Use of proxies and reference quintiles obtained from minimal model analysis for determination of insulin sensitivity and pancreatic beta-cell responsiveness in horses

OBJECTIVE: To develop proxies calculated from basal plasma glucose and insulin concentrations that predict insulin sensitivity (SI; L.min(-1) x mU(-1)) and beta-cell responsiveness (ie, acute insulin response to glucose [AIRg]; mU/L x min(-1)) and to determine reference quintiles for these and minimal model variables. ANIMALS: 1 laminitic pony and 46 healthy horses. PROCEDURE: Basal plasma glucose (mg/dL) and insulin (mU/L) concentrations were determined from blood samples obtained between 8:00 AM and 9:00 AM. Minimal model results for 46 horses were compared by equivalence testing with proxies for screening SI and pancreatic beta-cell responsiveness in humans and with 2 new proxies for screening in horses (ie, reciprocal of the square root of insulin [RISQI] and modified insulin-to-glucose ratio [MIRG]). RESULTS: Best predictors of SI and AIRg were RISQI (r = 0.77) and MIRG (r = 0.75) as follows: SI = 7.93(RISQI) - 1.03 and AIRg = 70.1(MIRG) - 13.8, where RISQI equals plasma insulin concentration(-0.5) and MIRG equals [800 - 0.30(plasma insulin concentration 50)(2)]/(plasma glucose concentration - 30). Total predictive powers were 78% and 80% for RISQI and MIRG, respectively. Reference ranges and quintiles for a population of healthy horses were calculated nonparametrically. CONCLUSIONS AND CLINICAL RELEVANCE: Proxies for screening SI and pancreatic beta-cell responsiveness in horses from this study compared favorably with proxies used effectively for humans. Combined use of RISQI and MIRG will enable differentiation between compensated and uncompensated insulin resistance. The sample size of our study allowed for determination of sound reference range values and quintiles for healthy horses.     

Seasonal Variation in Serum Concentrations of Selected Metabolic Hormones in Horses

Background: Determination of adrenocorticotropic hormone (ACTH) concentration is a commonly used test in the evaluation of endocrine causes of equine laminitis, but the concentration in healthy horses can be high at certain times of year, which alters the specificity of the ACTH test. Objective: To determine if circulating concentrations of ACTH, cortisol, glucose, insulin, and thyroxine vary month to month in healthy horses and in horses with equine metabolic syndrome (EMS). Animals: Nine healthy adult horses were studied on their farm/stable over the course of 1 year. After the diagnosis of EMS, 10 laminitic horses residing at the same farm/stable were also studied. Methods: Prospective study of healthy and laminitic horses. Plasma/serum samples were analyzed for concentrations of hormones and glucose. Results: ACTH was the only analyte to show a discrete seasonal pattern, with concentrations in healthy and EMS horses frequently outside of the reference range (9–35 pg/mL) in August through October. Insulin was elevated (>40 μIU/mL) in EMS horses during most months and median serum glucose was generally higher in EMS horses (100 mg/dL, range, 76–163 mg/ dL) than in controls (94 mg/dL, range, 56–110 mg/dL), but no seasonal patterns for insulin or glucose were found. Conclusions and Clinical Importance: An increased ACTH concentration in horses in late summer or autumn should be interpreted with caution. In contrast, insulin concentration is maintained within the reference range throughout the year in healthy horses, thus an increased insulin concentration at any time of year should raise suspicions of EMS, ECD, or both.     

Use of proxy measurements of insulin sensitivity and insulin secretory response to distinguish between normal and previously laminitic ponies

Reasons for performing study: Insulin resistance may be a risk factor for pasture‐associated laminitis. Diagnosis of insulin resistance could help identify individuals at increased risk of laminitis. Objective: To calculate proxy measurements of insulin sensitivity (reciprocal of the square root of insulin: RISQI and quantitative insulin sensitivity check index: QUICKI) and insulin secretory response (modified insulin‐to‐glucose ratio: MIRG) based on basal glucose and insulin concentrations in normal (NP) and previously laminitic (PLP) ponies. Methods: Proxies were calculated in 7 NP and 5 PLP from 20 separate measurements of insulin and glucose taken in spring, summer and winter when ponies were adapted to eating either pasture or hay. Proxies were RISQI: Insulin^‐0.5, QUICKI: 1/(log[fasting Insulin]+ log[fasting Glucose]) and MIRG: (800?0.3×[Insulin‐50]²)/[Glucose‐30]. A modified insulin‐to‐glucose ratio for ponies (MIGRP) was investigated using: (3000?0.012 ×[Insulin‐500]²)/[Glucose‐30]. Statistical analysis used linear mixed models. Results: Diet did not significantly affect measurements, so values were pooled for further analysis. RISQI (mean ± s.d.) was lower in PLP (0.26 ± 0.15 [mu/l]^‐0.5) than NP (0.29 ± 0.12 [mu/l]^‐0.5; P = 0.05). QUICKI was lower in PLP (0.31 ± 0.05) than NP (0.33 ± 0.04; P = 0.047). There was no difference in MIRG between NP and PLP. MIGRP (median [interquartile range]) was greater in PLP (4.0 [7.9][mu_ins]²/10·l·mg_gluc) than NP (2.6 [3.2][mu_ins]²/10·l·mg_gluc; P = 0.022). In spring, NP had higher RISQI and QUICKI and lower MIGRP than PLP (P<0.001). In PLP, RISQI and QUICKI were higher in summer than spring (P<0.02) and MIGRP was lower in summer than other seasons (P<0.01). In NP, RISQI, QUICKI and MIGRP were each different between seasons (P<0.017). MIRG did not vary with season. Conclusions: RISQI, QUICKI and MIGRP, but not MIRG, differentiated between NP and PLP. None of the proxies accurately identified individual PLP. Seasonal changes in insulin sensitivity and insulin secretory response were apparent. Potential relevance: Current proxy measurements cannot determine an individual's laminitis susceptibility. MIGRP may be useful in hyperinsulinaemic animals.     

Effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses

OBJECTIVE: To determine effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses. ANIMALS: 6 adult Standardbreds. PROCEDURES: In a balanced crossover study, horses received dexamethasone (0.08 mg/ kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution (control treatment) during a 21-day period. Horses underwent a 3-hour frequently sampled IV glucose tolerance test (FSIGT) 2 days after treatment. Minimal model analysis of glucose and insulin data from FSIGTs were used to estimate insulin sensitivity (Si), glucose effectiveness (Sg), acute insulin response to glucose (AIRg), and disposition index. Proxies for Si (reciprocal of the inverse square of basal insulin concentration [RISQI]) and beta-cell responsiveness (modified insulin-to-glucose ratio [MIRG]) were calculated from basal plasma glucose and serum insulin concentrations. RESULTS: Mean serum insulin concentration was significantly higher in dexamethasone-treated horses than control horses on days 7, 14, and 21. Similarly, mean plasma glucose concentration was higher in dexamethasone-treated horses on days 7, 14, and 21; this value differed significantly on day 14 but not on days 7 or 21. Minimal model analysis of FSIGT data revealed a significant decrease in Si and a significant increase in AIRg after dexamethasone treatment, with no change in Sg or disposition index. Mean RISQI was significantly lower, whereas MIRG was higher, in dexamethasone-treated horses than control horses on days 7, 14, and 21. CONCLUSIONS AND CLINICAL RELEVANCE: The study revealed marked insulin resistance in healthy horses after 21 days of dexamethasone administration. Because insulin resistance has been associated with a predisposition to laminitis, a glucocorticoid-induced decrease in insulin sensitivity may increase risk for development of laminitis in some horses and ponies.     

Glycemic index of cracked corn, oat groats and rolled barley in horses

Muscle glycogen synthesis depends on glucose availability. This study was undertaken to determine the glycemic and insulinemic response of horses to equal amounts of hydrolyzable carbohydrates (starch and sugar) in the form of one of three grain meals or intragastric administration of a glucose solution. In a randomized crossover design, seven horses were fed each of three grain meals (cracked corn, steamed oat groats, or rolled barley) or were infused intragastrically with glucose solution at 2 g of hydrolyzable carbohydrate (starch plus sugar) per kilogram of BW. The quantity of hydrolyzable carbohydrate ingested was not different among all treatments (P = 0.70). Plasma glucose concentration peaked in all four treatments by 1.5 to 2 h after feeding. Plasma glucose concentration remained higher than baseline in oat groats or barley-fed horses throughout 8 h, whereas plasma glucose returned to baseline by 5 to 6 h in corn-fed horses or after glucose administration. Meal consumption was slower in oat groats-fed horses than in corn-fed ones, which may confound the glycemic and insulinemic responses observed after grain feeding. Plasma glucose area under the curve (AUC) was 63% both in corn and oat groats and 57% in barley-fed horses compared with that of horses administered glucose (P = 0.13). Serum immunoreactive insulin concentration peaked between 2 and 3 h after feeding or glucose administration, and barley-fed horses had lower serum immunoreactive insulin concentration by 3 to 4 h than corn-fed horses or after glucose administration (P < 0.05). We conclude, in horses, ingestion of oat groats, corn, and barley result in similar plasma glucose AUC and, compared with the glycemic index of 100 as the glucose reference, corn, oat groats, and barley had a glycemic index of approximately 60.     

Effects of a supplement containing chromium and magnesium on morphometric measurements, resting glucose, insulin concentrations and insulin sensitivity in laminitic obese horses

Reasons for performing study: Obesity and insulin resistance are risk factors for laminitis in equids and supplements containing chromium and magnesium might improve insulin sensitivity. Hypothesis: A supplement containing chromium, magnesium and other nutraceuticals would alter morphometric measurements, blood variables, and insulin sensitivity in laminitic obese horses. Methods: Twelve previously laminitic obese (body condition score ≥ 7/9) horses were randomly allocated to treatment (n = 6) and control (n = 6) groups and 2 obese horses with clinical laminitis were included in the treatment group. Treated animals received 56 g supplement with 0.25 kg oats once daily for 16 weeks. The supplement contained chromium (5 mg/day as yeast), magnesium (8.8 g/day as oxide/proteinate), and other nutraceuticals. Insulin‐modified frequently sampled i.v. glucose tolerance tests were performed with hay provided at 0, 8 and 16 weeks, and insulin sensitivity was estimated by minimal model analysis. Physical measurements were collected at the same points. Horses were not exercised. Results: Hyperinsulinaemia (>30 µu/ml) was detected in 12 of 14 horses prior to treatment. Glucose and insulin data from one mare with clinical laminitis were excluded because of persistent pain. Mean ± s.d. insulin sensitivity was 0.64 ± 0.62 × 10^?4 l/min/mu prior to treatment for the remaining 13 horses. Time and treatment × time effects were not significant for any of the variables examined, with the exception of resting insulin concentrations, which significantly increased over time (P = 0.018). Health status remained the same. Conclusions: The supplement containing chromium and magnesium evaluated in this study did not alter morphometric measurements, blood variables, resting insulin concentrations or insulin sensitivity in laminitic obese horses. Potential relevance: Additional research is required to determine the appropriate use of chromium and magnesium supplements in horses.     

Comparison of Insulin and Glucose Metabolism in Horses with Pituitary Pars Intermedia Dysfunction Treated Versus Not Treated with Pergolide

Equine pituitary pars intermedia dysfunction (PPID) is known to alter glucose/insulin metabolism. This study evaluated changes in parameters relating to glucose/insulin metabolism and determined whether there is a difference between pergolide-treated and untreated animals. We hypothesized that glucose/insulin dynamics in PPID horses receiving pergolide would be different than those in untreated horses. A total of 38 horses with diagnoses of PPID were included in the study (average age: 24 years). A total of 25 horses were untreated; 13 horses were treated with pergolide (>3 months). Parameters relating to glucose/insulin metabolism were determined in all horses, as follows: adrenocorticotropin-releasing hormone (ACTH), insulin, fructosamine, triglyceride, glucose, modified insulin-to-glucose ratio (MIRG), and reciprocal of the square root of insulin (RISQI). A combined glucose-insulin test (CGIT) was performed in 23 horses as not all owners agreed to the testing. Treated animals showed a tendency to have lower ACTH, but results were not significant. All animals had fructosamine levels exceeding reference values (mean value 314 ± 32 μmol/L; reference range: <280 μmol/L). There were no statistically significant differences between insulin, glucose, ACTH, triglycerides concentrations, RISQI/MIRG calculations, and CGIT results of pergolide-treated PPID and those of untreated horses. Five horses (13.2%) had combined hyperglycemia/hyperinsulinemia, whereas 7 horses (18.4%) displayed hyperglycemia, and 3 horses (7.9%) showed hyperinsulinemia alone. Forty percent of the horses with altered glucose/insulin metabolism were treated with pergolide. Based on RISQI and MIRG calculations, 19 animals displayed changes in glucose/insulin metabolism. Fourteen of twenty-three horses (61%) showed signs of insulin resistance in CGIT results. In conclusion, PPID horses frequently show alterations in glucose/insulin metabolism, but no significant differences were found between treated and untreated animals. Changes in insulin/glucose dynamics may not be a useful indicator of response to pergolide treatment.     

Different responses of protein synthesis to refeeding in various muscles of fasted chicks

1. The change in the rate of protein synthesis of different muscles, concentrations of plasma insulin, plasma insulin-like growth factor-I (IGF-I) and other plasma components were investigated after refeeding in fasted chicks. 5.2 g of the complete diet was refed. This was the maximum that could be force-fed with water. 2. The fractional synthesis rates (FSR) of breast (M. pectoralis major) and leg (M. gastrocnemius) muscles were measured after injection of L-[2, 6-(3)H]phenylalanine. Plasma insulin and IGF-I concentration were determined by radioimmunoassay. 3. In the breast muscle, FSR was significantly reduced by 2-d fasting. The FSR had recovered completely after 1 h of refeeding and was maintained until 6 h. The change in FSR after refeeding was associated with the change in ribosomal efficiency (K(RNA); absolute synthesis rate per unit RNA), while no change in ribosomal capacity (C(S); RNA: protein ratio) was observed. 4. In the leg muscle, FSR was decreased by 2-d fasting and increased gradually toward 6 h after refeeding but did not reach the level of the fed control. In contrast to the breast muscle, no significant changes in Cs and K(RNA) in the leg muscle were observed. 5. Plasma glucose concentration increased significantly at 1 h after refeeding but returned to the fasted level after 24 h. Plasma insulin concentration in chicks refed for 1 h was higher than in the fasted group. There was no significant change in plasma IGF-I concentration. 6. These results suggest that the FSR of breast muscle was more sensitive to refeeding than that of leg muscle which may be explained, in part, by differences in sensitivity to the change in circulating plasma insulin concentration after refeeding.     

Clinical significance of plasma mannose concentrations in healthy and diabetic dogs

Circulating levels of monosaccharides can act as a reflection of systemic glucose/ energy metabolism. Characteristic changes observed in these levels can be seen in patients with diabetes and other metabolic disorders. There have been a few reports describing the significance of mannose metabolism as an energy source under physiological and pathological conditions. However, the relationship between circulating levels of mannose and the pathophysiology of diabetes mellitus are unknown in dogs. This study examined circulating levels of mannose between healthy control and diabetic dogs and evaluated the clinical significance of mannose levels in dogs. Diabetic dogs demonstrated a higher circulating level of mannose in comparison to normal healthy control dogs. Plasma mannose was positively correlated with plasma glucose and fructosamine, respectively. Interestingly, plasma mannose levels were affected by plasma insulin levels. In the context of feeding and glucose tolerance tests, plasma mannose levels responded to changes in circulating insulin levels. Circulating plasma mannose levels decreased after feeding in both control and diabetic animals in spite of observed insulin level differences. However, when glucose tolerance tests were given, a positive correlation between mannose levels and insulin levels was observed. Therefore, plasma mannose levels obtained via glucose tolerance testing may be used as a new diagnostic method for evaluating insulin resistance or deficiency in diabetic dogs.     

Association of admission plasma D-dimer concentration with diagnosis and outcome in horses with colic

Background: Coagulopathies detected in horses with gastrointestinal problems seem to be associated with poor outcome. Plasma D‐Dimer concentration is a sensitive test for assessing coagulopathies. Hypothesis: Plasma D‐Dimer concentration tested on admission is related to diagnosis and outcome in horses with colic. Animals: Four hundred and ninety three horses referred for evaluation of abdominal pain. Methods: Prospective observational clinical study. Horses were grouped according to diagnosis (medical and surgical intestinal obstructions, ischemic disorders with and without intestinal resection, enteritis, peritonitis), outcome (survivors, nonsurvivors), and number of coagulopathies (normal profile, 1 or 2 coagulopathies, subclinical disseminated intravascular coagulation [DIC]). Blood samples were collected on admission and plasma D‐Dimer concentration, clotting times (PT and aPTT), and antithrombin activity were determined. Positive likelihood ratios (LR+) were calculated for evaluation of D‐Dimer cut‐off values, which were later tested in a logistic regression model. Results: Horses with enteritis or peritonitis had significantly (P < .001) higher plasma D‐Dimer concentrations and more severe coagulopathies on admission than horses with other diagnoses. Nonsurvivors also had significantly (P < .001) higher plasma D‐Dimer concentrations at presentation than did survivors, and those horses with subclinical DIC on presentation had an odds ratio (OR) 8.6 (95% confidence interval [CI], 3.3–22.5, P < .001) for nonsurvival. Finally, D‐Dimer concentrations >4,000 ng/mL had a LR+ of 5.9 and an OR 8.8 (95% CI, 4.5–17.1, P < .001) for nonsurvival. Conclusion and Clinical Importance: Plasma D‐Dimer concentration measured on admission can be used to facilitate diagnosis and outcome prediction in horses with colic. A potential cut‐off value for nonsurvival was found at approximately 4,000 ng/mL.     

Physical characteristics, blood hormone concentrations, and plasma lipid concentrations in obese horses with insulin resistance

OBJECTIVE: To compare obese horses with insulin resistance (IR) with nonobese horses and determine whether blood resting glucose, insulin, leptin, and lipid concentrations differed between groups and were correlated with combined glucose-insulin test (CGIT) results. ANIMALS: 7 obese adult horses with IR (OB-IR group) and 5 nonobese mares. PROCEDURES: Physical measurements were taken, and blood samples were collected after horses had acclimated to the hospital for 3 days. Response to insulin was assessed by use of the CGIT, and maintenance of plasma glucose concentrations greater than the preinjection value for > or = 45 minutes was used to define IR. Area under the curve values for glucose (AUC(g)) and insulin (AUC(i)) concentrations were calculated. RESULTS: Morgan, Paso Fino, Quarter Horse, and Tennessee Walking Horse breeds were represented in the OB-IR group. Mean neck circumference and BCS differed significantly between groups and were positively correlated with AUC values. Resting insulin and leptin concentrations were 6 and 14 times as high, respectively, in the OB-IR group, compared with the nonobese group, and were significantly correlated with AUC(g) and AUC(i). Plasma nonesterified fatty acid, very low-density lipoprotein, and high-density lipoprotein-cholesterol (HDL-C) concentrations were significantly higher (86%, 104%, and 29%, respectively) in OB-IR horses, and HDL-C concentrations were positively correlated with AUC values. CONCLUSIONS AND CLINICAL RELEVANCE: Measurements of neck circumference and resting insulin and leptin concentrations can be used to screen obese horses for IR. Dyslipidemia is associated with IR in obese horses.     

Decreased expression of p63, a regulator of epidermal stem cells, in the chronic laminitic equine hoof

Reasons for performing study: Abnormal epidermal stem cell regulation may contribute to the pathogenesis of equine chronic laminitis. Objective: To analyse the involvement of p63, a regulator of epidermal stem cell proliferative potential, in chronic laminitis. Methods: Epidermal tissues from skin, coronet and lamellae of the dorsal foot were harvested from 5 horses with chronic laminitis and 5 control horses. Tissues were analysed using histopathology, immunofluorescence microscopy and quantitative immunoblotting Results: Hoof lamellae of laminitic horses had a lower frequency of p63 positive cells than control lamellae, particularly in the distal region. Quantitative immunoblotting confirmed reduced p63 expression in the laminitic distal lamellar region. The decreased p63 expression in laminitic epidermal lamellae was most apparent in the abaxial region adjacent to the hoof wall and highly associated with the formation of terminally differentiated, dysplastic and hyperkeratotic epidermis in this region, whereas lamellae from control horses maintained high p63 expression throughout the axial‐abaxial axis. Conclusions: Expression of p63 in equine skin resembles that reported in other species, including man and rodents, suggesting that p63 can serve as a marker for the proliferative potential of equine epidermal stem cells. p63 expression was significantly lower in the chronic laminitic hoof than in that of control horses, suggesting laminitic hoof epithelium has more limited proliferative potential with a shift towards differentiation. This may reflect reduced activity of epidermal stem cells in laminitic hoof. It is proposed that p63 contributes to the maintenance of hoof lamellae and that misregulation of p63 expression may lead to epidermal dysplasia during lamellar wedge formation. Potential relevance: This study suggests that loss of epidermal stem cells contributes to the pathogenesis of equine laminitis. Autologous transplantation of p63‐positive epidermal stem cells from unaffected regions may have regenerative therapeutic potential for laminitic horses.     

Plasma amylin and insulin concentrations in normoglycemic and hyperglycemic cats.

The recently discovered pancreatic peptide amylin is postulated to be involved in the pathogenesis of feline diabetes mellitus. However, plasma amylin concentrations in normal and diabetic cats have not yet been published. The aim of the present study was to validate a commercial amylin radioimmunoassay kit for the measurement of feline amylin in unextracted plasma, and to measure plasma amylin concentrations in normal and diabetic cats. The kit had satisfactory specificity, sensitivity, accuracy, and precision, and can be recommended for measurement of feline amylin in unextracted EDTA plasma, when nonspecific binding of plasma samples is used in the calculation of measured amylin concentration. Fasting amylin concentration in cats with normal glucose tolerance was 97 +/- 4 pmol/L. Plasma amylin increased in parallel with insulin after glucose administration in cats with normal and impaired glucose tolerance. In contrast to cats with normal glucose tolerance, cats with impaired glucose tolerance had markedly delayed amylin and insulin secretion. Diabetic cats had basal hypoinsulinemia combined with hyperamylinemia. Hyperamylinemia may lead to reduced insulin secretion and insulin resistance, and contribute to the development of feline diabetes. In conclusion, feline amylin can be measured in unextracted EDTA plasma. Fasting amylin concentrations are approximately 100 pmol/L, and amylin and insulin are cosecreted in cats with normal and impaired glucose tolerance. Increased amylin concentrations may contribute to the development of feline diabetes mellitus.     

Correlation of Plasma Insulin Concentration with Laminitis Score in a Field Study of Equine Cushing's Disease and Equine Metabolic Syndrome

This study aimed to investigate endocrinologic test values and the response to treatment of two commonly encountered causes of endocrinopathic laminitis, equine Cushing's disease (ECD) and equine metabolic syndrome (EMS), in a veterinary practice setting. In particular, the study aimed to determine whether insulin concentration correlated to the severity of clinical laminitis in horses with EMS or ECD. Twenty-five horses were included in the study and assigned to one of three groups: ECD (n = 6), EMS (n = 10), and controls (n = 9). Blood samples were collected at an initial visit and then at regular intervals for the next 12 months. Plasma concentrations of adrenocorticotropin (ACTH), cortisol, and insulin and serum concentrations of glucose and total thyroxine (T4) were obtained. Horses with ECD had significantly higher plasma ACTH concentrations than EMS horses or controls. Horses with EMS and ECD both had significantly higher plasma insulin concentrations than control horses, which was correlated with the Obel grade of laminitis (r = 0.63). After treatment, there was a trend for a reduction in plasma ACTH concentration in horses with ECD. A program of diet and exercise for horses with EMS resulted in reductions in both plasma insulin concentrations and bodyweight, which was variable, depending on the individual. There was a significant correlation between the change in plasma insulin concentration and Obel grade of laminitis (r = 0.69). This study has highlighted the importance of baseline plasma insulin concentration as a potential indicator of the susceptibility of horses to laminitis and the response to a program of diet and exercise.     

Effect of rapid intravenous administration of 50% dextrose solution on phosphorus homeostasis in postparturient dairy cows

BACKGROUND: Dextrose is commonly administered to postparturient dairy cows, which often have low plasma phosphorus concentration ([P]) as a result of anorexia and sudden onset of lactation. Intravenous (IV) dextrose administration causes hypophosphatemia in other species. HYPOTHESIS: Bolus administration of dextrose to postparturient dairy cows results in a transient decrease in plasma [P]. ANIMALS: Six healthy postparturient dairy cows. METHODS: Using a crossover design, cows were administered 500 mL of 50% dextrose solution IV or a sham treatment. Plasma concentrations of glucose ([glucose]), immunoreactive insulin ([IRI]), and phosphorus were monitored for 12 hours after each treatment. Urine [P], [glucose], and volume and salivary [P] were also determined. RESULTS: Plasma [glucose], [IRI], and [P] were stable during sham treatment. Plasma [P] decreased rapidly after dextrose administration, dropping by 35% in 1 hour and remaining below baseline for 90 minutes. Salivary [P], urine [P], and urine volume per hour remained stable after dextrose administration, but glucose was detected in urine for up to 6 hours. The amount of glucose excreted in urine in 12 hours (11.9+/-4.5 g) was less than 5% of the administered dose. Regression analysis revealed a stronger association between plasma [P] and [IRI] than between plasma [P] and [glucose], suggesting that hyperinsulinemia drove the hypophosphatemia. CONCLUSION AND CLINICAL IMPORTANCE: Results indicate that low plasma [P] should be expected in cows that have received IV dextrose within 1 hour before blood sampling. Caution is advised when administering dextrose solution to cows already at risk of hypophosphatemia.     

Quantitative assessment of increased sensitivity of chronic laminitic horses to hoof tester evoked pain

Reasons for performing study: To evaluate quantitative sensory testing (QST) of the feet of laminitic horses using a power‐assisted hoof tester. Hypothesis: Hoof Compression Thresholds (HCTs) can be measured reliably and are consistently lower in horses with chronic laminitis than in normal horses. Methods: HCTs of chronic laminitic (n = 7) and normal horses (n = 7) were repeatedly measured using a hydraulically powered and feedback controlled hoof tester. Data from 2 tests, at 3 sites in both forefeet, during 3 sessions were collected and statistically analysed using linear mixed models. Results: The mean ± s.e. HCT for the laminitic horses was 29.6 ± 3.5 kg/cm² and for horses in the normal group was 59.8 ± 4.3 kg/cm². Residual variance was the largest of the error components and was greater (P<0.001) for the normal horses; none of the other components significantly differed between the 2 groups. Averaging of HCTs from each foot could produce a test with intraclass correlation coefficients of 0.83 for the normal group and 0.87 for the laminitic group, with an estimated sensitivity of 0.94 and a specificity of 0.93. This test would permit detection with 80% power and 95% confidence of a reduction of over 40% in the difference in mean HCTs between laminitic and normal horses following effective treatment provided that the experimental groups are of 9 or more horses. Conclusions: HCTs can be safely and reliably measured experimentally using this hoof tester. The level of variability found indicates that, under these conditions, treatments may need to produce at least a 40% improvement to be detected. Simplification of the hoof tester, training of the horse and repeated testing may permit the method to be used clinically to detect changes in the HCTs of individual laminitic horses but these potential improvements will require further investigation. Potential relevance: Measurement of HCTs can provide an additional means for assessing the effectiveness of treatments for alleviation of chronic equine laminitis.     

Glucose tolerance and insulin sensitivity in ponies and Standardbred horses

The existence of an innate insulin insensitivity in ponies was investigated and compared with the situation in larger breeds of horse. Ponies that were fat or had previously suffered laminitis were found to be far more intolerant to oral glucose loading (1 g/kg bodyweight [bwt]) than normal ponies or Standardbreds. These ponies also exhibited a far greater response in plasma insulin levels after glucose loading. Insulin response tests (0.4 iu/kg bwt insulin intravenously) showed only a minimal and very protracted response in both the fat and laminitic groups. The relevance of these findings in regulation of carbohydrate and lipid metabolism, and their role in the pathogenesis of hyperlipaemia, are discussed.     

Obesity induced changes to plasma adiponectin concentration and cholesterol lipoprotein composition profile in cats

Feline obesity generally results in aberrations to plasma metabolite levels, such as lipid concentrations and lipoprotein composition. This study sought to investigate the resultant effect of obesity on cholesterol lipoprotein composition and circulating adiponectin concentrations in cats. Plasma glucose, lipids (triglyceride, cholesterol and free fatty acid), insulin and adiponectin concentrations, and cholesterol lipoprotein composition were measured and compared between body condition score (BCS) determined normal healthy control and obese cats. Although the obese group demonstrated higher levels of plasma cholesterol, glucose, and triglycerides, as compared to healthy controls, the difference was insignificant thus indicating that the BCS determined obese cats may have been overweight and not morbidly obese. Plasma insulin levels were significantly higher (25–30%) versus healthy control animals thereby possibly hinting at the ensuing emergence of obesity induced insulin resistance. However, the BCS determined obese cat demonstrated a significant reduction (p < 0.05) in plasma adiponectin concentration and a significant increase (p < 0.05) in LDL-cholesterol % as compared to age matched healthy control animals. This would indicate that changes in plasma adiponectin concentration and cholesterol lipoprotein composition may be good early indicators of obesity in cats.     

Effects of oral administration of levothyroxine sodium on concentrations of plasma lipids, concentration and composition of very-low-density lipoproteins, and glucose dynamics in healthy adult mares

OBJECTIVE: To evaluate glucose and lipid metabolism in healthy adult horses administered levothyroxine sodium (L-T4). ANIMALS: 12 healthy adult mares. PROCEDURE: 8 horses received an incrementally increasing dosage of L-T4 (24, 48, 72, or 96 mg of L-T4/d) for weeks 1 to 8. Each dose was provide between 7 AM and 8 AM in the morning grain meal for 2 weeks. Four additional horses remained untreated. Serum concentrations of nonesterified fatty acids, triglyceride (TG), total cholesterol (TC), and very-low-density lipoprotein (VLDL) were measured and composition of VLDL examined in samples obtained between 8 AM and 9 AM at weeks 0, 2, 4, 6, and 8. Glucose dynamics were assessed by use of a combined IV glucose-insulin tolerance test (IVGITT) conducted before and at the end of the 8-week treatment period. Data for each combined IVGITT were interpreted by use of the minimal model. RESULTS: Plasma TG, TC, and VLDL concentrations significantly decreased over time in treated horses. At the completion of the 8-week treatment period, mean plasma VLDL concentration was 46% of the mean value for week 0 in treated horses. Insulin sensitivity significantly increased (> 2-fold) in treated horses, but glucose effectiveness and net insulin response were not affected. Levothyroxine sodium significantly increased the rate of insulin disposal. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of L-T4 decreases blood lipid concentrations, improves insulin sensitivity, and increases insulin disposal in horses. Levothyroxine sodium may have potential as a treatment for horses with reduced insulin sensitivity.