ACVIM Required Reading - Endocrine/Metabolic Dz

Question 1

List the three core phenotypic features of Equine Metabolic Syndrome (EMS).

Answer 1

1. Increased adiposity - regional or generalised (obesity). Regional adiposity is characterized by expansion of subcutaneous adipose tissues surrounding the nuchal ligament in the neck (cresty neck), development of fat pads close to the tail head, or fat accumulation behind the shoulder or in the prepuce or mammary gland region.
2. Insulin resistance (IR) characterized by hyperinsulinaemia or abnormal glycemic and insulinaemic responses to oral or IV glucose and/or insulin challenges.
3. A predisposition toward laminitis i.e. clinical or subclinical laminitis that has developed in the absence of recognised causes e.g. grain overload, colitis, RFM.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 2

List phenotypic features in addition to the core three which may warrant consideration.

Answer 2

• Hypertriglyceridaemia or dyslipidaemia; reported in some cases of EMS.
• Hyperleptinemia resulting from increased secretion of the hormone leptin by adipocytes in response to IR or a state of leptin resistance.
• Arterial hypertension; detected in the summer in laminitis- prone ponies; important in human metabolic syndrome.
• Altered reproductive cycling in mares.
• Increased systemic markers of inflammation in association
  with obesity.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 3

List three core areas of focus when obtaining the history of a horse with potential EMS.

Answer 3

1. Factors related to obesity i.e. diet and exercise. Often referred to as ‘easy keepers’ or ‘good doers’.
2. History of previous laminitis episodes and relationship to changes in pasture or feeding of grain.
3. Familial information. No firm evidence at this time but reports of familial links.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 4

List potential clinical signs of EMS.

Answer 4

• Regional adiposity, obesity, bilateral lameness attributable to laminitis, and/or evidence of previous laminitis such as divergent growth rings on the hooves.
• Cresty neck score of 3/5 or more i.e. ‘‘Crest enlarged and
  thickened, so fat is deposited more heavily in middle of
  the neck than toward poll and withers, giving a mounded
  appearance. Crest fills cupped hand and begins losing
  side-to-side flexibility.’’
• Neck circumference (at midpoint between poll and withers) > 0.71 was used as cut-off for development of pasture-associated laminitis in ponies.
• Assess BCS and weight (via weight tape or scale).

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 5

Describe the pathophysiology of increased adiposity in EMS.

Answer 5

• Environmental factors: chronic overfeeding in assoc with limited physical activity appears to be a contributing factor.
• Genetic factors: enhanced efficiency with respect to the utilisation of dietary energy e.g. ponies and wild horses designed to gain weight in Summer in preparation for poor Winter nutrition –> obesity w modern management.
• Inflammation: adipose tissue is an endocrine organ that releases adipokines incl. leptin, resistin, adiponectin, visfatin, and apelin –> inflammatory cytokines released from macrophages and adipocytes e.g. TNFa, IL-1, IL-6 –> cycle of enhanced adipose tissue inflammation, adipokine synthesis, and secondary acute phase protein synthesis by the liver i.e. obesity = chronic inflam.
• Whether obesity induces IR or the IR horse is more predisposed to obesity has not been determined.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 6

Describe the pathophysiology of insulin resistance (IR) in EMS.

Answer 6

• IR involves defects of insulin signaling such as reduced insulin receptor tyrosine kinase activity and reduced postreceptor phosphorylation steps that impinge on metabolic and vascular effects of insulin.
• Two theories link obesity to IR:
  (1) the down-regulation of insulin signalling pathways induced by adipokines and cytokines.
  (2) the accumulation of intracellular lipids in insulin-sensitive tissue such as skeletal muscle (lipotoxicity).
• When the storage capacity of adipose tissues is exceeded, skeletal muscle, liver, and pancreatic
  tissues attempt to utilise fats by increasing b-oxidation,
  but lipid can accumulate within these tissues and alter
  normal cellular functions, including insulin signaling.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 7

Describe the pathophysiology of laminitis in EMS.

Answer 7

• IR and/or hyperinsulinemia predispose ponies to pasture- associated laminitis. Proposed mechanisms: endothelial cell dysfunction w/in blood vessels of the foot, digital vasoconstriction, impaired glucose uptake by epidermal laminar cells, altered epidermal cell function or mitosis and MMP activation by glucose deprivation or ROS.
• Insulin acts on vascular endothelial cells –> activation of phosphatidylinositol 3-kinase (PI3K) pathway –> NO synth –> vasodilation AND activation of the mitogen-activated protein kinase (MAPK) pathway –> endothelin-1 (ET-1) synth –> vasoconstriction.
• IR states in people –> inhibition of PI3K pathway and reflex overstimulation of MAPK pathway.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 8

Is there a breed predisposition for EMS?

Answer 8

Anecdotally, Welsh, Dartmoor, and Shetland ponies and
Morgan Horse, Paso Fino, Arabian, Saddlebred, Spanish
Mustang, and Warmblood breeds appear to be more
susceptible to EMS and TBs and SBs less susceptible.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 9

Is there an age predisposition for EMS?

Answer 9

Most horses with EMS are between 5 and 15 years of age when vet/farrier services are first requested for laminitis.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 10

What is in the influence of season on the development of pasture-associated laminitis?

Answer 10

• Highest incidence at time of highest NSC content in pasture = US: May-June, UK: June-July.
• Aspects of the EMS phenotype in ponies may be latent under conditions of lower or restricted dietary
  WSC content, but become apparent when carbohydrate intake increases.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 11

How is EMS diagnosed in horses and ponies?

Answer 11

• History, PE, foot rads.
• Blood glucose: hyperglycemia is rare because most animals maintain an effective compensatory insulin secretory response in the face of IR, however, are often toward the higher end of reference range indicating partial loss of glycemic control (think DM if persistent hyperglyc).
• Serum insulin: hyperinsulinemia (>20 uU/mL) in the absence of confounding factors such as stress, pain, and a recent feed provides evidence of IR; not present in all cases so…
• Dynamic testing is preferred = OST or CGIT.
• Anemia is sometimes detected in EMS horses.
• Elevated GGT activity in some cases has corresponded with hepatic lipidosis, detected via biopsy/necropsy.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 12

What are the ideal testing conditions when measuring insulin and glucose concentrations?

Answer 12

• When animal is not painful/stressed as cortisol and epinephrine lower tissue insulin sensitivity and raise resting glucose and insulin concentrations.
• Between 8am and 10am.
• After an approximate 6-8 hour fast.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 13

Describe the Combined Glucose-Insulin Test (CGIT) for diagnosis of EMS.

Answer 13

• Obtain pre-inj blood for baseline glucose and insulin (plain and sodium fluoride tubes), inj 150 mg/kg 50% dextrose solution IV, immediately followed by 0.10 U/kg insulin IV.
• Blood glucose concentrations are measured at 1, 5, 15, 25, 35, 45, 60, 75, 90, 105, 120, 135, and 150 mins and serum insulin at 45mins post-injection.
• Normal horse: blood gluc below baseline by 45 mins.
• IR: insulin concentrations >100 mU/mL at 45 mins.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 14

Describe the Oral Sugar Test (OST) for diagnosis of EMS.

Answer 14

• Fasting the horse for 6–8 hr, take baseline blood (plain and sodium fluoride), give oral corn syrup at 0.15 mL/kg PO, collect blood 75 minutes after corn syrup. .
• Baseline insulin conc: positive for IR if >20 µU/ml.
• • 75 mins insulin conc: positive > 60 µU/ml, equivocal if 45-60 µU/ml.
• Baseline glucose conc: normal range 80-125 mg/dL.
• • 75 mins glucose conc: excessive response >125 mg/dL.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 15

Regional adiposity and laminitis are clinical signs of
PPID as well as EMS and some horses with PPID have reduced glucose tolerance. In addition there is suggestion that horses with EMS are predisposed to developing PPID. What factors can help distinguish between PPID and EMS?

Answer 15

1. Age at onset: EMS generally younger.
2. Additional clinical signs of PPID: delayed or failed shedding of the winter haircoat, hirsutism, excessive sweating, polyuria/ polydipsia, and skeletal muscle atrophy.
3. A positive test for PPID: baseline ACTH, TRH-stim, LDDT.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 16

What management change is recommended to improve insulin sensitivity in horses in the presence of appropriate structural integrity of the foot?

Answer 16

• Regular exercise. In people improves IR even in the absence of weight loss.
• Start with 2–3 20-30min exercise sessions per week (riding and/or longeing). Gradually increase intensity and duration of exercise.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 17

Outline nutritional recommendations for horses with EMS.

Answer 17

1. Feed a diet with slow rate of feed intake and gastric emptying –> minimise postfeeding increases in the circulating glucose and insulin.
   - Increase energy density of hay by adding in soaked (unmolassed) beet pulp or vegetable oil.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 18

What medications have been used to treat horses and ponies with EMS? Is there evidence to support their use?

Answer 18

• Most horses and ponies with EMS can be effectively managed by controlling the horse’s diet, instituting an exercise program, and limiting/eliminating pasture access.
  1. Metformin: a biguanide drug that enhances the action of insulin within tissues at the postreceptor level most likely by
  promoting AMP-dependent protein kinase. Inhibition
  of gluconeogenesis and glycogenolysis within the
  liver appears to be its main mode of action along with
  many other insulin- and noninsulin-related effects; dose: 15mg/kg PO q12h –> improved insulin sensitivity in hyperinsulinaemic horses and ponies.
• Safety studies not performed in horses, therefore care giving long-term.
• Bioavailability worse than in humans; further investigation of appropriate dosing schedules may improve efficacy.
  2. Levothyroxine sodium: induces weight loss and improves insulin sensitivity when given at the same time as diet and exercise changes; dose: 48mg/day for >350kg, 24mg/day for smaller ponies for 3-6mo. Once idea BWt attained wean off by halving for 2 wks then halving again for 2wks.
• Benefits of treating with levothyroxine at lower dosages for longer periods have not been evaluated scientifically.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 19

Is there evidence to support administration of dietary supplements to horses with EMS?

Answer 19

Chromium, magnesium, cinnamon, and chasteberry
(Vitex agnus-castus) are commonly recommended for the
management of EMS. There is insufficient scientific evidence to support the use of these supplements.

Ref: ACVIM Consensus Statement (2010) - EMS.

Question 20

What would be the advantage of a Continuous Glucose Monitoring System (CGMS) in performing a CGIT for diagnosis of EMS?

Answer 20

Protocols that minimize patient handling and multiple blood sample acquisitions may improve the diagnostic accuracy of the CGIT because stress can contribute to decreased insulin sensitivity. 6 Continuous glucose monitoring systems
(CGMS), developed for monitoring glucose regulation
in diabetic humans, have been employed in veterinary
medicine.7 With CGMS, interstitial fluid glucose concentrations
are assessed every 5 minutes (288 measurements/
24 h), decreasing the need for patient restraint.

Ref: J. Vet. Intern. Med. (2011); 25 (1) 162–165.

Question 21

How do Continuous Glucose Monitoring Systems work?

Answer 21

The CGMS needle into the skin (hair clipped) and attached with tissue glue and interstitial fluid glucose concentrations are assessed every 5 minutes (288 measurements/24 h).

Ref: J. Vet. Intern. Med. (2011); 25 (1) 162–165.

Question 22

Are Continuous Glucose Monitoring Systems (CGMS) as accurate as intermittent blood draws when performing a CGIT for diagnosis of EMS?

Answer 22

• Yes. Glucose curves obtained using CGMS had high concordance with the concentration of glucose in blood.
• Optimal concordance was evident when CGMS data were compared with blood glucose concentrations with a 15-minute delay (concordance co-efficient = 0.854).

Ref: J. Vet. Intern. Med. (2011); 25 (1) 162–165.

Question 23

Pioglitazone (PG) improves insulin sensitivity in people with IR. What is this drug? Does it have the same effect in horses?

Answer 23

• Pioglitazone (PG) is a synthetic ligand for peroxisome proliferator-activated receptor gamma (PPARg), an intracellular receptor and transcription factor. Transcription of genes controlled by PPARg increases the efficiency of insulin-stimulated glucose clearance from blood.
• PG did not improve insulin sensitivity in a model whereby horses were given 1mg/kg PO q24h for 14d, LPS was administered to induce IR on day13 and FSIGT were performed on days 0, 12 and 14.
• However, transcript abundance of glucose and lipid transporters was altered in both skeletal muscle and subcutaneous adipose tissue –> a higher dose/longer tx period may result in improved insulin sensitivity in horses.

Ref: J. Vet. Intern. Med. (2011); 25 (2) 356-364.

Question 24

The translocation of glucose transporter 4 (GLUT4) to the cell surface is the limiting step for glucose uptake in insulin sensitive tissues. Phosphorylation of AS160 (signalling protein) suppresses or alters GAP activity so GLUT4 exocytosis is permitted. In humans and rats with IR AS160 is reduced. GLUT12 also translocates to the normal muscle cell plasma membrane in response to insulin in people.
What role do GLUT4, GLUT12 and AS160 (a gene regulating GLUT4 pathways) play in IR mares?

Answer 24

• IR decreases basal cell-surface GLUT4 expression, but not GLUT12, by an AS160-independent pathway, without affecting total GLUT4 and GLUT12 content in skeletal muscle of mares with IR.
• IR induces defects in the skeletal muscle glucose transport pathway by dec active cell-surface GLUT4.

Ref: J. Vet. Intern. Med. (2011); 25 (2) 315-321.

Question 25

Significant seasonal changes in hormone concentrations occur in horses. Do the results of the CGIT change significantly in healthy horses in line with changes in the seasons?

Answer 25

No clinically relevant differences were seen in the results of the CGIT performed in February, May, June, August, September, and November, suggesting that season minimally affects results of this test in normal aged horses.

Ref: J. Vet. Intern. Med. (2012); 26 (4) 1035-1041.

Question 26

Is the CGIT repeatable when performed on the same healthy horse twice three weeks apart?

Answer 26

• 9 adult, healthy SBs and 9 adult, healthy Icelandic horses.
• No. Calculated parameters for the glucose curve of the CGIT had low repeatability, whereas the parameters for the insulin curve had high repeatability.

Ref: J. Vet. Intern. Med. (2013); 27 (6) 1543–1550.

Question 27

Is the CGIT repeatable when performed on the same horse in their home environment and 24 hours post-transport?

Answer 27

No. There was an effect of stress on the glucose dynamics but not on the insulin dynamics of the CGIT.

Ref: J. Vet. Intern. Med. (2013); 27 (6) 1543–1550.

Question 28

Is there breed variation in CGIT results?

Answer 28

Yes. There was an effect of breed (Standarbred versus Icelandic horse) as well as stress on the glucose dynamics (Icelandic horse nadir after 60min not 45min), but not on the insulin dynamics of the CGIT.

Ref: J. Vet. Intern. Med. (2013); 27 (6) 1543–1550.

Question 29

Is there are a relationship between plasma insulin, leptin, and lipid levels, and measures of oxidative stress with adiposity in mature light breed horses?

Answer 29

• Study of 300 adult light breed horses, blood drawn after kept off concentrates overnight, BCS score recorded.
• Overconditioned (BCS 7) and obese (BCS 8-9) horses had higher plasma insulin and leptin levels than
  optimally conditioned (BCS 4-6) horses.
• Obese horses had higher triglyceride levels and lower red blood cell gluthathione peroxidase activities than optimally conditioned horses.

Ref: J. Vet. Intern. Med. (2013); 27 (3) 576-582.

Question 30

What is the significance of the association between BCS and high insulin, leptin and triglyceride levels and low RBCS glutathione peroxidase activity in overweight horses and laminitis?

Answer 30

Maintaining horses at a BCS

Question 31

Do plasma concentrations of TNF, IL-1b, IL-6 or SAA correlate with BCS, signalment or insulin concentration in healthy, adult, light-breed horses?

Answer 31

• 114 healthy, adult, light-breed horses samples.
• Plasma TNF and IL-6 concentrations were higher in females than males.
• IL-6 concentrations correlated with age.
• Plasma SAA concentrations correlated with both insulin and BCS.

Ref: J. Vet. Intern. Med. (2013); 27 (1) 157-163.

Question 32

What is the potential significance of the correlation between plasma SAA concentration, plasma insulin concentration and BCS in adult horses?

Answer 32

• Concentrations of SAA correlated with BCS and insulin, independent of age or sex.
• It is possible that SAA is a component of laminitis pathophysiology.

Ref: J. Vet. Intern. Med. (2013); 27 (1) 157-163.

Question 33

Describe cortisol and ACTH responses following a TRH stimulation test (samples 0m, 14min, 30min post inj 1mg TRH) in healthy horses and horses with PPID, and the implications this has for diagnosis of PPID.

Answer 33

• Cortisol concentration increased in PPID horses, and ACTH increased in all groups.
• ACTH, but not cortisol concentration, was significantly higher in PPID horses compared with normal horses.
• A relationship between cortisol concentration and ACTH concentration was seen in normal horses, but not in horses with PPID i.e. ACTH and cortisol concentrations are disassociated in horses with PPID.
• Measuring ACTH concentration after TRH administration appears superior to measuring cortisol concentration as a
  diagnostic test for PPID.

Ref: J. Vet. Intern. Med. (2011); 25 (5) 1431-1438.

Question 34

Is there a seasonal influence on ACTH and alpha-MSH concentrations measured following a TRH stimulation test in healthy horses? What are the implications of these findings?

Answer 34

• Endogenous and TRH-stimulated ACTH and a-MSH concentrations were significantly different across months with higher concentrations in the summer and fall.
• These results support previous evidence of a seasonal influence on the equine pituitary-adrenal axis.
• More research is warranted to determine if seasonal reference ranges for TRH stimulation testing need to be defined.

Ref: J. Vet. Intern. Med. (2011); 25 (3) 579-585.

Question 35

Is seasonal variation in plasma a-MSH and ACTH concentrations in horses influenced by geographic location or breed?

Answer 35

• Mean seasonal a-MSH concentrations were similar in all healthy groups at all locations, but in the fall, plasma ACTH concentrations were higher in southern locations and the peak occurred earlier in northern locations.
• Plasma ACTH but not a-MSH concentrations were higher in Morgan horses compared with light breed horses.
• Hormone concentrations of ponies did not differ from those of horses during either season.
• Concentrations of both hormones were high in the fall compared with the spring in horses with PPID.

Ref: J. Vet. Intern. Med. (2011); 25 (4) 872-881.

Question 36

Is seasonal variation in plasma a-MSH and ACTH concentrations in horses influenced by the presence of PPID?

Answer 36

Horses with PPID maintain seasonal regulation of PI hormone output.

Ref: J. Vet. Intern. Med. (2011); 25 (4) 872-881.

Question 37

Is CT a useful diagnostic modality in horses with PPID?

Answer 37

• Yes. The pituitary glands of PPID-affected horses are larger in height and width than those of aged horses without signs of PPID on CT examination.
• There was no difference between pituitary gland measurements made at the terminal CT scans and necropsy.

Ref: J. Vet. Intern. Med. (2011); 25 (5) 1144-1151.

Question 38

In a retrospective study of horses diagnosed with PPID from 1993-2004:

• Did frequency of diagnosis change with time?
• What was the survival rate >4.5 years post-discharge?
• Would owners have treated another horse for PPID?

Answer 38

• Diagnostic frequency increased with time.
• 50% survival after 4.5 years (78% of those were euthanised for conditions relating to PPID).
• 97% of owners would treat a second horse for PPID.

Ref: J. Vet. Intern. Med. (2012); 26 (4) 1027-1034.

Question 39

Is the mean of 2 measurements of ACTH concentration more reliable in assessing PPID than a single measurement?

Answer 39

• No. Paired measurement of ACTH concentration offers no advantage over a single measurement.
• Using histology as the gold standard, optimal sensitivity
  and specificity for diagnosing PPID were 69.4 and 80.9% for a single measurement and 72.2 and 76.2% for paired.
• The area under the ROC curve was 0.72 and 0.73 for single and paired measurements vs histopathologic dx.

Ref: J. Vet. Intern. Med. (2015); 29 (1) 355-361.

Question 40

How do T3, T4 and TSH concentrations in healthy foals compare to those in adult horses?

Answer 40

• TT4 and TT3 high at birth, peak at 2-3 days (10x adult), decline to adult concentrations by 3-4 weeks of age.
• fT4 and fT3 high at birth, decline to adult concentrations by 10-14 days of age.
• TSH declined to adult concentrations by 12 hours of age.

TRH stimulation tests identified significant differences in T4 among all 3 groups of foals, whereas T3 was similar in premature and term hospitalized foals and different from normal foals.

Ref: J. Vet. Intern. Med. (2014); 28 (4) 1301-1309.

Question 41

How do T3, T4 and TSH concentrations in sick term foals, premature hospitalised foals and healthy foals?

Answer 41

• TT3 and fT3 were significantly lower in both premature and term hospitalised foals compared to normal foals.
• TT4 and fT4 were not different between normal and term hospitalized foals, but were significantly lower than in premature foals of both of these groups.
• TSH was not different among the 3 groups.
• TRH stimulation tests identified significant differences in T4 among all 3 groups, whereas T3 was similar in premature and term hospitalized foals and different from normal foals.

Ref: J. Vet. Intern. Med. (2014); 28 (4) 1301-1309.

Question 42

How do T3, T4 and TSH concentrations in surviving sick (premature or full term) foals compare to those in non-survivors?

Answer 42

• All significantly lower in non-survivors with the exception of TT4.

Ref: J. Vet. Intern. Med. (2014); 28 (4) 1301-1309.

Question 43

A syndrome called transient hypothyroxinemia of prematurity (THOP) has been described in premature human infants, with serum T4 concentrations correlated with gestational age. The clinical relevance of THOP in human infants is that inadequate TH concentrations during this critical period of development result in motor and cognitive deficits that persist throughout life.
Are TH concentrations in premature foals lower than those of full term foals?

Answer 43

• T3 was lower in premature foals than healthy foals but was not lower than full term sick foals.
• T4 was lower in premature foals than healthy and sick full term foals.
• TSH response to TRH was significantly higher in premature foals compared to normal foals.

Ref: J. Vet. Intern. Med. (2014); 28 (4) 1301-1309.

Question 44

Do T3, T4, resting TSH and post-TRH stimulation test TSH concentrations in healthy adults horses and sick adult horses? What do these findings indicate?

Answer 44

• T3 and T4 concentrations are decreased in sick horses compared to healthy horses.
• TSH is not significantly different in sick and healthy horses.
• TSH fails to increase proportionally to the changes in THs, indicating hypothalamic–pituitary axis dysregulation.

Ref: J. Vet. Intern. Med. (2014); 28 (2) 609-617.

Question 45

Do T3, T4, resting TSH and post-TRH stimulation test TSH concentrations in sick adults horses vary in correlation with disease severity?

Answer 45

• Negative correlations existed between all THs, except TSH, and objective illness severity scores.
• TT3 and fT3 were decreased with mild dz. TT3 progressively decreased with moderate and severe dz.
• TT4 and fT4D remained normal with mild dz, but
  decreased progressively with dz severity.
• TSH increased with mild dz, but remained normal with moderate or severe dz.

Ref: J. Vet. Intern. Med. (2014); 28 (2) 609-617.

Question 46

What advanced diagnostic imaging modality has been reported to successfully diagnose a functional parathyroid adenoma in a pony? What were the accompanying clinicopathologic abnormalities?

Answer 46

• Technetium 99m nuclear scintigraphy of the neck using 200 millicuries of technetium Tc 99m sestamibic IV.
• An abnormal circular area of uptake was identified at the thoracic inlet at the level of the point of the shoulder on midline.
• Sonography of the thoracic inlet focused on the region identified by scintigraphy identified a hypoechoic structure located between the jugular veins.
• Persistently high total and ionised serum calcium concentrations with concurrently increased serum PTH concentration and lack of evidence of renal failure.
• > 15% decrease in PTH conc 15 mins post-PT removal.

Ref: J. Vet. Intern. Med. (2014); 28 (2) 687-692.

Question 47

The clinicopathologic characterization of ketosis includes high serum concentrations of NEFAs and ketone bodies and low concentrations of glucose. How do plasma leptin and insulin concentrations and leptin and hormone sensitive lipase mRNA expression in adipose tissue change with ketosis in dairy cows?

Answer 47

• Plasma leptin and insulin concentrations are lower in ketotic vs non-ketotic cows.
• The mRNA abundance of leptin and HSL are lower in ketotic vs non-ketotic cows.
• NB small cow numbers (10/group) and weak significant (P=0.03-0.05) for these findings.

Ref: J. Vet. Intern. Med. (2012); 26 (2) 415-417.

Question 48

Obesity in horses is postulated to be on the rise. Was this statement supported by the findings of a study of BCS of horses in Virginia?

Answer 48

• 1.7% underconditioned, 47.3% optimally conditioned, 32.3% overconditioned, 18.7% obese.
• The prevalence of overconditioned and obese horses in this population was higher than reported in previous studies and indicates that obesity might be an emerging problem in horses.

Ref: J. Vet. Intern. Med. 2012;26(6):1413–1418.

Question 49

Are there difference in pancreatic insulin secretion and peripheral insulin sensitivity in ewes with pregnancy toxaemia or those with high susceptibility (German Blackheaded Mutton breed) or low susceptibility (Finnish Landrace breed) to pregnancy toxaemia?

Answer 49

• Insulin secretion after glucose admin was significantly lower in the HR and PT than in the LR ewes.
• The baseline rate of lipolysis was significantly increased in the HR ewes, but the NEFA clearance was similar in both
  risk groups, albeit delayed in the PT ewes.
• The baseline b-HB concentration was significantly higher in the PT than in the HR and LR ewes. In the HR and in the PT ewes, the plasma b-HB concentrations did not decrease after glucose administration.
• There is reduced pancreatic first-phase insulin response and impaired insulin-dependent inhibition of ketone body formation during late pregnancy in the HR and PT ewes.
• This insulin resistance might represent one causative factor in the pathogenesis of ovine pregnancy toxaemia.

Ref: J. Vet. Intern. Med. 2013; 27(2):359–366.