Diabetes Flashcards
What different tests do we have for DM? [6]
- Random Glc test
- Fasting Glc test
- HbA1c test
- Oral Glucose Tolerance Test (OGTT)
- Blood & Urine Ketones
- Urine glucose
All DM tests are indicative of DM, which tests are considered diagnostic and what values would indicate diabetes? [4]
Fasting Venous Plasma Glc > 7mmol/l
Random Venous plasma Glc > 11.1mmol/l
OGTT >11.1mmol/l after 2 hours
HbA1C > 48mmol/mol
Explain the OGTT [3]
What result is abnormal? [1]
1) Take a fasting glucose
2) Give them oral glucose load
3) Test again after 2 hours
If its still raised then its +ve for diabetes (should normally return to normal within 1 hour of ingesting glucose)
What do we need to diagnose Diabetes Mellitus? [2]
2 +ve diagnostic tests (fasting or random glucose, OGTT or HbA1c)
OR
1 +ve diagnostic test + Symptoms
What is HbA1c? [3]
Glycated Haemoglobin [1]
Sugar in the blood binds to haemoglobin, the amount that does is directly proportional to the total amount of Glucose. [1]
So HbA1c levels reflect the level of glucose in the blood over the last 8-12w [1]
When can we not use an HbA1c test? [7]
- Children or young people
- Pregnant women
- The acutely ill
- Meds that affect glucose e.g. CCS or antipsychotics
- Acute pancreatic damage
- Renal Failure
- HIV infection
Basically anything that would alter recent glucose levels renders HbA1c useless
How would you diagnose DKA? [2]
Clinical diagnosis and blood/urine ketone testing.
Describe the biochem results of a patient with DKA? [4]
1) High glucose
2) Low Bicarbonate (kessmauls resp)
3) Low Na+ (diluted by movement of water)
4) High urea, potassium & Creatinine (dehydration reduces excretion)
When would you want to test C-peptide? [2]
If a patient was having recurrent hypoglycemia. Test their insulin levels to see if thats the source and its raised.
When insulin is self-injected, laboratory studies will show high plasma insulin levels in combination with low plasma C-peptide levels during the hypoglycemic episode. With sulfonylurea consumption, the clinical picture may mimic an insulinoma with high plasma levels of both C-peptide and insulin; a positive drug screen can render the diagnosis.
What would you want to monitor to keep an eye out for long-term complications? [3]
Urine Albumin/creatinine Ratio (for nephropathy)
Lipids & BP for CV disease
Investigations DKA
- Initial [5]
- After the patient is stable what additional investigations would you order? [3]
Inititial Investigations:
- ABCs
- Vital Signs
- IV access
- Clinical Assessment
- Glucose fingerprick test
First Investigations:
- Lab Blood Glucose to confirm
- ABGs (Low CO2 from hyperventilation & acidosis)
- Urinalysis and blood ketones
- U&E + FBC
Prediabetes definition
Also known as…
impaired glucose levels which are above the normal range but not high enough for a diagnosis of diabetes mellitus
How do we define prediabetes through investigations? [3]
- patients identified at high risk should have a blood sample taken
- a fasting plasma glucose of 6.1-6.9 mmol/l or
- an HbA1c level of 42-47 mmol/mol (6.0-6.4%)
So normal is <6 mmol/l and 41 HbA1c on fasting glucose
DM is >7 mol/l and 48 HbA1c is DM on fasting plasma
How do you identify high risk people in the first instance before investigating for prediabetes?
all adults aged 40 and over, people of South Asian and Chinese descent aged 25-39
Management of prediabetic patients [3]
NICE guidelines 2012
- lifestyle modification: weight loss, increased exercise, change in diet
- at least yearly follow-up with blood tests is recommended
- metformin for adults at high risk ‘whose blood glucose measure (fasting plasma glucose or HbA1c) shows they are still progressing towards type 2 diabetes, despite their participation in an intensive lifestyle-change programme’
Impaired fasting glucose vs Impaired glucose tolerance
impaired fasting glucose (IFG) - due to hepatic insulin resistance
impaired glucose tolerance (IGT) - due to muscle insulin resistance
*patients with IGT are more likely to develop T2DM and cardiovascular disease than patients with IFG
Impaired fasting glucose definition
Impaired glucose tolerance definition
- a fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG)
- impaired glucose tolerance (IGT) is defined as:
1. fasting plasma glucose less than 7.0 mmol/l AND
2. OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
What is the mainstay and first line options of Type 1 treatment? [2]
Lifestyle changes and Insulin!
How is insulin delivered? [2]
Why is it delivered any other route
By SC or IV
Because its a polypeptide inactivated by the GI tract so it doesnt work orally
What are the types of insulin? [5]
- Rapid acting
- Short Acting
- Intermediate Acting
- Long acting
- Continuous SC insulin infusion (CSII)
What changes the time insulin takes to take effect? [2]
Soluble insulin associates into hexamers in SC fat.
- It needs to dissociate into monomers in order to diffuse into capillaries.
- Altering the structure/solubility of insulin affects how long it takes to dissociate
Describe a twice daily insulin regime [1]
Timings [2]
Mix of rapid and intermediate acting insulin Before breakfest (BB) & before tea (BT)
Describe a thrice daily insulin regime? [1]
Timings [2]
Mix of rapid and intermediate BB
Rapid BT
Intermediate Bbed
Describe a 4x daily insulin regime? [2]
Mix of: Short acting insulin BB, BL & BT
Then Intermediate Bbed or long acting insulin at a fixed time once per day
How is Type 2 Diabetes treated?
Name drugs from 1st to 3rd line
Lifestyle modifications
1st line - Metformin (OHG)
2nd line - A Sulphonyurea (E.g. glimepiride)
3rd line - A thiazolidinedione (e.g. pioglitazone) (aka Glitazones)
Further 3rd line meds include:
DPP-IV inhibitors - SGLT-2 inhibitors - GLP-1 agonist - Insulin
What does metformin do? [1]
It increases insulin sensitivity
What aspects of hypoglycemia is it important to educate patients on? [4]
- How to test their blood sugar
- How to recognise the signs of a hypo
- How to treat it
- How to avoid it
Treatment of hypoglycaemia
Give 3 options for non-hospital and hospital settings
Follow up [1]
Rapid acting carb e.g. 200ml of fruit juice
OR 1mg IM glucagon
OR if in hospital then 80ml 20% glucose
Follow up with a long acting carbohydrate
How do patients avoid based on causes of hypoglycemia? [4]
- Blood glucose monitoring
- Rotate & check injection sites
- Review diet (carb counting)
- Maybe change the insulin regime
What are the rules for driving and Hypos?
What are the contraindications for driving that the DVLA impose on diabetics [2]
Diabetics have to check their glucose within 2 hours of driving [1] and repeat on long journeys [1]
They should carry short acting carbs in the car
If they can’t recognise a hypo [1] or have >1 severe hypo a year they can’t drive [1]
How would we advise a patient to deal with DKA at home? [6]
1) They think they’re getting symptoms
2) Test their ketones
3) +ve? Test Blood Glc
4) Elevated? Take an extra insulin dose
5) still high after 4 hours? Take another dose
6) Call diabetes team, notify them of possible DKA
How do we treat DKA? [7]
Fluid replacement 0.9% NaCl 1L for 1st hour
- Once BM <15 mmol/l start 5% dextrose infusion
Insulin:
- IV infusion 0.1 unit/kg/hour
- Continue long acting insulin usual dose
- Stop short acting insulin
Correct hypokalaemia
Management of DM complications
How do we manage diabetic nephropathy? [4]
- Glycaemic control
- BP control
- ACE inhibitor slows progression & treats BP
- CVD risk factor control
Diarrhoea is a potential diabetic autonomic neuropathy, how do you treat it? [1]
Loperamide (i.e. imodium)
Gastric stasis and vomiting is a potential diabetic autonomic neuropathy, how do you treat it?
Domperidone.
Dopamine antagonist that acts as an antiemetic and progastrokinetic
Postural Hypotension is a potential diabetic autonomic neuropathy, how do you treat it? [3]
Advice: avoid getting up to quickly
NSAIDS or Fludrocortisone
Erectile dysfunction is a potential diabetic autonomic neuropathy, how do you treat it? [1]
Phosphodiesterase inhibitors e.g. Viagra
Management of peripheral neuropathy
- Rx [2]
- Non pharmacological [3]
Pain relief:
- Capsaicin cream
- Amitriptyline
Protection of feet from ulceration:
- Fitted footwear
- Regular podiatry visits
- Foot screening and risk assessment
How do we treat maculopathy? [3]
Grid laser therapy
Glc Control
BP control
Treatment: proliferative retinopathy [2]
Describe rationale for each [4]
Natural progression if untreated [2]
We can do a vitrectomy if theres a vitreous haemorrhage
Laser photocoagulation destroys ischaemic retina [1] , reducing Endothelial Growth Factors [1] causing the new vessels to regress [1]
If untreated, scarring can occur which can lead to retinal detachment.
CV risk reduction is an example of primary prevention [4]
Lifestyle mods
Control BP to <130/80
Smoking cessation services
Statin therapy - simvastatin for over 40 and in younger patients with significant complications
Package of care for people with T2DM [11]
- Blood glucose levels (annually)
- Blood Pressure (annually)
- Blood Lipids (annually)
- Eyes Screened (annually)
- Feet checked (annually)
- Kidney function (annually)
- Weight
- Smoking Cessation Support
- Individual Care plan
- Education Course
- Emotional and psychological support
Targets HBA1C depend on management:
Lifestyle AND/OR metformin only
Already on one drug, but HbA1c has risen to 58 mmol/mol (7.5%)
Lifestyle AND/OR metformin only:
- Target for 48
Already on one drug, but HbA1c has risen to 58 mmol/mol (7.5%)
- Target for 53
Fluid replacement regime in DKA admission with systolic BP >90 mmHg (for 19 hours)
1L over 1st hour 0.9% NaCl 1L over next 2h 0.9% NaCl with KCl - Another 1L over next 2h - Another 1L over next 4h - Another 1L over next 4h - Another 1L over next 6h
Main complication of treating DKA in young people Specific age range Symptoms Onset Mx
Fluid therapy can cause cerebral edema so slower infusion is needed
- 18-25yo
- need 1:1 nursing to monitor neuro-observations, headache, irritability, visual disturbance, focal neurology etc
- Usually occur 4-12h after commencement of treatment
- CT head and senior review
Goals of management of HHS
What NOT to do…
- Normalise the osmolality (gradually)
- Replace fluid and electrolyte losses
- Normalise blood glucose (gradually)
Don’t use insulin in first instance, fluid replacement alone can facilitate a gradual decline in BM and plasma osmolarity. Because most patients with HHS are insulin sensitive (e.g. it usually occurs in T2DM), administration of insulin can result in a rapid decline of serum glucose and thus osmolarity.
Fluid replacement in HHS [2]
Aim?
What is a safe rate of fall of plasma glucose? [2]
Intravenous (IV) 0.9% sodium chloride solution is the first line fluid for restoring total body fluid.
2nd line if unresponsive: 0.45% NaCl
Aim: achieve positive balance of 3-6L by 12h, replace remaining losses within next 12h
A safe rate of fall of plasma glucose of between 4 and 6 mmol/hr is recommended. The rate of fall of plasma sodium should not exceed 10 mmol/L in 24 hours.
Complications of HHS treatment
When can you expect total normalization?
What target blood glucose is used?
Cardiovascular collapse
Central pontine myelinolysis
Complete normalisation of electrolytes and osmolality may take up to 72 hours.
A target blood glucose of between 10 and 15 mmol/L is a reasonable goal.
Why can insulin treatment cause cardiovascular collapse?
Insulin treatment prior to adequate fluid replacement may result in cardiovascular collapse as the water moves out of the intravascular space, with a resulting decline in intravascular volume.
When would insulin be indicated in HHS?
What ROA and dose of insulin would be recommended?
If significant ketonaemia is present (3β-hydroxy butyrate is more than 1 mmol/L) this indicates relative hypoinsulinaemia and insulin should be started at time zero (e.g. mixed DKA / HHS picture).
The recommended insulin dose is a fixed rate intravenous insulin infusion given at 0.05 units per kg per hour.
Potassium in HHS
Patients with HHS are potassium deplete but less acidotic than those with DKA so potassium shifts are less pronounced
Hyperkalaemia can be present with acute kidney injury
Replace as required
What are the drugs used for Type 2? (1st/2nd/3rd line)
How does Metformin Work?
It increases insulin sensitivity
Pros [4] & Cons of Metformin [3]
- Well tolerated
- Effective
- Weight neutral
- Improves mortality & CV complications
Cons:
- GI side effects
- Vit B12 malabsorption
- Lactic Acidosis
What do Sulphonyureas do? [2]
Give an example
Glimepiride
Blocks ATP-sensitive K+ channels leading to increased insulin secretion
Pros [4] and cons of Sulphonyureas? [2]
Contraindications [4]
Pros:
- Rapid action so good for the acutely ill
- Well tolerated
- Rapid titration
Cons:
- Risk hypo
- Weight gain
- Contraindicated in pregnant/breastfeeding
- Cautioned in renal/hepatic disease
MOA Thiazolidinediones[2]
Give an eg
Pioglitazone
Increases insulin sensitivity in muscle/fat/liver by acting on PPar gamma receptors
Pros [2] and cons [4] of Thiazolidinediones
- Effective for insulin resistance
- Safe with CV system
Cons:
- Weight gain
- Fluid retention
- Increases bone turnover -> fractures
- Bladder cancer
Example of a DPP-IV inhibitor and how they work?
Saxagliptin
DPP-IV is an enzyme that breaks down incretin hormones.
Inhibitors extend incretin half-lives.
Incretin hormones cause glucose dependant insulin release and glucagon inhibition
Pros and cons of DPP-IV?
- Well tolerated
- Usuable in renal impairment
- Weight neutral
- No Hypo risk
Cons:
- Small effects
- CI in pregnancy/breastfeeding
- PAncreatitis/pancreatic cancer
- Nausea
Example and function of SGLT-2 inhibitors? [3]
Gliflozins e.g. empagliflozin
Inhibit Sodium Glucose Transporter 2 in the proximal tubule of the kidney.
Thus increases Glc & Na excretion in urine
Effects of SGLT-2 inhibitors?
Diuretic Effect - Postural hypotension & dehydration
Glucouric Effect - Weight loss from pissing out so many calories
Na Excretion - Lowers BP
Greater risk of urogenital infections
Which Type 2 meds are injectable and which ones oral?
Oral:
- Metformin
- Sulphonyureas
- Thiazolidinediones
- DPP-IV inhibitors
- SGLT2 Inhibitors
Injected:
- Insulin
- GLP-1 analogue
Example and function of GLP-1 analogues?
Liraglutide
GLP-1 is an incretin hormone.
DPP-IV resistant analogues are injected (which cause Glc dependant Insulin release & glucagon inhibition) which have a much longer biological half-life.
What drugs can replace sulphonyurea’s as 2nd line Type 2 treatment if neccessary? [3]
- Thiazolidinediones e.g. pioglitazone
- DPP-IV inhibitors e.g. Sitagliptin
- SGLT-2 inhibitors e.g. Empagliflozin
How do DPP-IV inhibitors work? [4]
They inhibit DPP-IV, an enzyme that breaks down incretin hormones [1]
This prolongs the life of incretins [1] allowing them to cause Glc Dependant Decrease in Glucagon [1] release and Increase in Insulin Release [1]
Pros [4] and cons [4] of DPP-4 inhibitors?
Pros
- Well tolerated
- Weight Neutral
- Works in renal impairment
- No hypoglycaemic risk
Cons:
- small effect
- CI in pregnant/breastfeeding
- risk of pancreatitis/pancreatic cancer
- Nausea
How do GLP-1 analogues work? [3]
Similar to DDP-IV inhibitors.
GLP-1 is an incretin [1], the analogues are resistant to DPP-4 degradation [1] so have a longer half life causing:
- Glc dependant insulin release and glucagon inhibition [1]
Pros [1] & Cons [1] of GLP-1 Analogues?
Pros - Do cause some weight loss for those overweight
Cons - Nausea (by delaying gastric emptying)
Example of each Type 2 drug? [5]
Biguanides - Metformin
Sulphonyureas - Glimepiride
Thiazolidinediones - Pioglitazone
DPP-IV inhibitors - Saxagliptin
GLP-1 Analogue - Liraglutide
T2DM patients on metformin
Indications to start?
HbA1c rises to 58 mmol/l [3]
Metformin is 1st line if HbA1c has risen to 48mmol/mol on lifestyle measures.
HbA1c remains 58mmol/mol: triple therapy or consider insulin therapy
- Eg METFORMIN + GLIPTIN + SULFONYLUREA
Further management of T2DM for second line therapy
T2DM patients who can’t tolerate metformin: what to do when HbA1c rises to 58 mmol/mol?
When would insulin therapy be considered?
• GLIPTIN + PIOGLITAZONE
If despite double therapy, HbA1c remains at 58 mmol/mol
When starting insulin therapy what must be continued?
Continue metformin
If triple therapy is not effective, management of T2DM
If triple therapy is not effective or tolerated consider switching one of the drugs for a GLP-1 mimetic:
* BMI ≥ 35 kg/m² and specific psychological or other medical problems associated with obesity or
* BMI < 35 kg/m² and for whom insulin therapy would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities
* only continue if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 months
