , A.A. Adams , and K.L. Urschel 1 1 Department of Animal and Food Sciences, University of Kentucky, Lexington, KY, 40546, Gluck Equine Research Center, University of Kentucky, Lexington, KY, 40546 Equine pituitary pars intermedia dysfunction (PPID), also known as equine Cushing’s syndrome, typically occurs in horses older than 15 years of age and is characterized by hair coat abnormalities, muscle atrophy, increased susceptibility to chronic infections and laminitis. Moreover, a reduction in insulin sensitivity has been described in horses with PPID compared to younger adult horses (Klinkhamer et al., 2011); however, the difference in insulin sensitivity between horses with PPID and agedmatched controls has not been well characterized. The objective of this study was to determine if aged horses with PPID had reduced insulin sensitivity when compared to healthy aged horses. In this study, twelve horses older than 20 years of age were classified as either PPID (n1⁄46; 25.0 2.5 yrs; mean SD) or Control (n1⁄46; 25.7 2.0 yrs). PPID classification was based on a resting ACTH greater than 50 pg/mL (PPID: 98.4 73.7 pg/mL; Control: 23.3 8.2 pg/mL) and serum cortisol greater than 1 mg/dL19-20 hours post dexamethasone administration (PPID: 2.27 0.92 mg/dL; Control: 0.46 0.32 mg/dL). Insulin sensitivity was evaluated using euglycemic-hyperinsulinemic clamp (EHC) procedures where insulin was infused at a constant rate (1.2 mIU/kg/min) for 120 minutes and the glucose infusion rate was adjusted to maintain plasma glucose concentrations within 10% of baseline. Blood samples were taken before and then every 15 minutes during the clamp procedures and plasma was analyzed for glucose and insulin concentrations. Insulin sensitivity was assessed using the rate of glucose infusion needed to maintain euglycemia during EHC procedures and by the calculation of two proxies of insulin sensitivity that used baseline glucose and insulin concentrations: the reciprocal of the square root of insulin (RISQI) and the modified insulin-to-glucose ratio (MIRG). Plasma insulin concentrations increased by w9-fold during the EHC procedures compared to baseline (P 0.05) in either group. During the last 30 minutes of the EHC, the rate of glucose infusion required to maintain euglycemia in horses with PPID (11.7 2.04 mmol/min/kg; mean SE) was similar to that in the control horses (13.0 2.04 mmol/min/kg) (P1⁄40.67). No significant differences between PPID and Control were found for either RISQI (PPID: 0.27 mU/L-0.5; Control: 0.34 mU/L-0.5; Pooled SE: 0.03; P1⁄40.16) or MIRG (PPID: 7.27 mUinsulin/[10*L*mgglucose]; Control: 6.61 mUinsulin/ [10*L*mgglucose]; Pooled SE: 0.89; P1⁄40.61) indices. While reduced insulin sensitivity may occur as a normal part of aging in horses, it does not appear to be directly associated with PPID.