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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