Lipids

Lipids
Dr Thomas Fox
ST5 Diabetes and Emdocrinology
Derriford 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
ApolipoproteinB
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/Lstart 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 CoAreductase 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

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Lipids

by PeninsulaEndocrine on Aug 12, 2011

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Lipids — Presentation Transcript