HALF DONE Drugs in Diabetes Flashcards
What are the hormone secreting cells of the pancreas, and what glucose regulating hormones do they secrete?
Islets of Langerhans:
- Insulin (β/B cells)
- Glucagon (α/A cells)
- Somatostatin (δ-cells)
What are three other glucose regulating hormones and their sources?
- Adrenaline (adrenal medulla)
- Glucocorticoids (adrenal cortex)
- Growth hormone (pituitary)
What is the normal range for glucose in the blood?
3.5 - 5.5 mmol/L
How does insulin, glucagon, adrenaline, glucocorticoids and growth hormone effect blood glucose?
Stimulated by high blood glucose, insulin decreases blood glucose.
The 4 others - glucagon, adrenaline, glucocorticoids and growth hormone - cause increased blood glucose levels.
Describe the 3 stimuli for the release of insulin.
Insulin release is stimulated by:
- Increased blood glucose
- Amino acids and FAs
- Peptide gut hormones (Incretins)
Once stimulus for insulin release is received, what happens next?
Insulin is stored in β cell granules as pro-insulin.
Protease cleaves pro-insulin, releasing insulin and a C-peptide
What are insulin’s metabolic targets and its action?
- CHO
- Fat
- Protein
CHO:
- Decrease gluconeogenesis and glycogenolysis
- Increase glycolysis and glycogenolysis
- Increase glucose uptake
Protein
- Increase AA uptake
- Increase protein synthesis
- Decrease protein breakdown
Fat
- Increase fat storage (lipogenesis)
- Decrease fat breakdown (lipolysis)
What type of receptor is the insulin receptor, and what is it’s major intracellular substrate?
Insulin receptor - receptor tyrosine kinase.
Insulin binding = dimerisation and auto-phosphorylation.
Major substrate = IRS-1
- Activates pathways to store energy
- Glucose into cells
- GLycogen synthase
What is diabetes mellitus and how can it present?
Diabetes mellitus is a group of disorders characterised by hyperglycaemia, caused by insulin deficiency.
Can present with:
- Polyuria, polydipsia, polyphagia
- Weight loss
- Poor healing and infections (e.g. foot ulcer)
What is the lab measurement diagnosis of diabetes and prediabetes?
Diabetes:
- Fasting blood glucose (FBG) >7.0mmol/L
- 2H after meal (OGTT) >11.1mmol/L
Pre-diabetes:
- FBG = 5.6 - 6.9 mmol/L
- OGTT = 7.8 - 11.0 mmol/L
What is glycated haemoglobin?
What levels are normal/diabetes/pre-diabetes?
Covalent modification of haemoglobin that occurs with raised blood glucose.
- Reflect long term measurement of glucose levels
- Normal = <6%
- Pre-diabetes = 6.0 - 6.4%
- Diabetes = >6.5%
What type of tissue effects occur in diabetes?
Catabolic effets:
- Opposite of what insulin does to CHO, fat and protein
- Increased blood sugar
- Increased blood lipids
- Increased protein breakdown
What are the two types of diabetes and their causes?
Type 1 DM
- ABSOLUTE insulin deficiency
- Auto-immune destruction of β cells
- Juveline onset
Type 2 DM
- RELATIVE insulin deficiency
- Peripheral resistance to normal insulin levels through progressive decrease in β cell function/mass
- Associated with obesity
What are the acute and chronic complications of diabetes?
Acute: Diabetic ketoacidosis
- Fats are used for energy, producting acetyl-CoA which is converted to ketones (decreased pH, hyperosmolar state)
Chronic: Vascular disease
- Macrovascular (HTN, heart attack, stroke)
- Microvascular (eyes, kidney)
What is the significance of vascular complications in diabetics?
75% of diabetics die from a cardiovascular event.
Describe two microvascular and two macrovascular complications of diabetes
Microvascular
- Eyes: Diabetic retinopathy, cataracts, glaucoma → blindness
- Kidneys: Diabetic nephropathy → decreased GFR
Macrovascular
- Hypertension
- Myocardial infarct
Why are foot ulcers common in diabetics?
Diabetic neuropathy prevents patient from feeling pain. Combined with immunosuppression, the ulcer formation, and subsequent infection of the ulcer is common and costly.
Can result in gangrene and amputation.
What are the three fatures of T1D treatment?
- Insulin treatment
- Diet tracking and exercise
- Monitoring of glycaemic control
Describe the administration strategy of insulin therapy.
Insulin is administered subcutaneously. Injection sites must be rotated to prevent scarring that affects uptake.
What are the three types of insulin, with examples, peak time and duration?
Ultra rapid acting - peaks @ 30-60mins, duration = 3-4 hours
Examples: Aspart, Lispro
Short acting - peaks @ 1-2 hours, duration = 6-8 hours
Examples: Regular/Neutral
Long acting - no peak (flat action), duration = 24h
Examples: Glargine, Detemir
Onset is half of minimum peak time.
Onset for long acting = 1 - 2 hours.
What are the two main types of T1D insulin treatment to mimic normal insulin levels?
Ideal control involves:
- Constant basal insulin production
- Post-prandial insulin surge
Basal-Bolus regimen
- Long acting insulin at night (basal)
- Prandial rapid acting insulin (bolus)
Insulin Pump
- Basal infusion + patient activated bolus
- Decreasd day-to-day glycaemic varaibility
What is intensive insulin therapy?
What are the positives and drawbacks?
Intensive insulin pump or injection therapy.
Results in much longer time until GFR decreases over lifespan, compared to conventional diabetes therapy.
However, there is an increased risk of hypoglycaemic events, and fear of these can reduce willingness to do intestine therapy.
What are three side effects of insulin therapy?
- Hypoglycaemia
- Weight gain (common, compliance issue)
- Injection site scarring and lipohypertrophy (poor absorption)
How do you treat varying degrees of hypoglycaemia from insulin therapy?
Mild hypoglycaemia? Have a sweet snack
Severe hypoglycaemia? Glucose, glucagon (oral if safe, IV)
