T2DM pharm Flashcards
Dietary advice for T2DM
encourage high fibre, low glycaemic index sources of carbohydrates
include low-fat dairy products and oily fish
control the intake of foods containing saturated fats and trans fatty acids
limited substitution of sucrose-containing foods for other carbohydrates is allowable, but care should be taken to avoid excess energy intake
discourage the use of foods marketed specifically at people with diabetes
initial target weight loss in an overweight person is 5-10%
HbA1c target - with just lifestyle measures
48mmol/mol
HbA1c target - lifestyle measures + metformin
48 mmol/mol
HbA1c target - includes any drug which may cause hypoglycaemia
53mmol/mol
1st line agent if HbA1c > 48mmmol/mol
metformin
Options HbA1c has risen to 58mmol/mol already on metformin
sulfonylurea
gliptin
pioglitazone
SGLT-2 inhibitor
Criteria for GLP1 mimetic
if triple therapy is not effective, not tolerated or contraindicated then consider combination therapy with metformin, a sulfonylurea and a glucagon-like peptide1 (GLP1) mimetic if:
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
Should metformin be continued when starting insulin
Yes
Example of GLP-1 mimetic and how does it work
Exenatide
Increases insulin secretion and inhibits glucagon secretion
what is a potentially beneficial effect of GLP-1 mimetics
Typically result in weight loss
How is exenatide usually given
Exenatide must be given by subcutaneous injection within 60 minutes before the morning and evening meals. It should not be given after a meal.
Major adverse effect of GLP-1 mimetics
Nausea and vomiting
Link to severe pancreatitis
How do DPP-4 inhibitors work
dipeptidyl peptidase-4, DPP-4 inhibitors increase levels of incretins (GLP-1 and GIP) by decreasing their peripheral breakdown
When do NICE recommend use of DPP-4 inhibitors
NICE suggest that a DPP-4 inhibitor might be preferable to a thiazolidinedione if further weight gain would cause significant problems, a thiazolidinedione is contraindicated or the person has had a poor response to a thiazolidinedione
Adverse effects of DPP-4 inhibitors
GI problems
Dizziness
Peripheral oedema
Pancreatitis
How do SGLT-2 inhibitors work
SGLT-2 inhibitors reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.
Examples of SGLT-2 inhibitors
Examples include canagliflozin, dapagliflozin and empagliflozin.
Important adverse effects of SGLT-2 inhibitors
urinary and genital infection (secondary to glycosuria). Fournier’s gangrene has also been reported
normoglycaemic ketoacidosis
increased risk of lower-limb amputation: feet should be closely monitored
Key potential beneficial side effect of SGLT-2 inhibitors
Weight loss
Metformin mechanism of action
increases insulin sensitivity
decreases hepatic gluconeogenesis
may also reduce gastrointestinal absorption of carbohydrates
Adverse effects of metformin
gastrointestinal upsets are common
reduced vit b12 absorption
lactic acidosis with severe liver disease or renal failure
Metformin contraindications
CKD(review)
Periods where there is tissue hypoxia(MI, AKI, severe dehydration)
iodine-containing x-ray contrast media
Advice regarding stopping metformin in imaging procedures using iodine-containing contrast
metformin should be discontinued on the day of the procedure and for 48 hours thereafter
Fasting glucose and HbA1c which indicate pre diabetes
a fasting plasma glucose of 6.1-6.9 mmol/l or an HbA1c level of 42-47 mmol/mol (6.0-6.4%) indicates high risk
Mx of pre diabetes
Lifestyle modification: weight loss, increased exercise, change in diet
at least yearly follow-up with blood tests is recommended
NICE recommend metformin for adults at high risk
What are the two main types of impaired glucose regulation
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
Definition of impaired fasting glucose
a fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG)
Definition of impaired glucose tolerance
impaired glucose tolerance (IGT) is defined as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
What should patients with IFG be offered
people with IFG should then be offered an oral glucose tolerance test to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn’t have diabetes but does have IGT
Example of a sulfonylurea
Gliclazide
Sulfonylureas mechanism of action
Sulfonylureas bind to and close ATP-sensitive K+ (KATP) channels on the cell membrane of pancreatic beta cells, which depolarizes the cell by preventing potassium from exiting. This depolarization opens voltage-gated Ca2+ channels. The rise in intracellular calcium leads to increased fusion of insulin granules with the cell membrane, and therefore increased secretion of mature insulin
Side effects of sulfonylureas
Abdominal pain; diarrhoea; hypoglycaemia; nausea
Weight gain
Which conditions cause lower than expected levels of HbA1c
Sickle cell anaemia
GP6D deficiency
Hereditary spherocytosis
Which conditions cause higher than expected levels of HbA1c
Vitamin B12/folic acid deficiency
IDA
Splenectomy
What is hyperosmolar hyperglycaemic state
Very high blood glucose levels (often over 40 mmol/L) develop as a result of a combination of illness, dehydration and an inability to take normal diabetes medication due to the effect of illness
Characterised by severe hyperglycaemia with marked serum hyperosmolarity, without evidence of significant ketosis
Characteristic features of HHS that differentiate it from DKA
Hypovolaemia.
Marked hyperglycaemia (30 mmol/L or more) without significant hyperketonaemia (<3 mmol/L) or acidosis (pH>7.3, bicarbonate >15 mmol/L).
Osmolality usually 320 mosmol/kg or more
Illnesses which can precipitate HHS
MI Infections Strokes Hyper/Hypothermia Pancreatitis PE
HHS symptoms
Signs of gross dehydration
Focal or global neurological dysfunction
Generalised weakness + visual impairment
Nausea and vomiting(less than dka)
Confusion
Seizures
IX in HHS
Urinalysis shows marked glycosuria with normal or slightly elevated ketones
Capillary glucose
Serum osmolarity usually >320mmol/L
ABG
Initial general measures in HHS mx
A-E
NG tube if impaired consciousness and risk of aspiration
Consider transfer to HDU
Alert acute med/diabetic team
Main principles of HHS management
Measure osmolality to monitor response to treatment
IV 0.9% NaCl
Low-dose IV insulin only once blood glucose no longer falling with iv fluids alone
Monitor for complications(fluid overload, cerebral oedema)
Prophylactic anticoagulation
Complications of HHS
Ischaemia or infarction VTE ARDS DIC Rhabdymylosis Cerebral oedema
How can serum osmolality
it can be estimated by 2 * Na+ + glucose + urea
criteria for bariatric surgery
BMI 40-50
Other conditions such as T2DM and HTN
What is whipple’s triad
should be present in cases of true hypoglycaemia:
hypoglycaemic symptoms, accompanying low blood glucose concentration, and resolution of symptoms after raising the blood glucose concentration to normal
When should fast-acting carbohydrates be used via mouth for mx of hypoglycaemia
Any patient with a blood-glucose concentration less than 4 mmol/litre, with or without symptoms, and who is conscious and able to swallow
Mx of hypoglycaemia which does not respond to fast-acting carbohydrates
intramuscular glucagon or glucose 10% intravenous infusion
Thiamine supplementation in alcoholics
When is glucagon not appropriate
Ineffective in patients whose liver glycogen is depleted(should not be used in anyone who has fasted for a prolonged period or has adrenal insufficiency)
Glucagon may be less ineffective in patients taking a sulfonylurea
Why is glucose 50% not recommended
it is hypertonic, thus increases the risk of extravasation injury, and is viscous, making administration difficult
Mx of hypoglycaemia if unresponsive to glucagon
glucose 10% intravenous infusion, or alternatively glucose 20% intravenous infusion should be given.
