insulin resistance, metabolic syndrome and diabetes

Question 1

insulin resistance

Answer 1

• when given a conc of insulin theres a subnormal glucose response
• high insulin with normal/high glucose
• can be pre-receptor, receptor or post receptor

Question 2

what is insulin resistance associated with

Answer 2

1. obesity
2. type 2 diabetes
3. endocrine disorders e.g. Cushing
4. metabolic syndrome

Question 3

what are the key components of the metabolic syndrome

Answer 3

central obesity

plus 2 of:

• hypertension
• abnormal glucose
• high triglycerides
• low HDL

Question 4

how to recognise a patient with insulin resistance

Answer 4

1. metabolic syndrome cluster
2. acanthuses nigricans
3. PCOS

Question 5

how does increased visceral fat cause insulin resistance

Answer 5

1. increased visceral fat and therefore stored triglyceride –> larger adipocytes
2. large adipocytes are resistant to the ability of insulin to suppress lipolysis
3. increased lipolysis leads to increased release of non-esterified fatty acids (NEFA) and glycerol
4. NEFA and glycerol, plus inflammatory cytokines released by visceral adipose tissue aggravate insulin resistance in muscle and liver

may also cause lipotoxicity in beta cells

Question 6

consequences of insulin resistance - glucose

Answer 6

• hepatic glucose output not suppressed
• IMGU in muscle reduced
• therefore only hyperinsulinaemia can maintain normal glucose levels

Question 7

consequences of insulin resistance - fat

Answer 7

metabolic - rise in FFA, triglycerides

hormones - adipoctyokines

Question 8

other factors causing insulin resistance

Answer 8

• inherited factors

- environmental (intrauterine or obesity)

Question 9

what is blocked by insulin resistance

Answer 9

in insulin resistant states, insulin signalling is blocked by inhibition of phosphorylation of IRS protein

Question 10

what is the role of IRS proteins

Answer 10

• glucose transport
• glycogen synthesis
• anti-lipolysis

Question 11

Are adiponectin and/or resistin implicated in insulin resistance?

Answer 11

Adiponectin and resistin may provide a link between obesity and insulin resistance

• Adiponectin deficiency may play a role in development of insulin resistance and type 2 diabetes
• Resistin is secreted by adipocytes of obese mice and decreases adipocyte glucose uptake

Question 12

consequences of insulin resistance on beta cells

Answer 12

glucose rise –> glucose toxicity in beta cell
FFA –> lipotoxicity in beta cell, liver and muscle and fat gets ‘full up’

now beta cells start to fail

• decreased beta cell mass (genetic or maternal)
• decreased beta cell function: less pulses
  - lipotoglucotoxicity
  - incretin dysfunction

Beta cell dysfunction is progressive!

Question 13

what are the consequences from truncal obesity (insulin resistance)

Answer 13

• glucose intolerance: type 2 diabetes
• hypertension
• dyslipidaemia
• endothelial dysfunction
  inflammatory markers procoagulant state

Question 14

define diabetes mellitus

Answer 14

metabolic syndrome characterised by the presence of hyperglycaemia due to defective insulin secretion, insulin action or both

Question 15

values for normal fasting and diabetes fasting

Answer 15

normal = less than or equal to 6

diabetes = greater than or equal to 7

Question 16

HbA1c values

Answer 16

normal = <40mmol/mol

abnormal = 41-49

diabetes = >50mmol/mol

Question 17

classification of type 1 diabetes

Answer 17

• immune-mediated B cell destruction

- idiopathic

Question 18

classification of type 2 diabetes

Answer 18

• obesity related

- insulin resistance

Question 19

consequences of diabetes

Answer 19

microvascular

• retinopathy
• peripheral neuropathy
• nephropathy

macro

• IHD
• PVD
• CVA

Question 20

retinopathy

Answer 20

• slient

- leading cause of blindness in western world

Question 21

neuropathy

Answer 21

• burning, numbness
• ulcers and foot infections –> amputation
• proteinuria –> reduced GRF
• commonest cause of ESRF
• high mortality

Question 22

signs and symptoms of diabetes type 1

Answer 22

• autoimmune beta cell destruction
• abrupt symptoms
• younger
• no family Hx
• ketosis prone
• require insulin usually from diagnosis and to sustain life

Question 23

management of diabetes

Answer 23

• lifestyle factors of diet and exercise paramount
• medication to control glucose
  
  • insulin in type 1 (50% in type 2)
  • metformin
  • sulphonylurea
  • insulin incretin therapy
• attend to BP, lipids, smoking etc