PPRNet Practice Guidelines
Diabetes
Mellitus Clinical Practice Guidelines
Practice guideline: Glycosylated
hemoglobin (A1C) monitoring in patients with DM every 6 months, with a goal A1C
< 7 %
Prospective randomized clinical trials such as the Diabetes Control and
Complications Trial (DCCT) and the U.K. Prospective Diabetes Study (UKPDS) have
shown that improved glycemic control is associated with sustained decreased
rates of retinopathy, nephropathy, and neuropathy. In these trials, treatment
regimens that reduced average A1C to 7% (1% above the upper limits of normal)
were associated with fewer long-term microvascular complications; however,
intensive control was found to increase the risk of severe hypoglycemia and
weight gain. Epidemiological studies support the potential of intensive glycemic
control in the reduction of CVD.
A1C testing should be performed routinely in all patients with diabetes, first
to document the degree of glycemic control at initial assessment and then as
part of continuing care. Since the A1C test reflects mean glycemia over the
preceding 2–3 months, measurement approximately every 3 months is required to
determine whether a patient’s metabolic control has been reached and
maintained within the target range. An A1c of 7% correlates to a mean plasma
glucose value of approximately 170 mg/dl [i]. For any individual patient, the
frequency of A1C testing should be dependent on the clinical situation, the
treatment regimen used, and the judgment of the clinician. The A1C test should
be performed at least two times a year in patients who are meeting treatment
goals (and who have stable glycemic control) and quarterly in patients whose
therapy has changed or who are not meeting glycemic goals.
Additional resource: Standards
of Medical Care for Patients With Diabetes Mellitus (pdf) [i]
Back to
Guideline Menu
*
Two new trials examine the impact of glycemic goals in
patients with type 2 diabetes
February
2008: The National Heart Lung and Blood Institute announced that they were
stopping one arm of the ACCORD trial early.
Results were published in the New England Journal of Medicine in June of 2008.
Study highlights:
- In over 10,000 patients with type 2 DM randomized to “intensive glucose control” (goal A1C < 6%, achieved A1C 6.4%) or “conventional control” (goal A1C 7-7.9%, achieved A1C 7.5%), more patients died in the intensive group (257 pts) compared to the conventional group (203 pts) (Number needed to harm = 100).
- All categories of diabetes medications (including insulin and thiazolidinediones) were used more frequently in the intensive group. Weight gain, hypoglycemia and fluid retention occurred more frequently in these patients.
- Blood pressure and lipid arms of the trial are ongoing – we
will learn more about those outcomes in 2009.
- The trial was designed to answer the question of "Is lower A1C better?" in pts w/type 2 DM and from these results, we learn that it does not provide a mortality benefit.
Click here for more information from the National Institutes of Health
February 2008:
Investigators from Denmark
published the Steno-2 trial,
a multifactorial intervention which focused on glycemic, blood pressure and
lipid goals as well as appropriate medication use in 160 patients with type 2 DM
and microalbuminuria.
Study highlights:
·
- Compared to the ACCORD trial, fewer patients died in the
intensive group (24pts) vs conventional (40pts).
·
- Patients in the intensive group achieved A1Cs of 7.7-7.9,
lower BPs and LDLs compared to A1Cs in the conventional group of 8-9%.
·
- Thiazolidinediones were not used in either group.
·
- This trial shows the benefit of a
multifactorial intervention targeting existing goals in at-risk pts.
Practice guideline: Blood
pressure monitoring in patients with
DM every six months, with a goal BP < 130/80 mmHG
The UKPDS (U.K. Prospective Diabetes Study) and the Hypertension Optimal
Treatment (HOT) trials both demonstrated improved outcomes, especially in
preventing stroke, in patients assigned to lower blood pressure targets.
In the UKPDS epidemiological study, each 10-mmHg decrease in mean systolic blood
pressure was associated with reductions in risk of 12% for any complication
related to diabetes, 15% for deaths related to diabetes, 11% for myocardial
infarction, and 13% for microvascular complications. Optimal outcomes in the HOT
study were achieved in the group with a target diastolic blood pressure of 80
mmHg (achieved 82.6 mmHg). Randomized clinical trials demonstrate the benefit of
targeting a diastolic blood pressure of<![endif]> less than or equal to 80
mmHg. Epidemiological analyses show that blood pressures greater than or equal
to 120/70 mmHg are associated with increased cardiovascular event rates and
mortality in persons with diabetes. Therefore, a target blood pressure goal of
<130/80 mmHg is reasonable if it can be safely achieved.
Practice guideline: ACE inhibitor or ARB for diabetic patients
with hypertension
Many studies have shown that in hypertensive patients with type 1 diabetes, ACE
inhibitors can reduce the level of albuminuria and the rate of progression of
renal disease to a greater degree than other antihypertensive agents that lower
blood pressure by an equal amount. Other studies have shown that there is
benefit in reducing the progression of microalbuminuria in normotensive patients
with type 1 diabetes and normotensive and hypertensive patients with type 2
diabetes.
Additional resources: Treatment
of Hypertension in Adults With Diabetes [ii]
Preserving
Renal Function in Adults With Hypertension and Diabetes: A Consensus Approach [iii]
(MD Consult login required)
Practice guideline: LDL-cholesterol,
HDL-cholesterol, and triglyceride measurements annually in patients with DM,
with LDL-C < 100 mg/dl, HDL-C> 45 mg/dl, and triglycerides <150 mg/dl
A number of secondary CHD prevention trials have included small numbers of adult
type 2 diabetic subjects. In the Scandinavian Simvastatin Survival Study (4S)
trial, simvastatin (HMG CoA reductase inhibitor or "statin")
significantly reduced CHD incidence and total mortality (borderline significantly)
in diabetic subjects with high LDL cholesterol and with previous clinical CHD.
In the Cholesterol and Recurrent Events (CARE) study, pravastatin reduced CHD
incidence significantly in diabetic subjects with average LDL levels and with
previous clinical CHD. In the Helsinki Heart Study, gemfibrozil (fibric acid
derivative) was associated with a reduction in CHD in diabetic subjects without
prior CHD (although this result was not statistically significant). In the
Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial
(VA-HIT), gemfibrozil was associated with a 24% decrease in cardiovascular
events in diabetic subjects with prior cardiovascular disease.
The CARDS trial Collaborative Atorvastatin in Diabetes Study (The Lancet Aug 2004;9435:685-696) is the first primary prevention trial focused on lipid-lowering therapy in patients with diabetes. Over 2800 patients with diabetes, at least one risk factor (ie, HTN, retinopathy) and baseline LDL of less than 160 mg/dl were randomized to atorvastatin (Lipitor) 10 mg or placebo. At 4 years, patients in the atorvastatin arm experienced fewer MIs or strokes with a number needed to treat of 32 compared to placebo.
Additional resource: Management
of Dyslipidemia in Adults With Diabetes [iv]
Practice guideline: Aspirin therapy for patients with DM > 40 years of age
A meta-analysis of 145 prospective controlled trials of anti-platelet therapy in
men and women after myocardial infarction, stroke or transient ischemic attack,
or positive cardiovascular history (vascular surgery, angioplasty, angina, etc.)
has been reported by the Anti-Platelet Trialists (APT). Reductions in vascular
events were about one-quarter in each of these categories, and diabetic subjects
had risk reductions that were comparable to non-diabetic individuals. There was
a trend toward increased risk reductions with doses of aspirin of 325 mg/day or
less. It was estimated that 38 ± 12 vascular events per 1,000 diabetic patients
would be prevented if they were treated with aspirin as a secondary prevention
strategy. Comparable results were seen in males and females.
These results are supported by the Early Treatment Diabetic Retinopathy Study (ETDRS).
This population consisted of type 1 and type 2 diabetic men and women, about 48%
of whom had a history of cardiovascular disease. The study, therefore, may be
viewed as a mixed primary and secondary prevention trial. The relative risk for
myocardial infarction in the first 5 years in those randomized to aspirin
therapy was lowered significantly to 0.72 (CI 0.55–0.95).
The Hypertension Optimal Treatment (HOT) Trial examined the effects of 75 mg/day
of aspirin vs. placebo in 18,790 hypertensive patients who were randomized to
achieve diastolic blood pressure goals of 90, 85, or 80 mmHg. There were 1,501
diabetic subjects in this trial. Aspirin significantly reduced cardiovascular
events by 15% and myocardial infarction by 36%. The relative effects of aspirin
were similar in non-diabetic and diabetic subjects. Fatal bleeding episodes
including intracerebral bleeding were equal in the aspirin and placebo groups,
while nonfatal minor bleeding episodes were more common in the aspirin group.
This study provides further evidence for the efficacy and safety of aspirin
therapy in diabetic patients with well-controlled hypertension [v].
The U.S. Physicians’ Health Study was a primary prevention trial in which a
low dose aspirin regimen (325 mg every other day) was compared with placebo in
male physicians. There was a 44% risk reduction in the treated group, and
subgroup analyses in the diabetic physicians revealed a reduction in myocardial
infarction from 10.1% (placebo) to 4.0% (aspirin), yielding a relative risk of
0.39 for the diabetic men on aspirin therapy.
Additional resource: Aspirin
Therapy in Diabetes [v]
Practice guideline: Urinary microalbumin measured annually in patients with DM, with ACE inhibitor or ARB prescribed for patients with microalbuminuria
Back
to Guideline Menu
Because of the high proportion of patients who progress from microalbuminuria to
overt nephropathy and subsequently to ESRD, use of ACE inhibitors or ARBs is
recommended for all patients with microalbuminuria or advanced stages of
nephropathy. The effect of ACE inhibitors appears to be a class effect, so
choice of agent may depend on cost and compliance issues. Many studies have
shown that in hypertensive patients with type 1 diabetes, ACE inhibitors can
reduce the level of albuminuria and the rate of progression of renal disease to
a greater degree than other antihypertensive agents that lower blood pressure by
an equal amount. Other studies have shown that there is benefit in reducing the
progression of microalbuminuria in normotensive patients with type 1 diabetes
and normotensive and hypertensive patients with type 2 diabetes.
Screening for microalbuminuria can be performed by three methods: 1) measurement
of the albumin-to-creatinine ratio in a random spot collection; 2) 24-h
collection with creatinine, allowing the simultaneous measurement of creatinine
clearance; and 3) timed (e.g., 4-h or overnight) collection. Microalbuminuria is
present if urinary albumin excretion is greater than or equal to 30 mg/24 h
(equivalent to 20 µg/min on a timed specimen or 30 mg/g creatinine on a random
sample). Short-term hyperglycemia, exercise, urinary tract infections, marked
hypertension, heart failure, and acute febrile illness can cause transient
elevations in urinary albumin excretion. If assays for microalbuminuria are not
readily available, screening with reagent tablets or dipsticks for microalbumin
is an alternative. Because reagent strips only indicate concentration and do not
correct for creatinine as the spot urine albumin-to-creatinine ratio does, they
are subject to possible errors from alterations in urine concentration. All
positive tests by reagent strips or tablets should be confirmed by more specific
methods. There is also marked day-to-day variability in albumin excretion, so at
least two of three collections done in a 3- to 6-month period should show
elevated levels before designating a patient as having microalbuminuria.
Definitions
of abnormalities in albumin excretion
Additional resource: Diabetic
Nephropathy [vi]
i.
Standards of Medical Care in Diabetes. Diabetes Care 2007;30:S4-S41.
ii. Hypertension Management in Adults With Diabetes. Diabetes Care 2004; 27:S65-67.
iii. Preserving Renal Function in Adults With Hypertension and Diabetes: A Consensus Approach. American Journal of Kidney Diseases 2000;36(3):646-61
iv. Dyslipidemia Management in Adults With Diabetes. Diabetes Care 2004 ;27:S68-71.
v. Aspirin Therapy in Diabetes. Diabetes Care 2004; 27:S72-73.