L6b: Endocrine Pancreas Pathogenesis and Evaluation

What is the primary cause of Type I diabetes mellitus in dogs?

Destruction of pancreatic beta cells leading to insulin deficiency (immune-mediated or idiopathic).

what are the causes of physiological hyperglycemia?

1. post-prandial

2. stress

3. pregnancy

what species are effected by stress potentially leading to physiological hyperglycemia?

cats and cows

what is the hormone in late pregnancy that can lead to physioloical hyperglycemia?

progesterone

what are the types of pathological hyperglycemia?

1. sustained

2. transient

what are the differentials for pathological hyperglycemia?

1. diabetes mellitus

2. PPID

3. acromegaly

4. hyperadrenocorticism

what are the differentials for transient hyperglycemia?

1. hyperthyroidism

2. acute pancreatitis

3. sepsis

how can post-prandial increases be avoided?

fast patient prior to the test

What is the primary cause of Type II diabetes mellitus?

Insulin resistance and/or pancreatic amyloidosis causing inadequate insulin action.

Which species is most affected by Type I diabetes mellitus?

Dogs

Which species is most affected by Type II diabetes mellitus?

Cats (with some cases in dogs).

what type of diabetes is always insulin dependent?

type 1

What are the key features of Type I DM pathophysiology?

• ↓ Insulin production

• ↓ glucose uptake

• ↑ gluconeogenesis,

• hyperglycemia

What are the key features of Type II DM pathophysiology?

• Poor tissue response to insulin

• glucose toxicity

• hyperglycemia.

What hormonal change occurs due to perceived starvation in diabetes?

Increased glucagon production

what is an abnormality seen in a chem panel that indicates diabetes?

******persistent fasting hyperglycemia

• glucosuria

• potential ketonuria

Which test helps differentiate sustained hyperglycemia from transient elevations?

Fructosamine is elevated in sustained hyperglycemia and helps diagnose chronic DM

what test should you run on a stressed cat that had glucosuria?

serum fructosamine

What urine findings accompany persistent hyperglycemia in diabetes mellitus?

Glucosuria, with possible ketonuria.

What CBC/UA findings are commonly seen with stress or inflammatory states in diabetes patients?

1. Stress leukogram

2. increased PCV and protein

3. increased MCV.

How does glucosuria affect USG and how should this be addressed?

Glucosuria can act as an osmotic diuretic and alter USG; adjust USG accordingly.

Which liver-related enzymes are often elevated in diabetes mellitus?

ALT, AST, ALP, and GGT.

What lipid-related changes can accompany diabetes mellitus?

Elevated cholesterol and triglycerides

what will liver disease do to glucose levels?

increase

what will liver failure do to glucose levels?

decrease

hypercholerolemia and hyperlipidemia in DM are often…

secondary to hepatic lipidosis or other concurrent conditions such as hyperadrenocorticism

MCQ: What is the primary distinction between Type I and Type II DM in dogs and cats?

Type I: beta-cell destruction with insulin deficiency; Type II: insulin resistance (often with amyloidosis).

MCQ: 10 yearr-old neutered male pothound presents polyuria, polydipsia and weight loss. Blood glucose levels are 300 mg/dL and urinalysis reveals glucosuria.

What is the most likely explanation for the urinalysis findings?

dog has diabetes mellitus with blood glucose exceeding the renal threshold

how does cortisol influence glucose?

hyperglycemia from increased production but decreased reuptake

how does epinephrine affect glucose and insulin?

increase glucose, reduce insulin

when does insulin resistance happen?

the body’s cells don’t respond properly to a normal amount of insulin

what can cause insulin resistance before binding to receptor?

insulin binding antibodies

what are the hormonal causes of insulin resistance?

1. glucocorticoids

2. acromegaly

3. progestagens

4. thyroid hormones

what can lead to insulin resistance?

1. hormonal changes

2. obesity

3. inflammation/infection

How does obesity affect insulin sensitivity in cats?

Obesity decreases insulin sensitivity by more than 50% in obese cats; insulin resistance is often reversible, and some cats may remit.

What insulin-related threshold suggests insulin resistance in animals?

Insulin requirements >1.5–2.5 U/kg/day or fructosamine >700 μmol/L.

obese insulin resistant cats may have concurrent

cushings/acromegaly

what are the causes of insulin resistance in cats?

1. obesity

2. acromegaly

3. renal disease

4. hyperadrenocorticism

5. hyperthyroidism

6. infection and steroids

Intravenous Glucose Tolerance Test

Used to detect decreased tolerance in persistently hyperglycemic dogs

What characterizes Equine Metabolic Syndrome (EMS)?

Insulin dysregulation with increased laminitis risk; obesity and regional adiposity are common features.

Which animals are most commonly affected by Equine Metabolic Syndrome?

Ponies, donkeys, Arabians, mustangs.

What is the primary pathophysiologic mechanism underlying EMS?

Insulin dysregulation leading to hyperinsulinemia and abnormal glucose handling.

What is the recommended treatment approach for EMS?

Diet and exercise management to improve insulin regulation.

What is considered a normal IVGTT result in dogs?

Glucose returns to normal by 60 minutes; prolonged return suggests glucose intolerance.

What does a prolonged half-time (T1/2) on IVGTT indicate?

Glucose intolerance or impaired glucose tolerance.

What is the clinical use of measuring insulin concentration?

Helpful in animals with hypoglycemia when interpreted with glucose levels.

What are some limitations of insulin concentration testing?

Reference ranges may not exist for all species; some methods not validated for cats; strict sample handling is required.

What is required for proper handling of insulin concentration samples?

Harvest serum within 30 minutes of clotting; assay promptly or freeze the sample.

What systemic condition is often linked with obesity and IR in horses and other species?

Metabolic syndrome

• IR

• hypertriglyceridemia

• hypertension,

• laminitis risk in horses

What are the components of Equine Metabolic Syndrome (EMS)?

IR, hypertriglyceridemia, hypertension, increased laminitis risk.

What is a key clinical feature of EMS aside from insulin dysregulation?

Increased regional fat deposition and reduced ability to lose weight.

What is the general management focus for EMS in horses?

Dietary management and exercise to improve insulin regulation.

What is a characteristic risk factor for EMS in horses?

Thrifty individuals such as ponies, donkeys, Arabians, and mustangs.

How do hepatic lipidosis and liver enzymes relate to diabetes?

Diabetes can be associated with hepatic lipidosis and altered liver enzymes (ALT, AST, ALP, GGT) and bilirubin; lipidosis can complicate DM.

What hepatic enzymes are commonly elevated in diabetics?

ALT, AST, ALP, GGT.

What lipid abnormality may accompany diabetes mellitus?

Hypercholesterolemia and hypertriglyceridemia.

What is the effect of insulin on potassium in cells?

Insulin drives potassium into cells, which can cause hypokalemia.

What electrolyte disturbance can accompany organic acidosis in DM besides potassium shift?

Hypokalemia; hyponatremia and hypochloremia can occur with metabolic acidosis.

What does ketonuria indicate in a diabetic patient?

Presence of ketone bodies in urine, indicating ketosis from insulin deficiency and lipolysis.

How does hyperglycemia affect MCV on automated counters?

Hyperglycemia can cause spurious increases in MCV.

What is a primary feature of diabetic polyuria?

Osmotic diuresis due to glucosuria leading to dehydration.

What is the role of fructosamine in diabetes diagnosis?

Elevated fructosamine indicates sustained hyperglycemia and helps differentiate chronic DM from transient stress hyperglycemia.

What are common signs of diabetes mellitus in companion animals?

Polyuria, polydipsia, weight loss, glucosuria.

What does ‘glucose toxicity’ refer to in feline Cushing’s or DM contexts?

Chronic hyperglycemia causing further insulin resistance and impaired glucose regulation.

What is the role of amylin in DM pathogenesis?

Amylin aggregates as islet amyloid, damaging beta cells and promoting insulin resistance.

Which factor can cause insulin resistance besides obesity?

Inflammation/infection (e.g., pancreatitis, gingivitis, cystitis) and hormonal disorders.

What test result would you expect in a diabetic patient with stress hyperglycemia and glucosuria?

Glucosuria may be present if glucose exceeds renal threshold during stress; not always present in all stress cases.

What is the significance of post-prandial glucose testing?

Post-prandial increases should be avoided by fasting prior to testing to avoid confounding results.

What is the typical consequence of glucosuria on urinary concentration (USG) in diabetics without correction?

Glucosuria can falsely elevate USG readings; adjust interpretation accordingly.

Which hormones contribute to raising blood glucose during stress?

Glucocorticoids and catecholamines (epinephrine) promote gluconeogenesis and glycogenolysis.

What is the primary test for diagnosing EMS in horses?

Clinical evaluation of insulin dysregulation and response to diet/exercise; EMS testing often includes insulin and glucose dynamics.

What do you call a test that measures how quickly an animal clears glucose after a dextrose load?

Intravenous Glucose Tolerance Test (IVGTT).

How is IVGTT interpreted in normal dogs?

Glucose normalizes by 60 minutes after dextrose administration.

What is the typical IVGTT finding in dogs with glucose intolerance?

Prolonged half-time (T1/2) beyond 60 minutes.

What does insulin measurement add to hypoglycemia evaluation?

Helps assess whether hypoglycemia is due to insufficient insulin or excessive glucose clearance.

Why is sample handling crucial for insulin assays?

Improper handling can alter insulin measurement; prompt processing or freezing preserves accuracy.

What is a common veterinary teaching point about post-prandial hyperglycemia in tests?

Fasting before post-prandial testing helps avoid artificially high glucose readings.

What key diagnostic category includes both IR and metabolic syndrome in horses?

Equine Metabolic Syndrome (EMS) and related metabolic derangements.

What is the relationship between hepatic involvement and diabetes in small animals?

Diabetes can accompany hepatic lipidosis; liver enzymes and bilirubin may be elevated.

What is the significance of ketones in diabetic urine?

Ketonuria indicates ketosis from lipid breakdown due to insulin deficiency.

What is the typical diabetic renal threshold in cats compared to dogs?

Cats have a higher renal threshold (~280–290 mg/dL) than dogs (180–200 mg/dL).