Recommendations and Rationale
Screening for Type 2 Diabetes Mellitus in Adults
U.S. Preventive Services Task Force (USPSTF)
This statement summarizes the current U.S. Preventive Services
Task Force (USPSTF) recommendation on screening for type 2 diabetes mellitus in
adults, and updates the 1996 recommendation contained in the Guide to
Clinical Preventive Services, Second Edition1.
Summary of Recommendation
|
Contents
Clinical
Considerations
Scientific
Evidence
Recommendations of Others
References
Members of the Task Force
Contact the Task Force
Available Products
Task Force Ratings Strength of Recommendations and Quality of Evidence |
Clinical Considerations
- In the absence of evidence of direct benefits of routine screening for
type 2 diabetes, the decision to screen individual patients is a matter of
clinical judgment. Patients at increased risk for cardiovascular disease may
benefit most from screening for type 2 diabetes, since management of
cardiovascular risk factors leads to reductions in major cardiovascular
events. Clinicians should assist patients in making that choice. In
addition, clinicians should be alert to symptoms suggestive of diabetes
(i.e., polydipsia and polyuria) and test anyone with these symptoms. - Screening for diabetes in patients with hypertension or hyperlipidemia
should be part of an integrated approach to reduce cardiovascular risk.
Lower targets for blood pressure (i.e., diastolic blood pressure <80
mm Hg) are beneficial for patients with diabetes and high blood pressure.
The report of the Adult Treatment Panel III of the National Cholesterol
Education Program recommends lower targets for low-density lipoprotein
cholesterol for patients with diabetes. Attention to other risk factors such
as physical inactivity, diet, and overweight, is also important, both to
decrease risk for heart disease and to improve glucose control. - Three tests have been used to screen for diabetes: fasting plasma
glucose (FPG), 2-hour post-load plasma glucose (2-hour PG), and hemoglobin
A1c (HbA1c). The American Diabetes Association (ADA) has recommended the FPG
test (>126 mg/dL) for screening because it is easier and faster to
perform, more convenient and acceptable to patients, and less expensive than
other screening tests. The FPG test is more reproducible than the 2-hour PG
test, has less intraindividual variation, and has similar predictive value
for development of microvascular complications of diabetes. Compared with
the FPG test, the 2-hour PG test may lead to more individuals being
diagnosed as diabetic. HbA1c is more closely related to FPG than to 2-hour
PG, but at the usual cut-points it is less sensitive in detecting lower
levels of hyperglycemia. The random capillary blood glucose (CBG) test has
been shown to have reasonable sensitivity (75 percent at a cut-point of >120
mg/dL) in detecting persons who have either an FPG level >126 mg/dL
or a 2-hour PG level >200 mg/dL, if results are interpreted according
to age and time since last meal; however, the random blood glucose test is
less well standardized for screening for diabetes. - The ADA recommends confirmation of a diagnosis of diabetes with a
repeated FPG test on a separate day, especially for patients with borderline
FPG results and patients with normal FPG levels for whom suspicion of
diabetes is high. The optimal screening interval is not known. The ADA, on
the basis of expert opinion, recommends an interval of every three years but
shorter intervals in high-risk persons. - Regardless of whether the clinician and patient decide to screen for
diabetes, patients should be encouraged to exercise, eat a healthy diet, and
maintain a healthy weight, choices that may prevent or forestall the
development of type 2 diabetes. More aggressive interventions to establish
and maintain these behaviors should be considered for patients at increased
risk for developing diabetes, such as those who are overweight, have a
family history of diabetes, or have a racial or ethnic background associated
with an increased risk (e.g., American Indians). Intensive programs of
lifestyle modification (diet, exercise, and behavior) should also be
considered for patients who have impaired fasting glucose or impaired
glucose tolerance, since several large trials have demonstrated that these
programs can significantly reduce the incidence of diabetes in these
patients. Evidence and recommendations regarding counseling about diet,
physical activity, and obesity are provided in the USPSTF evidence summaries
“Counseling to
Promote a Healthy Diet,” “Counseling
to Promote Physical Activity,” and “Screening
and Treatment for Obesity in Adults,” available on the Agency for
Healthcare Research and Quality Web site at
http://www.preventiveservices.ahrq.gov.
Scientific Evidence
Epidemiology and Clinical Consequences
The burden of suffering caused by type 2 diabetes is enormous. Among
individuals aged 40-74, the prevalence increased from 8.9 percent for the period
1976-80, to 12.3 percent for the period 1988-94.4
Current prevalence in the United States is likely even higher due to the
increasing prevalence of obesity.5
Patients with type 2 diabetes are at increased risk for both microvascular and
macrovascular disease. Microvascular disease contributes to high rates of
blindness, end stage renal disease, and lower extremity amputations.
Macrovascular disease accounts for a 2 to 4-fold increased risk for heart
disease and stroke. In addition, a substantial number of people who have
elevations in blood glucose not meeting criteria for diabetes (impaired fasting
glucose or impaired glucose tolerance) are at increased risk for progression to
diabetes and for cardiovascular disease.
The 10-year incidence of blindness among those with type 2 diabetes of 20-25
years’ duration is between 5 and 15 percent, and the 10-year incidence of visual
deterioration (doubling of the visual angle) is between 35 and 45 percent, with
the higher rates for those requiring insulin.6
The highest risk is among those who have a longer time to develop visual
complications because of onset of diabetes at a younger age.7-8
Some patients with diabetes manifest diabetic nephropathy, a condition that
can progress to chronic renal failure (CRF). The incidence of CRF among those
without macroalbuminuria at diagnosis of type 2 diabetes is about 0.5 percent
after 15 years of diabetes duration and 10 percent after 30 years. The incidence
of CRF is substantially higher (about 12 percent after 15 years) among those
with macroalbuminuria at time of diagnosis of diabetes.9
Two cohort studies found that the 20-25-year cumulative incidence of lower
extremity amputation (LEA) in patients with type 2 diabetes is between 3 and 11
percent.10-11
In the United Kingdom Prospective Diabetes Study (UKPDS) cohort, between 1 and 2
percent of participants had had an amputation within 10 years12.
In the Wisconsin Epidemiologic Study of Diabetic Retinopathy population-based
cohort, about 7 percent of those with type 2 diabetes of short duration had had
an amputation within 14 years.13
Elevated blood glucose is an independent risk factor for cardiovascular
disease (CVD). The risk increases with the level of glucose. The absolute
prevalence of established CVD at diagnosis of type 2 diabetes ranges from 8 to
23 percent (depending on the presence of other CVD risk factors) and at least 14
prospective cohort studies have found that the risk for CVD events in diabetic
men is about twice that in nondiabetics, even after adjusting for age,
hypertension, dyslipidemia, and smoking.3
For women, the adjusted CVD risk among diabetics is elevated as much as fourfold
compared with nondiabetics. In the UKPDS cohort of diabetic patients undergoing
conventional treatment, there were 17 events of myocardial infarction (MI), 5
events of stroke, and 12 events of diabetes-related deaths, respectively, per
1,000 patient-years.12
Diabetes also imposes a significant economic burden. In 1997, the U.S. health
care system spent some $98 billion on medical care and lost productivity for
people with type 2 diabetes.14
Many individuals who satisfy the criteria for type 2 diabetes have not been
diagnosed. Data from the third National Health and Nutrition Examination Survey
(NHANES III) showed that 3 percent of the adult population aged 20 and older had
not been diagnosed and yet met the diagnostic criteria for diabetes.4
Accuracy and Reliability of Screening Tests
Determining the accuracy of screening tests for type 2 diabetes is
complicated by uncertainty of what is the most appropriate gold standard for
comparison. Definitions of diabetes were originally developed using results of
2-hour PG to identify a population at substantially increased risk for
retinopathy. The criterion for an abnormal FPG level was developed based on
2-hour PG, and recently revised downward (from 140 mg/dL to 126 mg/dL) to make
the sensitivity of FPG comparable with that of 2-hour PG. Additional
criteria—impaired fasting glucose (110-125 mg/dL) and impaired glucose tolerance
(140-199 mg/dL for 2-hour PG)—have been developed to define persons who have
less severe elevations of blood glucose. A study using NHANES III data
demonstrated that, compared with FPG, the 2-hour PG as a screening test leads to
more individuals being diagnosed as diabetic.4
Large population-based studies have examined the sensitivity of 2-hour PG,
FPG, and HbA1c for identifying patients with retinopathy. Sensitivity and
specificity for detecting retinopathy were in the range of 75-80 percent for all
three tests using the following thresholds: FPG >126 mg/dL, 2-hour PG
> 200 mg/dL, or HbA1c >6.4 percent.15-17
Other studies have examined whether these tests predict future cardiovascular
disease (CVD) events. A recent meta-regression analysis of 20 observational
studies found that both FPG and 2-hour PG were significantly associated with
future CVD events in a continuous graded fashion, beginning at levels consistent
with impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) and
increasing more steeply at the highest glucose levels.18
Among those with previously undiagnosed type 2 diabetes who are in the low range
of “diabetic level” FPG (i.e., FPG between 126 and 140 mg/dL), HbA1c was normal
in about 60 percent of those tested, indicating it may be less sensitive for
detecting lower levels of hyperglycemia.
In clinical practice, the requirement for a screening test to be fasting (as
with the FPG) or post-glucose load (as with 2-hour PG) presents logistical
problems. A well-conducted, population-based study found that random CBG had
sensitivity and specificity in the 75-80 percent range for detecting type 2
diabetes defined by older criteria (i.e., FPG > 140 mg/dL or 2-hour PG
greater than or equal to 200 mg/dL), but only if results were interpreted
according to age and time since last meal.19
Effectiveness of Early Treatment
No trial has been conducted to establish whether systematic screening for
diabetes improves health outcomes compared with usual care. Establishing the
health benefits of screening for type 2 diabetes is complex because under
current practice many patients with diabetes are detected through haphazard
screening: about 50 percent of adults over 45 may have been screened for
diabetes in a 3-year period.20
The USPSTF attempted to compare the expected health outcomes from a strategy
of systematic screening to those from existing care. In the absence of direct
evidence from a trial of screening, the USPSTF examined indirect evidence to
estimate whether screening, early diagnosis, and treatment of type 2 diabetes
were likely to improve four health outcomes compared with usual care/clinical
detection:
Additionally, the results from recent RCTs demonstrate the effectiveness of
intensive lifestyle interventions in reducing the incidence of diabetes in
individuals with impaired fasting glucose or impaired glucose tolerance. Three
large trials in the United States, Finland, and China have demonstrated that
intensive programs of lifestyle modification (diet, exercise, and behavior
modification) can reduce incidence of diabetes by up to 58 percent in these
patients.21-23
Visual Impairment
Although early retinopathy is present in a substantial portion of patients
with diabetes at the time of initial diagnosis, severe retinopathy (i.e., that
requiring treatment) and visual problems usually develop later in the course of
disease. Two well-performed RCTs have shown that tight glycemic control reduces
the relative risk for development or progression of retinopathy by 29-40
percent.12-24
After 10 years of followup in the UKPDS, 7.6 percent of those in the tight
control group required laser photocoagulation compared with 10.3 percent of
patients in the conventional treatment arm; however, no difference in visual
outcomes was detected.25,26
One large well-performed RCT found that tighter control of systolic blood
pressure (improvement of approximately 10 mm Hg) among hypertensive diabetics
decreased the need for retinal photocoagulation by an absolute 4.1 percent and
reduced deterioration in visual acuity by an absolute 9.2 percent over 7.5
years.27
The incidence of blindness, however, was similar in both groups (3.3 percent vs.
2.4 percent) in this study.
The USPSTF concluded that, although retinal photocoagulation is effective in
reducing the incidence of visual impairment among those with severe retinopathy
or macular edema, most patients detected by routine screening will not require
this intervention. Further, although tight glycemic control reduces the
development and progression of retinopathy, its effects on serious visual
impairment are less clear and probably occur 10 years or more after the
diagnosis of diabetes. The degree to which tight glycemic control during the
preclinical period between screening and clinical detection (when glucose levels
are lower compared with later stages of the disease) reduces retinopathy and
later visual impairment is even less certain.
Chronic Renal Failure
Three treatments have been examined to reduce the incidence of CRF among
diabetics: tight glycemic control, tight blood pressure control, and medications
that interrupt the angiotensin-renin system (angiotensin converting enzyme [ACE]
inhibitors and angiotensin receptor blockers [ARBs]).
Evidence from several RCTs shows that tight glycemic control, and tight blood
pressure control, reduce the development and progression of albuminuria in those
with type 2 diabetes, but neither intervention had a statistically significant
effect on the incidence of CRF.12,24,27
Good evidence shows that ACE inhibitors or ARBs, or both, reduce the development
and progression of albuminuria and CRF among those with type 2 diabetes.28-37
Two of these studies, both involving diabetics with macroalbuminuria, found a
reduction in CRF in patients taking ARBs compared with placebo.32,33
Evidence is mixed as to whether ACE inhibitors are more effective than
beta-blockers in reducing development and progression of albuminuria.
Between 3 and 8 percent of individuals with diabetes (detected clinically or
by screening) have macroalbuminuria. As a result, most patients detected by
screening will be at low risk (<1 percent) for developing CRF over the next 15
years.
The USPSTF concluded that, although tight glycemic and blood pressure control
and use of ACE inhibitors and ARBs reduce the development and progression of
albuminuria, it could not determine whether initiating these treatments earlier
as a result of screening would have an important impact on CRF.
Lower Extremity Amputations
Three types of treatment have been tested to reduce LEA: tight glycemic
control, tight blood pressure control, and foot care programs. The UKPDS
reported a trend toward a lower incidence of amputations with both tight
glycemic control12
and tight blood pressure control27,
but the differences did not attain statistical significance. A recent
well-conducted systematic review examined the efficacy of foot care programs on
the incidence of foot ulcers and amputations, and its findings were
inconclusive.38
Well-conducted trials of diabetics at high risk for foot ulcers found that
intensive programs including patient education, special shoes, and health care
interventions can reduce the incidence of both foot ulcers and LEAs by as much
as 60 percent.39,40
The USPSTF concluded that LEA in diabetics occurs primarily as a late
complication related to the development of distal sensory neuropathy and
peripheral vascular disease, both of which take time to develop. Although foot
care programs, and perhaps tight glycemic and blood pressure control, may reduce
LEA over the long term, the Task Force found no evidence that early
implementation of these interventions during the time between screening and
clinical detection would have an impact on the later development of LEA.
Cardiovascular Disease
Four treatments to reduce the incidence of CVD events among patients with
diabetes have been studied in high-quality RCTs: tight glycemic control, tight
blood pressure control, treatment of dyslipidemia, and aspirin. No RCT has
demonstrated a statistically significant reduction in total CVD events from
tight glycemic control. The UKPDS trial (after 10 years of followup) showed a
trend toward reduced CVD events in patients randomized to tight glycemic
control.12
These patients had lower rates of myocardial infarction (14.7 vs. 17.4 events
per 1,000 patient-years) and sudden death (0.9 vs. 1.6 events per 1,000
patient-years) than those receiving conventional management. Further, there were
no reductions in stroke (Relative Risk [RR], 1.11), heart failure (RR, 0.91),
angina (RR, 1.02), or all-cause mortality (RR, 0.94).
A number of recent RCTs have examined various aspects of the treatment of
hypertension among patients with type 2 diabetes. Principal findings are that an
aggressive approach to blood pressure control among patients with diabetes
reduces CVD events by a relative 50 percent27,41;
treatment of isolated systolic hypertension among older patients with diabetes
reduces CVD events by a relative 34-69 percent42,43;
treatment of those with diabetes and at least one other CVD risk factor with
ramipril (regardless of whether they have hypertension) reduces CVD events by a
relative 22 percent and all-cause mortality by a relative 16 percent37;
and ACE inhibitors and ARBs are useful antihypertensive agents for diabetics.41,44
Several secondary prevention trials of treatments for patients with lipid
abnormalities had enough patients with diabetes to permit subgroup analyses.
Lipid treatment reduced the incidence of coronary heart disease (CHD) events by
about the same relative percentage among those with diabetes as among those
without diabetes (relative risk reduction between 19 and 42 percent).45-47
No primary prevention trial of lipid therapy has included sufficient numbers of
patients with diabetes to perform reliable analyses, although trends in these
trials are also in the direction of benefit. The Heart Protection Study (HPS)
found that including simvastatin in the treatment regimen of diabetic patients
reduces major vascular events (myocardial infarction, stroke, and
revascularization) from 25 percent to 20 percent, i.e., prevents one major
vascular event in 20 patients, over a 5-year period.48
Aspirin reduces CHD in both diabetics and nondiabetics, with a comparable
relative risk reduction (about 30 percent) in both groups.49-51
Potential Harms of Screening and Treatment
Screening for type 2 diabetes could cause harm in several ways. A diagnosis
of diabetes could potentially cause “labeling” in asymptomatic individuals
(i.e., anxiety or a negative change in self-perception, or both) and could lead
to social consequences (e.g., loss of insurability). However, there is little
evidence that patients found to have diabetes at screening experience any
adverse effect of labeling.52
Early detection could subject individuals to the potential risks of treatment
for longer than if the diagnosis was made clinically, with uncertain benefits.
Finally, screening could produce false-positive results, especially since there
is not yet complete consensus on criteria for diagnosing diabetes in
asymptomatic persons. Further complicating the issue are natural history data
that show that between 30 and 50 percent of persons labeled as having impaired
glucose tolerance or impaired fasting glucose will revert to normal glycemia
without developing type 2 diabetes.53-59
False-positive screening tests could contribute to psychological distress, a
problem known to exist for other conditions.
Treatments for diabetes are relatively safe. Tight glycemic control at a time
when glycemic levels are relatively low (i.e., the time between screening and
clinical diagnosis) can induce hypoglycemia. In the UKPDS, 2.3 percent of people
on insulin suffered a major hypoglycemic episode each year, as did 0.4-0.6
percent of those on oral hypoglycemic agents.12
ACE inhibitors60
and statins61,62
have reasonably low levels of serious adverse effects. Finally, although the
impact of diabetes treatment on quality of life has been a concern, data from
RCTs indicate that better glycemic control among symptomatic patients improves
quality of life, although these findings may not apply to patients detected by
screening during the preclinical phase.12,63-65
The USPSTF concluded that, despite the potential for harm in patients whose
diabetes is detected by screening, the magnitude of the problem is unknown. The
potential harm for patients is an important consideration because, even if early
detection is assumed to be beneficial, several thousand people in the general
population may need to be screened to prevent a single diabetes-related
complication over a 5-year period.3
When screening is targeted to patients with hypertension or hyperlipidemia,
however, the number needed to screen to prevent a cardiovascular event is
substantially lower.3
