diabetes & insulin

Question 1

does insulin resistance cause increased risk of alzheimer’s?

Answer 1

yes

Question 2

what causes insulin production to fall as insulin resistance increases in type 2 diabetes?

Answer 2

B- cell dysfunction

Question 3

what factors in type 2 diabetes cause heart failure?

Answer 3

hyperlipidemia and hyperglycaemia

Question 4

does insulin resistance have symptoms?

Answer 4

no

Question 5

what are the 3 mechanisms of insulin resistance?

Answer 5

impairment of insulin signalling (e.g. skeletal muscle insulin resistance)
inflammation (e.g. adipose tissue insulin resistance)
pathways selective hepatic insulin resistance

Question 6

what is the gold standard for measurement of insulin sensitivity?

Answer 6

hyperinsulinemic-euglycemic clamp

Question 7

how is insulin resistance reversed?

Answer 7

eating less, exercise, medication

Question 8

what is the definition of diabetes?

Answer 8

loss of glucose homeostasis leading to hyperglycaemia

Question 9

what fasting blood glucose level is classed as hyperglycaemia?

Answer 9

> 7mM

Question 10

what fasting blood glucose level indicates pre-diabetes?

Answer 10

6-7mM (4-6 would be normal, and <4 is hypoglycaemia)

Question 11

what do the different cells of pancreatic islets secrete?

Answer 11

alpha cells - secrete glucagon
beta cells - secrete insulin
delta cells - secrete somatostatin
PP cells - secrete pancreatic polypeptide

Question 12

where is insulin synthesised?

Answer 12

rough endoplasmic reticulum of pancreatic beta cells as preproinsulin
it is then cleaved to form insulin

Question 13

what is the structure of insulin?

Answer 13

2 polypeptide chains linked by disulfide bonds and a connecting peptide

Question 14

what is the shortest acting insulin?

Answer 14

insulin lispro

Question 15

what is the longest acting insulin?

Answer 15

insulin glargine- can be administered as a single bedtime dose

Question 16

what are the 2 phases of insulin release?

Answer 16

5 % of insulin granules are immediately available for release – RRP – readily releasable pool

Reserve pool must undergo preparatory reactions to become mobilised and available for release

Question 17

what happens to insulin release in T2DM?

Answer 17

In poorly controlled T2DM insulin secretion weakens and flattens.

This is likely due to downregulation of the sensing process (e.g. limited glucokinase activity flux, mitochondrial exhaustion –> reduced ATP production, or run down of insulin stores).

Question 18

how do sulphonylureas work?

Answer 18

they mimic the action of ATP to depolarise beta cells

Question 19

what is type 1 diabetes?

Answer 19

autoimmune destruction of pancreatic beta cells

Question 20

what do you need to diagnose type 1 diabetes?

Answer 20

presence of specific antibodies and declining C-peptide production.

Question 21

how do you diagnose gestational diabetes?

Answer 21

FBG > 5.5
declining beta cell function
diagnosed in the second or third trimester

Question 22

how do you treat gestational diabetes and what are the risks?

Answer 22

metformin and lifestyle advice

big risk factor for developing T2DM in future (12x increased risk)

Question 23

what is MODY?

Answer 23

maturity onset diabetes of the young
has common features of types 1 & 2
monogenic diabetes with beta cell dysfunction but no autoimmune destruction
can be misdiagnosed as type 1

Question 24

what is donohue syndrome (leprechaunism)?

Answer 24

• Rare autosomal recessive mutation in the insulin receptor gene
• Severe insulin resistance
• Developmental abnormalities
  – elfin facial appearance
  – growth retardation
  – absence of subcutaneous fat, decreased muscle mass
• Caused by defects in insulin binding or insulin receptor signalling

Question 25

what is rabson mendenhall syndrome?

Answer 25

• Rare autosomal recessive genetic trait
• Severe insulin resistance, hyperglycemia and
  compensatory hyperinsulinemia
• Developmental abnormalities
• Acanthosis nigricans (hyperpigmentation)
• Fasting hypoglycaemia (due to hyperinsulinemia)
• Diabetic ketoacidosis
• Severe cases linked to mutations in the insulin receptor that reduce sensitivity

Question 26

what are the symptoms of diabetic ketoacidosis?

Answer 26

Vomiting
Dehydration
Increased heart rate
Distinctive acetone smell on breath

Question 27

what is the most common cause of diabetic ketoacidosis?

Answer 27

type 1- not taking insulin properly e.g. missing a dose

Question 28

what are the diagnostic thresholds of blood glucose?

Answer 28

random or 2 hr glucose >=11.1mmol/L
or
fasting glucose >=7mmol/L
or
HbA1c >= 48mmol/L

if asymptomatic, repeat confirmatory test must also be done

threshold is set on relation to the risk of diabetic retinopathy

Question 29

what are the threshold levels for gestational diabetes set by?

Answer 29

risk to foetus (not retinopathy)

Question 30

what is a marker of endogenous insulin secretion?

Answer 30

C-peptide - can show how well the pancreas is working

Question 31

what are the symptoms of high blood glucose?

Answer 31

Polyuria
Thirst and polydipsia
Blurred vision
Genital Thrush
Fatigue
Weight loss

can rarely also have loss of vision or retinal changes

Question 32

what is the HbA1c?

Answer 32

measure of the amount of glycated haemoglobin (glucose attached to haemoglobin) over 90 days

Question 33

what is Hb1Ac measured in?

Answer 33

mmol/mol (used to be %)

Question 34

what is the target HbA1c in patients with type 2 diabetes on treatment?

Answer 34

53mmol/mol (7%)

a target of 48mmol/mol (6.5%) can be used at diagnosis.

targets can be individualised to patients.

Question 35

what is the glycaemic index (GI)?

Answer 35

rank of rate at which food makes blood glucose rise

Question 36

what type of exercise causes hyperglycaemia?

Answer 36

Anaerobic activity, competition or insufficient insulin
Avoid exercise if BG >14 mmol/L or ketones present (additional fast acting insulin may be required)

Question 37

what are the 2 types of prandial insulins and what is the difference between them?

Answer 37

insulin analogues-
onset 10-15 mins
peak action 60-90 mins
duration 4-5 hours

soluble insulin-
onset 30-60 mins
peak 2-4 hours
lasts 5-8 hours

Question 38

what are the 2 types of basal insulins and what are the differences?

Answer 38

isophane ‘basal’ insulins-
intermediate/long acting
peak after 4-6 hours

analogue basal insulin-
long duration of action
less peak activity (flatter profile)
can be given once or twice a day

Question 39

what type of insulin should most T1DM patients be on?

Answer 39

analogue basal insulin (e.g. glargine)

Question 40

when is diabetes found in cystic fibrosis?

Answer 40

CTRDM is found in >25% at 20 years
usually found in severe mutations
prone to complications
preferrebly insulin treated

Question 41

what types of pancreas transplantation are there?

Answer 41

kidney-pancreas transplant- end stage renal failure, severe hypo or metabolic complication, incapacitating clinical/ emotional problems, high chance of rejection

islet autotransplantation- same indications to receive

Question 42

when would you consider weight reduction surgery in diabetes?

Answer 42

BMI over 40, or BMI over 35 with obesity related co-morbidity e.g. T2DM

Question 43

what is the risk of a child getting T1DM if both parents have it?

Answer 43

30%

Question 44

what is the risk of a child getting T2DM if both parents have it?

Answer 44

around 70% (40% if only 1 parent has it)