P O S I T I O N S T A T E M E N T Dyslipidemia Management in Adults With Diabetes AMERICAN DIABETES ASSOCIATION
(Ͻ40 mg/dl), and modestly elevated trig-lycerides (4). MODIFICATION OF RATIONALE FOR
of alcohol or estrogen may also contribute
LIPOPROTEINS BY TREATMENT OF MEDICAL NUTRITION DYSLIPIDEMIA — The rationale for THERAPY AND PHYSICAL
the treatment of diabetic dyslipidemia is
ACTIVITY — There is little evidence LIPOPROTEIN RISK
from clinical trials to determine the effect
FACTORS FOR CVD — Available
of different dietary interventions on the
lipid abnormalities are associated with in-
With Diabetes” (1). Type 2 diabetes is as-
servational studies suggest that patients
patients both with and without diabetes.
risk of cardiovascular disease (CVD).
physical activity have fewer cardiovascu-
PREVALENCE OF DYSLIPIDEMIA IN TYPE 2 DIABETES — The most common pat-
tern of dyslipidemia in patients with type
CLINICAL TRIALS OF LIPID
activity will lead to decreased triglycer-
2 diabetes patients is elevated triglyceride
LOWERING IN DIABETIC
ides and increased HDL cholesterol levels
levels and decreased HDL cholesterol lev-
SUBJECTS — The recently completed
Heart Protection Study has been the larg-
lesterol levels. Patients with diabetes who
lesterol in those with type 2 diabetes is not
significantly different from that in those
scription for MNT and for increased phys-
individuals who do not have diabetes.
ical activity. The proportion of saturated
dl. In this trial, patients with diabetes as-
fat in the meal plan should be reduced.
lesterol may be present. In particular, pa-
tients with diabetes tend to have a higher
compensate for the reduction in saturated
duction was similar across all LDL subcat-
fat. Some (but not all) studies suggest that
egories examined, including patients with
risk of cardiovascular events. Insufficient
lower pretreatment LDL cholesterol levels
have better metabolic effects than a high-
carbohydrate diet, although other experts
tions on the measurement of particle size
fied vascular disease (3). Numerous other
fication may make weight loss more diffi-
cult in obese patients with diabetes.
lipid levels may be affected by factors un-
related to glycemia or insulin resistance,
typically reduces LDL cholesterol 15–25
gemfibrozil. In the Veterans Affairs High-
mg/dl (0.40 – 0.65 mmol/l). Lifestyle in-
tervention may be evaluated at regular in-
t e r v a l s , w i t h c o n s i d e r a t i o n o f
associated with a 24% decrease in cardio-
vascular events in diabetic subjects with
● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●
MODIFICATION OF LIPOPROTEINS BY
The recommendations in this paper are based on the evidence reviewed in the following publication:Management of dyslipidemia in adults with diabetes (Technical Review). Diabetes Care 21:160 –178, 1998. GLUCOSE-LOWERING
The initial draft of this paper was prepared by Steven M. Haffner, MD. This paper was peer-reviewed,
AGENTS — Interventions to improve
modified, and approved by the Professional Practice Committee and the Executive Committee, November
glycemia usually lower triglyceride levels
1997. Most recent review/revision, 2003. Abbreviations: ADA, American Diabetes Association; CHD, coronary heart disease: CVD, cardiovascular
disease; MNT, medical nutrition therapy; NCEP, National Cholesterol Education Program.
2004 by the American Diabetes Association.
DIABETES CARE, VOLUME 27, SUPPLEMENT 1, JANUARY 2004
Dyslipidemia Management
prevention would not be able to “save”
Table 1—Order of priorities for treatment of
large numbers of these diabetic patients. diabetic dyslipidemia in adults TREATMENT GOALS FOR
mmol/l), a variety of treatment strategies
LIPOPROTEIN THERAPY — N o
the effect of implementing different lipid
treatment goals, including the question of
tection Study (3), in people with diabetes
over the age of 40 years with a total cho-
lesterol Ն135 mg/dl, suggest that statin
for patients with complex lipid abnormal-
ities. Current trials are examining these
mic control in patients with diabetes and
of LDL cholesterol is considered the first
dyslipidemia for a number of reasons (1).
High-dose statins (in those who also have
patients. If values are at low-risk levels
factor for CVD in people with diabetes.
The initial therapy for hypertriglyceride-
mia is lifestyle intervention with weight
loss, increased physical activity, restricted
intake of saturated fats, incorporation of
cholesterol levels for adults with diabetes
lesterol levels are Ͼ40 mg/dl (1.02 mmol/
l); and triglyceride levels are Ͻ150 mg/dl
[11.3 mmol/l]), severe dietary fat restric-
Decision for treatment of high LDL before elevatedtriglyceride is based on clinical trial data indicating
safety as well as efficacy of the available agents. The
combination of statins with nicotinic acid, feno-
of elevated LDL cholesterol generally fol-
fibrate, and especially gemfibrozil may carry an in-
recommendations for patients with triglyceride lev-
sued. Insulin therapy (alone or with insu-
ference (9), with the following caveats.
lin sensitizers) may also be particularly
effective in lowering triglyceride levels.
ated after lifestyle intervention has been
both triglyceride and LDL cholesterol. Fe-
mic control (or at least after the achieve-
Ͼ100 mg/dl, pharmacological therapy be possible), the physician should con- with statin therapy, and may be useful inshould be initiated at the same time that
sider adding a fibric acid and/or niacin.
therapy is dependent on the clinician’s
diabetes, it is difficult to raise HDL cho-
therapy are 1) an LDL cholesterol level of
Ն130 mg/dl (3.35 mmol/l) and 2) a goal mmol/l), strong consideration should be intervention. Nicotinic acid, whichof Ͻ100 mg/dl (2.60 mmol/l) for LDL
given to pharmacological treatment of tri-
glyceridemia to minimize the risk of pan-
with diabetes, and fibrates can effectively
statins are moderately effective in reduc-
doses of nicotinic acid (Յ2 g nicotinic ac-
ing triglyceride levels in markedly hyper-
a large proportion of diabetic patients die
Ն300 mg/dl [3.40 mmol/l]). Gemfibrozil deterioration may be easily remediable by
before they reach the hospital, a preven-
should not be initiated alone in diabetic
adjustment of hypoglycemic medications.
DIABETES CARE, VOLUME 27, SUPPLEMENT 1, JANUARY 2004
Position Statement
smoking cessation, increased physical ac-
CVD. It seems reasonable that if patients
lipid profile in patients with diabetes.
tivity) may increase HDL cholesterol.
with type 1 diabetes have LDL cholesterol
● Patients who do not achieve lipid goals
apy may be initiated. Several options are
atins with nicotinic acid, fenofibrate, and
sively treated. Improved glycemic control
especially gemfibrozil has been associated
with increased risk of myositis, although
the risk of clinical myositis (as opposed to
type 2 diabetes for reduction of CVD (e.g.,
● Lowering LDL cholesterol with a statin
elevated creatinine phosphokinase levels)
is associated with a reduction in cardio-
● In people with diabetes over the age of
bination of gemfibrozil and a statin or in
CONCLUSIONS
patients with renal disease. Combinations
of statins with nicotinic acid and fibrates
the risk of CVD in patients with diabetes.
are extremely effective in modifying dia-
Primary therapy should be directed first at
● In children and adolescents with diabe-
lowering LDL levels. The goal is to reduce
LIPID-LOWERING AGENTS
ioral interventions is also an LDL choles-
initial pharmacological therapy should be
● Lower triglycerides to Ͻ150 mg/dl (1.7
to use statins. A cholesterol absorption in-
hibitor, a resin, niacin, or fenofibrate may
doses of statins may be moderately effec-
goal or in the case of statin intolerance.
● Lowering triglycerides and increasing
combination therapy. With the use of sta-
a fibric acid, such as fenofibrate, or niacin
lar events in patients with clinical CVD,
very high-dose statin therapy (e.g., simva-
● Combination therapy using statins and
statin 80 mg or atorvastatin 40 or 80 mg)
lifestyle intervention. Additional triglyc-
eride lowering can be achieved with fibric
restricted to patients with both high LDL
References
1. Haffner SM: Management of dyslipidemia
goals have been achieved, laboratory fol-
RECOMMENDATIONS
low-up every 6 –12 months is suggested.
view). Diabetes Care 21:160 –178, 1998
2. Turner RC, Millns H, Neil HA, Stratton
CONSIDERATIONS IN THE
● In adult patients, test for lipid disorders
RR: Risk factors for coronary artery dis-
TREATMENT OF ADULTS WITH TYPE ONE DIABETES —
mellitus (UKPDS 23). BMJ 316:823– 828,
mal levels of lipoproteins, unless they are
may get a lipid profile very similar to that
ised placebo-controlled trial. Lancet 361:
tion of lipoproteins may be abnormal, but
4. Rubins HB, Robins SJ, Collins D, Fye CL,
the effects of these compositional abnor-
● Lifestyle modification focusing on the
malities in relation to CVD are unknown.
There is relatively little observational data
no clinical trials relating lipoproteins to
DIABETES CARE, VOLUME 27, SUPPLEMENT 1, JANUARY 2004
Dyslipidemia Management
on Detection, Evaluation and Treatment of
tervention Trial Study Group. N Engl
5. American Diabetes Association: Nutrition
9. American Diabetes Association: Detection
disease: a statement for healthcare profes-
and management of lipid disorders in dia-
betes (Position Statement). Diabetes Care
betes (Consensus Statement). Diabetes Care
6. American Diabetes Association: Physical
8. NCEP Expert Panel on Detection, Evalua-
Pyo¨ra¨la¨ K, Laakso M: Mortality from cor-
Statement). Diabetes Care 27:S58 –S62,
onary heart disease in subjects with type 2
terol in Adults: Executive Summary of the
diabetes and in nondiabetic subjects with
and without prior myocardial infarction.
DIABETES CARE, VOLUME 27, SUPPLEMENT 1, JANUARY 2004
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