Diabetes Treatment Flashcards
What are the different types of DM?
T1DM (beta cell destruction) T2DM (insulin resistance, beta cell dysfunction) Gestational DM T3c DM (pancreatic insufficiency) Steroid induced Diabetes MODY NDM
How is DM diagnosed in the PRESENCE of Sx?
Random plasma glucose < 11mol/L OR Fasting blood glucose > 7mmol/L OR 2hr plasma glucose >11mmol/L, 2hr after 75g OGTT
What Sx usually present for DM?
polyuria
polydipsia
weight loss
How is DM diagnosed in the ABSENCE of Sx?
Dx should NOT be based on one sample
2 samples on separate dates, of either: fasting, random, 2hr post-load
Which Dx criteria are often used for DM?
ADA 1997 diagnostic criteria
table that can be referred to
In the insulin deficient state, what metabolic compounds change?
- increased glucose
- increased FFAs (used as energy)
- increased lipase
- increased acetoacetic acid, cholesterol and TGs
What is the aim of insulin therapy?
- aim to normalise BMs
- prevent DM complications
- restore normal QoL
CAVEAT: can lead to hypoglycaemia
What is the relationship between hypoglycaemia and retinopathy risk? What does this mean?
inverse:
lower the risk of (severe) hypoglycaemia, the higher the risk of retinopathy
means that good glycemic control is NEEDED to minimise risk of retinopathy
How are exogenous insulin doses given to mimic endogenous secretion?
Basal level maintained with bolus (low, steady release of active insulin)
pre-prandial doses given, that are short-lived and rapidly acting
What are the normal endogenous insulin signalling patterns?
Biphasic insulin secretion
Two key elements:
- short-lived, rapidly generated peaks post-prandially
- Low/basal level of insulin to control glucose between meals
What are the short acting type of Insulin?
Actrapid
Humulin S
What are the different types of human insulin preparations?
- short acting
- rapid acting analogue
- medium and long acting insulin
- mixed insulins- long acting analogue mixture
- analogue mixture
What are the types of rapid-acting insulin in the UK?
- Novorapid (takes effect 10-20 mins after injection)
- Humalog (15-30’)
- Apidra (10-20’)
New Gen.
Fiasp. (~5’)
What are the types of basal insulins?
- Type 1 (Lantus, Levemir, Trojeo)
- Type 2 (intermediate acting (Humulin I, Insulatard)
- Gestational DM (intermediate acting, Humulin I)
- New generation (Degludec, Toujeo)
What are the 3 types of BD pre-mixed insulin regimes?
- once-daily basal insulin
- twice-daily mix-insulin
- basal-bolus therapy
What are the main types of error when administering insulin?
- prescribing errors
- delivery errors (of insulin in syringe to patient)
- dispensing error
What are the devices used for insulin delivery?
- insulin syringes
- cartridges for infusion pens
- pre-filled insulin pens
What are the side effects of using the same site for injection of SC insulin?
lipohypertrophy
What is the acute metabolic complication of insulin deficiency (T1DM)
DKA
- hyperglycaemia
- osmotic diuresis
- dehydration
- circulatory collapse
Caused by ketosis resulting in ketone body release
What are the ‘sick day rules’ for DM Mx?
- never stop insulin and check for ketones
- measure MBs 4x a day
- if BM < 11mol/L continues normal insulin
If BM 11-17 mol/L, add extra 4 units with meal - if BM >17mmol/L add extra 6 units with meals
- if nausea and vomiting and BM > 17mmol/L, call Dr
What are the benefits of using a intradermal continuous BM sensor?
- portable
- continuous monitoring
- Dr can monitor and discuss results with patients
What are common causes of hypoglycaemia?
- missed/delayed meals
- OD or mis-timed insulin or SU
- weight loss or frailty
- increased physical activity
- poor injection technique
- renal/hepatic impairment
- heat, EtOH, resolving infection
What are the autonomic signs of hypoglycaemia?
- hunger
- confusion
- sweating
- shaking
- dizziness
- tachycardia
Caused by adrenaline and GcG release
What are the neuroglycopaenic signs of hypoglycaemia?
- confusion
- drowsiness
- reduced coordination
- slurred speech
- atypical behaviour
- SEVERE: low GCS, coma, convulsions
When does impaired cerebral function usually present for hypo?
[glucose] < 3.5mmol/L
What is the immediate Rx for hypo?
- 15-20g glucose
- recheck BM 10-15’ later
- if BM < 4mmol/L, give glucose again
- recheck BM and document
- give slow acting carbs.
- analyse cause of hypo and r/v Rx
- Refer to DM specialist nurse
How do insulin pumps work?
Canule is inserted subcutaneously to deliver insulin
Insulin pump is connected to cannula via flexible tubing delivers insulin from pump to the infusion site
Continuous monitoring of capillary blood BM
What is the step-wise management for T2DM?
- diet and exercise
- oral monotherapy
- oral combination
- insulin ± oral agents
What happens hen there is failure of oral therapy for T2DM management?
will have to start on exogenous insulin
What are the hypoglycaemic agents used in T2DM Mx?
- Metformin (biguanides)
- sulphonylureas
- glitazones
- alpha-glucosidase inhibitors (e.g. acarbose)
- GLP1- analogues (subcut)
- DPPIV inhibitors
- SGLT2 inhibitos
- exogenous insulin
What is the mechanism of action for metformin?
(MULTIFACTORIAL)
- reduced hepatic gluconeogenesis
- reduced fatty acid oxidation
- increased kinase activity of INS receptor
- Increased translocation of GLUT-4 transporter
- increased glycogenesis
What is the mechanism of action for sulphonylureas?
- stimulates GSIS
- Potent (risk of hypo)
- Mediates closure of ATP-dependent K+ channels, promoting Ca2+ influx and GSIS
What are some GLP1 analogues/agonists?
- Exenatide
- Liraglutide
- Lixisenatide
In which physiological test, is the incretin effect most apparent?
IVGTT (or IPGTT in murine)
and OGTT
(incretin effect only seen when there is an enteral load of carbohydrate via gut promoting secretion of incretins from small intestine
What trend is seen for incretin response in T2DM patients?
reduced incretin response
compared to non-DM controls
What are the systemic impact of incretin hormones?
Beta cell
Enhances GSIS
Alpha cell
Suppresses GCG secretion
Liver
Suppresses hepatic gluconeogenesis
Stomach
Slows rate of gastric emptying
Brain
Promotes satiety and reduces appetite
What are Gliptins?
= DPP4 inhibitors
- alogliptin
- sitagliptin
- liagliptin
- saxagliptin
What is the mechanism of action of DPP4i?
DPP4 usually catalyses breakdown of active GLP-1
by inhibiting this process, half life of GLP-1 (and its actions) are prolonged
What are the longer term actions of GLP-1?
- increases insulin biosynthesis
- promotes beta cell differentiation
What are e.g. of SGLT2i?
- dapaglifozin
- canagliflozin
- empagliflozin
What is the mechanism of action for SGLT2i?
SGLT2 usually responsible for reabsorbing the majority of glucose in the PCT
By blocking this transporter, a larger proportion of glucose in blood is excreted renally
What is the risk associated with SGLT2i for DM Mx?
increased risk of UTIs
Because the urine is much more glucose rich - good nutrient pool for bacteria (e.g. E. coli)
Also should consider for routine urine dipsticks
Aside from T2DM, what else is metformin used to treat?
- PCOS
- NAFLD
What is the mechanism of action of metformin?
- activation of AMPK
- increases insulin sensitivity
- reduced hepatic gluconeogenesis
- reduces GI absorption of carbohydrates
What are the adverse effects of metformin?
- GI upsets (nausea, anorexia, diarrhoea)
- reduced vitamin B12 absorption
- lactic acidosis (can be with severe liver disease or renal failure)
What are the contraindications for metformin use?
- CKD
- tissue hypoxia can lead to concomitant lactic acidosis e.g. post-MI
- EtOH abuse
What is the mechanism of action of sulphonylureas?
- increasing insulin secretion
- decrease hepatic clearance of insulin
What are common side effects of suphonylureas?
- hypoglycaemia
- weight gain
What are the rarer adverse effects of sulphonylureas?
- hyponatraemia
- BM suppression
- hepatotoxicity
- peripheral neuropathy
What is the mechanism for developing hyponatraemia after taking sulphonylureas?
syndrome of inappropriate ADH secretion
