Laminitic metabolic profile in genetically predisposed ponies involves exaggerated compensated insulin resistance

Abstract

Twenty years ago Jeffcott and associates proposed a clinical syndrome of laminitis and hyperlipaemia that involved adrenal stress and insulin resistance in ponies predisposed to insulin resistance by a thrifty gene. Our primary purpose was to quantitatively determine a metabolic profile for this clinical syndrome. An inbred herd of 170 ponies had no clinical cases of laminitis in March, 2004, but 13 active cases developed at the end of May and were studied on day 1 or 2 of initial diagnosis. This was based on hesitant gait, posture, hoof temperature and bouncing digital pulse. All 13 cases of clinical laminitis (CL) developed in a group of 54 ponies that had previously been positive for laminitis (PL), while no cases developed (p < 0.0001) in the remaining 116 ponies that had never exhibited laminitis (NL). This result established the predictive value of a pre‐laminitic metabolic syndrome in apparently healthy ponies, which is a phenotypic representation of a genotype characterized as dominance with partial suppression that may be amenable to nutritional intervention. The advent of clinical laminitis occurred at the same time as an 83% increase (p = 0.039) of starch in the pasture, which was attributable to a rich growth of clover. Ponies were gathered, weighed, scored for body condition, and sampled for blood between 08:00 and 10:00 hours. Body condition scores were higher (p = 0.002) in the CL and PL groups (6.5 ± 0.1) than the NL (6.1 ± 0.1). Plasma analysis revealed higher (p < 0.001) concentrations of insulin in the affected group (92 ± 2, 32 ± 6 and 15 ± 2 μIU/ml in CL, PL and NL respectively) and triglycerides (58 ± 6, 44 ± 4, and 44 ± 4 mg/dl), but no differences were found for glucose, non‐esterified fatty acids, and cortisol. Plasma insulin and glucose concentrations were applied as proxies that indicate low insulin sensitivity and extremely high pancreatic β‐cell response, together indicating a transition state between compensated and uncompensated insulin resistance in the CL group that might be regarded as exaggerated compensation. For comparison, in two cases of subacute laminitis studies on the 8th day of the disease, insulin resistance was uncompensated. The effectiveness of the extreme pancreatic response in the prodromal stage is also indicated by the lack of hyperglycaemia and only mild elevation of serum triglycerides. Absence of hypercortisolaemia suggests that affected ponies were not undergoing adrenal stress. Collectively these results indicate a changing role of insulin resistance in laminitis: a compensated predisposing factor in healthy but genetically predisposed ponies, then a pathogenetic component as a transient exaggerated compensation during the advent of laminitis, and finally uncompensated insulin resistance later in the course of the disease.