Effects of dry period energy intake on insulin resistance, metabolic adaptation, and production responses in transition dairy cows on grass silage-based diets.

High energy intake in the dry period has reportedly had adverse effects on mobilization of body reserves, dry matter intake, and productivity of dairy cows. We investigated whether grass silage (GS) fed ad libitum (high energy intake, HEI; 141% of daily metabolizable energy requirements) in an 8-wk dry period affects metabolic adaptation-specifically, peripheral insulin resistance-compared with a total mixed ration consisting of GS, wheat straw, and rapeseed meal (55/40/5%; controlled energy intake, CEI; 108% of metabolizable energy/d) fed ad libitum. Multiparous Ayrshire dairy cows (n = 16) were used in a randomized complete block design until 8 wk after parturition. Commercial concentrates were fed 1 and 2 kg/d during the last 10 to 6 and 5 to 0 d before the expected calving date, respectively. Postpartum, a similar lactation diet with ad libitum access to GS and increasing concentrate allowance (maximum of 16 kg/d) was offered to all. The HEI group gained more body weight and had higher plasma insulin, glucose, and ß-hydroxybutyrate concentrations than the CEI group prepartum. Postpartal plasma glucose tended to be higher and milk yield was greater from wk 5 onward for HEI compared with CEI cows. An intravenous glucose tolerance test (IVGTT) was performed at -13 ± 5 d and 9 ± 1 d relative to calving. The HEI cows had greater insulin response to glucose load and smaller area under the response curve for glucose than CEI cows in prepartal IVGTT. Thus, compensatory insulin secretion adapted to changes in insulin sensitivity of the peripheral tissues, preserving glucose tolerance of HEI cows. Higher insulin levels were needed in HEI cows than in CEI cows to elicit a similar decrement of nonesterified fatty acid concentration in prepartal IVGTT, suggesting reduced inhibition of lipolysis by insulin in HEI cows before parturition. In conclusion, high energy intake of moderately digestible GS with low concentrate feeding in the close-up dry period did not have adverse effects on metabolic adaptation, insulin sensitivity, and body mobilization after parturition. Instead, this feeding regimen was more beneficial to early-lactation performance than GS-based total mixed ration diluted with wheat straw.

Pharmacokinetics, disposition, and plasma concentrations of dimethyl sulfoxide (DMSO) in the horse following topical, oral, and intravenous administration.

Compartmental models were used to investigate the pharmacokinetics of intravenous (i.v.), oral (p.o.), and topical (TOP) administration of dimethyl sulfoxide (DMSO). The plasma concentration-time curve following a 15-min i.v. infusion of DMSO was described by a two-compartment model. Median and range of alpha (t1/2α ) and beta (t1/2ß ) half-lives were 0.029 (0.026-0.093) and 14.1 (6.6-16.4) hr, respectively. Plasma concentration-time curves of DMSO following p.o. and TOP administration were best described by one-compartment absorption and elimination models. Following the p.o. administration, median absorption (t1/2ab ) and elimination (t1/2e ) half-lives were 0.15 (0.01-0.77) and 15.5 (8.5-25.2) hr, respectively. The plasma concentrations of DMSO were 47.4-129.9 µg/ml, occurring between 15 min and 4 hr. The fractional absorption (F) during a 24-hr period was 47.4 (22.7-98.1)%. Following TOP administrations, the median t1/2ab and t1/2e were 1.2 (0.49-2.3) and 4.5 (2.1-11.0) hr, respectively. Plasma concentrations were 1.2-8.2 µg/ml occurring at 2-4 hr. Fractional absorption following TOP administration was 0.48 (0.315-4.4)% of the dose administered. Clearance (Cl) of DMSO following the i.v. administration was 3.2 (2.2-6.7) ml hr-1  kg-1 . The corrected clearances (ClF ) for p.o. and TOP administrations were 2.9 (1.1-5.5) and 4.5 (0.52-18.2) ml hr-1  kg-1 .

Effects of dietary energy allowance and decline in dry matter intake during the dry period on responses to glucose and insulin in transition dairy cows.

We assessed whether high energy intake during the early dry period [144% of metabolizable energy (ME) requirements/d] followed by a gradual restriction of energy intake in the close-up dry period (119% of ME/d; HEI) impaired whole-body insulin sensitivity compared with a controlled energy intake (100% of ME/d; CEI) throughout the 6-wk dry period. Multiparous Ayrshire dairy cows (n = 16) were blocked by body weight, body condition score, and expected date of parturition and were used in a randomized complete block design until 10 d after parturition. Cows were fed either HEI or CEI diets based on grass silage during the first 3 wk of the dry period and grass silage supplemented with a commercial concentrate (30% of ME intake) during the final 3 wk of gestation. After calving, all cows were fed grass silage ad libitum and an increasing amount of commercial concentrate (maximum 9 kg at d 10 postpartum). Intravenous glucose tolerance tests (IVGTT) and intravenous insulin challenges were performed -10 ± 5 d (n = 15) and +10 ± 1 d (n = 14) relative to parturition. Following glucose injection, we did not find any treatment effects on glucose and insulin responses. The prepartal nonesterified fatty acid (NEFA) response of the HEI group was blunted, basal NEFA and the decrement of NEFA were smaller, and the area under the response curve (AUC) of NEFA was less negative in HEI cows than in CEI cows. The NEFA response reversed after parturition; the NEFA AUC of the HEI group was more negative than that of the CEI group. We did not find similar responses after insulin injection. Across the treatments, NEFA AUC correlated strongly with the basal NEFA concentration during the IVGTT pre- and postpartum. Calculated and model-based indices characterizing the overall glucose tolerance and ß-cell function and the insulin sensitivity were higher after parturition than during the dry period. Consistent with the lower basal insulin, the acute insulin release after the glucose infusion was smaller in postpartal IVGTT than in prepartal IVGTT. The results suggest that whole-body insulin sensitivity of the cows increased after parturition. However, the role of peripheral insulin sensitivity in the regulation of glucose partitioning seems to be minor relative to the major change in insulin secretion and clearance during the periparturient period.

Diurnal patterns of grazing behavior and humoral factors in supplemented dairy cows.

Offering feed supplements to grazing dairy cows results in a reduction in grazing time. However, the effect differs depending on the time of day that feeds are offered. To understand the physiological basis for this, associations among circulating factors known to be associated with intake regulation in monogastric species and grazing behavior in the dairy cow were investigated. Seventeen multiparous cows at 28 ± 5 d in milk grazed together and consumed 4.4 kg of dry matter/d of a pelleted concentrate feed supplement, equally split, at the a.m. and p.m. milking. Grazing behavior was recorded over 4 consecutive days in all 17 cows. Blood was sampled from 10 of the 17 cows every 4h over a 48-h period following the grazing behavior measurements; sampling times were staggered by 2h to provide a diurnal profile of humoral factors. Grazing profiles illustrated major grazing bouts after the a.m. and p.m. milking; however, the p.m. grazing bout was characterized as the most intensive and time spent grazing was unaffected by supplementation. Associations among proportion of cows grazing and circulating hormones and metabolites differed throughout the day. During the a.m., relationships were consistent with those reported in monogastric species, with ghrelin and nonesterified fatty acids decreasing and insulin increasing with feeding. In comparison, during the major grazing bout predusk, ghrelin concentrations increased until sunset, despite the large proportion of cows grazing, before declining; this is consistent with ghrelin stimulating the predusk grazing bout. Results indicate that humoral factors known to affect hunger and satiety in monogastric animals may also have a potential role in the physiological regulation of diurnal and feeding behavior in ruminants.

Pharmacokinetics of dexamethasone following intra-articular, intravenous, intramuscular, and oral administration in horses and its effects on endogenous hydrocortisone.

This study investigated and compared the pharmacokinetics of intra-articular (IA) administration of dexamethasone sodium phosphate (DSP) into three equine joints, femoropatellar (IAS), radiocarpal (IAC), and metacarpophalangeal (IAF), and the intramuscular (IM), oral (PO) and intravenous (IV) administrations. No significant differences in the pharmacokinetic estimates between the three joints were observed with the exception of maximum concentration (Cmax ) and time to maximum concentration (Tmax ). Median (range) Cmax for the IAC, IAF, and IAS were 16.9 (14.6-35.4), 23.4 (13.5-73.0), and 46.9 (24.0-72.1) ng/mL, respectively. The Tmax for IAC, IAF, and IAS were 1.0 (0.75-4.0), 0.62 (0.5-1.0), and 0.25 (0.08-0.25) h, respectively. Median (range) elimination half-lives for IA and IM administrations were 3.6 (3.0-4.6) h and 3.4 (2.9-3.7) h, respectively. A 3-compartment model was fitted to the plasma dexamethasone concentration-time curve following the IV administration of DSP; alpha, beta, and gamma half-lives were 0.03 (0.01-0.05), 1.8 (0.34-2.3), and 5.1 (3.3-5.6) h, respectively. Following the PO administration, the median absorption and elimination half-lives were 0.34 (0.29-1.6) and 3.4 (3.1-4.7) h, respectively. Endogenous hydrocortisone plasma concentrations declined from a baseline of 103.8 ± 29.1-3.1 ± 1.3 ng/mL at 20.0 ± 2.7 h following the administration of DSP and recovered to baseline values between 96 and 120 h for IV, IA, and IM administrations and at 72 h for the PO.

Pharmacokinetic profile and pharmacodynamic effects of romifidine hydrochloride in the horse.

Romifidine HCl (romifidine) is an α(2)-agonist commonly used in horses. This study was undertaken to investigate the pharmacokinetics (PK) of romifidine following intravenous (i.v.) administration and describe the relationship between PK parameters and simultaneously recorded pharmacodynamic (PD) parameters. Romifidine (80 µg/kg) was administered by i.v. infusion over 2 min to six adult Thoroughbred horses, and plasma samples were collected and analyzed using liquid chromatography-mass spectrometry. Limit of quantification was <0.1 ng/mL. PD parameters and arterial blood gases were measured for 300 min following romifidine administration. Statistical PD data analysis included mixed-effect modeling. After i.v. administration of romifidine, the plasma concentration-vs.-time curve was best described by a two-compartmental model. Terminal elimination half-life (t(1/2ß) ) was 138.2 (104.6-171.0) min and volumes for central (V(c)) and peripheral (V(2)) compartments were 1.89 (0.93-2.39) and 2.57 (1.71-4.19) L/kg, respectively. Maximum plasma concentration (C(max)) was 51.9 ± 13.1 ng/mL measured at 4 min following commencement of drug administration. Systemic clearance (Cl) was 32.4 (25.5-38.4) mL · min/kg. Romifidine caused a significant reduction in heart rate and cardiac index and an increase in mean arterial pressure (P < 0.05). Sedation score and head height values were significantly different from the baseline values for 120 min (P < 0.05). The decline in cardiovascular and sedative effects correlated with the decline in plasma romifidine concentration (P < 0.05). In conclusion, a highly sensitive analytical technique for the detection of romifidine in equine plasma allowed detailed description of its PK profile. The drug produces long-lasting sedation in horses that corresponds with the long terminal elimination half-life of the drug.

Exercising upper respiratory videoendoscopic evaluation of 100 nonracing performance horses with abnormal respiratory noise and/or poor performance.

REASONS FOR PERFORMING STUDY: Although well documented in racehorses, there is paucity in the literature regarding the prevalence of dynamic upper airway abnormalities in nonracing performance horses. OBJECTIVE: To describe upper airway function of nonracing performance horses with abnormal respiratory noise and/or poor performance via exercising upper airway videoendoscopy. METHODS: Medical records of nonracing performance horses admitted for exercising evaluation with a chief complaint of abnormal respiratory noise and/or poor performance were reviewed. All horses had video recordings of resting and exercising upper airway endoscopy. Relationships between horse demographics, resting endoscopic findings, treadmill intensity and implementation of head and neck flexion during exercise with exercising endoscopic findings were examined. RESULTS: Dynamic upper airway obstructions were observed in 72% of examinations. Head and neck flexion was necessary to obtain a diagnosis in 21 horses. Pharyngeal wall collapse was the most prevalent upper airway abnormality, observed in 31% of the examinations. Complex abnormalities were noted in 27% of the examinations. Resting laryngeal dysfunction was significantly associated with dynamic arytenoid collapse and the odds of detecting intermittent dorsal displacement of the soft palate (DDSP) during exercise in horses with resting DDSP was only 7.7%. Exercising endoscopic observations were different from the resting observations in 54% of examinations. CONCLUSIONS: Dynamic upper airway obstructions were common in nonracing performance horses with respiratory noise and/or poor performance. Resting endoscopy was only helpful in determining exercising abnormalities with recurrent laryngeal neuropathy. POTENTIAL RELEVANCE: This study emphasises the importance of exercising endoscopic evaluation in nonracing performance horses with abnormal respiratory noise and/or poor performance for accurate assessment of dynamic upper airway function.

Analysis of conformational variations of the cricoid cartilages in Thoroughbred horses using computed tomography.

REASONS FOR PERFORMING STUDY: Loss of arytenoid abduction is a common post operative complication of laryngoplasty without a definitive cause. It has been a clinical impression during laryngoplasty surgery that there is great conformational variability along the caudal edge of the Thoroughbred cricoid cartilage that could impact post operative retention of suture position. A change in suture position would probably lead to some loss of abduction. Defining any structural variability of the cricoid would be an initial step in determining whether this variability could impact on the retention of suture position. HYPOTHESIS: Anatomical variations in the larynx of Thoroughbred horses may be detected and measured using objective analysis and computed tomography. METHODS: Larynges were harvested from 15 mature Thoroughbred horses. Helical CT scans were performed on each specimen. Three independent observers performed a series of measurements on 2D and 3D reconstruction images using digital software. Measurements included the lateral cricoid angle, the caudal cricoid prominences, the distance to the cricoid slope, the angle of the cricoarytenoid joints (CAJ), the cricoid thickness and the suture angle. Mean, standard deviation, coefficient of variation and linear regression analysis were performed among all observers and all measurements. RESULTS: Notable conformational differences were evident on the 3D reconstructions. The highest degree of variability was found in 3 measurements: the distance to the lateral cricoid slope, the lateral cricoid angle and the cricoid thickness. A larger left CAJ angle directly and significantly correlated with a larger suture angle. CONCLUSIONS: There are notable conformational differences among cricoid specimens in the Thoroughbred larynx. POTENTIAL RELEVANCE: The morphometric differences identified may impact on optimal prosthesis placement and long-term retention. Since a larger lateral cricoid angle may facilitate abduction loss secondary to a displaced and loosened suture, alternative techniques for suture placement may be of value to prevent arytenoid abduction loss.

Measurement of C-peptide concentrations and responses to somatostatin, glucose infusion, and insulin resistance in horses.

REASONS FOR PERFORMING STUDY: Hyperinsulinaemia is detected in horses with insulin resistance (IR) and has previously been attributed to increased pancreatic insulin secretion. Connecting peptide (C-peptide) can be measured to assess pancreatic function because it is secreted in equimolar amounts with insulin and does not undergo hepatic clearance. HYPOTHESIS: A human double antibody radioimmunoassay (RIA) detects C-peptide in equine serum and concentrations would reflect responses to different stimuli and conditions. METHODS: A validation procedure was performed to assess the RIA. Six mature mares were selected and somatostatin administered i.v. as a primed continuous rate infusion, followed by 50 nmol human C-peptide i.v. Insulin and C-peptide concentrations were measured in horses (n = 6) undergoing an insulin-modified frequently sampled i.v. glucose tolerance test, and in horses with insulin resistance (n = 10) or normal insulin sensitivity (n = 20). RESULTS: A human RIA was validated for use with equine sera. Endogenous C-peptide secretion was suppressed by somatostatin and median (range) clearance rate was 0.83 (0.15-1.61) ml/min/kg bwt. Mean + or - s.d. C-peptide-to-insulin ratio significantly (P = 0.004) decreased during the glucose tolerance test from 3.60 + or - 1.95 prior to infusion to 1.03 + or - 0.18 during the first 20 min following dextrose administration. Median C-peptide and insulin concentrations were 1.5- and 9.5-fold higher, respectively in horses with IR, compared with healthy horses. CONCLUSIONS: Endogenous C-peptide secretion decreases in response to somatostatin and increases after dextrose infusion. Results suggest that relative insulin clearance decreases as pancreatic secretion increases in response to dextrose infusion. Hyperinsulinaemia in insulin resistant horses may be associated with both increased insulin secretion and decreased insulin clearance. POTENTIAL RELEVANCE: Both C-peptide and insulin concentrations should be measured to assess pancreatic secretion and insulin clearance in horses.

Comparison of hematologic and biochemical results on blood obtained by jugular venipuncture as compared with intravenous catheter in adult horses.

BACKGROUND: During hospitalization, horses typically undergo frequent blood sampling for diagnostic testing and monitoring. The need for numerous samples in hospitalized horses makes acquisition from an intravenous catheter (IVC) both convenient and less stressful to the patient. HYPOTHESIS: We hypothesized that there would be no significant difference in the plasma chemistry and CBC variables from blood samples obtained from a jugular catheter as compared with direct jugular venipuncture. ANIMALS: Fifty adult hospitalized horses; 25 receiving constant rate crystalloid therapy, and 25 receiving low volume IV medication. METHODS: This study was conducted using a prospective, blinded, cross-over design. Samples were obtained sequentially by direct venipuncture of the jugular vein and aspiration from an IVC in the contralateral vein after an appropriate presample of blood was obtained and discarded. Samples were submitted for blinded analysis including CBC, plasma chemistry analysis, stall side plasma glucose concentration, PCV, and total protein concentration. Data obtained were analyzed using a Student's t-test with compensation for unequal variances between the 2 groups. Analyses were Bonferroni corrected for a 5% 2-tailed hypothesis test. RESULTS: There were no statistically significant or clinically relevant differences associated with sampling method (venipuncture versus catheter) regardless of fluid administration status in any of the 24 analytes measured. CONCLUSIONS AND CLINICAL IMPORTANCE: Blood samples obtained by IVC have clinically equivalent values to those taken by direct venipuncture in commonly performed analyses. Additional investigation is warranted to establish if this technique is associated with increased complications such as phlebitis or bacteremia.

Sequential plasma lactate concentrations as prognostic indicators in adult equine emergencies.

BACKGROUND: Sequential lactate concentration ([LAC]) measurements have prognostic value in that hospitalized humans and neonatal foals that have a delayed return to normolactatemia have greater morbidity and case fatality rate. HYPOTHESIS: Prognosis for survival is decreased in horses with a delayed return to normal [LAC]. ANIMALS: Two hundred and fifty adult horses presented for emergency evaluation excepting horses evaluated because of only ophthalmologic conditions, superficial wounds, and septic synovitis without systemic involvement. METHODS: Prospective observational study. [LAC] was measured at admission and then at 6, 12, 24, 48, and 72 hours after admission. The change in [LAC] over time ([LAC]deltaT) was calculated from changes in [LAC] between sampling points. RESULTS: Median [LAC] was significantly (P < .001) higher at admission in nonsurvivors (4.10 mmol/L [range, 0.60-18.20 mmol/L]) when compared with survivors (1.30 mmol/L [range, 0.30-13.90 mmol/L]) and this difference remained at all subsequent time points. The odds ratio for nonsurvival increased from 1.29 (95% confidence interval 1.17-1.43) at admission to 49.90 (6.47-384) at 72 hours after admission for every 1 mmol/L increase in [LAC]. [LAC]deltaT was initially positive in all horses but became negative and significantly lower in nonsurvivors for the time periods between 24-72 hours (- 0.47, P = .001) and 48-72 hours (- 0.07, P = .032) when compared with survivors (0.00 at both time periods) consistent with lactate accumulation in nonsurvivors. CONCLUSIONS AND CLINICAL IMPORTANCE: These results indicate that lactate metabolism is impaired in critically ill horses and [LAC]deltaT can be a useful prognostic indicator in horses.

Metabolic modeling using statistical and spreadsheet software: Application to the glucose minimal model.

Kinetic non-linear metabolic models are used extensively in medical research and increasingly for clinical diagnostic purposes. An example of such a model is the Glucose Minimal Model by Bergman and colleagues [1]. This model is similar to pharmacokinetic/pharmacodynamic models in that like pharmacokinetic/pharmacodynamic models, it is based on a small number of fairly simple ordinary differential equations and it aims to determine how the changing concentration of one blood constituent influences the concentration of another constituent. Although such models may appear prima facie, to be relatively simple, they have gained a reputation of being difficult to fit to data, especially in a consistent and repeatable fashion. Consequently, researchers and clinicians have generally relied on dedicated software packages to do this type of modeling. This article describes the use of statistical and spreadsheet software for fitting the Glucose Minimal Model to data from an insulin modified intravenous glucose tolerance test (IM-IVGTT). A novel aspect of the modeling is that the differential equations that are normally used to describe insulin action and the disposition of plasma glucose are first solved and expressed in their explicit forms so as to facilitate the estimation of Glucose Minimal Model parameters using the nonlinear (nl) optimization procedure within statistical and spreadsheet software. The most important clinical parameter obtained from the Glucose Minimal Model is insulin sensitivity (SI). Using IM-IVGTT data from 42 horses in one experiment and 48 horses in a second experiment, we demonstrate that estimates of SI derived from the Glucose Minimal Model fitted to data using STATA and Excel, are highly concordant with SI estimates obtained using the industry standard software, MinMod Millennium. This work demonstrates that there is potential for statistical and spreadsheet software to be applied to a wide range of kinetic non-linear modeling problems.

Application of the intravenous glucose tolerance test and the minimal model to patients with insulinoma: insulin sensitivity (Si) and glucose effectiveness (Sg) before and after surgical excision.

BACKGROUND: The unmodified frequently sampled intravenous glucose tolerance test (FSIGT) has not previously been used to assess insulin/glucose kinetics in patients with insulinoma. OBJECTIVE: To measure insulin sensitivity (Si) and glucose effectiveness (Sg) by means of the FSIGT in patients with insulinoma, before and after surgical removal of the tumour. SUBJECTS AND METHODS: FSIGTs were performed in five patients, before and approximately 3 months post-surgery, and in 11 controls. Si and Sg were estimated using Minimal Model computer analysis of dynamic glucose and insulin data. RESULTS: Si was lower in insulinoma patients before, compared with after surgery (3.37 +/- 0.62 vs. 6.24 +/- 1.09 SE [x10(-4)] min(-1)microU(-1) ml, P < 0.05). Sg was similar in patients pre- and post-surgery (3.0 +/- 0.67 vs. 2.4 +/- 0.6 [x10(-2)] min(-1), NS). CONCLUSIONS: Insulin sensitivity improves after excision of an insulinoma. Glucose effectiveness is not influenced by chronic hyperinsulinaemia and hypoglycaemia.

Comparing subpopulations of plasma progesterone using cluster analyses.

The production of progesterone during the luteal phase of the estrous cycle regulates early embryonic development, uterine function, and luteal function. Plasma progesterone concentrations were measured during a spontaneous estrous cycle in lactating Holstein-Friesian cows of New Zealand or North American ancestry, fed either fresh pasture or a total mixed ration. Subpopulations of profiles were identified using 2 approaches: 1) shape-based clustering and 2) trait-based clustering. Subpopulations of profiles were compared using key progesterone profile components, which described the early and late luteal phase of the estrous cycle. The application of resistant nonlinear smoothing functions across raw progesterone profiles resulted in a high degree of agreement between the raw data and smoothed estimates (R(2) = 0.93). Both clustering techniques resulted in the identification of 3 similar subpopulations of progesterone profiles. The distribution of animals in these defined subpopulations and the association with cow strain and diet were examined. The early luteal phase was similar for the shape-based categories, but differed in the trait-based analyses. Differences in the late luteal phase and the onset of functional luteal regression in the different clusters were evident for both the shape- and trait-based analyses. The distribution of animals across the subpopulations identified by shape-based clustering was not associated with either cow strain or diet. However, within the 3 subpopulations identified using trait-based clustering, cow strain affected the shape of the progesterone profile. Isolation of 3 subpopulations within a small data set showed that otherwise normal progesterone profiles exhibit significant variation. The differences in the luteal phase of these subpopulations, in particular progesterone early in the luteal phase and the early onset of functional luteal regression, may provide an insight into factors associated with subfertility.

Optimisation of the frequently sampled intravenous glucose tolerance test to reduce urinary glucose spilling in horses.

REASONS FOR PERFORMING STUDY: The frequently sampled i.v. glucose tolerance test (FSIGTT) is used to evaluate glucose and insulin dynamics in horses, but it has not been determined whether urinary glucose spilling (UGS) affects results. HYPOTHESIS: UGS occurs in horses during the FSIGTT and this problem can be minimised by adjusting the dextrose and insulin dosages used. METHODS: Six mature mares were included in this study. In the first phase, 6 FSIGTT procedures were performed in each horse to evaluate 6 different dextrose dosages. Six different insulin dosages were evaluated during the second phase of the study after administration of 300 mg/kg bwt dextrose. Area under the glucose (AUCg) and insulin (AUCi) curves were calculated and minimal model analyses performed. UGS was measured in the third and fourth phases of the study during the combined glucose insulin test and established FSIGTT. A new FSIGTT was developed and evaluated. RESULTS: Positive linear effects of dextrose dosage on AUCg, AUCi and acute insulin response to glucose were detected, with AUCg reaching a plateau at doses > or =200 mg/kg bwt. Insulin dosage had an inverse linear effect on AUCg, but other values remained unaffected. UGS occurred during all 3 tests and was the highest for the established FSIGTT and the lowest for the new FSIGTT. The type of FSIGTT performed did not affect minimal model results. CONCLUSIONS: Results indicate that the dextrose dosage of 300 mg/kg bwt used in the established FSIGTT is too high. UGS can be reduced by lowering the dextrose dosage to 100 mg/kg bwt. POTENTIAL RELEVANCE: A new FSIGTT involving the administration of 100 mg/kg bwt dextrose followed by 20 mu/kg bwt insulin 20 min later is recommended for use in horses because this test provides adequate data for minimal model analysis while minimising UGS.

Type 2 diabetes mellitus with pancreatic beta cell dysfunction in 3 horses confirmed with minimal model analysis.

REASONS FOR PERFORMING STUDY: Type 2 diabetes mellitus (T2DM) is diagnosed rarely in equine practice although it may be under-recognised. A greater awareness of the condition and therapeutic considerations would be to the benefit of such cases presenting in practice. More investigation into the pharmacological management of these cases is needed. OBJECTIVES: Three cases of diabetes mellitus were investigated using a specific test for insulin sensitivity and pancreatic beta cell function in order to define accurately and characterise the existence of T2DM in all 3 subjects. METHODS: The insulin-modified frequently sampled i.v. glucose tolerance test was performed in each case and the data so obtained were subject to minimal model analysis of insulin-glucose dynamics. Cases were then monitored following treatment using a combination of dietary modification, metformin, glibenclamide and pergolide. RESULTS: Marked insulin resistance was identified in each case and, furthermore, severe pancreatic beta cell dysfunction was present therefore classifying each case as end stage T2DM. Treatment was nevertheless associated with restoration of normoglycaemia in all cases. CONCLUSIONS: T2DM in horses may be more common than generally considered.In some cases individuals may respond to therapy aimed at restoring insulin sensitivity and pancreatic function. Drugs used in other species for the treatment of T2DM have not yet been adequately tested in horses. POTENTIAL RELEVANCE: T2DM should be considered as an important differential diagnosis in mature to elderly horses and ponies suffering from weight loss, polydipsia and polyuria. Clinicians should be encouraged to offer treatment and management advice when such cases are encountered.

An investigation of the action of Neutral Protamine Hagedorn human analogue insulin in dogs with naturally occurring diabetes mellitus.

BACKGROUND: Neutral Protamine Hagedorn human analogue insulin (Humulin N) is commonly used for treatment of canine diabetes mellitus (DM). However, blood glucose and serum insulin concentrations in Humulin N-treated dogs with naturally occurring DM have not been reported. OBJECTIVE: To investigate blood glucose and serum insulin concentrations in the clinical setting of client-owned Humulin N-treated dogs with naturally occurring, well-regulated DM. ANIMALS: Ten client-owned dogs with naturally occurring, well-regulated DM. METHODS: In this clinical study, blood glucose and serum insulin concentrations were measured when dogs received food and insulin (T(0)), at approximately every half hour for the next 2 hours, and then approximately every 2 hours for an additional 8 hours. Insulin duration of action was defined as the number of hours from T(0) to the lowest blood glucose concentration and until blood glucose concentration returned to an interpolated value of 70% of basal blood glucose concentration (Glucose(b)). RESULTS: Mean percent of insulin-induced blood glucose suppression was 49.9 +/- 17.1% (median, 46%; range, 29-78%). Insulin duration of action ranged from 4 to 10 hours. Blood glucose concentration increased initially and returned to Glucose(b) within 0.6-2.2 hours after T(0) in 5 dogs. This initial blood glucose surge then was followed by blood glucose suppression in all 5 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that Humulin N administered SC twice daily is an effective mode of treatment for dogs with naturally occurring DM. Postprandial hyperglycemia is present in some well-regulated diabetic dogs treated with Humulin N.

Association of blood lactate concentration and outcome in foals.

BACKGROUND: Lactate concentration in blood or plasma ([LAC]) and change in [LAC] are associated with survival in sick foals. HYPOTHESIS: [LAC] and change in [LAC] over time are associated with survival at 96 hours and discharge in neonatal foals. Furthermore [LAC] and change in [LAC] over time correlate with blood culture results and blood pressure at admission. ANIMALS: Two hundred and twenty-five foals consecutively admitted to a Neonatal Intensive Care Unit. METHODS: Retrospective case review. Foals

Prospective evaluation of coagulation in critically ill neonatal foals.

BACKGROUND: Coagulopathy is a potentially underrecognized complication of sepsis and septic shock in critically ill neonatal foals. HYPOTHESIS: Critically ill neonatal foals have abnormalities in coagulation that are associated with disease severity and outcome. ANIMALS: Foals <72 hours old admitted to a neonatal intensive care unit. METHODS: Prospective, observational study. Blood was collected at admission, 24, and 48 hours for platelet count, prothrombin time, activated partial thromboplastin time, antithrombin activity and concentrations of fibrin degradation products, and fibrinogen in plasma from all foals. RESULTS: Sixty-three foals were enrolled and classified as Septic Shock (12), Septic (28), and Other (23). At least 1 abnormal value was found in 18/28 (64%) samples from the Septic Shock group, 66/85 (78%) from the Septic group, and 30/59 (51%) from the Other group (P= .01). Coagulopathy (3 or more abnormal values) was present in 7/28 (25%) samples in the Septic Shock group, 14/85 (16%) samples in the Septic group, and 3/59 (5%) samples in the Other group (P= .0028). Clinically detectable bleeding occurred in 8/12 (67%) Septic Shock cases, 11/28 (39%) Septic cases, and 3/23 (13%) Other cases (P= .009). Foals in Septic Shock were 12.7 times more likely to have clinical evidence of bleeding than those in the Other group (95% CI 2.3-70, P= .004). Treatment with fluids or plasma did not have a detectable effect on coagulation values. CONCLUSIONS AND CLINICAL IMPORTANCE: Coagulopathy commonly occurs in critically ill neonatal foals, especially those with sepsis and septic shock.

Reproducibility of airway responsiveness in horses using flowmetric plethysmography and histamine bronchoprovocation.

BACKGROUND: Inflammatory airway disease has a high prevalence in horses, but is often a diagnostic challenge. Flowmetric plethysmography and histamine bronchoprovocation (FP/HBP) is a simple and effective tool for diagnosis, but reproducibility of these measurements made over time has not been established. HYPOTHESIS: We hypothesize that the measurement of airway responsiveness in horses using FP/HBP is consistent over both short and long periods of time. ANIMALS: Twenty-nine healthy adult horses from 2 university herds. METHODS: In this prospective experimental study, airway responsiveness was determined in each horse at day 0 (baseline [BL]) with FP/ HBP, using PC35 (provocative concentration of histamine needed to increase Delta(flow) by 35%) as a measure of airway responsiveness. Each horse was re-tested 1-4 weeks after BL (short-term [ST]) and again at 3-12 months after BL (long-term [LT]). RESULTS: In the ST period, 23/27 (85%) of the horses had a PC35 that was within 1 doubling concentration of histamine of their BL value, with a mean change of 0.52 doubling concentrations (95% CI 0.26-0.79, range 0-2.06). For the LT data, 19/26 (73%) of horses were within 1 doubling concentration of their BL value, with a mean change of 0.81 doubling concentrations (95% CI 0.45-1.17, range 0.14-3.10). There was no significant difference in reproducibility between the 2 groups of subjects. CONCLUSIONS AND CLINICAL IMPORTANCE: Repeated measurements of airway responsiveness obtained with FP/HBP show acceptable reproducibility over time periods up to a year. However, caution must be used when testing horses when ambient air temperature is low.