final exam Endocrine Pancreas & Diagnostics of Glucose Metabolism

Hormones Overview

- Chemical messengers

- Secreted by glands

- Travel through blood stream to target tissue

What keeps hormones regulated

Negative feedback mechanisms

negative feedback system

A reaction that causes a decrease in function in response to some kind of stimulus.

What part of the pancreas is primarily involved in glucose regulation

Endocrine

What part of the pancreas is primarily involved with digestion

Exocrine

What leads to fibrosis

Chronic Inflammation

Fibrosis

Nonfunctional scar tissue

What conditions are associated with pancreatic fibrosis

- Pancreatitis

- Diabetes mellitus type 1

- Exocrine pancreas insufficiency (EPI)

Types of endocrine pancreas cells

- Alpha cells

- Beta cells

- Delta cells

- F cells

What hormones does the endocrine pancreas produce

- Glucagon

- Insulin

- Somatostatin

- Pancreatic polypeptide

What endocrine pancreas cell produces glucagon

Alpha cells

What endocrine pancreas cell produces Insulin

Beta cells

What endocrine pancreas cell produces Somatostatin

Delta cells

What endocrine pancreas cell produces pancreatic polypeptide

F cells

What cells make up the majority of the endocrine pancreas

Beta cells

Second most abundant endocrine pancreas cell

Alpha cells

Where does glucose come from

- Digestion of carbohydrates

- Gluconeogenesis in the liver

- Gluconeogenesis from VFAs in the rumen

Gluconeogenesis Liver

Process of glycogen being converted to glucose

What hormones decrease blood glucose

Insulin

What hormones increase blood glucose

- Glucagon

- Growth hormone

- Corticosteroids

- Catecholamines

- Hormones associated with obesity & pregnancy

Endocrine pancreas diagnostic tests

- Blood glucose curves

- Continuous glucose monitoring (CGM)

- Fructosamine

- Beta hydroxybutyrate

- Glycosylated hemoglobin (A1C)

- Insulin Testing

Quickest method to test blood glucose

Whole blood -> glucometer

Why do samples for glucose samples need to be separated and ran quickly

Glucose drops over time in WB samples because the RBCs will consume the glucose over time

Why is sodium fluoride as a glucose preserver not always recommended

Causes RBC lysis which can dilute the sample

Sampling causes of decreased blood glucose

- Prolonged contact w/ RBCs

- Marked leukocytosis, erythrocytosis, or thrombocytosis

- Bacterial contamination

- Storage at increased temps due to increased cell metabolism

- Septic body cavities

Normal glucose measurement

80-120 mg/dL

Hypoglycemic glucose measurement

< 60-80 mg/dL

Mildly hyperglycemic glucose measurement

120-200 mg/dL

Significant hyperglycemic glucose measurement

> 200-250 mg/dL

Causes of hyperglycemia

- Postprandial

- Diabetes mellitus

- Excess growth hormone (acromegaly in cats)

- Excitement/Epinephrine Leukogram

- Glucocorticoids

Causes of hypoglycemia

- Insulin administration

- Insulinoma

- Sepsis

- Toxin (xylitol)

- Juvenile hypoglycemia

- Liver disease

- Addison's disease

- Pregnancy toxemia

- Ketosis

- Iatrogenic (prolonged exposure of plasma to RBCs)

Glucosuria

Hyperglycemia exceeds renal threshold for reabsorption of glucose

How is glucosuria measured

Dipstick

What condition does hyperglycemia AND glucosuria usually indicate

Diabetes Mellitus

Blood glucose curve

Glucose measured w/ glucometer every 1-4hrs for 12-24hr

When do we run a blood glucose curve

- When starting a new insulin

- 7-14 days after an insulin change

- Every 3mo in diabetics doing well

- Whenever a diabetic is having symptoms of high or low BG

If BG on a blood glucose curve goes < 80 what should we do?

Lower insulin dose

If BG on a blood glucose curve never goes <200 what should we do?

Consider increasing the dose

Challenges of BG curve

- Collecting samples at correct times can be hard

- Stress hyperglycemia in clinic interferes with interpretation

- Glucose naturally fluctuates a lot day to day

- Night glucose can be different from day time glucose

Alternatives to blood glucose curve

- Continuous glucose monitor (CGM)

- Fructosamine

What device do we use when measuring continuous glucose

Freestyle libre (meant for humans)

What does a continuous glucose monitor measure

Interstitial glucose over 10-14 days

Interstitial glucose

- Glucose present in the fluid surrounding tissue cells in the skin

- Delayed measure of blood glucose

Fructosamine

- Marker of glucose concentrations over past 2-3 days

- Glycosylated protein formed from GLU binding to plasma protein

What falsely lower fructosamine

Severely low ALB & hyperthyroidism

What is a fructosamine test useful for

- Rule out excitement leukogram cats

- Dx early DM and monitor treatment

Glycosylated Hemoglobin (Hgb A1C)

- Formed by irreversible binding of Hgb to glucose

- Represents glucose levels in past 3-4mo (or RBC lifespan)

Ketones

- Produced by catabolism of fatty acids

- Negative energy balance

Ketones examples

- Acetone

- Acetoacetic acid

- Beta-hydroxybutyric acid (BHB)

What ketone is produced first

Beta-hydroxybutyric acid (BHB)

Ketonemia

ketones in the blood

Ketonuria

ketones in the urine

Ketoacidosis

Acidemia and ketonemia

Dangers of ketones

CNS depression and acidosis

What is the most common ketone in patients with DKA

Beta-hydroxybutyric acid (BHB)

What test detect acetone or acetoacetic acid but not BHB

Urine dipstick

What can we use to measure BHB

- Blood test (enzymatic calorimetric test method)

- Ketone meter (Point of care meters that have electrochemical reaction)

Glucose Tolerance Test

A test of the body's ability to metabolize glucose

What glucose tolerance test would indicate diabetes

Prolonged hyperglycemia and glucosuria

When do we run insulin tests

- Investigating insulinoma

- Must be done when BG < 50-60 mg/dL

Insulin tests

- Insulin level (cats & exotics)

- Insulin:GLU ratio (dogs & horses)

What stimulates insulin secretion

Hypreglycemia

How does insulin combat hyperglycemia

- Binds to receptors that transport GLU into cells

- Stimulates the liver to convert excess GLU to glycogen

Hyperinsulinemia

- State of excessive insulin production

- Cancer, insulin resistance

Insulin:Glucose Ratio

- measures the ratio of insulin & glucose in an animal

- When BG is low, insulin should be low

When BG is low and insulin is higher than expected what does this indicate?

Beta cell tumor

Conditions associated with insulin resistance

- Hyperadrenocorticism (Cushing's Dz)

- Acromegaly (Pituitary tumor producing growth growth hormone)

What has the opposite effect on insulin

Glucagon

When do we run a glucagon test

Insulin:glucose ratio is not diagnostic

Glucagon test result in diabetics

Flat response (insulin can't be produced)

Glucagon test result with beta cell tumor

Excessive insulin response and hypoglycemia follow

Somatostatin

Suppresses growth hormone

Pancreatic polypetide

Suppresses food intake

Diabetes Mellitus

Hyperglycemia resulting from insufficient insulin or insulin resistance

DM lab results

- BG >250

- Urine glucose +

- Fructosamine elevated

What do we give to treat DM

Insulin q 12hr and dietary management

Type 1 DM

- Insufficient insulin production

- Mostly dogs

- Autoimmune destruction of pancreatic islets

- irreversible

Type 2 DM

- Insulin resistance

- Mostly cats

- Obesity causes cells to be less responsive to insulin

- Possibly reversible with insulin and diet

Diabetic Ketoacidosis (DKA)

- Complication of unregulated DM

- Negative energy balance results in ketone production

- Ketones are acidic and cause illness

Key features of DKA

- Hyperglycemia

- Ketonuria and ketonemia

- Metabolic acidosis

- Diabetic (GLU elevated, glucosuria)

- Ketones (BHB increased, urine ketones +)

DKA Tx

- Aggressive fluid therapy

- Moitoring electrolytes

Hyperosmolar Non-Ketotic Syndrome

- Unregulated diabetic with severe hyperglycemia but no ketone production (no DKA)

- Develops hyperosmolar blood

- Worse than DKA (dehydration, shock, neurological issues)

- BG >600 mg/dL

Equine Metabolic Syndrome

- Insulin resistance (like type 2 diabetes in cats)

- BGs are often normal or mildly elevated, no glucosuria or DKA

- Insulin levels elevated

Equine Metabolic Syndrome C/S

Obesity (fat deposits on crest, tailhead and laminitis

Equine Metabolic Syndrome Triggers

High concentrate diets, obesity, and genetics

Juvenile Hypoglycemia

Immature liver in miniature and toy puppies has poor glycogen storage

Juvenile Hypoglycemia Tx

- Frequent meals

- IV fluids w/ dextrose