K. H. Treiber

Prediction of incipient pasture-associated laminitis from hyperinsulinaemia, hyperleptinaemia and generalised and localised obesity in a cohort of ponies

REASONS FOR PERFORMING STUDY The ability to predict ponies at increased risk of laminitic episodes, when exposed to nutrient dense pasture, would facilitate management to avoid disease. OBJECTIVES To identify variables and clinically useful cut-off values with reproducible diagnostic accuracy for the prediction of ponies that subsequently developed laminitis when exposed to nutrient dense pasture. METHODS A cohort of predominantly Welsh and Dartmoor ponies from a closed herd was evaluated in March 2006 (n = 74) and March 2007 (n = 57). Ponies were categorised as never laminitic or previously laminitic according to reported laminitic history and as clinically laminitic (CL) if laminitis was observed within 3 months following evaluation. Body condition score (BCS), cresty neck score (CNS), girth and neck circumferences (NC), withers height, blood pressure and hoof surface temperature, and plasma insulin, glucose, triglyceride, leptin, cortisol, ACTH, uric acid and TNF-alpha concentrations were measured. Analysis of sensitivity, specificity and receiver operating characteristic curves was used to evaluate the diagnostic accuracy for a variable to predict CL ponies. RESULTS Variables with diagnostic accuracy for the prediction of CL ponies included insulin, leptin, BCS, CNS, and NC:height ratio. Specific cut-off values of insulin (>32 mu/l), leptin (>73 ng/ml), BCS (> or = 7), CNS (> or = 4) and NC:height ratio (>0.71) had reproducible diagnostic accuracy for the prediction of laminitis. Combining tests did not result in higher diagnostic accuracy than individual tests of insulin or leptin during either evaluation. CONCLUSIONS Tests of insulin and leptin concentrations and measures of generalised (BCS) and localised (CNS or NC:height ratio) obesity were beneficial in the prediction of laminitic episodes. POTENTIAL RELEVANCE These results highlight the importance of monitoring and reducing insulin concentration, and generalised and regional obesity in ponies to reduce risk of laminitis.

Insulin Resistance in Equids: Possible Role in Laminitis

Insulin is a major regulatory hormone in glucose and fat metabolism, vascular function, inflammation, tissue remodeling, and the somatotropic axis of growth. Insulin resistance alters insulin signaling by decreasing insulin action in certain resistant pathways while increasing insulin signaling in other unaffected pathways via compensatory hyperinsulinemia. In humans, altered insulin signaling is implicated in reduced glucose availability to insulin-sensitive cells, vasoconstriction and endothelial damage, and inflammatory response. Although no direct evidence exists for insulins role in these mechanisms in the laminitic horse, changes in the glucose availability, vasculature, and inflammation were all demonstrated in hoof separation. Insulin resistance was first implicated in the pathogenesis of laminitis in the 1980s using tolerance tests. Our present findings provide the first specific evidence of insulin resistance as a major predisposing condition for laminitis. Specific quantitative characterization of insulin resistance is essential toward identifying the following: 1) ponies in need of special management to avoid laminitis, and 2) potential management strategies to avoid laminitis by increasing insulin sensitivity, including reducing obesity, increasing exercise, and moderating dietary carbohydrates, particularly starch.

Inflammatory and redox status of ponies with a history of pasture-associated laminitis

Inflammatory and redox signals could render lamellar tissue susceptible to damage and contribute to higher risk for laminitis in obese or insulin resistant ponies just as these factors contribute to health risks in humans with metabolic syndrome. This study evaluated circulating markers of inflammatory and redox status in ponies that had a history of recurrent bouts of pasture-associated laminitis (PL, n = 42) or had never developed clinical laminitis (NL, n = 34) under the current management conditions. There were no differences (P > 0.05) between PL and NL ponies for markers of antioxidant function (glutathione, glutathione peroxidase, superoxide dismutase) or increased oxidative pressure (malondialdehyde, apoptosis, 3-nitrotyrosine). Inflammatory status, as indicated by fibrinogen concentration, was also not different between pony groups (P = 0.84). However, PL ponies had higher (P < 0.001) plasma concentrations of the pro-inflammatory cytokine TNF-alpha than NL ponies. This suggests that a predisposition to laminitis is associated with increased circulating inflammatory cytokines. TNF-alpha could also represent a contributing factor to increased insulin resistance observed in laminitis prone ponies. These results provide new insight into potential mechanisms and risk factors underlying laminitis.

Insulin sensitivity and glucose dynamics during pre-weaning foal development and in response to maternal diet composition.

Nutritional management of animals during pregnancy can affect glucose and insulin dynamics in the resulting offspring through influences on fetal development. Additionally, high starch feeding in mature horses is associated with reduced insulin sensitivity and an increased risk for diseases such as obesity and laminitis. However, no study has yet evaluated the effect of feeding a high starch diet to pregnant mares on glucose and insulin dynamics in their offspring. Twenty late-gestation mares maintained on pasture were provided two-thirds of digestible energy requirements from isocaloric, isonitrogenous low starch (LS, n=10) or high starch (HS, n=10) feed. Their foals were assessed with an insulin-modified frequently sampled intravenous glucose tolerance test at 5, 40, 80, and 160 d of age. Baseline glucose concentrations, insulin sensitivity, and insulin-independent glucose clearance in 5-d foals were all greater than values observed in mature horses and declined towards mature values as foals reached 160 d of age. Baseline glucose concentrations were all within normal range, but higher in foals born from HS mares through 80 d of age. Insulin sensitivity was not different between dietary groups until a trend for lower insulin sensitivity in HS foals emerged at 160 d of age. These data are the first to characterize decreasing insulin sensitivity and glucose tolerance in Thoroughbred foals from 5 to 160 d of age. This study also presents the first data examining glucose and insulin dynamics in developing foals in response to maternal high starch diet.

Evaluation of the effects of pregnancy on insulin sensitivity, insulin secretion, and glucose dynamics in Thoroughbred mares

OBJECTIVE To characterize the effects of pregnancy on insulin sensitivity (SI) and glucose dynamics in pasture-maintained mares fed supplemental feeds of differing energy composition. ANIMALS Pregnant (n = 22) and nonpregnant (10) healthy Thoroughbred mares. PROCEDURES Pregnant and nonpregnant mares underwent frequently sampled intravenous glucose tolerance tests at 2 times (period 1, 25 to 31 weeks of gestation; period 2, 47 weeks of gestation). Following period 1 measurements, mares were provided a high-starch (HS; 39% starch) or high-fat and -fiber (14% fat and 70% fiber) supplemental feed. From a subset of mares (n = 12), blood samples were collected hourly for 24 hours to assess glycemic and insulinemic response to feeding while pastured. The minimal model of glucose and insulin dynamics was used to estimate SI, glucose effectiveness, and acute insulin response to glucose from tolerance testing data. RESULTS Pregnant mares during period 1 had a lower SI and glucose effectiveness and higher acute insulin response to glucose than did nonpregnant mares. The SI value decreased in nonpregnant but not pregnant mares from periods 1 to 2. Pregnant mares fed HS feed had a greater glycemic and insulinemic response to feeding than did any other group. CONCLUSIONS AND CLINICAL RELEVANCE Pregnant mares had slower glucose clearance and greater insulin secretion at 28 weeks of gestation than did nonpregnant mares. Glucose and insulin responses to meal feeding, particularly with HS feed, were greater in pregnant mares, indicating that pregnancy enhanced the postprandial glycemic and insulinemic effects of starch-rich feed supplements.