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Basics ⬇

Outline

BASICS

Definition!!navigator!!

  • Blood insulin concentrations can be used to evaluate a horse's ability to regulate its blood glucose
  • Insulin secretion is closely tied to blood glucose concentrations in normal horses. Insulin concentrations are low (<20 μU/mL) with fasting but increase rapidly when glucose or a meal high in soluble carbohydrates is consumed
  • Blood insulin concentrations may be consistently elevated (>50 μU/mL) in horses with insulin dysregulation, which is commonly observed with EMS or PPID
  • Insulin response or tolerance tests may better reflect a horse's endocrine status than a one-time measurement
  • Insulin tolerance test—give 0.1 IU/kg IV regular insulin and determine blood glucose at baseline and 30 min. Blood glucose should decrease by 50% at 30 min
  • Blood insulin response can also be measured after administering 0.5 g/kg IV dextrose. Insulin should be low when starting, increase within 5 min of the dextrose load, and then decrease rapidly once blood glucose levels begin to drop. Serum glucose should normalize within 1–2 h after dextrose administration. An elevated blood insulin 3 h after beginning the test is clear evidence of insulin resistance
  • The combined glucose–insulin test—administer 150 mg/kg 50% solution dextrose IV, immediately followed by 0.10 U/kg regular insulin IV. Collect blood at 45 min. Insulin resistance is present if blood glucose is above baseline and/or insulin above 100 μU/mL
  • The most common pathologic processes leading to abnormal insulin concentrations are EMS or PPID

Pathophysiology!!navigator!!

  • Inappropriately low blood insulin—pancreatitis, leading to destruction of beta cells and development of type 1 diabetes mellitus
  • Increased insulin levels in hypoglycemic horse—insulin-secreting tumor (i.e. insulinoma) or iatrogenic insulin administration
  • Increased blood insulin levels in hyperglycemic horses—peripheral insulin resistance or an insulin antagonist (e.g. cortisol)
  • Increased blood insulin with normal blood glucose concentration—insulin dysregulation associated with EMS or PPID
  • Horses with hyperlipemia may also exhibit insulin resistance

Systems Affected!!navigator!!

The endocrine system is primarily affected by abnormal blood insulin and insulin response tests—decreased insulin is diagnostic of diabetes mellitus; increased insulin is most commonly associated with insulin dysregulation.

Signalment!!navigator!!

  • Ponies tend to have higher blood insulin levels than horses and are more prone to hyperlipemia
  • No sex difference
  • Obese animals, particularly ponies, are more insulin resistant than are thinner animals
  • PPID tends to occur in old horses (>18 years)

Signs!!navigator!!

  • The most common signs in horses with an abnormal insulin response test are those of equine insulin dysregulation/metabolic syndrome—obesity with abnormal fat distribution, infertility, and laminitis. However, prolonged fasting (>6 h) causes tissue insulin resistance in any horse
  • The eyelids can look swollen, and the supraorbital fat pad may look bulged
  • The horse may be dull or depressed
  • Similar clinical signs, with the addition of hypertrichosis (previously referred to as hirsutism) or an abnormal haircoat, weight loss, polyuria and polydipsia, and chronic infections particularly sinusitis and hoof abscess, are seen in horses with PPID
  • Clinical signs in horses with type 1 diabetes mellitus—weight loss, polyuria and polydipsia, lethargy, or depression
  • Signs of excess insulin caused by exogenous overdose or insulinoma are those of hypoglycemia—muscle trembling, ataxia, nystagmus, depression, and facial twitching, leading to convulsions, coma, and death
  • Signs of hyperlipemia include depression, anorexia, and icterus

Causes!!navigator!!

  • The primary cause of increased blood insulin, abnormal response to an insulin response test, or increased insulin after IV glucose is peripheral insulin resistance or the presence of insulin antagonists. Exogenous or endogenous corticosteroids are the most common insulin antagonists but other hormones (e.g. growth hormone, epinephrine) also have this effect
  • The most common reason for increased blood insulin without insulin resistance is an insulin-secreting tumor
  • The most common reason for type 1 diabetes mellitus is pancreatic damage presumably due to parasite migration

Risk Factors!!navigator!!

  • Obesity, particularly in ponies, is associated with insulin resistance, as is hyperlipidemia. PPID is associated with the development of abnormal insulin secretion
  • Glucocorticoid administration or increased cortisol from a stress response may also lead to insulin resistance and hyperglycemia

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

  • Polyuria, polydipsia, and glucosuria in horses with suspected endocrine disorders should alert the practitioner to a disorder in glucose homeostasis and, thus, in insulin levels
  • Hypoglycemia from excess insulin—myositis, neurologic disease, and hepatic failure
  • Determination of abnormally low blood glucose should cause the practitioner to suspect inappropriate insulin levels

Laboratory Findings!!navigator!!

Drugs That May Alter Laboratory Results

  • Corticosteroids
  • α2-Agonists (xylazine, detomidine)

Disorders That May Alter Laboratory Results

Delayed separation of serum or plasma from cells falsely lowers blood glucose values, making interpretation of insulin levels more difficult.

Valid if Run in a Human Laboratory?

Yes. It is important to have laboratory-specific reference ranges as insulin results can vary markedly depending on which assay is used.

CBC/Biochemistry/Urinalysis!!navigator!!

  • Horses with abnormal insulin levels caused by PPID may have a stress response with mature neutrophilia, lymphopenia, and eosinopenia. They may also have increased blood glucose and glucosuria
  • Horses with type 1 or 2 diabetes mellitus have hyperglycemia
  • Horses with insulinoma or exogenous insulin overdose have hypoglycemia
  • Horses with hyperlipemia may have increased bilirubin. Increases in hepatic enzyme activity may be observed if hepatic lipidosis is present

Other Laboratory Tests!!navigator!!

  • Pituitary function—endogenous ACTH determination (fall), TRH stimulation test (winter, spring, summer)
  • Increased resting ACTH and positive TRH response test are consistent with PPID

Imaging!!navigator!!

In cases of hyperglycemia associated with PPID, increased pituitary gland size may be depicted with specialized modalities—CT.

Other Diagnostic Procedures!!navigator!!

In cases of hyperglycemia associated with type 1 diabetes mellitus, findings from an exploratory laparotomy or abdominocentesis may be consistent with a damaged pancreas but should be considered extremely low-yield procedures because the pancreas is normally difficult to visualize and pancreatic tumors often are microscopic.

Treatment ⬆ ⬇

Outline

TREATMENT

Appropriate Health Care!!navigator!!

  • Horses with hypoglycemia require inpatient medical management if the disease is severe and IV dextrose to maintain blood glucose at adequate levels
  • Horses with hyperlipemia also require inpatient medical management that includes IV dextrose, balanced electrolyte solutions, caloric replacement, heparin, and exogenous insulin
  • All other horses with abnormal insulin levels may be treated as outpatients

Nursing Care!!navigator!!

  • Carefully monitor hypoglycemic animals to prevent them from collapsing and injuring themselves
  • Horses with laminitis need corrective hoof trimming and shoeing and an appropriate diet

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 any horse with insulin resistance on a low-carbohydrate diet
  • Restrict or increase caloric intake until a condition score of 4–6 out of 10 is achieved
  • Horses that are insulin resistant that are underconditioned should receive additional calories in the form of high-quality complex fiber or fat such as beet pulp or rice bran

Client Education!!navigator!!

  • Horses with PPID may be managed with medication and nursing care, but their prognosis is quite variable. Owners need to understand that treatment of PPID is palliative and required for life
  • Encourage clients to maintain their horses at condition scores of 4–6 out of 10 and to prevent obesity from developing

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

  • The agent most commonly used to treat PPID is pergolide (0.5–2 mg/day)
  • Insulin-deficient horses (i.e. type 1 diabetes mellitus) require insulin supplementation, with the dose being changed in response to the blood glucose level. Protamine zinc insulin (0.5 IU IM BID) normalized blood glucose in a case report of a pony with insulin deficiency
  • Exogenous insulin for the treatment of hyperlipemia—protamine zinc insulin (0.075–0.4 IU/kg SC or IM BID or SID). Regular insulin (0.4 IU/kg) has also been used

Precautions!!navigator!!

  • Dextrose for injection should always be available when administering insulin. If signs of hypoglycemia occur, treat immediately with IV dextrose. Horses that are being tested using the 2-step insulin test may be given IV dextrose after the 30 min sample is collected. This will prevent further decrease in blood glucose concentrations and minimize the chances of symptomatic hypoglycemia developing
  • Horses that receive an overdose of pergolide may exhibit anorexia, lethargy, and ataxia

Follow-up ⬆ ⬇

FOLLOW-UP

Patient Monitoring

  • Retest horses with PPID every 4–6 weeks with endogenous ACTH determination or TRH response testing. Abnormal results indicate the need for an increased dose or a change in medication. If a horse has been stable for several months, testing can be performed less frequently
  • Check the glucose level of horses with diabetes mellitus receiving insulin therapy at least twice a day. Insulin doses should be increased or decreased in response to blood glucose values outside the normal range.

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

  • Hypertrichosis, chronic infections, and laminitis are commonly associated with PPID
  • Obesity, laminitis, and hyperlipemia are commonly associated with the insulin resistance that accompanies EMS

Pregnancy/Fertility/Breeding!!navigator!!

Pregnant mares tend to have higher blood insulin levels than nonpregnant horses. This tendency is most profound during early gestation, but blood glucose levels remain normal.

Abbreviations!!navigator!!

  • ACTH = adrenocorticotropic 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;30:1726–1731.

Dunbar LK, Mielnicki KA, Dembek KA, et al. Evaluation of four diagnostic tests for insulin dysregulation in adult light-breed horses. J Vet Intern Med 2016;30:885–891.

Author(s) ⬆

Authors: Heidi Banse and Janice Kritchevsky

Consulting Editors: Michel Levy and Heidi Banse