diabetes mellitus

Question 1

what is T1 DM

Answer 1

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

Question 2

what are the symptoms of T1 DM

Answer 2

thirst
tiredness
weight loss
polyuria (cont glucose and KBs)
ketoacidosis
hypertriglyceridaemia
hyperglycaemic coma

Question 3

metabolic consequences of T1 DM

Answer 3

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

Question 4

what does the liver look like in a type 1 diabetic

Answer 4

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)

Question 5

what are ketone bodies

Answer 5

occurs normally under all conditions bur inc during starvation dramatically (prolonged low I:G ratio)

Question 6

why does inc lipid mobilisation stimulate KB formation

Answer 6

inc demand for gluconeogeneis depletes oxaloacetate

dec capacity of TCA cycle, inc level of AcCoA present (substrate for KB)

Question 7

how are KBs formed

Answer 7

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

Question 8

how does T1 DM affect the muscle

Answer 8

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

Question 9

how does T1 DM affect the adipose tissue

Answer 9

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)

Question 10

how does T1 DM affect the plasma and urine

Answer 10

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

Question 11

possible life threatening consequences of diabetes

Answer 11

hyperglycaemia and ketoacidosis 
hyerosmolar T1DM 
hyperglycaemic state (non-ketotic hyperosmolar coma) T2DM

Question 12

Long term effects of diabetes

Answer 12

predisposition of CV disease and organ damage
retinopathy - cataracts, glaucoma and blindness
nephropathy
neuropathy

Question 13

what is glucose when in excess

Answer 13

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

Question 14

how is diabetes diagnosed

Answer 14

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)

Question 15

what is glycerinated haemoglobin

Answer 15

HbA1c can reflect average blood glucose levels over 8-12 weeks (RBC lifespan)
longer term gauge

Question 16

how is T1 DM treated

Answer 16

aim to mimic normal daily insulin secretion
peaks after meals then dec to basal levels
number of possibilities (direct onset time and duration insulin)

Question 17

what is T2 DM

Answer 17

not enough insulin to keep BG normal

combo of impaired insulin sec, inc peripheral insulin resistance, inc hepatic glucose output

Question 18

causes of T2 DM

Answer 18

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

Question 19

what can cause mechanisms of insulin resistance

Answer 19

mutations in insulin receptor gene (rare)

defects in insulin signalling pathway (common)

Question 20

what is peripheral insulin resistance induced by

Answer 20

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

Question 21

what are features of T2 DM

Answer 21

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

Question 22

metabolism in T2 DM

Answer 22

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)

Question 23

treatment of T2 DM

Answer 23

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