Diabetes Mellitus Management Flashcards
What advice would you give to someone with diabetes?
Exercise to increase insulin sensitvity Health eating low saturated fats, low sugar, high starch, moderate protein Avoid 'diabetic' foods Lose weight Reduced energy intake Stop smoking Limit salt intake Foot care Attend reviews
What diet would you recommend?
Low saturated fat Low sugar High starch High fibre Low salt
How is T1 DM managed?
Monitor HbA1c - target of 48mmol/mol 6.5%
Self monitoring, 4x a day
Offter multiple daily injection basal-bolus insulin regimens
Twice daily insulin
Rapid acting insulin analogues injected before meals for mealtime insulin replacement
How is T1 DM managed?
Monitor HbA1c - target of 48mmol/mol 6.5%
Self monitoring, 4x a day
Offer multiple daily injection basal-bolus insulin regimens,
Twice daily insulin,
Rapid acting insulin analogues injected before meals for mealtime insulin replacement
Blood glucose targets:
5-7mmol/l on walking and
4-7mmol/L before meals
Add metformin if BMI>25kg/m2
How is T2DM managed? What are the HbA1c targets for each?
Lifestyle 48mmol/mol 6.5%
Lifestyle + metformin 48mmol/mol 6.5%
Any drug which may cause hypoglycaemia (e.g. lifestyle+sulfonylurea) 53mmol/mol 7%
Already on one drug but HbA1c has risen to 58mmol/mol (7.5%) - 53mmol/mol (7%)
What is second line? when do you consider this?
If HbA1c > 58mmol/mol (7.5%), dual therapy:
Metformin + DPP4 inhibitor (gliptin)
MEtformin + pioglitazone
Metformin + sulfonylurea
Metformin + SGLT2 inhibitor (glifazon)
Or if intolerant/CI to metformin then
Gliptin (DPP4i) + sulfonyurea
Gliptin (DPP4i) + pioglitazone
Pioglitazone + sulfonylurea
What is third line? when do you consider this?
If HbA1c > 58mmol/mol (7.5%) on dual therapy, triple therapy with: Meformin, DPP4i (gliptin), sulfonylurea Metformin, pioglitazone, sulfonylrea Metformin, sulfonylurea, SGLT2i Metformin, pioglitazone SGLT2i
OR
Insulin based therapy
If metformin not tolerated and HbA1c > 58mmol/mol (7.5%) on dual therapy—> Insulin based therapy
What if triple therapy is not effective, not tolerated or contraindicated and BMI>35
Metformin
Sulfonylurea
GLP1 mimetic
What is the MOA, route and SE, CI of metformin?
Biguanide
Reduces insulin resistance – increases receptor sensitivity. Inhibits hepatic gluconeogenesis. Stimulated uptake of glucose into muscle and adipose. Decreases absorption of glucose from the GI tract. Also reduces LDLs and VLDLs.
Oral
SE:
GI upset, abdo pain ,nausea, diarrhoea
Lactic acidosis
(weight neutral, no risk of hypos)
CI:
Hepatic, renal or cardiac disease
eGFR <30ml/min due to risk of lactic acidosis
Renal elimination
Half life 4 hours
What is the MOA, route, SE, example of sulfonylurea?
Increase insulin secretion from pancreatic beta cells.
Supplement endogenous insulin: bind to and antagonise K+/ATP channels in beta cells which reduces potassium currents, depolarising the cell, increasing calcium entry, increasing exocytosis of insulin
Oral
E.g. Glicazide, glimepride
SE: Hypoglycaemia Weight gain Hyponatraemia GI disturbance
DDI: Highly bound to plasma proteins
Longer duration but less fine-tuned control
What is the MOA, route, SE, example of thiazolidinediones?
AKA glitazone
Pioglitazone
Bind the peroxisome proliferator-activated receptor-γ (PPAR-γ) which is a nuclear hormone receptor. This then binds the retinoid X receptor, and the complex goes on to upregulate genes involved in insulin signalling.
Increase insulin senstivity
Promote adipogenesis and fatty acid uptake
Oral OD
SE Weight gain Fluid retention - oedema Increases LDL/HDL (no risk of hypoglycaemia)
CI: heart failure
DDI: Heavily bound to plasma proteins – affected by competitive binding
Longer duration but less fine tuned control
What is the MOA, route, SE, example of DPP4 inhibitors? AKA?
GLIPTINS (sitgliptin)
Increases incretin levels which inhibit glucagon secretion by blocking DPP4 which destroys incretin. Inhibits DPP-4 which breaks down GLP-1, has the same action as GLP-1 analogues therefore.
Oral
SE
Risk of pancreatitis but well tolerated
What is the MOA, route, SE, example of SLGT2 inhibitors? AKA?
Gliflozins e.g. empagliflozin
Block reabsorption of glucose in the proximal convoluted tubule and promotes excretion of excess glucose in the urine
Oral
UTI
Thrush
Weight loss
hypoglycaemia
What is the MOA, route, SE, example of GLP1 agonists, indication?
Tides (e.g. exenatide, liraglutide)
Incretin mimetics
Incretins are gut peptides that augment insulin release
Increases insulin levels, decreases glucagon levels, decreases appetite, slows gastric emptying
Patients must have BMI > 35 and psychological or medical problems associated with obesity.
Would benefit from weight loss
OR BMI < 35kg/m2 and insulin is unacceptable because of occupational implications or weight loss would benefit other comorbidities
To continue: 1% reduction in HbA1c and 3% reduction in weight after 6 months
Subcut
Nausea and vomiting (decreased gastric motility)
Pancreatitis
Weight loss
What does incretin do? Which medications work on incretin pathway?
Inhibits glucagon secretion and stimulate insulin release
Glucagon is responsible for raising blood sugar by promoting gluconeogenesis, glycogenolysis, break down of fatty acids
DPP4-inhibitors stop DPP4 enzymes inactivating incretins increase incretin levels, inhibiting glucagon secretion
GLP-1 agonists imitate incretin, inhibiting glucagon secretion and increase insulin release
Which diabetic medications result in weight loss?
SGLT2-inhibitors (-gliflozins)
GLP-1 agonists (-tides)
Which diabetic medications may cause weight gain?
Sulfonylureas (glicazide, gliceride)
Thiazolidinedions (pioglitazone)
Insulin
Which diabetic medications may cause weight gain?
Sulfonylureas (glicazide, gliceride)
Thiazolidinedions (pioglitazone)
Insulin
What insulin types are there?
Short medium and long acting
Pre-mixed with short acting and long acting
What are common insulin regimes?
BD - twice daily premixed insulins by pen - good for regular lifestyle
QDS - before meals ultra fast insulin + bedtime long acting analogue - good for flexible lifestyle adjusting doses with meal size or exercise
Once daily before bed long-acting insulin: good initial insulin regimen when switching from tablets in T2DM
What is DAFNE?
Dose adjusting for Normal Eating
Training in flexible, intensive insulin dosing improves glycemic control and well-being
What should you tell diabetics if they become unwell?
Continue medication/insulin
Increase frequency of blood glucose monitoring to four hourly or more frequent
Encourage fluid intake - 3L in 24 hours
May need to take sugary drinks to maintain carbohydrate intake if struggling to eat
Sick day supply box
Get help from nurse or GP if concerned and glucose levels are rising
Admit if vomiting, dehydrated, ketotic, child or pregnant
What can you consider if attempts to reach HbA1c targets with daily injections have resulted in hypoglycaemia or unable to achieve target?
Insulin pumps
What are the side effects of insulin therapy? How can these be addressed?
Hypoglycaemia:
teach signs of hypoglycaemia - sweating, anxiety, blurred vision, confusion, aggression
take 10-20g of short acting carbohydrates
glucagon kit for emergency
Lipodystrophy:
Atrophy of the subcutaneous fat
Prevented by rotating the injection site
What are the classes of oral hypoglycaemics?
Biguanide - metformin Sulfonylureas - Gliclizide Thiazoledinediones - Pioglitazone DPP4 inhibitors - sitagliptin GLP-1 analogues - eventide SGLT2 inhibitors - dpaagliflozin
What are the classes of insulin?
Ultra-rapid - novorapid/humalog - 5-15 mins
Short acting - Actrapid/humulin S - 30-60 min
Intermediate acting - isophane 2-4 hours
Long acting - insulin glargine 2-6 hours
What are the MOA and ADRs of ultra-rapid insulin?
Onset in 5-15 minutes.
Replaces endogenous insulin – stimulates uptake of glucose into liver, muscle and adipose tissue, decreases hepatic glucose output, inhibits glycogenolysis, promotes fat uptake
Hypoglycaemia, possibly leading to diabetic coma Weight gain Lipohypertrophy Injection site Discomfort Insulin allergy
What are the MOA and ADRs of short acting insulin?
Start to work in 30-60 minutes.
Replaces endogenous insulin – stimulates uptake of glucose into liver, muscle and adipose tissue, decreases hepatic glucose output, inhibits glycogenolysis, promotes fat uptake
Hypoglycaemia, possibly leading to diabetic coma Weight gain Lipohypertrophy Injection site Discomfort Insulin allergy
What are the MOA and ADRs of intermediate acting insulin?
Start to work in 2-4 hours.
Replaces endogenous insulin – stimulates uptake of glucose into liver, muscle and adipose tissue, decreases hepatic glucose output, inhibits glycogenolysis, promotes fat uptake
Hypoglycaemia, possibly leading to diabetic coma Weight gain Lipohypertrophy Injection site Discomfort Insulin allergy
What are the MOA and ADRs of long acting insulin?
Start to work in 2-6 hours.
Replaces endogenous insulin – stimulates uptake of glucose into liver, muscle and adipose tissue, decreases hepatic glucose output, inhibits glycogenolysis, promotes fat uptake
Hypoglycaemia, possibly leading to diabetic coma Weight gain Lipohypertrophy Injection site Discomfort Insulin allergy
TReatment streps in T2DM combination therapy
• Lifestyle & diet
• If HbA1c is still greater than 6.5%:
o Metformin
• If HbA1c is still greater than 6.5%:
o add Sulphonylurea (glibenclamide)
• If HbA1c is still greater than 7.5%
o add Thiazolidinediones
o Or insulin
• If HbA1c is still greater than 7.5%
o Insulin + metformin + sulphonylurea
What do you need to monitor in DM?
HbA1c - glycosylated Hb blood glucose over 120 days
Renal, hepatic, CVS and near function to determine signs of vascular damage
What medication would you give to someone who would benefit from weight loss?
Exenatide (GLP1 agonist)
