physiology of diabetes mellitus and insulin resistance

Question 1

what is diabetes mellitus

Answer 1

inability to make insulin or inability of insulin to act properly on targets. leading to glucose in the urine

Question 2

what are common sources of diabetes mellitus is the issue is with production of insulin

Answer 2

• prancreatectomy
• pancreatitis
• auto-immunity
• islet cell hypoplasia
• chemical toxicity

Question 3

what factors might cause insulin to not work on the target

Answer 3

• progesterone/agen
• growth hormone
• clucocoticoids
• glucagon
• catecholamines
• thyroid
• obesity

Question 4

list causes of insulin resistance

Answer 4

physiological: pregnancy, stress
pathological: obesity, hereditary predisposition, concurrent diseases, endocrinopathies

Question 5

what is insulin resistance

Answer 5

when the body’s cells dont respond to the insulin produced or injected

Question 6

what are cuases of diabetes mellitus in dogs

Answer 6

• usually a genetic susceptibility
• immune mediated destruction of beta cells
• pancreatitis with beta cell destruction
• obesity-induced insulin resistance
• insulin antagonistic disease/conditions
• insulin antagonistic drugs

Question 7

what hormones antagonise insulin action

Answer 7

• cortisol
• growth hormone
• catecholamines
• glucagon
• progesterone

Question 8

what are the most common pathogenesis for diabetes mellitus in dogs

Answer 8

• immune mediated T cell destruction of beta calls (autoantibodies against insulin and/or beta cells = progressive decrease in glucose-stimulated insulin secretion)
• pancreatitis with beta cell destruction (spontaneous inflammation of pancreas with associated residual damage to islets of beta cells

Question 9

discuss causes of diabetes in cats

Answer 9

• obesity/diet induced insulin resistance
• islet amyloidosis
• pancreatitis
• insulin antagonistic drugs
• insulin antagonistic disease
• genetics

Question 10

discuss the most common reasons for diabetes in cats

Answer 10

• obesity associated via high carbohydrate diet and glucose toxicity leading to insulin resistance

Question 11

why does obesity lead to insulin resistance

Answer 11

• inadequate number of insulin receptors
• defective insulin receptor structure
• cell signalling pathway
• defective GLUT4 transport proteins
• problems with translocation of GLUT4 to the membrane
• interference with the function of GLUT4

Question 12

what is islet amyloid polypeptide and how is it related to diabetes mellitus

Answer 12

• co-secreted with insulin by feline beta cells
• chronis increased secretion occurs with obesity and insulin resistant states
• may be consequence of chronic hyperglycaemia/glucose tox
• amylin deposited in the islets as amyloid
• amyloid fibrils are cytotoxic leading to apoptosis of islet cells leading to defective insulin seretion
• if deposition is progressive, leads to diabetes mellitus (basically chokes islet cells)

Question 13

discuss prevalence of insulin dependent diabetes mellitus

Answer 13

• most common form
• almost 100% of dogs but 50-70% of cats
• permanent insulin deficiency
• animals need exogenous insulin

Question 14

what are causes of non-insulin dependent diabete mellitus in dogs and cats

Answer 14

cats: obesity induced insulin resistance (already making lots of insulin)
dogs: insulin antagonism usually by drugs or another condition

Question 15

what is equine metabolic disorder

Answer 15

• primary disorder is insulin resistance
• strong link with obesity/regional adiposity
• most common Cs is laminitis
• see high levels of insulin and glucose

Question 16

what are the classic clinical signs of diabetes mellitus

Answer 16

• PU/PD
• polyphagia
• weight loss

Question 17

why is PU/PD a sign of diabetes mellitus

Answer 17

osmotic diuresis
- in normal blood glucose cases, the kidney reabsorbs the glucose and it doesnt enter the urine
- in hyperglycemic animal, blood glucose has exceeded renal threshold and you get glucose in the urine (insulin not able to control blood glucose levels)

Question 18

why does polyphagia result from diabetes mellitus

Answer 18

• hypothalamic satiety centre cant sense glucose concentrations if insulin isnt there to facilitate
• if brain doesnt sense glucose, thinks there isnt any so stimulates hunger
• cant inhibit appetitie centre

Question 19

why is weight loss a result of diabetes mellitus

Answer 19

• insulin:glucagon ratio falls and promotes the starvation process (continual interprandial period despite eating)
• stores are mobilised and catabolised
• leads to breakdown of protein stores and muscle wasting

Question 20

why do you get cataracts from diabetes mellitus

Answer 20

• glucose is taken into the lens
• normally, glucose is metabolised to lactate which diffuses out of lens
• excess glucose that cant be converted to lactate is converted to fructose and sorbitol (these do not diffuse out)
• trapped fructose and sorbitol draws water into the lens

Question 21

what occurs in ketoacidosis

Answer 21

• glucose does not enter the cells as easily
• when insulin/glucagon ratio favour catabolsim
• shift to fat metabolism for energy
• mobilize fatty acids (fat cant turn into glucose)
• more fatty acids = ketones
• ketones build up = metabolic acidosis
• animals appear ill (vomiting, diarrhea, anorexia = dehydration)

Question 22

how is diabetes mellitus diagnosed

Answer 22

• persistent fasting hyperglycemia after blood glucose curve test
• persistent glucosuria
• fructosamine elevated
• increased liver enzymes
• hypercholesterolemia
• hypertriglyceridemia
• visible lipid in the serum/plasma
• high USG
• ## ketones in urine

Question 23

how does stress impact blood glucose

Answer 23

• stress induces cortisol and catecholamines and hyperglycemia
• usually dont see glucosuria, but if diagnosing DM, recheck urine in non-stressed environment