Insulin, diabetes and cholesterol Flashcards
Short acting insulin
Soluble insulin. Onset 30 mins. Administed IV in emergency but effects are shorter (humilin S, actrapid)
Insulin lispro (humalog) and insulin aspart (novorapid) are insulin analogues. These have a faster onset and shorter action
Intermediate acting insulin
Isophane insulin (humulin I). Suspension of insulin-protamine complex. Enzymes degrade protamine and the insulin is absorbed.
Onset in 1-2hrs, peaks at 4-12hes but effects last for 24hrs
Long acting insulin
Insulin zinc suspension
Insulin glargine
Long acting insulin analogues that are taken once per day. Given as a SC injection.
Common insulin regimes
OD: long acting or intermediate insulin at bedtime (glargine)
BD: Biphasic insulin injected 2x before breakfast and evening meal e.g. lispro
Basal bolus: intermediate/ long acting given at night. Short acting at mealtimes.
Insulin infusion pump (lispro, aspart)
Adverse effect of insulin therapy
Hypoglycaemia: due to insulin overdose or low calorie intake
Insulin antibodies (allergy)
Lipohypertrophy/atrophy: local allergic reaction causing lipid deposition
Weight gain
Metformin
Biguanide. 1st line treatment for Diabetes mellitus
Decreases gluconeogenesis and glycogenolysid. Decreases carbohydrate absoption.
Increases glucose uptake and fatty acid oxidation in muscle. Increases GLUT4 Receptors in skeletal muscle.
Reduces appetite by acting on GLP1 pathway
Half-life 3hrs. Excreted unchanged renally. Contraindicated in renal patients. (or any major organ disease)
Adverse effects: nausea, vomiting, B12 malabsorption (may exacerbate neuropathy)
Sulphonylureas
Tolbutamide, glibenclamide, gliclazide
Blocks K-ATP channels in beta cells of the pancreas, causing depolarisation and insulin release.
Causes weight gain
Only effective if beta cells are still functioning. Risk of hypoglycaemia and beta cell burnout.
Effects enhanced in patients with poor renal function and elderly.
Thiazolidinediones (glitazones)
Increase sensitivity to insulin by binding to PPAR-gamma and increasing transcription of insulin sensitive genes.
Decreases gluconeogenesis, increases glucose uptake in muscles and incrases fatty acid oxidation
Also activates adiposites - weight gain.
Adverse effects: hepatotoxic, causes weight gain, fluid retention and GI distubance. Rosiglitazone icnraeses CV events
Because the affect transcription, effects may not be apparent fro 3 months. Not all patients respond.
Acarbose
alpha-glucosidate inhibitor
Enzyme normally breaks down carbohydrates in the GUT. Inhibtion causes decreased breakdown and absorption.
Used in patients whose diabetes in inadequaely controlled by diet and other agents.
causes flatulence and diarrhoea
Incretins mimetics
Mimick the effects of GLP-1
GLP-1 is released from L-cells in the ileum and lowers blood glucose in response to meals by increasing insulin, decreasing glucagon and slowing gastric emptying. Also acts on the brain to promote satiety and reduces appetite.
e.g. exanatide, lixisenatide, liraglutide
Given as subcutanous injection.
Weight neutral. Can cause hypoglcaemia and GI disturbance
DPP4 inhibitors
Gliptins
GLP-1 is normally rapdily broken down by DPP4 within 2 hrs. Gliptins are synthetic drugs that competitively inhibit DPP4 to increase GLP1 and prolong incretin response (normally reduced in diabetics)
Administered orally.
e.g. sitagliptin
Adverse effects of insulin
Hypoglycaemia
Weight gain
Allergy
Lipohypertrophy and lipoatrophy
Combination therapy for diabetes mellitus
Insulin + metformin, glitazones, gliptins
NICE recommendations treatment of Diabetes mellitus
Lifesyle measures - diet, weight loss, exercise
Drug treatment given if HbA1c is over 6.5%. Metformin 1st line.
Consider sulfonylureas if metformin not tolerated, is patient is not overweight and if blood glucose is very high (rapid response required).
Second line: Sulphonylurea, DPP-4 inhibitor, Thiazolidinedione
If HbA1c > 7.5 add insulin or gliptin (insulin+metformin+sulfonylurea)
HbA1c criteria for diagnoss of diabetes
HbA1c of >48 mmol (6.5%) is diagnostic of diabetes.
Value less than this does not rule out diabetes, should be checked with glucose tests.
Situations where HbA1c is not suitable for diagnosis of diabetes
Children and young adults
Patients with suspected type 1 diabetes
Patients at risk who are acutely ill
Pregnancy
Patients with anaemia
Criteria for diagnosing diabetes
Symptoms plus:
- random blood glucose > 11.1 mmol/l
- fasting plasma glucose >7 mmol/l
- 2hr plasma glucose concentration >11mmol/l in an OGTT
Two different tests should be performed on different days and value should be in the normal range.
Diabetes care checklist
Advice: diet, weight control, physical activity, no smoking
Blood pressure: <130/80
Cholesterol: Total <4, LDL<2
Diabetes control: HBA1c <6.5
Eyes: check yearly
Feet: check yearly
Guardian drugs: aspirin, ACEr/ARB
Treatment of DKA
Fluids
K+ replacement
Glucose if hypoglycaemia
Sliding scale insulin infusion
Treat underlying cause
Monitor blood glucose, blood gases and electrolytes
Orlistat
Primary function is to prevent absorption of fats. Inhibits pancreatic lipase, which reduces caloric intake
Clinical indications for lipid lowering therapy
After MI
In patients with known CHD
Primary prevention of CV event
Diabetes mellitus, reduces CV risk
Classes of lipid lowering drugs
Statins
Fibrates
Inhibitoes of cholesterol absorption
Nicotinic acid derivatives
Omega 3
Statins
Inhibit HMG-CoA reductase.
Reversible and competitive
Decreases hepatic cholesterol synthesis and upreglates LDL receptors which increase clearance of LDLs from the plasma into the lievr.
e.g. simvastatin, lovastatin. Arvostatin = long acting
Used in primary prevention of arterial disease in patients at high risk ogf MI, secondary prevention of MI and stroke in patients with atheroma
Fibrates
lipid loweing agent
Reduces VLDLs and therefore triglycerides.
Causes a reduction in LDL and increase in HDL.
Increases transcription of lipoprotein lipase and apoproteins.
First line drugs in patients with a very high plasma triglyceride
e.g. gemifibrosil, benzafibrate
Adverse effects: myositis, poor clearance in renal patients
Cholesterol inhibitors
reduces cholesterol absorption and decreases LDLs from the duodenum. Doesn’t affect absorption of fat soluble vitamins
What is the mechanism of action of nicotinic acid in lowering cholesterol?
Inhibites hepatic VLDL secretion, reduces triglyceride and LDL levels and increases HDLs.
Adverse effects: flusing, palpitations, GI disturbance
How do anionic exchange resins lower cholesterol
Increase excretion of bile acids.
Binds to bile acids forming an insoluble complex. This causes more cholesterol to be converted into bile acids and increases HMG-CoA reductase activity.
Resins are not absorbed, therefore cause GI effects: bloating, constipation
Given as a powder taken with liquid.
e.g. cholestyramine, colestipol
Also reduces absorption of other drugs. Other drugs should be taken 1hr before.
Drug given to maintain blood glucose in gestational diabetes
Metformin
