Metabolic Block - MasterClass 3

Question 1

T2DM 1st line medication

Answer 1

Standard release metformin

SE:
GI upset common so start with 500mg OD for a week so patient can tolerate and then titrate dose upwards - 500mg BD for a week then 3 times a day - titrate up the dose to minimise risk of GI side effects. 
Abdominal pain 
Anorexia 
Diarrhoea (usually transient) 
Nausea 
Taste disturbance 
Vomiting 

Rare SE: 
Decr B12 absorption 
Erythema 
Lactic acidosis (withdraw treatment) 
Pruritus 
Urticaria 

Use with caution in renal impairment (avoid if eGFR below 30) risk of lactic acidosis
Monitor renal function

Weight reduction with calorie restricted diet
Social prescribing - like exercise programs , diet advise programs that Gp’s can refer to

Question 2

If diabetes not controlled by metformin

Answer 2

Dual therapy with :

• metformin and a DPP4 inhibitor OR
• metformin and pioglitazone
  OR
• metformin and sulfonylurea - glicazide , gliparimade - stimulates insulin risk , high risk of hypoglycaemia - good choice however can cause weight gain and hypo

If still not controlled then triple therapy

Question 3

Sulphonylurea

Answer 3

Glicazide

Main risk is hypoglycaemia but uncommon and indicates excessive dosage

Sulphonylurea induced hypoglycaemia May persist for many hours and must always be treated in hospital.

Question 4

DPP- 4 inhibitors

Answer 4

Break down GLP which is an incretin - gut hormone you release when you eat to slow gastric emptying and increase insulin secretion and stop gluconeogenesis

Question 5

Glitazones

Answer 5

Pioglitazones

Heart failure patients shouldn’t get these as can get a lot of weight gain as well

Question 6

Anti hyperglycaemics

Answer 6

DPP4 inhibitors 
GLP-1 analogues 
Alpha glucosidase inhibitors 
Thiazolidinediones 
SGLT-2 inhibitors 
Insulin 

Read block 8 notes for mechanisms of action

Question 7

Features of DKA (diabetic ketoacidosis)

Answer 7

Triad of:

• Ketosis- >3mmol/L ketonaemia or sig ketonuria (more than 2+ on standard grime sticks)
• Acidosis <15.0mmol/L and/or venous ph <7.3
• hyperglycaemia (but may be near normal in some cases) >11mmol/L or known diabetes mellitus
• Well or unwell - people with DKA look unwell - lethargic/tired
• diabetes or hyperglycaemic (have they taken their medication)
• is this the first time they’ve been this say for a better week
• steroids - known drug that causes blood sugars to go up

Question 8

Immediate management of DKA

Answer 8

• ABCDE assessment
• Fluid resuscitation with IV 0.9% NaCI 500mLs Over 15 mins - for resus - lots of flood and quickly whereas maintenance is slow fluid over hours just to keep rehydrated
• give foxes rare intravenous insulin infusion (IV insulin ) after fluid therapy commenced to stop ketogenesis

Establish monitoring regime - hourly blood glucose and hourly ketone measurement with atleast 2 hourly potassium and bicarbonate for first 6 hours

Overall aim : replace floods , glucose and correct electrolyte imbalances

Question 9

Intravenous insulin

Answer 9

Reduction in blood glucose
Suppression of Lipolysis
Resolution of ketonaemia

Question 10

How is insulin produced for treatment of diabetes

Answer 10

Genetic engineering through implanting of an insulin gene in bacteria grown in vats from which insulin was removed

Question 10

Short acting and ultra short acting insulin- difference ?

Answer 10

Humulin S and Actrapid - short acting

Humalog and Novorapid - ultra short acting - these have had their molecular structures altered to make them more readily absorbed from injection sites - quicker time for absorption - these were developed to speed up tome from subcutaneous injection to clinical effect - so people can inject just before meals - to improve blood glucose control and reduce pre meal and nocturnal hypoglycaemia

Question 11

Which other type of insulin is combined with quick acting Insulin in a multiple daily insulin regimen ?

Answer 11

Intermediate or long acting insulin

NPH such as isulatard or Humulin I
Or analogue long acting insulin such as lantus or levemir

Quick acting insulins in DKA

Question 12

Biphasic insulins

Answer 12

Humalog Mix25 and Novomix 30

Mixture of an analogue quick acting insulin with an NPH(Isophane) form of the insulin to give a combo of rapid action and a delayed action - number refers to % of quick acting in the mixture
So covering Breakfast to lunch - quick acting and lunch to teatime - intermediate

Useful in T2DM and occasionally in adults with learning difficulties who have type 1 DM and cannot cope with a multiple daily insulin regimen (basal bolus )

Question 13

Long acting insulins

Answer 13

Lantus genetically altered to make it soluble at a slightly acidic ph( in the cartridge) but when at W physiological ph close to 7.0 it crystallises out at the injection site thus retarding the absorption into the blood stream at the injection site and giving it close to a 24 hr duration of action

Levemir has had a fatty acid moiety stuck to the end of the beta chain which binds to human albumin in the blood and in the interstitial fluid at the injection site and thus retarding the action by delaying absorption into the blood stream

Question 14

U100

Answer 14

100 units of insulin per ML

Question 15

Disadvantages of insulin Degludec which comes as both U100 and U200?

Answer 15

Dosing errors but manufacturer only supplies degludec in pre filled pens which have units hard wired into pen so reducing this potential error

Degludec - slow acting insulin - different mechanism of action as it exists as a smaller particle in the bile