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.
Objective—To determine pharmacokinetics and plasma steady-state kinetics of metformin after oral or nasogastric administration in insulin-resistant (IR) ponies
Animals—8 IR ponies
Procedures—Metformin (30 mg/kg) was administered to 8 ponies via nasogastric tube Blood samples were collected at intervals for 24 hours. Plasma concentrations of metformin were measured via liquid chromatography-electrospray tandem mass spectroscopy Pharmacokinetic variables were determined via noncompartmental analysis. Metformin (15 mg/kg, PO, twice daily [8 am and 5 pm]) was administered to 4 ponies for an additional 20 days, and blood samples were obtained every 2 days. Plasma concentration at steady state (Css) was determined.
Results—Mean ± SD elimination half-life (t1/2) of metformin was 11.7 ± 5.2 hours, maxima plasma concentration was 748 ± 269 ng/mL at 54 ± 32 minutes, mean area under the curve was 355 ± 92μg•h/mL, and apparent clearance was 90.6 ± 28.1 mL/min/kg. The Css was 122 ± 22 ng/mL.
Conclusions and Clinical Relevance—Metformin reportedly enhances insulin sensitivity of peripheral tissues without stimulating insulin secretion, but bioavailability in horses is low. The t1/2 of metformin in IR ponies was similar to that in humans. Actual clearance of metformin adjusted for bioavailability in IR ponies was similar to that in humans; however, during chronic oral administration at dosages reported in efficacy studies, the Css of metformin was less than values associated with therapeutic efficacy in humans The apparent lack of long-term efficacy of metformin in horses is likely attributable to low bioavailability, rather than to rapid clearance. (Am J Vet Res 2010;71:1201-1206)
Objective—To evaluate a human radioimmunoassay (RIA) and equine and high-range porcine (hrp) species-specific ELISAs for the measurement of high serum insulin concentrations in ponies.
Samples—Serum samples from 12 healthy nonobese ponies (7 clinically normal and 5 laminitis prone; 13 to 26 years of age; 11 mares and 1 gelding) before and after glucose, insulin, and dexamethasone administration.
Procedures—Intra-and interassay repeatability, freeze-thaw stability, dilutional parallelism, and assay agreement were assessed.
Results—Assay detection limits were as follows: RIA, < 389 μU/mL; equine ELISA, < 175 μU/mL; and hrp ELISA, 293 to 8,775 μU/mL. Mean ± SD intra- and interassay repeatability were respectively as follows: RIA, 6.5 ± 5.1 % and 74 ± 3.4%; equine ELISA, 10.6 ± 11.0% and 9.0 ± 4.6%; and hrp ELISA, 19.9 ± 172% and 173 ± 16.6%. Freezing and thawing affected measured concentrations. Dilutional parallelism in the RIA was only evident when insulin-depleted equine serum was used as a diluent (percentage recovery, 95.7 ± 274%); in the ELISAs, dilutional parallelism was observed when a zero calibrator was used. Agreement between RIA and equine ELISA results was good for samples containing concentrations < 175 μU of insulin/mL (bias, −18.5 ± 25.5 μU/mL; higher in RIA). At higher concentrations, assay agreement was poor between RIA and equine ELISA results (bias, −185.3 ± 98.7 μU/mL) and between RIA and hrp ELISA results (bias, 25.3 ± 183.0 μU/mL).
Conclusions and Clinical Relevance—Agreement among results of the 3 assays was variable, and dilutional parallelism was only evident with the RIA when insulin-depleted equine serum was tested. Caution is recommended when evaluating high insulin concentrations measured with the RIA or ELISAs.
Objective—To compare effects of oral supplementation
with an experimental potassium-free sodiumabundant
electrolyte mixture (EM-K) with that of oral
supplementation with commercial potassium-rich
mixtures (EM+K) on acid-base status and plasma ion
concentrations in horses during an 80-km endurance
Animals—46 healthy horses.
Procedure—Blood samples were collected before
the ride; at 21-, 37-, 56-, and 80-km inspection points;
and during recovery (ie, 30-minute period after the
ride). Consumed electrolytes were recorded. Blood
was analyzed for pH, PvCO2, and Hct, and plasma was
analyzed for Na+, K+, Cl–, Ca2+, Mg2+, lactate, albumin,
phosphate, and total protein concentrations. Plasma
concentrations of H+ and HCO3–, the strong ion difference
(SID), and osmolarity were calculated.
Results—34 (17 EM-K and 17 EM+K treated) horses
finished the ride. Potassium intake was 33 g less and
Na+ intake was 36 g greater for EM-K-treated horses,
compared with EM+K-treated horses. With increasing
distance, plasma osmolarity; H+, Na+, K+, Mg2+,
phosphate, lactate, total protein, and albumin concentrations;
and PvCO2 and Hct were increased in all
horses. Plasma HCO3–, Ca2+, and Cl– concentrations
were decreased. Plasma H+ concentration was significantly
lower in EM-K-treated horses, compared with
EM+K-treated horses. Plasma K+ concentrations at
the 80-km inspection point and during recovery were
significantly less in EM-K-treated horses, compared
with EM+K-treated horses.
Conclusions and Clinical Relevance—Increases in
plasma H+ and K+ concentrations in this endurance
ride were moderate and unlikely to contribute to signs
of muscle fatigue and hyperexcitability in horses. (Am J Vet Res 2005;66:466–473)
Objective—To determine whether pasture, and specifically the addition of fructan carbohydrate to the diet, induces exaggerated changes in serum insulin concentration in laminitispredisposed (LP) ponies, compared with ponies with no history of the condition, and also to determine insulin responses to the dexamethasone suppression test.
Animals—10 LP and 11 control adult nonobese mixed-breed ponies.
Procedures—Insulin-modified IV glucose tolerance tests were performed (5 ponies/group). In diet studies, ponies were kept on pasture and then changed to a hay diet (10 ponies/group). Second, ponies were maintained on a basal hay diet (4 weeks) before being fed a hay diet supplemented with inulin (3 g/kg/d [1.4 g/lb/d]). Serum insulin and plasma glucose concentrations were analyzed before and after dietary changes. Serum cortisol and insulin concentrations were also measured in a standard dexamethasone suppression test.
Results—The LP ponies were insulin resistant (median insulin sensitivity of 0.27 × 104 L•min−1•mU−1 in LP ponies, compared with 0.64 × 104 L•min−1•mU−1 in control ponies). Median insulin concentration in LP ponies was significantly greater than that in control ponies at pasture, decreased in response to feeding hay, and was markedly increased (5.5fold) following the feeding of inulin with hay. The LP ponies had a greater increase in serum insulin concentration at 19 hours after dexamethasone administration (median, 222.9 mU/L), compared with control ponies (45.6 mU/L).
Conclusions and Clinical Relevance—Nonobese ponies predisposed to develop laminitis had compensated insulin resistance, and this phenotype was revealed by feeding plant fructan carbohydrate or by dexamethasone administration.