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
What are the most common causes of insulin resistance in cats?
- chronic insulin resistance with beta cell exhaustion
- pancreatic amyloidosis
- increased beta hepatic glucose production
- obesity
- glucose toxicity
- corticosteroid excess
- excess growth hormone (acromegaly)
What dog breeds are considered low risk for developing diabetes?
- German Shephers
- Collie
- Shetland Sheepdog
- Golden Retriever
- Cocker Spaniel
- American Pit Bull
- Boxer
(more common in smaller dogs, especially terriers)
What are the 4 most common clinical signs associated with diabetes mellitus in stable dogs?
- PU/PD - osmotic diuresis due to glucosuria
- polyphagia
- weight loss with sustained appetite
- cataracts - can develop quickly!
- obesity
- hepatomegaly
- diabetic neuropathy: plantigrade stance, hindlimb weakness
What are the 2 most common development of diabetes mellitus in sick animals?
- ketoacidosis (DKA)
- non-ketotic hyperosmolar syndrome
What are signs associated with severe diabetic ketoacidosis?
- weight loss
- PU/PD
- dehydration
- labored breathing
- lethargy/collapse/stupor
What are signs associated with non-ketotic hyperosmolar syndrome? In what animals is this most common?
- decreased GFR
- chronically high BG
- development of idiogenic osmoles (slow correction to avoid brain edema!)
cats - have some insulin production, which decreases ketones in the blood
What is seen on the CBC in diabetic patients?
typically normal
- can develop leukocytosis and toxic neutrophils if there is concurrent pancreatitis or infection
What serum biochemistry results are commonly seen in dogs and cats?
DOGS = increased glucose over 200, glucosuria, ketonuria
CATS = increased glucose over 300 (stress hyperglycemia common!), ketonuria
What is the preferred way of diagnosing diabetes in cats?
- at home repeated BG or urine measurements (unless they’re in DKA)
- fructosamine
What are 4 additional findings of serum biochemistry in patients with diabetes mellitus? What else should be checked?
- increased cholesterol and triglycerides
- increased ALT and ALP
- low sodium - glucose related hyperosmolarity dilutes out sodium in blood
- normal K and P with low stores
thyroid status in dogs and cats > 6 y/o
How is the urinalysis affected by diabetes? Why is a culture typically necessary?
- USG > 1.025 (normal)
- glucosuria
- ketonuria
- bacteriuria (bacteria use glucose for energy)
diabetic animals may not have pyuria with a UTI - dilute urine can mask bacterial identification on sediment exam
What are some common comorbidities seen with diabetes mellitus and must be screened for?
- pancreatitis: pancreatic lipase immunoreactivity
- obesity
- hyperthyroidism
- acromegaly
- hyperadrenocorticism
What are the treatment goals for diabetes mellitus?
- eliminate clinical signs
- address concurrent disorders and contributing factors
- control hyperglycemia with insulin, diet, weight loss/exercise, or oral hypoglycemic drugs
- avoid hypoglycemia and DKA
What are the ideal BG goals when controlling diabetes in dogs and cats?
- DOGS = 80-200 mg/dL
- CATS = 80-300 mg/dL
(rarely going to be exact or perfect!)
avoid hypoglycemia!
What is transient/reversible diabetes mellitus? What are 5 common causes?
DM associated with insulin resistance (Type 2) usually in cats, where the correction will decrease insulin requirement
- newly diagnosed patients with glucose toxicity**
- obesity
- pancreatitis
- corticosteroid excess - HAC, exogenous
- progestogen excess - diestrus bitch/queen, exogenous
What are the positive predictors of diabetic remission in cats? Negative predictor?
- intensively managed DM within 6 months
- prior glucocorticoid therapy
diabetic neuropathy
What is the most common treatments that result in diabetic remission in cats?
feeding a high protein, low carbohydrate diet and giving insulin (glargine, detemir)
- feed portioned meals (no free feeding, unless on ultralong acting insulins or SGLT2 inhibitors)
- canned foods > dry foods
What diet is preferred in cats with diabetes? What are 4 pros?
high protein, low carb canned foods
- maximizes metabolic rate
- limits risk of hepatic lipidosis during weight loss
- improves satiety, does not impact palatability
- prevents lean muscle mass loss
Why is a high protein, low carbohydrate diet recommended for diabetic patients?
- protein normalizes fat metabolism and provides consistent energy source
- arginine stimulates insulin secretion
How does diet management in diabetic dogs compare to cats?
- moderate to high fiber in dogs promotes weight loss and slows glucose absorption from the GIT
- can have any diet as long as it works well and is consistent
- diet changes are considered if DM becomes difficult to control
When is the ideal time to feed and give insulin?
feed a meal at the time of insulin dosage with no feeding in between
What additional management is especially helpful in diabetic patients?
exercise —> facilitates weight loss, lowers glucose
- must be consistent type, amount, and intensity
What are 4 indications for oral hypoglycemic drugs for diabetes management? How does it affect the pancreas?
- obesity or normal BW
- lack of ketones
- Type 2 diabetes - CATS
- owner unwilling or unable to inject insulin
- beta cell protective - can reverse glucose toxicity
- may accelerate beta cell loss due to stimulatory effect
What are 4 contraindications for oral hypoglycemic drugs?
- hypoglycemia
- development of ketosis
- lack of response
- toxicity
What hypoglycemic drugs are able to increase insulin secretions by beta cells? What are 5 side effects?
sulfonylureas - Glipizide, Glyburide —> take months to work
- hepatopathy
- vomiting
- cholestasis
- hypoglycemia
- worsens amyloid deposition
What hypoglycemic drug is able to inhibit glucose release by the liver and increase insensitivity to insulins?
biguanides - Metformin
+ Thiazolidinediones
What hypoglycemic drug is able to inhibit GI glucose absorption?
alpha glucosidase inhibitors - Acarbose —> rarely effective alone
What are incretins?
glucagon-like peptides (GLP-1) - metabolic or GI hormones that increase insulin secretion and promote expansion of beta cell populations, delay GI emptying, and increase satiety
- Victoza, Ozempic
What antidiabetic trace elements may be effective in treating diabetes?
- Vanadium
- Chromium
What SGLT2 inhibitors are effective in treating diabetes? How do they work?
- Bexacat (bexagliflozin) - tablet
- Senvelgo (velagliflozin) - oral solution
inhibit renal glucose reabsorption without inducing hypoglycemia —> does not completely inhibit reabsorption so that patients can maintain normoglycemia
(no PU/PD, UTIs, or hypoglycemia observed!)
In what patients do SGLT2 inhibitors work? Why?
TYPE 2 DIABETICS - must have endogenous insulin; not administered to cats receiving insulin, treated with insulin previously, or have insulin-dependent mellitus
when a diabetic has no insulin, they cannot metabolize ketone bodies, which causes a buildup in the body
What are diabetic cats treated with SGLT2 inhibitors at an increased risk for deceloping?
- DKA
- euglycemic diabetic ketoacidosis
(means they are type 1 diabetic)
