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  1. 1. Lipids<br />Dr Thomas Fox<br />ST5 Diabetes and Emdocrinology<br />Derriford Hospital<br />
  2. 2. Outline<br />Lipid physiology<br />Familial Hypercholesterolamia<br />Type I Diabetes<br />Type II Diabetes<br />Primary prevention<br />Case study<br />Pharmacotherapy<br />
  3. 3. Lipid physiology<br />TG - fuel source<br />Cholesterol<br />Steroid hormone synthesis<br />Cell membrane synthesis<br />Bile acid synthesis<br />Apoliporpteins<br />Assembly of lipoproteins<br />Structural integrity<br />Enzyme co-activators<br />Receptor ligands<br />
  4. 4. Lipoproteins<br />Packages to transport insoluble lipids in the blood<br />Chylomicrons (carry TG from gut to adipose tissues and skeletal muscle)<br />Chylomicron remnants<br />VLDL (carries TG from liver)<br />LDL (carries cholesterol fromliver)<br />IDL <br /> HDL (carries cholestero to the liver)<br />
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  6. 6. Familial Hypercholesterolaemia<br />Heterozygous genetic condition<br />Hypercholesterolaemia<br />Premature CV disease<br />Xanthomas<br />Frequency 1:500<br />In UK only 15% of 115.000 diagnosed<br />
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  8. 8. Causes<br />3 major mutations<br />LDL-R<br />ApolipoproteinB<br />An enzyme involved in the degradation of the receptor PCSK9 <br />
  9. 9. Diagnosis<br />On 4 clinical criteria<br />Possible FH<br />Definite FH<br />These patients are screened for DNA mutation<br />If DNA mutation found in index case then 100% sensitive and specific<br />Cascade testing (first and second degree)<br />
  10. 10. Cascade Screening<br />Relatives of FH should be screened before age 10 with<br />Genetics if mutation known<br />LDLC if mutation unknown<br />Do not use Framingham risk<br />
  11. 11. Management<br />High intensity statin therapy for all FH lifelong<br />add in ezetemibe<br />Specialist referral<br />Advice RE pregnancy<br />Aim to reduce LDL C by 50% from baseline<br />Lifestyle advice<br />Homozygous FH<br />Consider referral to cardiologist<br />
  12. 12. Management 2<br />LDL apheresis<br />Liver transplantation<br />
  13. 13. Lipid management in Type I diabetes<br />Patients with <br />Increased ACR, or<br />2 or more features of metabolic syndrome<br />BP>135/80<br />HDL < 1.2 (women) and 1.0 (men)<br />TG > 1.8<br />Waist circumference 80cm (women) 100cm (Men)<br />Evidence of insulin resistance (>1 Unit/kg/day)<br />Smoking, age, FH of CVD<br />Should be assumed to be at high arterial risk and started on statin<br />
  14. 14. Lipid management in type II Diabetes<br />IF >40 years consider high risk of CVD unless<br />Not overweight<br />Normotensive (<140/80mm/Hg)<br />No microalbuminuria<br />Non-smoker<br />No high risk lipid profile<br />No history or FHx of CVD<br />Then use UKPDS risk engine<br />
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  16. 16. Lipid management in type II Diabetes<br />If <40 years use statins if at high risk of CVD<br />Once started on cholesterol lowering therapy<br />Simvastatin 40mg<br />Reassess after 3 months<br />Yearly measurement thereafter<br />Aim for <br />LDL< 2.0mmol/L<br />TC < 4mmol/L<br />
  17. 17. Case study 1<br />50 year-old male<br />Type II diabetic<br />Obesity (BMI 36)<br />Recurrent pancreatitis<br />Treatments<br />NR 80 units tds<br />Glargin 180 units at night<br />Fenofibrate 267mg<br />Metformin 850mg bd<br />Aspirin<br />
  18. 18. Case study 2<br />HbA1C 9.5%<br />TC 8.3<br />TG 20.66<br />HDL 1.0<br />LDL not result<br />
  19. 19. TG and type II diabetes<br />If high TG perform full fasting sample<br />Assess secondary causes<br />EtOH<br />Hypothyroidism <br />Renal impairment<br />Hyperglycaemia<br />If TG remain>4.5mmol/Lstart fenofibrate<br />
  20. 20. Primary prevention<br />In those aged 40-75<br />If CV risk is >20% in next 10years treat after modifying other risk factors<br />GPs should screen their population and use risk assessment<br />Treatment with simvastatin 40mg and no need to recheck or treat to target LDL<br />Do not use fibrate, ezetemibe or anion exchange resins<br />
  21. 21. Statins<br />HMG CoAreductase inhibitor<br />Reduces intracellular cholesterol<br />Increase LDLR and cholesterol uptake<br />Reduces LDL <br />Increases HDL<br />
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  23. 23. Other drugs<br />Niacin/nicotinic acid (Niaspan)<br />Decreases hepatic VLDL production<br />Reduces LDL and TG<br />Fibrates<br />Increase lipoprotein lipase activity<br />Both increase HDL<br />Ezetemibe<br />Reduces cholesterol absorption from gut<br />Reduces LDL (no effect on HDL)<br />
  24. 24. Omacor (omega 3 fatty acids)<br />Reduces TG<br />Reduced death - secondary prevention of MI<br />
  25. 25. Dietary advice<br />Fat should make up<30% of calorie intake<br />Saturated fat <10% of calorie intake<br />Cholesterol <300mg/day<br />5 a day<br />2 portions oily fish per week<br />
  26. 26. Lifestyle Advice<br />30 mins exercise 3 times per week<br />Stop smoking advice<br />
  27. 27. Summary<br />Statins are an effective treatment for hypercholesterolaemia<br />Treat patients if C risk >20% over 10years<br />Almost all type II diabeteics are considered high risk and should be treated to targets of<br />TC <4mmol/L<br />LDL <2mmol/L<br />