Insulin, GLP-1 and oral hypoglycaemic agents

Question 1

Aim of diabetes treatment

Answer 1

• education for self management
• focus on lifestyle and diet changes
• psychological and social support
• CV RF control avoiding complications
• regularly screening for complications

Question 2

Diabetic Annual Review

Answer 2

• min. twice a year
• symptom review
• clinical issues review (glucose levels, BP, cholesterol, ACR in urine)
• screen for comp (eyes, feet, kidneys)
• identify issues at subsequent visit
• develop targets over next year

Question 3

Treatment to prevent complications

Answer 3

• smoking cessation (1 cig = 5 If diabetes)
• aim for 140/80 bp, 130/80 if CVD or renal d, use ACEi/CCB and need >2 bp treatments
• statin if diabetic >40 or <40 + RF for high cholesterol, aim for <4mmol/L and LDL <2 mmol/L
• yearly digital retinal photography
• yearly nerves and pulses in feet
• yearly ACR and estimate GFR

Question 4

How to assess glycaemic control?

Answer 4

• HbA1c = red cells survive 3 months, less than 53 mmol/mol good control
• SMBG = pre-prandial 4-7, post prandial 2 hour glucose 5-9
• fructosamine = 2 weeks glycated protein, if HbA1c invalid as haemoglobinopathy and useful in pregnancy glucose monitoring

Question 5

Diet and exercise advice for diabetes treatment

Answer 5

• low fat
• low sugar
• low salt
• high in fibre
• fruit and veg
• low carbs = low GI
• 30 mins vigorous exercise 3x a week
• aim for 3-5% weight reduction for glycemic control
• early oral hypoglycaemic agents if diet and lifestyle strategy fails

Question 6

Hyperglycaemia therapies

Answer 6

• sulfonylureas
• biguanides
• alpha glucosidase inhibitors
• TZD (glitazones)
• DPP4 inhibitors
• GLP-1 analogues
• insulin

Question 7

What is the United Kingdom Prospective Diabetes Study

Answer 7

• tight vs standard glycemic control
• microvascular disease reduced
• little effect on macrovascular disease

Question 8

How do sulfonylureas and PGRs work in the pancreas?

Answer 8

• insulin secretagogues
• stimulate insulin release from beta cells
• through opening K+ channels in beta cells
• side effects = weight gain, hypoglycaemia

Question 9

How do biguanides work?

Answer 9

• metformin
• improved insulin sensitivity in muscle and liver so can uptake glucose
• first line for T2D in majority
• reduces mortality
• reduces weight
• sometimes reduces cancer
• be wary with renal disease and don’t give if eGFR <30 as renally excreted and not cleared from blood

Question 10

How do alpha-glucosidase inhibitors work?

Answer 10

• drugs inhibiting intestinal absorption of glucose by blocking dissacharidases so stop converting to mono
• lower serum glucose levels
• but glucose moves into lower bowel attracting bacteria = wind

Question 11

How do TZD work?

Answer 11

• glitazones
• PPRGamma receptor agonists
• improve insulin resistance
• work on liver and muscle
• improve glucose uptake
• help pancreas B cell function and content

Question 12

What do GLP-1’s do?

Answer 12

• incretin
• increase insulin
• stimulate insulin from pancreas
• decrease glucagon secretion
• delay gastric emptying
• suppress appetite

Question 13

What is exendin-4?

Answer 13

• GLP-1 analogue
• injection
• suppresses appetite and stimulates insulin release
• only if BMI>35kg/m2 and poor glucose control

Question 14

What DPP-4 inhibitors do?

Answer 14

• gliptins
• inhibit enzyme breaking down GLP-1
• oral
• well tolerated
• 3rd line therapy

Question 15

When do we use different drugs according to NICE guidelines?

Answer 15

• first line metformin
• second add sulfonylurea
• third glitazone/gliptin/insuin
• then insulin + metformin + sulfonylurea

Question 16

Side effects of biguanides

Answer 16

• metformin
• nausea
• diarrhoea
• lactic acidosis
• renal failure

Question 17

Side effects of sulfonylureas and PGRs

Answer 17

• gliclazide
• repaglinide
• hypoglycaemia
• weight gain

Question 18

Side effects of glitazones

Answer 18

• piaglitazone
• weight gain
• oedema
• HF
• post menopausal fractures
• bladder cancer

Question 19

Side effects of alpha glucosidase inhibitors

Answer 19

• acarbose
• flatulence
• diarrhoea

Question 20

Side effects of DPP-IV inhibitors

Answer 20

• sitagliptin
• nasopharyngitis
• pancreatitis

Question 21

Side effects of GLP-1 agonists

Answer 21

• exenatide
• nausea
• diarrhoea
• pancreatitis
• pancreatic cancer

Question 22

How is glucose normally metabolised?

Answer 22

• ingest glucose
• digested and broken down by gut enzymes
• incretins released by gut = stimulation of insulin release from pancreas
• glucose absorbed in small intestine
• insulin acts on liver, muscle and adipose tissue stimulating glucose uptake

Question 23

Insulin effect on liver, muscle and adipose tissue?

Answer 23

• liver = glucose uptake and glycogen synthesis
• muscles = glucose uptake and glycogen synthesis
• adipose tissue = glucose uptake

Question 24

When do insulin levels peak?

Answer 24

• biphasic
• short lived rapid meal related insulin peaks
• low steady basal insulin profile

Question 25

Indications for insulin therapy

Answer 25

• T1D = essential for life
• T2D = inadequate glycemic control on tablets, tablet contraindication, symptomatic hyperglycaemia, pregnancy, infection/foot ulcers

Question 26

Types of insulin

Answer 26

HUMAN
- short acting Humulin S
- intermediate Humulin I
- biphasic mixture Humulin M3
ANALOGUE INSULIN
- rapid acting = lispro, novorapid
- long acting basal = lantus, levmir
- biphasic mixture = novomix 30

Question 27

Insulin injection sites

Answer 27

• subcutaneous fat
• abdomen fastest absorption then thighs then buttocks slowest
• not through clothing

Question 28

Insulin regime 3 types

Answer 28

• once daily/twice daily intermediate or long acting insulin, usually before bed or first thing in morning
• once/twice/three times daily premixed insulin
• basal-bolus therapy, 3 injections of rapid acting and 1 injection of long acting mimicking normal physiology