physiology of diabetes mellitus and insulin resistance Flashcards
what is diabetes mellitus
inability to make insulin or inability of insulin to act properly on targets. leading to glucose in the urine
what are common sources of diabetes mellitus is the issue is with production of insulin
- prancreatectomy
- pancreatitis
- auto-immunity
- islet cell hypoplasia
- chemical toxicity
what factors might cause insulin to not work on the target
- progesterone/agen
- growth hormone
- clucocoticoids
- glucagon
- catecholamines
- thyroid
- obesity
list causes of insulin resistance
physiological: pregnancy, stress
pathological: obesity, hereditary predisposition, concurrent diseases, endocrinopathies
what is insulin resistance
when the body’s cells dont respond to the insulin produced or injected
what are cuases of diabetes mellitus in dogs
- 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
what hormones antagonise insulin action
- cortisol
- growth hormone
- catecholamines
- glucagon
- progesterone
what are the most common pathogenesis for diabetes mellitus in dogs
- 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
discuss causes of diabetes in cats
- obesity/diet induced insulin resistance
- islet amyloidosis
- pancreatitis
- insulin antagonistic drugs
- insulin antagonistic disease
- genetics
discuss the most common reasons for diabetes in cats
- obesity associated via high carbohydrate diet and glucose toxicity leading to insulin resistance
why does obesity lead to insulin resistance
- 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
what is islet amyloid polypeptide and how is it related to diabetes mellitus
- 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)
discuss prevalence of insulin dependent diabetes mellitus
- most common form
- almost 100% of dogs but 50-70% of cats
- permanent insulin deficiency
- animals need exogenous insulin
what are causes of non-insulin dependent diabete mellitus in dogs and cats
cats: obesity induced insulin resistance (already making lots of insulin)
dogs: insulin antagonism usually by drugs or another condition
what is equine metabolic disorder
- primary disorder is insulin resistance
- strong link with obesity/regional adiposity
- most common Cs is laminitis
- see high levels of insulin and glucose
what are the classic clinical signs of diabetes mellitus
- PU/PD
- polyphagia
- weight loss
why is PU/PD a sign of diabetes mellitus
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)
why does polyphagia result from diabetes mellitus
- 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
why is weight loss a result of diabetes mellitus
- 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
why do you get cataracts from diabetes mellitus
- 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
what occurs in ketoacidosis
- 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)
how is diabetes mellitus diagnosed
- 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
how does stress impact blood glucose
- stress induces cortisol and catecholamines and hyperglycemia
- usually dont see glucosuria, but if diagnosing DM, recheck urine in non-stressed environment
