Glucagon-like peptide-1, insulin-like growth factor-1, and adiponectin in insulin-dysregulated ponies: effects of feeding a high nonstructural carbohydrate diet and association with prospective laminitis.

Endocrinopathic laminitis, related to equine metabolic syndrome and insulin dysregulation, causes marked pain and suffering in horses and represents a substantial cost to the horse industry. This study investigated the effect of feeding a diet high in nonstructural carbohydrates on concentrations of active glucagon-like peptide-1 (aGLP-1), total insulin-like growth factor-1 (IGF-1), and high-molecular-weight (HMW) adiponectin, in insulin-dysregulated ponies. Thirty-seven ponies were challenged with this diet for up to 18 d to induce hyperinsulinemia. Hormone concentrations were measured in selected samples on day 2 of the diet challenge period, over 4 h after feeding. Fourteen of the ponies developed mild laminitis induced by the diet challenge. Insulin and glucose responses to the diet have been reported previously. Feeding increased the concentrations of aGLP-1 (P < 0.05) and HMW adiponectin (P < 0.001), but there was no difference between the laminitic and nonlaminitic groups for either hormone. Concentrations of IGF-1 and insulin were inversely related, with IGF-1 being 32% lower in hyperinsulinemic/laminitic ponies compared with nonlaminitic ponies (P = < 0.05). These results indicate that unlike insulin and possibly IGF-1, concentrations of aGLP-1 and HMW adiponectin do not have a strong association with, or play a major role in, the pathogenesis of equine laminitis.

The oral glucose test predicts laminitis risk in ponies fed a diet high in nonstructural carbohydrates.

The aim of this study was to investigate the relationship between laminitis development in ponies and insulin/glucose concentrations in response to the oral glucose test (OGT) and a dietary challenge high in nonstructural carbohydrates (NSCs). After undergoing an OGT (1 g dextrose/kg BW in feed), 37 ponies with 2-h serum insulin concentrations ranging from 22 to 1,133 µIU/mL were subjected to a diet challenge period (DCP), consuming 12 g NSC/kg BW/d for up to 18 d. Insulin and glucose responses were measured on day 2 of the DCP. Clinical laminitis was diagnosed by blinded experts and confirmed radiographically. Basal ACTH levels and clinical signs were assessed to investigate concurrent putative pituitary pars intermedia dysfunction (PPID). The diet induced Obel grade 1 or 2 laminitis in 14 ponies (38%). The ponies that developed laminitis had higher maximum concentrations of blood glucose (P = 0.04) and serum insulin (P = 0.02) in response to the diet. The geometric mean (95% CI) blood glucose concentration for laminitis cases was 14.9 (12.9-17.2) mM, compared to 10.7 (9.2-12.5) mM for ponies who did not develop laminitis. Similarly, the geometric mean (95% CI) for serum insulin was 396 (301-520) µIU/mL for laminitis cases, compared to 216 (148-316) µIU/mL for ponies who did not develop laminitis. Laminitis incidence was likewise associated with insulin concentrations measured during the OGT. Laminitis occurred at frequencies of 0% (0/7) if postdextrose insulin (µIU/mL) was <50; 35% (8/23) if insulin was 50 to 195; and 86% (6/7) if insulin was >195 µIU/mL. Basal ACTH concentrations were above seasonally accepted reference ranges in 16/37 ponies, and 8 of these animals (50%) developed laminitis. This included all 5 ponies in the study that had clinical signs of PPID (100%). In contrast, hyperinsulinemia and laminitis occurred in only 3/11 ponies (27%) with elevated ACTH concentrations and no clinical signs of PPID (P = 0.009). Thus, laminitis occurrence was associated with higher glucose and insulin responses to both the OGT and challenge diet, and the frequency of laminitis can be predicted based on insulin and glucose hyperresponsiveness to these oral carbohydrate challenges.