Pathophysiology of DM Flashcards
What regulates insulin secretion ?
blood glucose (hyperglycaemia = more insulin)
AAs/FAs
GI hormones
autonomic nervous system (parasympathetic is increased, sympathetic is decreased)
stress
What physiological factors influence blood glucose ?
insulin, acting in …
- muscle = increased GLUT-4, less glucose/AAs/FAs/ketoacids released from stores
- adipose tissue = increased GLUT-4, less glucose/FAs/AAs/ketoacids released from stores
- liver = increased conversion of glucose into glycogen
glucagon does the opposite effects to release more glucose from stores
catecholamines lead to a net increase in glucose
- inhibition of insulin secretion
- beta2 adrenergic stimulus of hepatocytes to increase glycogenesis
- alpha2 adrenergic stimulus to increase GH releasing hormone
cortisol also acts to increase blood glucose by stimulating gluconeogenesis
What is the definition of DM ?
hyperglycaemia
“phenotype” is either hyperglycaemia and/or lack of insulin
Clinical signs of DM ?
polyuria due to osmotic diuresis in kidney tubule
leads to dehydration and ADH stimulation (thirst reflex) –> polyphagia
high specific gravity of urine
weight loss
ketoacidosis –> decreased blood pH, increased resp rate, renal loss and vomiting
hyperglycaemic coma
sorbitol build up –> osmotic stress on eyes leading to swelling of lens and myopic change (eventually diabetic cataracts)
Describe the vascular complications of chronic DM
atherosclerotic plaque
- coronary a. = myocardial infection
- cerebral a. = stroke
- peripheral vessels = infections, amputations and ulcers
capillary damage
- retinopathy
- neuropathy
- nephropathy
- ischemic damage to the tissue in question
Define and name the causes of Type 1 DM
characterised by insulin deficiency
- destruction or loss of function of beta cells
- autoimmune disease
- pancreatitis
- genetic predisposition
Define and name the causes of type 2 DM
lack of insulin action of loss of cell response to insulin
develops 2ndary to insulin resistance
- beta cell destruction :
hyperglycaemia –> glucotoxicity –> oxidative stress, ER stress, hypoxic stress and cytokine induction –> apoptosis, autophagy, failure of proliferation and dedifferentiation –> decreased cell number and function
Define gestational diabetes
gestation leads to increased leptin, decreased adiponectin, increased TNF-alpha and increased AFABP in the placenta AND inflammation, inadequate stress response and gluco-/lipotoxicity in non-placental cells such as immune and hepatocytes
this may all lead to insulin resistance, beta cell dysfunction or both
symptoms usually resolve following parturition
Define BMI
Body Mass Index
weight divided by height squared
How do we measure obesity ?
BMI
weight
waist circumference
skinfold thickness
total body water
bioimpedance analysis
whole body counting
tomography
MRI
Why does obesity predispose animals to DM ?
most abdominal blood drains into the liver
fat breakdown in the abdomen, therefore, will arrive in the liver in high quantities
high abdominal fat = abdomen more prone to inflammation
Management of Type 2 DM
Diabetes Prevention Programme (DPP)
- 7% loss of BW
- maintenance of weight loss
- <25% calorie dietary intake
- 1200-1800kcal a day
- 150 minutes a week of physical activity
Treatment options for DM
“diabetes reversal” –> first 5 years (must still have beta-cell function), take out some fat from the pancreas and liver, along with lifestyles changes
risk factor lowering (glucose levels, BP and cholesterol management)
medications :
- alpha-glucosidase inhibitors
- GLP-1 analogues
- SUs and rapid acting secretagogues
- insulin
- DPP-4 inhibitors
- TZDs
modern day preferred medication is incretin therapy
What does incretin therapy (administration of GLP-1) do to the body ?
stomach –> decreases gastric emptying
pancreas –> increased b cell proliferation and insulin synthesis, decreased b cell apoptosis. leads to more insulin secretion
muscle –> increased insulin sensitivity
liver –> decreased glucose production
heart –> increased cardioprotection and CO
brain –> increased neuroprotection and decreased appetite
