Diabetes Flashcards
What type of drug is Metformin?
Biguanide
What actions does Metformin have?
- reduce hepatic gluconeogenesis
- increase glucose uptake and utilisation in skeletal muscle (reduce insulin resistance)
- reduce carbohydrate absorption from the intestine
- increase fatty acid oxidation
- reduce circulating LDL and VLDL
What potential unwanted effects does Metformin have?
- dose-related GI disturbances (so should not be taken on a full stomach)
- lactic acidosis (rare but potentially fatal so should not be given routinely in patients with renal or hepatic disease, hypoxic pulmonary disease or shock)
- longterm use may affect B12 absorption
What are the clinical uses of Metformin?
- generally used as first-line drug treatment in T2DM
- can be combined with SUs
- occasionally used in T1DM alongside insulin
What is the target of SUs?
Potassium ATP channels on pancreatic beta cells
Name the commonly prescribed SUs
- gliclazide
- glimepiride
What is the action of SUs?
Reduce plasma glucose by stimulating insulin secretion (blocking of the channels causes depolarisation of the cell, Ca2+ entry and insulin secretion)
What are the potential unwanted effects of SUs?
- hypoglycaemia
- cardiovascular risk (greater than metformin)
- weight gain
- multiple drug interactions can result in severe hypoglycaemia (e.g. NSAID, warfarin, alcohol, MAOi)
What is the clinical use of SUs?
- commonly used in early T2DM
What is the only Thiazolidinedione licensed for use in the UK?
Pioglitazone
What is the target of Pioglitazone?
PPARy (mainly in adipocytes)
What is the action of Pioglitazone?
- enhances the effects of endogenous insulin so reduces the amount that is required to maintain a given level of blood glucose
- promotes transcription of genes that are important in insulin signalling
- causes differentiation of adipocytes
What unwanted effects can Pioglitazone cause?
- weight gain (due to fat cell differentiation)
- fluid retention (can precipitate or worsen HF: contraindicated)
- increased risk of fractures with chronic use (especially in women)
- increased risk of bladder cancer (monitor for haematuria)
- non-specific adverse effects e.g. headache, fatigue, and GI upset
Why were older Thiazolidinediones withdrawn?
Cardiovascular and hepatic risk
What is the clinical use of Pioglitazone?
For use in addition to other oral hypoglycaemic agents in T2DM
What type of drug is Acarbose?
Intestinal alpha-glucosidase inhibitor
What is the action of alpha-glucosidase inhibitors?
- delays carbohydrate absorption
- reduces post-meal blood glucose spike
What unwanted effects may be caused by alpha-glucosidase inhibitors?
- flatulence
- loose stools
- abdominal pain
- bloating
What is the clinical use of alpha-glucosidase inhibitors?
- Used in T2DM, particularly in obesity
- Can be co-administered with Metformin
What is the target of gliptin-type diabetes drugs?
DPP-4
What is DPP-4?
An enzyme which inactivates GLP-1
What is the action of gliptin-type diabetes drugs?
Reduces inactivation of GLP-1, so potentiates its effects:
- stimulate insulin secretion
- promote satiety
- regulates gastric emptying
What unwanted effects may come from gliptin-type diabetes medications?
Commonly: a range of GI symptoms Rarely: - liver disease - worsening of heart failure - pancreatitis ALSO: concerns over potential action as tumour promoters
What is the clinical use of gliptin-type medications?
T2DM in addition to other oral hypoglycaemic agents
What is the target of the Gliflozins?
Sodium Glucose Cotransporter type 2 (SGLT-2)
What are the three SGLT-2 inhibitors which are licensed in the UK?
- Empagliflozin
- Dapagliflozin
- Canagliflozin
What actions do SGLT-2 inhibitors have?
- reversibly block glucose reuptake in the proximal convoluted tubule to induce glucosuria and lower plasma glucose levels
- promotes weight loss
What unwanted effects can be brought on by SGLT-2i use?
- constipation
- increased risk of UTIs and thrush
- thirst
- polyuria
- increased risk of DKA
What is the clinical use of SGLT-2 inhibitors?
Additional therapy in T2DM
What are “incretin mimetics”?
GLP-1 analogues
How are GLP-1 analogues administered?
Subcutaneous injection
Give examples of GLP-1 analogues
- Exenatide
- Semaglutide
- Liragultide
What actions to GLP-1 analogues have?
- lower blood glucose post-meal by increasing insulin secretion, suppressing glucagon secretion and slowing gastric emptying
- promote satiety and so has modest weight loss effects
- reduce hepatic fat accumulation
- reduce mortality when used in combination with Metformin
What unwanted effects can GLP-1 analogues have?
- hypoglycaemia
- GI disturbances
- pancreatitis
- injection site reactions
What is the clinical indication for GLP-1 use?
- T2DM
- obese
- dual therapy has failed
- should be trialled for 6 months and continued only if shown to reduce weight and HbA1c
Define T1DM
Lack of glycaemic control due to autoimmune destruction of pancreatic beta cells and the resulting deficit in insulin secretion
What is the aetiology of T1DM?
Thought to be a combination of genetic predisposition and an environmental trigger
How is T1DM managed?
- exogenous insulin administration
- healthy diet and exercise can aid good glycemic control and minimise the risk of long-term complications but cannot reverse the disease or eliminate the need for insulin
Define T2DM
Lack of glycaemic control due to insulin resistance or insulin deficiency
What is the aetiology of T2DM?
Combination of environmental and genetic factors
What are the risk factors for T2DM?
- being overweight or obese
- central obesity
- eating an unhealthy diet
- physical inactivity
- having a first degree relative with T2DM
- hypertension
- hypercholesterolaemia
- being of south asian or afro-caribbean descent
- smoking
How is T2DM managed?
Depends on severity, progresses through the following:
- lifestyle modification (high fibre, low GI diet, regular exercise)
- oral glycaemic agents
- injected glycaemic agents
- insulin
Why is insulin administered by injection?
It is destroyed in the GI tract
How is insulin usually administered? How can it be administered?
- usually subcutaneous injection
- can be given IM or IV in emergencies
- can be given with peritoneal dialysis in patients with end stage real failure
What are the indications for insulin?
- T1DM
- T2DM with inadequate glycaemic control on oral hypoglycaemic agents (OHAs)
- T2DM when OHAs are contraindicated
- Impaired glucose tolerance in pregnancy (gestational diabetes)
What is diabetic ketoacidosis?
- excessive glucose
- lack of insulin
- glucose cannot be taken up into cells to be metabolised
- cells enter starvation-like state and use ketoacidosis to produce energy
How does DKA present?
- gradual drowsiness
- vomiting
- dehydration
What might trigger a DKA?
- infection
- surgery
- MI
- pancreatitis
- chemotherapy
- antipsychotics
- wrong insulin dose or non-compliance
Diagnostics for DKA?
1) acidosis (venous pH <7.3 or bicarb <15mmol/L)
2) hyperglycaemia (BM >11mmol/L) OR known diabetic
3) ketonaemia (>3mmol/L) or significant ketonuria (++ or more on dipstick)
What investigations should you order for a patient with suspected DKA?
- ECG
- CXR
- urine dip
- MSU
- capillary and lab glucose
- venous bloods: ketones, pH, U+E, bicarb, osmolality, FBC, cultures
- use ABG only if declining GCS or hypoxic *
What presentations might indicate a severe DKA and should prompt consideration of HDU/ICU?
- blood ketones >6mmol/L
- venous bicarb <5mmol/L
- blood pH <7
- K <3.5mmol/L
- GCS <12
- O2 sats <92% on air
- sysBP <90mmHg
- pulse >100 or <60
- anion gap above 16
What are the potential complications of DKA?
- cerebral oedema
- aspiration pneumonia
- hypokalaemia
- hypomagnesaemia
- hypophosphataemia
- thromboembolism
How does hypoglycaemia present?
- rapid onset
- sweating
- rapid pulse
- seizures
- may be accompanied by odd behaviour e.g. aggression
How do you manage hypoglycaemia?
CONSCIOUS, ORIENTATED, ABLE TO SWALLOW:
- 15-20g of quick acting carb snack (e.g. 200ml orange juice) and recheck BM after 10-15min
- repeat up to 3 times
CONSCIOUS BUT UNCOOPERATIVE:
- squirt glucose gel between teeth and gums
UNCONSCIOUS OR NOT RESPONDING TO TREATMENT:
- start glucose IVI or give glucagon 1mg IV or IM
- Expect a rapid recovery
- When glucose >4mmol/L and patient has recovered, give long acting carb (e.g. toast)
What does HHS stand for?
Hyperglycaemic hyperosmolar state
When might lactic acidosis occur in diabetics?
- septicaemia
- Metformin use
Blood lactate >5mmol/L
1) What is it?
2) What do you need to do?
1) Lactic acidosis
2) Management:
- get expert help
- stop metformin
- treat sepsis vigorously
- maintain BP to maintain tissue perfusion
Who tends to get HHS?
Unwell type 2 diabetics
How does HHS present?
- not a rapid onset: usually around ~1/52 history
- marked dehydration
- glucose >30mol/L
- ketones normal so pH normal
- osmolality typically >320mosmol/kg
What are the principles of HHS management?
- prevent occlusive events: give LMWH prophylaxis unless contraindicated
- rehydrate slowly
- replace K+ when urine output resumes
- only use insulin if not responding to treatment or if ketonaemic
- maintain glucose >10mmol/L for first 24h to avoid cerebral oedema
- look for the cause
What might precipitate HHS?
- MI
- drugs
- sepsis
- bowel infarct
