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Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
Lipids
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  • 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)
  • 5.
  • 6. Familial Hypercholesterolaemia
    Heterozygous genetic condition
    Hypercholesterolaemia
    Premature CV disease
    Xanthomas
    Frequency 1:500
    In UK only 15% of 115.000 diagnosed
  • 7.
  • 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/
  • 15.
  • 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
  • 22.
  • 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

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