| Management
of diabetic dyslipidemia |
Priorities for lowering
lipids/lipoproteins assigned by the American Diabetes Association |
| First
priority |
Lowering
of LDL cholesterol |
| Second
priority |
Lowering
of triglyceride levels |
| Third
priority |
Raising
levels of HDL cholesterol |
|
LDL goals recommended by the American Diabetes
Association in diabetic patients |
| Patient
Profile |
LDL
Goal |
| Pre-existing
CVD |
<
100 mg/dl |
| Absence
of CVD |
<
130 mg/dl |
|
|
Lifestyle
Intervention
- Exercise
This is likely to provide particular benefits for patients with
type 2 diabetes, as it improves insulin sensitivity and reduces
intra-abdominal fat, thereby reducing triglyceride and increasing
HDL levels. The American Diabetes Association recommends aerobic
exercise at 50 to 70% maximum O2 uptake for 20 to 45 minutes,
at least 3 days per week.
-
Reduction of saturated fat intake
Saturated fat should be replaced in the diet by carbohydrate
or by poly-unsaturated fat or mono-unsaturated fat. However,
mono-unsaturated fat may result in lower triglyceride levels
and better glycemic control than carbohydrate.
- Severe
restriction of dietary fat and complete avoidance of alcohol
is recommended in case of marked
Drug
Therapy
STATINS (HMG-COA REDUCTASE INHIBITORS) e.g. atorvastatin, simvastatin,
lovastatin
- Most effective
agents for reducing LDL cholesterol
- Also reduce
triglycerides and increase HDL cholesterol
- Do not
alter glycemic control
- Recommended
as first-line agents for management of diabetic dyslipidemia
since
• lowering of LDL is first priority
• substantial evidence of statins on CHD risk reduction
is available (Table).
|
|
Study
|
Drug
|
Lipid
or lipoprotein
|
Percent
change
|
CHD
even Reduction
|
|
4S
|
Simvastatin
20-40 mg daily
|
LDL-C
Triglycerides
HDL-C
|
-36%
-11%
+7%
|
55%
|
|
CARE
|
Pravastatin
40 mg daily
|
LDL-C
Triglycerides
HDL-C
|
-28%
-14%
+5%
|
25%
|
|
LIPID
|
Pravastatin
40 mg daily
|
LDL-C
Triglycerides
HDL-C
|
-25%
-11%
+5%
|
19%
|
|
-
|
Atorvastatin
10 mg daily
|
Total-C
LDL-C
Triglycerides
|
-27%
-36%
-21%
|
NA
|
4S=Scandinavian Simvastatin Survival Study; CARE=Cholesterol And
Recurrent Events study; LIPID=Long-term Intervention with Pravastatin
in Ischaemic Disease; NA=data not available
FIBRATES e.g. gemfibrozil, bezafibrate, fenofibrate
- Mainly
reduce triglyceride levels
- Also increase
HDL cholesterol
- Effect
on LDL cholesterol varies with the baseline triglyceride level.With
normal or slightly elevated triglyceride levels, LDL cholesterol
levels are lowered with fibrates, but when baseline triglyceride
levels are high, LDL levels rise because of improved VLDL metabolism
- Increase
LDL particle size
- Do not
alter glycemic control
- Since there
is little current evidence for reduction of CHD in diabetic
patients treated with diabetes, fibrates
are not generally used as first-line treatment for diabetic
dyslipidemia. Fibrates are used when more marked hypertriglyceridemia
is present (triglycerides > 440 mg/dl) or as second line
therapy in addition to a statin.
|
| Choice
of therapy for lipid abnormalities in diabetes mellitus |
|
Lipid
or lipoprotein
abnormality
|
First-line
therapy
|
Additional
Therapy
|
| Increased
LDL cholesterol |
Statina
|
Fibrate
Omega 3 fatty acids
Nicotinic acid
|
| Increased
LDL cholesterol |
Statin
|
Bile
acid sequestrant
Nicotinic acid
|
| Increased
triglyceride |
Fibrate
|
Statin
Omega 3 fatty acids
Nicotinic acid
|
| Reduced
HDL cholesterol |
Statinb
|
Fibrate
Nicotinic acid
|
Therapeutic
priority is to lower LDL cholesterol; b Will improve ratio of
LDL to HDL cholesterol.
|
| Hypolipidemic
therapy: Side effects and contraindications |
|
Class
|
Examples
|
Dosage
|
Main
side effects
|
Contraindications
|
|
Statins
|
Simvastatin
|
5-80
mg
once daily
10-80 mg
once daily
|
Gastrointestinal
disturbances,
liver enzyme elevation,
skeletal muscle
inflammation
|
Hypersensitivity,
active liver disease
or unexplained
persistent elevations
of liver enzymes,
pregnancy and lactation
|
|
Fibrates
|
Gemfibrozil
Bezafibrate Fenofibrate
|
1200
mg/day
400 mg daily
200 mg daily
|
Gatrointestinal
disturbances, headache, itching,muscle damage,increased
risk of developing gallstones,liver
enzyme elevations
|
Hypersensitivity,
hepatic or severe
renal dysfunction,
pre-existing
gall bladder disease
|
|
|
Further
Reading
- Drugs
2000; 59: 1101-1111
- Am J Cardiol
1987; 59: 750-755
- Diabetes
1997; 46: 327-334
- Diabetes
Care 1993; 16: 828-834
- Clinical
Therapeutics 1995;17:186-202
- 4th International
Symposium on Multiple Risk Factors in Cardiovascular Disease,
April 23-25, 1997; Washington DC, USA.
|
