diabetes mellitus Flashcards
what is T1 DM
insulin indépendant diabetes
lack insulin - inject it
mainly young (juvenile onset)
results from AI destruction of B cells of pancreas, sometimes following viral infection such as MMR
No FB inhibition by insulin on a cells, glucagon high
what are the symptoms of T1 DM
thirst tiredness weight loss polyuria (cont glucose and KBs) ketoacidosis hypertriglyceridaemia hyperglycaemic coma
metabolic consequences of T1 DM
blood insulin low despite high blood glucose, glucagon levels raised
metabolism stuck in starved phase
low I:G ratio - induction of catabolic enzymes and repression of anabolic enzymes
dec glucose uptake, inc glycogenolysis, lipolysis and protein breakdown
what does the liver look like in a type 1 diabetic
despite high blood glucose
liver gluconeogenic bc of high glucagon
lactate and AAs main substrate for glucose prod - muscle wasting
glycogen synthesis and glycolysis inhibited, liver can’t buffer blood glucose
FAs to lipolysis in liver for gluconeogensis, XS two TAGs and VLDL
XS acCoA from fa ox to KBs - ketoacidosis (KB and H+ in blood)
what are ketone bodies
occurs normally under all conditions bur inc during starvation dramatically (prolonged low I:G ratio)
why does inc lipid mobilisation stimulate KB formation
inc demand for gluconeogeneis depletes oxaloacetate
dec capacity of TCA cycle, inc level of AcCoA present (substrate for KB)
how are KBs formed
condensation of 2 molecules of AcCoA
acetoacetate and D-beta-hydroybutrate (can be converted back in peripheral tissues for use in TCA)
or non enzymatic decarboxylation from acetone
how does T1 DM affect the muscle
little glucose entry into muscle and peripheral tissues due to lack of insulin, contributes to hyperglycaemia
FA and KB oxidation as major source of fuel
proteolysis occurs to provide carbon skeletons for gluconeogensis - muscle wasting
how does T1 DM affect the adipose tissue
uptake of glucose diminished by loss of insulin
low I:GG ratio enhance lipolysis, BD of TAG and release of fa and glycerol into blood (energy prod in peripheral tissues and gluconeogenesis in liver)
how does T1 DM affect the plasma and urine
hyperglycaemia (prod XS, utilising less)
glucose conc exceeds renal threshold and excreted in urine (glycosuria) with loss of water and thirst
fa synthesis diminished so chylomicrons and VLDL can’t be metabolised properly - expression of lipoprotein lipase reg by insulin =hypertg and cm, inc susceptibly to CVD events
possible life threatening consequences of diabetes
hyperglycaemia and ketoacidosis hyerosmolar T1DM hyperglycaemic state (non-ketotic hyperosmolar coma) T2DM
Long term effects of diabetes
predisposition of CV disease and organ damage
retinopathy - cataracts, glaucoma and blindness
nephropathy
neuropathy
what is glucose when in excess
toxic generate ROS osmotic damager to cells glycosylation altering protein function formation of advanced glycation end products which inc ROS and inflammatory proteins kidney, eye, erythrocyte
how is diabetes diagnosed
fasting blood glucose levels (126mg/dl or 7mM. and above on 2 occasions, normal 70-110 and <6.1)
glucose tolerance test (after overnight fast, blood sample then drinks glycols drink with 75g glucose, sample blood glucose at 20min, 1 and 2 hours, >11.1mM at 2 hour)
what is glycerinated haemoglobin
HbA1c can reflect average blood glucose levels over 8-12 weeks (RBC lifespan)
longer term gauge
how is T1 DM treated
aim to mimic normal daily insulin secretion
peaks after meals then dec to basal levels
number of possibilities (direct onset time and duration insulin)
what is T2 DM
not enough insulin to keep BG normal
combo of impaired insulin sec, inc peripheral insulin resistance, inc hepatic glucose output
causes of T2 DM
insensitivity of target cells to insulin (defects in receptors and cell signalling)
impaired insulin secretion (amyloid deposits to reduce B cell mass)
linked to obesity
what can cause mechanisms of insulin resistance
mutations in insulin receptor gene (rare)
defects in insulin signalling pathway (common)
what is peripheral insulin resistance induced by
presence of XS fas - inhibit peripheral glucose disposal and enhance hepatic. glucose output
dysregulated adipokines from adipose tissue
also by defects in cellular translocation of glut-4 (and glucose uptake) in adipocytes, linked to obesity too
what are features of T2 DM
develops over many years (2-6% adults affected)
approx 90% diabetic pop
can survive long term with no insulin (older and obese)
ass with microvascular disease, stroke and atherosclerosis (inc VLDL and LDL)
can be asymptomatic or classic hyperglycaemic symptoms
KBs in low conc
metabolism in T2 DM
glucagon not raised to same extent (insulin present)
uncontrolled lipolysis, KB formation not a feature
hyperglycaemia from lack of glucose uptake
inc VLDL synthesis - hyperTG and microvascular disease (from diet and adipose tissue)
treatment of T2 DM
diet and exercise
oral hypoglycaemic agent eg
sulphonylureas (inc insulin sec, can =hypoglycaemia)
biguanides (eg metformin) or thiazolidinediones (eg Pioglitzaone) to inc tissue insulin sensitivity
glucosidase inhibitors (eg acarbose) to reduce absorption and digestion of carbs
