Insulin, diabetes and cholesterol

Question 1

Short acting insulin

Answer 1

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

Question 2

Intermediate acting insulin

Answer 2

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

Question 3

Long acting insulin

Answer 3

Insulin zinc suspension
Insulin glargine

Long acting insulin analogues that are taken once per day. Given as a SC injection.

Question 4

Common insulin regimes

Answer 4

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)

Question 5

Adverse effect of insulin therapy

Answer 5

Hypoglycaemia: due to insulin overdose or low calorie intake

Insulin antibodies (allergy)

Lipohypertrophy/atrophy: local allergic reaction causing lipid deposition

Weight gain

Question 6

Metformin

Answer 6

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)

Question 7

Sulphonylureas

Answer 7

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.

Question 8

Thiazolidinediones (glitazones)

Answer 8

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.

Question 9

Acarbose

Answer 9

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

Question 10

Incretins mimetics

Answer 10

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

Question 11

DPP4 inhibitors

Answer 11

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

Question 12

Adverse effects of insulin

Answer 12

Hypoglycaemia
Weight gain
Allergy
Lipohypertrophy and lipoatrophy

Question 13

Combination therapy for diabetes mellitus

Answer 13

Insulin + metformin, glitazones, gliptins

Question 14

NICE recommendations treatment of Diabetes mellitus

Answer 14

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)

Question 15

HbA1c criteria for diagnoss of diabetes

Answer 15

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.

Question 16

Situations where HbA1c is not suitable for diagnosis of diabetes

Answer 16

Children and young adults

Patients with suspected type 1 diabetes

Patients at risk who are acutely ill

Pregnancy

Patients with anaemia

Question 17

Criteria for diagnosing diabetes

Answer 17

Symptoms plus:

1. random blood glucose > 11.1 mmol/l
2. fasting plasma glucose >7 mmol/l
3. 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.

Question 18

Diabetes care checklist

Answer 18

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

Question 19

Treatment of DKA

Answer 19

Fluids

K+ replacement

Glucose if hypoglycaemia

Sliding scale insulin infusion

Treat underlying cause

Monitor blood glucose, blood gases and electrolytes

Question 20

Orlistat

Answer 20

Primary function is to prevent absorption of fats. Inhibits pancreatic lipase, which reduces caloric intake

Question 21

Clinical indications for lipid lowering therapy

Answer 21

After MI

In patients with known CHD

Primary prevention of CV event

Diabetes mellitus, reduces CV risk

Question 22

Classes of lipid lowering drugs

Answer 22

Statins

Fibrates

Inhibitoes of cholesterol absorption

Nicotinic acid derivatives

Omega 3

Question 23

Statins

Answer 23

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

Question 24

Fibrates

Answer 24

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

Question 25

Cholesterol inhibitors

Answer 25

reduces cholesterol absorption and decreases LDLs from the duodenum. Doesn’t affect absorption of fat soluble vitamins

Question 26

What is the mechanism of action of nicotinic acid in lowering cholesterol?

Answer 26

Inhibites hepatic VLDL secretion, reduces triglyceride and LDL levels and increases HDLs.

Adverse effects: flusing, palpitations, GI disturbance

Question 27

How do anionic exchange resins lower cholesterol

Answer 27

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.

Question 28

Drug given to maintain blood glucose in gestational diabetes

Answer 28

Metformin