diabetes

Question 1

which 2 tissues does insulin act on via GLUT-4?

Answer 1

striated skeletal muscle (including heart)

adipose tissue

Question 2

how does glucose transport occur?

Answer 2

facilitated diffusion via glucose transporters

cell membrane is impermeable to glucose

Question 3

what effect does insulin have on processes in the liver?

Answer 3

increased glucose uptake, glycogenesis

decreased glycogenolysis, gluconeogenesis, lipolysis

Question 4

what effect does insulin have on processes in the fat?

Answer 4

increased glucose uptake, lipogenesis

decreased lipolysis

Question 5

what effect does insulin have on processes in the muscle?

Answer 5

increased glucose uptake, glycogenesis, protein synthesis

decreased protein catabolism

Question 6

what is the difference between GLUT-4 and other glucose transporters and why is this relevant?

Answer 6

GLUT-4 is insulin regulated

GLUT-1 - 3 are insulin independent

if excess glucose is present in the blood and insulin is not responding properly then tissues supplied by GLUT 1-3 will still take up some glucose

Question 7

what is the overall effect of insulin resistance and T2DM on liver, fat and muscle tissues?

Answer 7

increased blood glucose (hyperglycaemia)

free fatty acids

(theoretically more amino acids since less protein synthesis)

Question 8

describe the glucose metabolism pathway to produce ATP.

Answer 8

glucose enters cell via GLUT-4 (insulin regulated) from bloodstream

glucose to pyruvate (glycolysis)

pyruvate to acetyl CoA (link reaction)

acetyl CoA undergoes TCA cycle (Krebs) to produce 30 molecules of ATP per glucose molecule

Question 9

what happens in T2DM (in terms of insulin)?

Answer 9

insulin resistance

insufficient insulin produced to a degree, maybe in later stages

Question 10

what is the body’s initial reaction to insulin resistance?

Answer 10

increased production of insulin to try and counteract

eventually β cells cannot produce enough insulin to meet requirements caused

Question 11

what are the 2 main pathophysiological problems in T2DM?

Answer 11

insulin resistance

impaired β cell function

Question 12

what causes increased risk of diabetes?

Answer 12

diabetes susceptibility genes (family history)

visceral fat especially resistant to insulin

diet

adipokines

• generally upregulate and downregulate insulin, adipose cells in obese people are dysfunctional and adipokines that reduce insulin sensitivity
• reduce insulin sensitivity by causing hyperplasia and hypertrophy in β cells
• amyloid clogs β cells and leads to hypertrophy

ethnicity (south Asian, African Caribbean)

sex

age

Question 13

what are the symptoms of diabetes?

Answer 13

thirst

unintended weight loss

increased urination

Question 14

what is impaired fasting glucose?

Answer 14

predominantly hepatic insulin resistance leads to continuous glucose output from the liver

Question 15

what is impaired glucose tolerance?

Answer 15

predominantly muscle insulin resistance plus impaired post prandial insulin release results in poor cellular glucose uptake

Question 16

what is pre diabetes?

Answer 16

impaired fasting glucose AND impaired glucose tolerance

state of impaired glucose metabolism that doesn’t quite meet diabetes criteria

Question 17

what is HbA1C? how can it be used to diagnose and monitor diabetes?

Answer 17

glycosylated haemoglobin

non enzymatic process to form, can occur with monosaccharides glucose, fructose and galactose (glucose less easily)

formation of HbA1C occurs proportionately to plasma glucose levels

Question 18

what are the advantages of an HbA1C test?

Answer 18

no need to fast and take a sugary drink beforehand (no prep - blood glucose taken 2 hours after 75g oral glucose load)

RBC life span is around 120 days therefore results show glucose levels over 3 months

Question 19

what are the disadvantages of an HbA1C test?

Answer 19

if RBCs die young results will be falsely low

co morbidity may interfere with the test

• pregnancy
• advanced kidney disease
• anaemia

Question 20

what are the fasting ranges of glucose in normal metabolism?

Answer 20

<5.5 mmol/L

Question 21

what are the ranges of post prandial glucose in both normal metabolism and impaired fasting glucose?

Answer 21

<7.8 mmol/L

Question 22

what is the range in a random test in normal metabolism, impaired fasting glucose and impaired glucose tolerance?

Answer 22

<11.1 mmol/L

Question 23

what are the impaired fasting glucose ranges for fasting glucose?

Answer 23

5.5 - 6.9 mmol/L

Question 24

what are the impaired glucose tolerance fasting glucose ranges?

Answer 24

<7 mmol/L

Question 25

what are the impaired glucose tolerance ranges for post prandial glucose?

Answer 25

7.8 - 11.1 mmol/L

Question 26

what are the ranges for fasting glucose, post prandial glucose and random glucose in T2DM?

Answer 26

fasting: >7 mmol/L

post prandial: >11.1 mmol/L

random: >11.1 mmol/L

Question 27

why is the urine dip glucose test the least useful (arguably)?

Answer 27

renal threshold for glucose (point at which blood glucose starts appearing in urine) is roughly 10 mmol/L

still below the ranges of true T2DM

Question 28

what are the advantages of metformin as a first line drug?

Answer 28

increase sensitivity to insulin (widespread effects across whole system)

no weight gain caused

oral administration (no injections)

cheap drug

reduces overall risk profile (reduces cardiovascular issues etc)

Question 29

how does metformin act?

Answer 29

acts on signalling cascade after binding of insulin to insulin receptor

allow translocation of GLUT-4 transporter to membrane, increased sensitivity to glucose

Question 30

what are behavioural insights?

Answer 30

approach that uses how people behave to encourage positive behaviour change

consier all aspects of behaviour (psychology, social anthropology, behavioural economics etc)

most useful where individuals want to make positive changes but struggle to do so

Question 31

what is the reason for the increased prevalence of T2DM?

Answer 31

more Type 2

diet etc, link with obesity

difficulty maintaining weight loss

Question 32

what are the microvascular (due to damage to small blood vessels) complications of diabetes?

Answer 32

retinopathy (could lead to blindness)

nephropathy (could lead to renal failure)

neuropathy (could lead to impotence)
also diabetic foot disorders (include severe infections, may lead to amputation)

Question 33

what are the macrovascular (due to damage to larger blood vessels) complications of diabetes?

Answer 33

cardiovascular diseases (e.g heart attacks, strokes, insufficiency in blood flow to legs)

• hyperglycaemia causes atherosclerosis