Single-injection glucose kinetics with compartmental modelling during rest and low-intensity exercise in horses.

REASONS FOR PERFORMING STUDY: Tools and criteria to evaluate and understand glucose metabolism are essential to optimise equine energy utilisation for exercise performance and reduced metabolic health risks. OBJECTIVES: To re-evaluate models of glucose kinetics in the horse at rest and during endurance type exercise using a single injection technique and compartmental modelling. METHODS: Twelve exercise trained Arabian geldings received a bolus of 100 µmol/kg bwt [6,6-(2) H]glucose i.v. while at rest and while running at ∼ 4 m/s on a treadmill. Tracer and tracee glucose curves from 4-150 min after the bolus dose (while the subject maintained its resting or exercising state) were described by a 2 term exponential decay curve. Compartmental modelling was performed simultaneously for each horse's resting and exercise curves using an 'exercise effect' parameter for each compartmental exchange rate during exercise. RESULTS: Exercise increased all rate constants and transport flows for glucose between compartments by 110-145% (P ≤ 0.004). Total glucose transport through the system increased from 8.9 ± 0.6 µmol/min/kg/bwt at rest to 25.0 ± 1.1 µmol/min/kg bwt during exercise (P < 0.001). Exercise decreased the volume of the primary glucose compartment by 8% (P = 0.006) and increased plasma glucose clearance rate by almost 200% (P < 0.001). Turnover times and mean residence times were decreased approximately 60% by exercise (P < 0.001), whilst turnover rates were increased 125% (P < 0.001). CONCLUSIONS: Single-injection tracer kinetics and compartmental modelling represent a valuable tool to quantify tracee availability to and use by tissue. POTENTIAL RELEVANCE: This technique could represent a beneficial tool for future studies exploring the role of glucose metabolism in equine exercise performance and metabolic disease.

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 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.

Does usefulness of potassium supplementation depend on speed?

REASONS FOR PERFORMING STUDY: Electrolyte mixtures given to counter sweat loss usually contain abundant potassium. However, increases in plasma [K+] occur with exercise and supplementation may further increase plasma levels, potentially increasing the risk of neuromuscular hyperexcitability and development of adverse clinical sequellae. This proposition requires study. OBJECTIVES: To compare effects of a K-rich electrolyte supplement (EM+K) to a K-free one (EM-K) on plasma [K+], [Ca++] and acid-base status during an endurance incremental exercise test on the treadmill. METHODS: The test consisted of 3 bouts (simulating loops in an endurance race) of 12 km performed at 6, then 7, then 8 m/sec with 25 min rest stops (S1, S2) between loops on 13 endurance trained Arabian horses (7 EM-K, 6 EM+K). Electrolytes were supplied orally 60 mins before exercise (Pre) and at each stop. Blood samples were taken before exercise and during exercise, each S and 120 mins of recovery (R). Blood was analysed for pH, PCO2, packed cell volume (PCV), plasma [Na+], [K+], [Cl-], [Ca++], glucose, and lactate [La-]; plasma [H+] and osmolality (osm) were calculated. The dietary cation anion difference (DCAD) was calculated to be -27 meq/dose EM-K and 109 meq in EM+K, respectively. RESULTS: Plasma [H+] decreased during the 6 and 7 m/sec loops, increased during the 8 m/sec loop, and returned to Pre at S1, S2 and R. Plasma [K+] was higher at 8 m/sec and plasma [Ca++] was overall lower in the EM+K group compared to EM-K. Other findings included higher overall PCV, overall glucose, and [La-] during the 8 m/sec loop (P<0.040) in EM+K compared to EM-K horses. CONCLUSIONS: EM+K supplementation leads to higher plasma [K+] increasing the risk of neuromuscular hyperexcitability during exercise. Acute effects of a lower DCAD in EM-K may have led to higher plasma [Ca++]. Potassium-rich electrolytes may have triggered the release of epinephrine, contributing to higher PCV, glucose release and increased lactate production. POTENTIAL RELEVANCE: Lower plasma [K+] and higher plasma [Ca++] with EM-K supplementation may help reduce the risk of conditions associated with neuromuscular hyperexcitability occurring especially during higher speeds in endurance races.

Glucose dynamics during exercise: dietary energy sources affect minimal model parameters in trained Arabian geldings during endurance exercise.

REASONS FOR PERFORMING STUDY: Glucose regulation is critical for health and exercise performance. OBJECTIVES: To quantify the effects of exercise and diet on insulin sensitivity (SI), glucose effectiveness (Sg), acute insulin response to glucose (AIRg) and disposition index (DI) in horses. METHODS: This study applied the minimal model of glucose and insulin dynamics to exercise-trained Arabian geldings during rest or constant moderate-intensity exercise after 8 weeks adaptation to feeds high in sugar and starch (SS, n = 6) or fat and fibre (FF, n = 6). Horses underwent 2 frequently sampled i.v. glucose tolerance tests (FSIGT). For both tests, a resting basal sample was collected, followed by an i.v. dose of 600 mg/kg bwt glucose defining 0 min of the test. Insulin (0.01 iu/kg bwt) was administered 20 min post glucose for each test. Resting horses were sampled for 240 min. The exercise FSIGT began after each horse had warmed-up for 25 min on the treadmill at which point they had reached the speed representing 60% of their predetermined lactate breakpoint maintained for the rest of the FSIGT. Exercising horses were sampled identically to rest, but for only 150 min post glucose. RESULTS: Exercise increased (P<0.008) SI, Sg and DI and decreased AIRg in all horses. Overall, horses adapted to FF tended to have higher SI (P = 0.070) and DI (P = 0.058). During exercise, FF horses tended to have higher (P< or =0.085) SI and DI, than SS horses and these variables tended to be increased more (P< or =0.075) by exercise in FF horses than SS horses. CONCLUSIONS: Insulin and glucose dynamics adjust during exercise, increasing plasma glucose uptake, presumably to meet demand by contracting skeletal muscle. Trained horses adapted to a high fat diet showed greater metabolic adjustment during exercise than trained horses adapted to a high starch and sugar diet, potentially allowing them to better meet energy demands. POTENTIAL RELEVANCE: Nutrition and exercise impact glucose and insulin dynamics, potentially influencing health and performance.

Insulin resistance and compensation in Thoroughbred weanlings adapted to high-glycemic meals.

Insulin resistance has been suggested to increase the risk of certain diseases, including osteochondrosis and laminitis. Our objective was to evaluate the effect of adaptation to high-glycemic meals on glucose-insulin regulation in healthy Thoroughbred weanlings. Twelve Thoroughbred foals were raised on pasture and supplemented twice daily with a feed high in either sugar and starch (SS; 49% nonstructural carbohydrates, 21% NDF, 3% crude fat on a DM basis) or fat and fiber (FF; 12% nonstructural carbohydrates, 44% NDF, 10% crude fat on a DM basis). As weanlings (age 199 +/- 5 d; BW 274 +/- 5 kg) the subjects underwent a modified frequently sampled i.v. glucose tolerance test. A series of 39 blood samples was collected from -60 to 360 min, with a glucose bolus of 300 mg/kg BW injected at 0 min and an insulin bolus of 1.5 mIU/kg BW at 20 min. All samples were analyzed for glucose and insulin, and basal samples also were analyzed for plasma cortisol, triglyceride, and IGF-I. The minimal model of glucose and insulin dynamics was used to determine insulin sensitivity (SI), glucose effectiveness, acute insulin response to glucose (AIRg), and disposition index (DI). Insulin sensitivity was 37% less (P = 0.007) in weanlings fed SS than in those fed FF; however, DI did not differ (P = 0.65) between diets because AIRg tended to be negatively correlated with SI (r = -0.55; P = 0.067). This finding indicates that the SI decrease was compensated by AIRg in the weanlings adapted to SS. This compensation was further demonstrated by greater insulin concentrations in SS-adapted weanlings compared with FF-adapted weanlings at 11 of 36 sample points (P < 0.055) and greater (P = 0.040) total area under the insulin curve in SS than in FF weanlings. Plasma cortisol and triglycerides did not differ between dietary groups, but IGF-I was greater (P = 0.001) in SS weanlings. Despite appearing healthy, horses adapted to high-glycemic feeds may exhibit changes in altered insulin sensitivity and compensation that increase the risk of diseases involving insulin resistance. These changes seem to be partially amenable to dietary management.

Growth rate consists of baseline and systematic deviation components in Thoroughbreds.

The objective of this study was to establish a procedure for differentiating a baseline curve from a systematic deviation in weight-age data, and hence to develop a physiological growth model for the Thoroughbred. A total of 2,698 records for 175 foals was obtained during a period of 8 yr (1994 to 2001). Weight-age data were fit with a sigmoid growth equation, W = A(1 + be(-kt))M, where W is BW at age t, A is the asymptotic value of W, b is a scaling parameter that defines the degree of maturity at t = 0, k is a rate constant, and M defines the point of inflection in the sigmoid curve in relation to age. Short-term systematic deviations in the weight-age data were identified by a goodness-of-fit procedure and illustrated in three-dimensional contour plots of the sigmoid equation parameters as they changed upon removal of selected subsets of the data. Based on features of the contour plots, a negative deviation between 210 and 420 d of age was set aside, with the remaining data establishing the baseline data set. The sigmoid growth equation was fit to the baseline data set using a nonlinear mixed model with repeated measures, and indicated a mature weight of 542 +/- 6.2 kg reached at 7 yr. The systematic deviation identified in this weight-age data set is present in other published Thoroughbred growth data and is likely to result in erroneous parameter estimates if not set aside before fitting sigmoid growth equations to the thus-modified weight-age data set. The techniques developed in this study enable identification of short-term systematic deviations in weight-age data and define a realistic baseline growth curve. Differentiation of these two components enables the development of a physiological model of growth that distinguishes between baseline growth and environmental influences, represented respectively, by the baseline curve and the systematic deviation.