section name header

Basics ⬇

Outline

BASICS

Definition!!navigator!!

  • Performed to evaluate a horse's ability to metabolize glucose appropriately. Glucose tolerance tests evaluate response to a glucose load, and are 1 method of testing for insulin dysregulation. Insulin tolerance tests may also be used (see chapter Insulin levels/insulin tolerance test)
  • In normal horses, insulin secretion is closely tied to blood glucose concentrations. Fasted insulin concentrations are quite low (<20 μU/mL) but increase rapidly when the horse receives glucose. In turn, this rapidly causes blood glucose to return to the normal range
  • Several glucose tolerance tests have been developed:
    • Oral sugar test—administer 0.15–0.45 mL/kg Karo Light Syrup and assess insulin and glucose at 60–90 min. Insulin <45 μU/mL is considered normal. Insulin 45–60 μU/mL is considered equivocal, and insulin >60 μU/mL is abnormal
    • The in-feed glucose test—administer 1 g/kg oral glucose in 0.5 g/kg chaff. Insulin >85 μU/mL at 2 h is considered abnormal
    • IV glucose tolerance test—administer dextrose (0.5 g/kg as a 50% solution IV). Either blood glucose alone or glucose and insulin are determined before and every 30 min after administration for 3 h. Glucose is not given orally to remove the confounding effects of poor intestinal absorption or delayed gastric emptying. Serum glucose should be normal within 2 h of administration and an elevated glucose 3 h after beginning the test is clear evidence of insulin dysregulation
    • The combined glucose-insulin test—administer dextrose (150 mg/kg 50% solution IV), immediately followed by 0.10 U/kg regular insulin. Collect blood at 45 min. Insulin resistance if blood glucose is above baseline and/or insulin above 100 μU/mL
  • Common diseases causing abnormal results include insulin dysregulation in horses with EMS or PPID (equine Cushing disease). Results will also be abnormal in cases of diabetes mellitus caused by insulin deficiency

Pathophysiology!!navigator!!

  • In oral glucose tolerance tests, increased serum insulin levels in euglycemic or hyperglycemic horses may result from insulin dysregulation, which may be due to peripheral (tissue) insulin resistance, increased pancreatic secretion (primary or secondary to increased stimulation by incretins), or alterations in insulin clearance
  • In IV glucose tolerance, increased serum insulin levels in euglycemic or hyperinsulinemic horses may be due to peripheral (tissue) insulin resistance, or alterations in pancreatic function or insulin clearance. IV glucose tolerance tests will not evaluate the role of incretin stimulation
  • Diabetes mellitus is associated with decreased circulating insulin and increased glucose tolerance test times. Type 2 is due to pancreatic exhaustion and type 1 is due to autoimmune pancreatic destruction. Diabetes mellitus is very rare in equids

Systems Affected!!navigator!!

Endocrine system—slow return of blood glucose to the normal range indicates abnormal insulin regulation.

Genetics!!navigator!!

EMS is thought to be in part heritable.

Incidence/Prevalence!!navigator!!

Prevalence of abnormal glucose tolerance is not known.

Geographic Distribution!!navigator!!

N/A

Signalment!!navigator!!

  • There are breed differences in response to an oral glucose load. Ponies and thrifty breeds (e.g. Andalusians) tend to have a physiologic degree of insulin resistance; thus, blood glucose returns to normal levels more slowly than in other horses
  • No sex differences
  • Frequently obese
  • PPID can be associated with alterations in glucose metabolism and tends to occur in old horses (>18 years)

Signs!!navigator!!

  • In horses with PPID—lethargy, exercise intolerance, hypertrichosis and failure to shed (or delayed shedding of) winter coat, tendency for chronic infections, pendulous abdomen, polyuria and polydipsia, laminitis
  • In horses with EMS—exercise intolerance, obesity, abnormal fat distribution (neck, tail-head, supraorbital), laminitis
  • In horses with diabetes mellitus—weight loss, polyuria and polydipsia, and lethargy or depression

Causes!!navigator!!

  • The primary cause for abnormal results is insulin dysregulation
  • Hyperglycemia and hypoinsulinemia indicate diabetes mellitus
  • Diet and fed status can influence oral glucose tolerance test results. Thus, the tests should be performed on horses consuming grass hay or other low-carbohydrate feeds (not grain). Fasting duration may influence results

Risk Factors!!navigator!!

  • PPID
  • Obesity

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

Polyuria, polydipsia, and glucosuria in horses with suspected endocrine disorders indicate a disorder in glucose homeostasis, and are generally consistent with diabetes mellitus.

Laboratory Findings!!navigator!!

Drugs That May Alter Laboratory Results

  • Corticosteroids
  • α2-Agonists (xylazine, detomidine)

Disorders That May Alter Laboratory Results

Delayed separation of serum from cells falsely lowers blood glucose values.

Valid if Run in a Human Laboratory?

Yes; however, note that there may be marked differences in insulin concentration depending upon which assay is used.

CBC/Biochemistry/Urinalysis!!navigator!!

  • Horses with abnormal glucose response associated with PPID may exhibit a stress response with mature neutrophilia, lymphopenia, and eosinopenia. They also may have glucosuria
  • Horses with type 1 or 2 diabetes mellitus have hyperglycemia. Horses with EMS have normal blood glucose levels in the face of increased insulin concentrations

Other Laboratory Tests!!navigator!!

Pituitary function—TRH stimulation (non-fall) or endogenous ACTH (fall) tests. If these results are consistent with PPID, that diagnosis is supported; if these results do not indicate PPID, suspect either a stress response or EMS.

Imaging!!navigator!!

  • Not diagnostic for abnormalities of glucose metabolism
  • Increased pituitary gland size may be visualized with specialized modalities—CT or venous contrast

Other Diagnostic Procedures!!navigator!!

N/A

Treatment ⬆ ⬇

Outline

TREATMENT

Appropriate Health Care!!navigator!!

  • Horses with hyperlipemia require inpatient treatment with IV dextrose, balanced electrolyte solutions, caloric replacement, heparin, and exogenous insulin
  • All other horses with abnormal test results can be treated as outpatients

Nursing Care!!navigator!!

Horses with laminitis need corrective hoof trimming and shoeing and dietary management.

Activity!!navigator!!

  • Limit the activity of horses with laminitis
  • Increase the activity of sound, obese horses in an effort to lose weight

Diet!!navigator!!

  • Horses with laminitis generally benefit from a low-carbohydrate, high-fiber diet
  • Keep horses with insulin dysregulation on a low-carbohydrate diet
  • Restrict or increase caloric intake in all horses until a condition score of 4–6 out of 9 is achieved

Client Education!!navigator!!

  • Horses with PPID may be managed with medication and nursing care, but their prognosis is quite variable. Some do well for several years; others are refractory to treatment. Inform owners that treatment of such horses is palliative and required for life
  • Encourage clients to maintain horses at condition scores of 4–6 out of 9 and to prevent obesity

Surgical Considerations!!navigator!!

N/A

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

  • Metformin may help improve insulin and glucose responses to an oral glucose test (15–30 mg/kg PO before feeding every 12–24 h)
  • The agent most commonly used to alter symptoms of PPID is pergolide (0.50–2 mg/horse/day PO)
  • Horses with insulin deficiency (i.e. diabetes mellitus) require insulin supplementation. Protamine zinc insulin (0.5 IU IM every 12 h) was reported to normalize blood glucose in a case report of a pony
  • Hyperlipemia—protamine zinc insulin (0.075–0.4 IU/kg SC or IM every 12–24 h). Regular insulin (0.4 IU/kg) has also been recommended
  • Regard these doses as starting points that should be changed in response to blood glucose levels

Contraindications!!navigator!!

N/A

Precautions!!navigator!!

Horses that receive overdoses of pergolide may exhibit anorexia, lethargy, and ataxia.

Possible Interactions!!navigator!!

N/A

Alternative Drugs!!navigator!!

N/A

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

  • Upon initial diagnosis, test horses with PPID in 4–6 weeks to determine treatment efficacy by endogenous ACTH determination or TRH stimulation test. Abnormal results indicate the need for an increased dose of the compound the horse is receiving or change in medication
  • Once stable, test horses with PPID less frequently (every few months)
  • For horses with abnormal glucose tolerance test results associated with EMS or PPID, monitor glucose tolerance in 3–4 months following implementation of therapy
  • Check the blood glucose level of horses with diabetes mellitus on insulin therapy twice a day. Increase or decrease insulin doses in response to blood glucose values outside the normal range

Possible Complications!!navigator!!

N/A

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

  • Hypertrichosis, chronic infections, and laminitis are commonly associated with PPID
  • Obesity, laminitis, and dyslipidemia are commonly associated with EMS

Age-Related Factors!!navigator!!

N/A

Zoonotic Potential!!navigator!!

N/A

Pregnancy/Fertility/Breeding!!navigator!!

N/A

Synonyms!!navigator!!

N/A

Abbreviations!!navigator!!

  • ACTH = adrenocorticotrophic hormone
  • CT = computed tomography
  • EMS = equine metabolic syndrome
  • PPID = pituitary pars intermedia dysfunction
  • TRH = thyrotropin-releasing hormone

Suggested Reading ⬆ ⬇

Bertin FR, Taylor SD, Bianco AW, Sojka-Kritchevsky JE. The effect of fasting duration on baseline blood glucose concentration, blood insulin concentration, glucose/insulin ratio, oral sugar test, and insulin response test results in horses. J Vet Intern Med 2016;30(5):1726–1731.

Frank N. Equine metabolic syndrome. Vet Clin North Am Equine Pract 2011;27:73–92.

Frank N, Tadros EM. Insulin dysregulation. Equine Vet J 2014;46:103–112.

Freestone JF, Shoemaker K, Bessin R, Wolfsheimer JK. Insulin and glucose response following oral glucose administration in well conditioned ponies. Equine Vet J Suppl 1992;11:13–17.

Author(s) ⬆

Authors: Janice Kritchevsky and Heidi Banse

Consulting Editors: Michel Lévy and Heidi Banse