LIPIDS

Dr Thomas FoxST5 Diabetes and EmdocrinologyDerriford Hospital

Outline

Lipid physiology Familial Hypercholesterolamia Type I Diabetes Type II Diabetes Primary prevention Case study Pharmacotherapy

Lipid physiology

TG - fuel source Cholesterol

Steroid hormone synthesis Cell membrane synthesis Bile acid synthesis

Apoliporpteins Assembly of lipoproteins Structural integrity Enzyme co-activators Receptor ligands

Lipoproteins

Packages to transport insoluble lipids in the blood Chylomicrons (carry TG from gut to

adipose tissues and skeletal muscle) Chylomicron remnants VLDL (carries TG from liver) LDL (carries cholesterol fromliver) IDL HDL (carries cholestero to the liver)

Familial Hypercholesterolaemia

Heterozygous genetic condition Hypercholesterolaemia Premature CV disease Xanthomas

Frequency 1:500

In UK only 15% of 115.000 diagnosed

Causes

3 major mutations

LDL-R Apolipoprotein B An enzyme involved in the degradation

of the receptor PCSK9

Diagnosis

On 4 clinical criteria Possible FH Definite FH These patients are screened for DNA

mutation If DNA mutation found in index case then

100% sensitive and specific

Cascade testing (first and second degree)

Cascade Screening

Relatives of FH should be screened before age 10 with Genetics if mutation known LDLC if mutation unknown

Do not use Framingham risk

Management

High intensity statin therapy for all FH lifelong add in ezetemibe

Specialist referral Advice RE pregnancy Aim to reduce LDL C by 50% from

baseline Lifestyle advice Homozygous FH

Consider referral to cardiologist

Management 2

LDL apheresis

Liver transplantation

Lipid management in Type I diabetes

Patients with Increased ACR, or 2 or more features of metabolic syndrome

BP>135/80 HDL < 1.2 (women) and 1.0 (men) TG > 1.8 Waist circumference 80cm (women) 100cm (Men) Evidence of insulin resistance (>1 Unit/kg/day)

Smoking, age, FH of CVD Should be assumed to be at high arterial

risk and started on statin

Lipid management in type II Diabetes

IF >40 years consider high risk of CVD unless Not overweight Normotensive (<140/80mm/Hg) No microalbuminuria Non-smoker No high risk lipid profile No history or FHx of CVD

Then use UKPDS risk engine http://www.dtu.ox.ac.uk/riskengine/

Lipid management in type II Diabetes

If <40 years use statins if at high risk of CVD

Once started on cholesterol lowering therapy Simvastatin 40mg Reassess after 3 months Yearly measurement thereafter Aim for

LDL< 2.0mmol/L TC < 4mmol/L

Case study 1

50 year-old male Type II diabetic Obesity (BMI 36) Recurrent pancreatitis

Treatments NR 80 units tds Glargin 180 units at night Fenofibrate 267mg Metformin 850mg bd Aspirin

Case study 2

HbA1C 9.5% TC 8.3 TG 20.66 HDL 1.0 LDL not result

TG and type II diabetes

If high TG perform full fasting sample Assess secondary causes

EtOH Hypothyroidism Renal impairment Hyperglycaemia

If TG remain>4.5mmol/L start fenofibrate

Primary prevention

In those aged 40-75 If CV risk is >20% in next 10years treat

after modifying other risk factors GPs should screen their population and

use risk assessment Treatment with simvastatin 40mg and

no need to recheck or treat to target LDL

Do not use fibrate, ezetemibe or anion exchange resins

Statins

HMG CoA reductase inhibitor Reduces intracellular cholesterol Increase LDLR and cholesterol

uptake

Reduces LDL Increases HDL

Other drugs

Niacin/nicotinic acid (Niaspan) Decreases hepatic VLDL production Reduces LDL and TG

Fibrates Increase lipoprotein lipase activity

Both increase HDL

Ezetemibe Reduces cholesterol absorption from gut Reduces LDL (no effect on HDL)

Omacor (omega 3 fatty acids) Reduces TG Reduced death - secondary prevention

of MI

Dietary advice

Fat should make up<30% of calorie intake

Saturated fat <10% of calorie intake

Cholesterol <300mg/day

5 a day

2 portions oily fish per week

Lifestyle Advice

30 mins exercise 3 times per week Stop smoking advice

Summary

Statins are an effective treatment for hypercholesterolaemia

Treat patients if C risk >20% over 10years

Almost all type II diabeteics are considered high risk and should be treated to targets of TC <4mmol/L LDL <2mmol/L