1. Lipids Dr Thomas Fox ST5 Diabetes and Emdocrinology Derriford Hospital

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

3. 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

4. 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)

6. Familial Hypercholesterolaemia Heterozygous genetic condition Hypercholesterolaemia Premature CV disease Xanthomas Frequency 1:500 In UK only 15% of 115.000 diagnosed

8. Causes 3 major mutations LDL-R ApolipoproteinB An enzyme involved in the degradation of the receptor PCSK9

9. 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)

10. 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

11. 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

12. Management 2 LDL apheresis Liver transplantation

13. 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

14. 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/

16. 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

17. 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

18. Case study 2 HbA1C 9.5% TC 8.3 TG 20.66 HDL 1.0 LDL not result

19. 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/Lstart fenofibrate

20. 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

21. Statins HMG CoAreductase inhibitor Reduces intracellular cholesterol Increase LDLR and cholesterol uptake Reduces LDL Increases HDL

23. 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)

24. Omacor (omega 3 fatty acids) Reduces TG Reduced death - secondary prevention of MI

25. 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

26. Lifestyle Advice 30 mins exercise 3 times per week Stop smoking advice

27. 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