Diabetes Flashcards
What is diabetes mellitus? What are 3 characteristics?
relative of absolute deficiency of insulin
- starvation in the face of excess sugar
- lack of insulin
- inability of insulin receptors to respond to stimulation
What are 4 results of the decreased insulin as a result of diabetes mellitus?
- persistent hyperglycemia
- protein catabolism to make glucose
- ketoacids buildup in the liver from fat mobilization
- glycogen accumulation in the liver
What is responsible for the metabolism and secretion of insulin?
beta cells in the Islet of Langerhans of the pancreas
What are the 3 primary targets of insulin? When is it synthesized and secreted?
- liver
- skeletal muscle
- adipose tissue
high blood glucose
What is the autocrine effect of insulin? What occurs in times of fasting?
stimulates further insulin release from beta cells
low constant basal release - keeps blood sugar regular
What are the 3 major sources of glucose?
- intestinal absorption
- glycogenolysis in liver and muscle
- hepatic gluconeogenesis
What are 7 effects of insulin deficiency (diabetes) on the body’s metabolism?
DECREASED…
- glucose uptake by the liver, muscle, and fat
- glycogen synthesis
- DNA synthesis
- amino acid uptake
- protein synthesis
- ion transport
- fatty acid synthesis
What are the 3 actions cause the increased circulating glucose seen in diabetes?
- lipolysis - fat breakdown to create glucose
- glycogenolysis - liver breaks down glycogen into glucose
- protein degradation into amino acids for gluconeogenesis
(+ ketosis)
What are the 2 major clinical signs of diabetes mellitus? What causes each?
- weight loss - protein catabolism for gluconeogenesis, lipid catabolism
- polyphagia - hypothalamic satiety center not activated by insulin or not responsive to hyperglycemia
What urinary effects does diabetes mellitus have? When does this occur?
- polyuria - osmotic diuresis
- glucosuria - glucose exceeds renal tubular resorption
DOG: BG > 200-220 mg/dL
CATS: BG > 250-300 mg/dL
When is clinical diabetes mellitus diagnosed?
based on persistent glucosuria, persistent fasting hyperglycemia, and presence of characteristic clinical signs
What are the 2 types of spontaneous diabetes mellitus?
TYPE 1 = insulinopenia (insulin-dependent), mostly seen in dogs
TYPE 2 = relative lack of insulin with resistance (non insulin-dependent), most commonly seen in fat cats (can convert to insulin dependence)
What causes secondary diabetes mellitus?
insulin antagonists - steroids, obesity
What signalment is associated with Type 1 diabetes? What is the most common initial presenting sign?
middle-aged to older Australian terriers and Miniatute/Standard Schnauzer —> 2x more common in females
cataracts
What signalment is associated with Type 2 diabetes? What is the most common initial presenting sign?
middle-aged to older Norwegian Forest, Tonkinese, Abyssinian, Burmese —> more common in neutered males
peripheral neuropathy - plantigrade stance, proprioceptive deficits
What are 4 possible causes of Type 1 diabetes?
- genetic susceptibility
- immune-mediated destruction*
- anti-beta cell antibodies
- pancreatitis
lack/loss of beta cells due to lass of functional pancreatic mass
What is insulin resistance? What is the most common cause of this in cats?
TYPE 2 diabetes (non-insulin dependent), where tissues do not respond appropriately to insulin —> increases demand for insulin secretion
islet amyloidosis = islet cell dysfunction/destruction
What are some additional contributing causes of both types of diabetes?
- pancreatitis
- endocrinopathy (acromegaly, hyperadrenocorticism)
- diabetogenic medications (glucocorticoids)
- diestrus/pregnanct
What is the most common cause of insulin resistance? How does obesity factor into this?
secretion of antagonistic hormones that cause receptor and/or post receptor insulin resistance —> visceral fat, cortisol, gut hormones, glucose
for every kg weight increase in cats, insulin sensitivity decreases by 15-30%
What is glucose toxicity? Lipotoxicty?
profound persistent hyperglycemia (BG > 300 mg/dL) causes pancreatic beta cell insulin release to be downregulated —> worsens hyperglycemia and beta cell burnout, most common in Type 2 diabetes
excess fatty acids causes glycogen storage instead of glucose release, resulting in more work for beta cells
What are the most common causes of insulin resistance in dogs? When is it commonly transient?
- chronic pancreatic inflammation
- pancreatic atrophy
- immune-mediated beta cell destruction
- corticosteroid excess: iatrogenic or Cushing’s
pregnancy or diestrus