Screening Adults for Type 2 Diabetes: A Review of the Evidence for
the U.S. Preventive Services Task Force
Susan L. Norris, MD, MPH; Devan Kansagara, MD; Christina Bougatsos, BS; and Rongwei Fu, PhD
Background: More than 19 million Americans are affected by type
2 diabetes mellitus, which is undiagnosed in one third of these
persons. In addition, it is estimated that more than 54 million adults
have prediabetes. Debate continues over the benefits and harms of
screening and then treating adults who have asymptomatic diabe-
tes or prediabetes.
Purpose: To update the 2003 U.S. Preventive Services Task Force
review on the evidence for potential benefits and harms of screen-
ing adults for type 2 diabetes and prediabetes in primary care
Data Sources: MEDLINE and the Cochrane Library for relevant
studies and systematic reviews published in English between March
2001 and July 2007.
Study Selection: Trials and observational studies that directly ad-
dressed the effectiveness and adverse effects of screening interven-
tions were included. Randomized, controlled trials were used to
assess the effectiveness of diabetes and prediabetes treatments. For
diabetes interventions, trials of patients with disease for 1 year or
less were included, as well as trials comparing outcomes among
diabetic and nondiabetic patients.
Data Extraction: Relevant data were abstracted in duplicate into a
Data Synthesis: Data were synthesized in a qualitative manner,
and a random-effects meta-analysis of the effects of interventions
in prediabetes on the incidence of diabetes was performed.
Limitations: Most of the data on diabetes treatment were not from
primary trial data but from subgroup analyses. Participants in in-
tensive lifestyle interventions for prediabetes may not be represen-
tative of general prediabetic populations.
Conclusion: Direct evidence is lacking on the health benefits of
detecting type 2 diabetes by either targeted or mass screening, and
indirect evidence also fails to demonstrate health benefits for
screening general populations. Persons with hypertension probably
benefit from screening, because blood pressure targets for persons
with diabetes are lower than those for persons without diabetes.
Intensive lifestyle and pharmacotherapeutic interventions reduce the
progression of prediabetes to diabetes, but few data examine the
effect of these interventions on long-term health outcomes.
Ann Intern Med. 2008;148:855-868.
For author affiliations, see end of text.
of the total U.S. population) had diabetes mellitus, one
third of whom had undiagnosed diabetes (1). In addition,
26.0% had impaired fasting glucose and impaired glucose
tolerance was even more prevalent (2). The prevalence of
diagnosed diabetes is increasing, particularly among obese
individuals (1, 3). The risk for death among persons with
diabetes is about twice that of persons without diabetes,
and cardiovascular events account for more than three
fourths of these deaths (4).
Type 2 diabetes often goes undiagnosed for many
years because hyperglycemia develops gradually and may
not produce symptoms (3, 5). Persons with diabetes are at
increased risk for microvascular and macrovascular compli-
cations, and duration of diabetes and degree of hypergly-
cemia are associated with an increased risk for microvascu-
lar complications (6–9). The prevalence of macrovascular
complications is elevated in persons with prediabetes (de-
fined as impaired fasting glucose, impaired glucose toler-
ance, or both) and in persons with newly diagnosed diabe-
tes (10–18). A substantial proportion of persons presenting
with a new cardiovascular event have undiagnosed diabetes
or prediabetes (10, 19–23). Several recent observational
studies and a meta-analysis suggest an association between
he 2002 National Health and Nutrition Examination
Survey estimated that 19.3 million U.S. adults (9.3%
chronic hyperglycemia and cardiovascular disease and stroke
Diabetes has a long preclinical phase, estimated at 10
to 12 years on the basis of the progression of microvascular
complications (28), and valid and reliable tests can detect
type 2 diabetes during this asymptomatic period (29). The
previous evidence review for the U.S. Preventive Services
Task Force (USPSTF) (29, 30) suggested that screening is
justified if the ensuing treatments offer incremental net
benefits compared with treatment at the time of clinical
presentation. In 2003, the USPSTF concluded that the
evidence was insufficient to recommend for or against rou-
tinely screening asymptomatic adults for type 2 diabetes or
Related article. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 846
Summary for Patients. . . . . . . . . . . . . . . . . . . . . . . I-30
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Annals of Internal Medicine
© 2008 American College of Physicians 855
prediabetes, but it did recommend screening for adults
with hypertension or hyperlipidemia (31).
This review summarizes evidence that has become avail-
able since the previous report to inform an update of the 2003
USPSTF recommendations on screening for type 2 diabetes
The methods of the USPSTF evidence reviews are
fully detailed elsewhere (32). The analytic framework
(Appendix Figure 1, available at www.annals.org) focuses
on decreasing the risk for complications from type 2 dia-
betes as a result of screening for diabetes. We did not
consider secondary prevention studies that exclusively en-
rolled persons with known cardiovascular disease, because
we considered those persons to have a potential preexisting
We searched MEDLINE and the Cochrane Library
for relevant English-language systematic reviews and stud-
ies published between March 2001 (6 months before the
end date of the previous search) and July 2007 related to 5
key questions. We also examined the reference lists of in-
cluded studies and ClinicalTrials.gov for relevant trials. We
evaluated all studies included in relevant systematic reviews
for potential inclusion. We included randomized, con-
trolled trials (RCTs) and observational studies that exam-
ined the effectiveness or adverse effects of screening and
diagnosis of type 2 diabetes. We used RCTs to assess the
effectiveness of diabetes and prediabetes treatments. For
diabetes interventions, we included trials with patients who
had disease for 1 year or less, as well as trials comparing
outcomes among diabetic and nondiabetic populations.
We used good-quality systematic reviews to assess the ad-
verse effects of treatment. Search strategies are available in
the full evidence report, which can be found at www.ahrq
An investigator screened titles and abstracts, and a ran-
dom sample of 1500 titles and abstracts was dual reviewed.
Two reviewers examined the full text of potentially relevant
articles to achieve consensus on inclusion (Figure). Data
were abstracted by one investigator and checked by an-
other. We assessed internal validity of individual trials by
examining factors that might introduce bias: adequate ran-
domization, allocation concealment, baseline comparabil-
Figure. Study flow diagram.
Potentially relevant articles identified through MEDLINE, PreMEDLINE,
Cochrane*, and other sources† (n = 8593)
Articles excluded during abstract review (n = 7409)
Included studies (in 90 articles)
(n = 69)
Included studies for KQ1
Research studies (n = 3)
Modeling studies (n = 7)
Included studies for KQ2
Research studies (in 11
articles) (n = 8)
Systematic reviews (n = 2)
Included studies for KQ3
Research studies (in 25
articles) (n = 11)
(in 8 articles) (n = 6)
Included studies for KQ4
(adverse effects of
Research studies (n = 8)
Included studies for KQ5
(adverse effects of
Systematic reviews (in
26 articles) (n = 24)
Excluded articles (n = 848):
Diabetes treatment study with diabetes duration >1 y: 143
Diabetes treatment study with unknown diabetes duration: 5
Wrong patient population: 92
Wrong treatment/intervention: 55
Wrong outcome: 128
Wrong study design or publication type or no data: 422
Non–English-language study: 3
Excluded background articles (n = 246)
Full-text articles reviewed for
more detailed evaluation
(n = 1184)
KQ ? key question. *Cochrane databases were the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and
Database of Abstracts of Reviews of Effects. †Other sources were reference lists and expert referrals.
Screening Adults for Type 2 Diabetes
856 3 June 2008 Annals of Internal Medicine Volume 148 • Number 11
ity of participants, blinding, and loss to follow-up. We
rated studies as good, fair, or poor quality by using stan-
dard USPSTF criteria (32). We rated systematic reviews on
the basis of established criteria, and we included only
good-quality reviews (33, 34). We assessed potential appli-
cability of individual studies to primary care practice on
the basis of the methods of participant recruitment and
We identified studies that modeled screening interven-
tions from our main search, as well as from a recent, good-
quality systematic review of screening for type 2 diabetes
by the National Health Service Research and Development
Health Technology Assessment Programme (35). We in-
dependently abstracted the relevant studies included in
that report and relied on their extensive assessments of
We performed a qualitative synthesis of abstracted
data that were generally too heterogeneous for quantitative
pooling, except for estimates of the effect of pharmaco-
therapeutic or lifestyle interventions on diabetes incidence
in prediabetic populations. We calculated these pooled es-
timates by using a hazard ratio and its SE from Cox regres-
sion; either a rate ratio or a risk ratio was calculated when
a hazard ratio was not reported (36–38). We tested for
statistical heterogeneity with the standard chi-square test
and obtained the overall estimates of relative risk by using
a random-effects model (39).
Role of the Funding Source
This study was funded by the Agency for Healthcare
Research and Quality (AHRQ) under a contract to support
the work of the USPSTF. Agency staff and USPSTF mem-
bers participated in the initial scope of this work and
reviewed interim analyses and the final report. A draft
version was distributed to content experts for review.
Agency approval was required before this manuscript
could be submitted for publication, but the authors are
solely responsible for the content and the decision to
submit it for publication.
Key Question 1
Is there direct evidence that systematic screening for type 2
diabetes, impaired fasting glucose, or impaired glucose toler-
ance among asymptomatic adults improves health outcomes?
We identified no RCTs examining the effectiveness of
a screening program for type 2 diabetes. A small, good-
quality, case–control study did not find benefit from
screening when microvascular complications were consid-
ered (40). Limited data from 2 cross-sectional studies did
not provide good-quality, direct evidence of the effective-
ness of screening for type 2 diabetes in either targeted or
general populations (41, 42).
Of modeling studies identified (35, 43–48), 2 recent
high-quality studies suggested that targeted screening for
type 2 diabetes among persons with hypertension may be
relatively cost-effective when macrovascular benefits of op-
timal blood pressure control are considered (35, 47), older
persons benefitted more than younger persons (35, 47),
and screening obese persons was more cost-effective than
mass screening (35).
The ADDITION (Anglo-Danish-Dutch Study of In-
tensive Treatment in People with Screen Detected Diabe-
tes in Primary Care) study (49), currently in progress, may
shed light on differences in baseline characteristics and
long-term health outcomes between persons with screening-
detected diabetes and those who present with symptoms.
Key Question 2
Does beginning treatment of type 2 diabetes early as a
result of screening provide an incremental benefit in health
outcomes compared with initiating treatment after clinical
We identified no studies that directly explored this
question by comparing treatment effects between persons
with screening-detected versus clinically detected diabetes,
nor did we identify new studies reporting treatment effects
in an exclusively screening-detected or recently diagnosed
diabetes cohort. Because of the lack of direct evidence, we
examined intervention studies comparing treatment effects
in diabetic versus nondiabetic populations (50–61) to ad-
dress the question: “Would early knowledge of a diabetes
diagnosis prompt a change in clinical management?”
Tight Glycemic Control
No new, completed studies have examined the effect
of glycemic control strategies in persons with newly diag-
nosed type 2 diabetes since the previous USPSTF review
(29). The UKPDS (United Kingdom Prospective Diabetes
Study) (62) remains the largest and most influential trial of
intensive glycemic control in persons with newly diag-
nosed, mainly clinically detected, type 2 diabetes. In the
UKPDS, persons assigned to intensive glycemic control
had a 25% reduction (95% CI, 7% to 40%) in micro-
vascular complications, mostly due to a reduced need for
retinal photocoagulation, as well as a nonsignificant 16%
relative risk reduction (CI, 71% to 100%) of myocardial
infarction (62). The UKPDS investigators estimated that
19.6 persons (CI, 10 to 500 persons) would need to be
intensively treated for 10 years to prevent 1 person from
developing any single clinical end point (62). A recent
meta-analysis combined results from the UKPDS and
other older trials examined in the last USPSTF review, and
it concluded that tight glycemic control resulted in a mod-
est reduction of macrovascular events, particularly periph-
eral vascular and cerebrovascular events, in persons with
vascular event, 0.81 [CI, 0.73 to 0.91]) (27). Examination
of the individual trials, however, showed largely nonsignif-
icant results, and it was unclear how overlapping popula-
tions from the UKPDS were accounted for in the meta-
Screening Adults for Type 2 Diabetes
3 June 2008 Annals of Internal Medicine Volume 148 • Number 11 857
It is unlikely that good-quality trial evidence of the
final health benefits of early glycemic control in a screen-
ing-detected population will ever be available because with-
holding treatment from persons with known diabetes is
unethical and the length of follow-up required might be
prohibitive. The ADDITION study (49) should provide
valuable information, although it will be assessing the
incremental benefit of very aggressive glycemic control
over current standards for glycemic control in a screened
Specific Antihypertensive Treatment
There is no clear evidence that persons with diabetes
detected by screening would respond differently to specific
antihypertensive regimens compared with persons without
diabetes. We found no new studies involving antihyperten-
sive agents in screening-detected individuals; however, we
identified 2 new trials comparing the effect of different
antihypertensive regimens in persons with and those with-
out diabetes (Appendix Table 1, available at www.annals
.org) (51, 52). The ALLHAT (Antihypertensive and Lipid-
Lowering Treatment to Prevent Heart Attack Trial) (51)
was an effectiveness trial showing no demonstrable advan-
tage of either a calcium-channel blocker or an angiotensin-
converting enzyme inhibitor over a thiazide diuretic in re-
ducing deaths or cardiovascular events in both the diabetes
and nondiabetes subgroups. A second study compared ve-
rapamil with either a ?-blocker or a thiazide diuretic and
found no evidence of a differential effect on cardiovascular
outcomes between those with and those without diabetes
(52). However, neither trial was originally powered to de-
tect differences between the diabetes and nondiabetes sub-
groups. A third trial (included in the previous USPSTF
review ) examined persons with hypertension and left
ventricular hypertrophy. It showed that persons with dia-
betes had lower cardiovascular mortality with losartan
compared with atenolol, and those without diabetes expe-
rienced a reduction in stroke with losartan (53, 54).
We identified 1 meta-analysis of antihypertensive trials
that compared outcomes between persons with and those
without diabetes (63). Angiotensin-receptor blockers pro-
vided significantly greater protection against congestive
heart failure for those with diabetes than for those without
diabetes. All of the studies of angiotensin-converting en-
zyme inhibitors compared with placebo were secondary
prevention trials, except for the HOPE (Heart Outcomes
Prevention Evaluation) trial, which was a combination of
primary and secondary prevention (64, 65) and was in-
cluded in the previous USPSTF review (29). The HOPE
trial showed that persons with type 2 diabetes and at least
moderate cardiovascular risk (age ?55 years and 1 addi-
tional cardiovascular risk factor) experienced a 25% relative
risk reduction (CI, 12% to 36%) in cardiovascular events,
cardiovascular deaths, and stroke with ramipril treat-
ment—a similar benefit to that achieved in persons with a
history of ischemic heart disease and no diabetes (64, 65).
Intensity of Antihypertensive Treatment
As discussed in the previous USPSTF review (29),
1 trial (the HOT [Hypertension Optimal Treatment] trial
) provided evidence that aggressive blood pressure con-
trol in persons with diabetes reduces cardiovascular mor-
bidity. In that trial, the diabetes subgroup experienced a
51% relative risk reduction in cardiovascular events from
more aggressive blood pressure control, a greater benefit
than that observed in nondiabetic patients (29, 66). We
did not identify new trials comparing intensive and less
intensive blood pressure treatment targets in persons with
and without diabetes. A recent meta-analysis presented
limited evidence that higher-intensity antihypertensive
treatment reduces the risk for major cardiovascular events
in persons with diabetes (relative risk, 0.64 [CI, 0.46 to
0.89]) but not in those without diabetes (63); the differ-
ential effect on cardiovascular mortality was less clear. The
ACCORD (Action to Control Cardiovascular Risk in Di-
abetes) trial, currently in progress, will examine the relative
benefits of very intensive blood pressure control compared
with more moderate standards (target systolic blood pres-
sure ?120 mm Hg vs. ?140 mm Hg) (67).
Initiation of Lipid-Lowering Treatment
Studies of intensive lipid-lowering treatment suggest
that persons with diabetes benefit to a similar extent as
those without diabetes. For this update, we identified 4
trials (Appendix Table 2, available at www.annals.org) (50,
55, 57, 58) and 1 meta-analysis (68) examining the effects
of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
reductase inhibitors on primary prevention of cardio-
vascular events and deaths in persons with and without
diabetes. In 1 trial, neither the diabetes group nor the non-
diabetes subgroup benefited from statin treatment in re-
ducing mortality or cardiovascular event rates, but the rate
of nonstudy statin use was high in the control group and
the differential reduction in low-density lipoprotein cho-
lesterol between study groups was relatively small (50). In
2 fair-quality trials, statin therapy did not significantly re-
duce the primary end point (coronary events in 1 trial and
coronary and/or stroke events in the other) in the diabetes
subgroup, but it did benefit the nondiabetes subgroup (55,
58). Comparisons between persons with and those without
diabetes were hampered by a relatively low absolute num-
ber of events in the diabetes subgroup.
The Heart Protection Study (57) was a large, good-
quality RCT examining the efficacy of an HMG-CoA re-
ductase inhibitor in primary and secondary prevention of
cardiovascular events and death. Persons with diabetes had
a similar reduction in cardiovascular events (relative risk
reduction, 27% [CI, 7% to 40%]) as did persons without
diabetes who had known vascular disease, and the benefit
Screening Adults for Type 2 Diabetes
858 3 June 2008 Annals of Internal Medicine Volume 148 • Number 11
was independent of initial low-density lipoprotein choles-
terol levels. Many in the diabetes subgroup had additional
cardiovascular risk factors, including smoking, hyperten-
sion, dyslipidemia (high triglyceride and low high-density
lipoprotein cholesterol levels), or a combination of these.
Although persons with shorter diabetes duration seemed to
benefit to a similar extent as those with much longer-
duration diabetes, power was insufficient to determine
whether participants with newly diagnosed diabetes (that
is, ?1 year) benefited to a significant extent.
A recent meta-analysis of 6 primary prevention trials—
the 4 just discussed, an older trial using a fibric acid deriv-
ative, and an older statin trial—reported that lipid-lower-
ing drug treatment seemed to be equally efficacious in per-
sons with and those without diabetes (68).
Aspirin for Primary Prevention
The previous USPSTF review (29) included several
trials of aspirin for primary prevention of cardiovascular
disease. The Antithrombotic Trialists’ Collaborative meta-
analysis showed a nonsignificant 7% relative risk reduction
in the incidence of vascular events in the high-risk diabetic
population (69), a result mainly driven by the results of the
ETDRS (Early Treatment Diabetic Retinopathy Study), in
which the incidence of fatal and nonfatal coronary events
decreased in the treatment group (relative risk, 0.83 [CI,
0.66 to 1.04]) (70). In the Physicians’ Health Study (71),
aspirin was associated with significant cardiovascular risk
reduction in persons with diabetes, and the benefit seemed
greater in those with diabetes than in those without.
We identified 2 new studies of low-dose aspirin for
primary prevention of cardiovascular events in persons
with and without diabetes (59, 60). In the Primary Preven-
tion Project (59), the subgroup with diabetes did not ex-
perience any benefit, whereas the subgroup without diabe-
tes experienced a reduction in the incidence of major
cardiovascular and cerebrovascular events (relative risk,
0.59 [CI, 0.37 to 0.94]). This fair-quality study was
stopped early, with a resultant low event rate in both
groups. Given the small size of the group with diabetes, the
trial was probably underpowered to detect a difference in
this subgroup. The Women’s Health Study (60), a large,
good-quality trial, showed that aspirin reduced the inci-
dence of ischemic stroke (relative risk, 0.42 [CI, 0.22 to
0.82]), but not cardiovascular events, in women with dia-
betes. There was no evidence that the effect of aspirin was
significantly more pronounced in women with diabetes
than in those without. The difference in results between
the Primary Prevention Project (59) and the Women’s
Health Study (60) may be due to differences in the popu-
lations considered or to the differential risks for stroke ver-
sus those for myocardial infarction (the rate of stroke was
higher than that of myocardial infarction in the Women’s
Key Question 3
Does beginning treatment of impaired fasting glucose or
impaired glucose tolerance early as a result of screening provide
an incremental benefit in final health outcomes compared
with initiating treatment after clinical diagnosis of type 2
Three studies reported cardiovascular outcomes with
intensive lifestyle interventions in persons with prediabetes
(36, 72, 73). In the DPP (Diabetes Prevention Program)
(36), neither the cumulative incidence of cardiovascular
disease nor the event rate differed among treatment groups;
however, the study was not adequately powered to examine
these outcomes (74). The STOP-NIDDM (Study to Pre-
vent Non–Insulin-Dependent Diabetes Mellitus) trial (72),
in which patients with impaired glucose tolerance were
randomly assigned to placebo or acarbose, showed a reduc-
tion in cardiovascular events of any type (hazard ratio, 0.51
[CI, 0.28 to 0.95]; absolute risk reduction, 2.5%). How-
ever, this study was limited by an attrition rate of 24%
overall, with a much higher rate in the treatment group. In
the DREAM (Diabetes Reduction Assessment with
Ramipril and Rosiglitazone Medication) trial (73, 75), the
incidence rate of the primary composite outcome of car-
diovascular events did not significantly differ between the
rosiglitazone and placebo groups (hazard ratio, 1.37 [CI,
0.97 to 1.94]) (75) (Appendix Table 3, available at www
Many studies have examined the effect of lifestyle in-
terventions on the incidence of type 2 diabetes among per-
sons with prediabetes (36, 38, 76–81), several of which
(36, 76, 80, 81) were included in the previous review (29).
In the DPP (36), the incidence of diabetes was reduced at
3-year follow-up with an intensive lifestyle intervention
(reduction in incidence, 58% [CI, 48% to 66%]) and with
treatment with metformin (reduction in incidence, 31%
[CI, 17% to 43%]), both compared with placebo. The
Finnish Diabetes Prevention study (76) examined a life-
style intervention, and the incidence rate of diabetes was
significantly reduced at mean follow-up of 3.2 years (haz-
ard ratio, 0.4 [CI, 0.3 to 0.7]). This was maintained 3 years
after completion of the intervention (hazard ratio, 0.57
[CI, 0.43 to 0.76]) (82). A Chinese study also reported a
significant decrease in the incidence of type 2 diabetes at
6-year follow-up with an intensive lifestyle intervention
(80). Two smaller, more recent trials examined the effect of
lifestyle interventions on incidence rates of diabetes among
persons with prediabetes and found a significant decrease
in incidence compared with usual care (38, 77).
Several recent studies examined the effect of pharma-
cotherapeutic interventions on diabetes incidence. In the
DREAM trial (73, 75), rosiglitazone reduced the incidence
of diabetes among persons with prediabetes when it was
administered for a median of 3.0 years (hazard ratio, 0.38
[CI, 0.33 to 0.44]) (75), whereas ramipril was not effective
in reducing the incidence of diabetes (73). In the STOP-
NIDDM trial (72), the incidence rate of type 2 diabetes
Screening Adults for Type 2 Diabetes
3 June 2008 Annals of Internal Medicine Volume 148 • Number 11 859
was reduced significantly in the acarbose treatment group
over the 3.3-year intervention (hazard ratio, 0.75 [CI, 0.63
In the XENDOS (XENical in the Prevention of Dia-
betes in Obese Subjects) study (83), which was rated fair-
to-poor quality because of high attrition, orlistat reduced
the incidence of type 2 diabetes over 4 years in patients
with impaired glucose tolerance (hazard ratio, 0.55 [CI not
reported]) (83). A meta-analysis of 3 other studies of orl-
istat produced similar results (37). Acarbose (84) and met-
formin (77) also decreased diabetes incidence at up to
3-year follow-up. Two studies of interventions in persons
with prediabetes are in progress, and published results are
not yet available (85, 86).
Results from our meta-analyses showed that the inci-
dence of type 2 diabetes was decreased with lifestyle inter-
ventions (pooled hazard ratio, 0.48 [CI, 0.40 to 0.58])
(Appendix Figures 2 and 3, available at www.annals.org).
Pharmacotherapeutic interventions also reduced diabetes
incidence (pooled hazard ratio, 0.65 [CI, 0.51 to 0.83]),
although the data were statistically heterogeneous largely
due to the effect of the rosiglitazone group of the DREAM
We did not identify any data to address the question
of whether there should be different treatment targets for
lipid levels and blood pressure for persons with prediabetes
compared with normoglycemic persons.
We identified only 1 study examining the comparative
effectiveness of different medications for treating hyper-
lipidemia, hypertension, and cardiovascular disease among
Table 1. Summary of Evidence*
VariableDesign Limitations Consistency
Key question 1: overall effect of screening on final outcomes
3 studies Case–control and cross-
sectional studies (40–42)
Data were limited; studies considered
microvascular complications only.
Studies were consistent.
Key question 2: diabetes treatment
8 studies RCTs with diabetes vs.
analyses); RCTs with duration
of T2DM ?1 y (50–52, 55,
Several studies were probably underpowered
for the diabetes subgroup. Baseline
characteristics differed between the
diabetes and nondiabetes subgroups.
Studies generally showed no evidence of a significant
differential effect between diabetes and nondiabetes
Key question 3: prediabetes treatment
11 studies RCTs (36–38, 72, 75–79, 83, 84) Mean follow-up, approximately 3 years;
longest follow-up, 7 years; only 3 studies
examined long-term health outcomes.
Lifestyle and drug interventions consistently produced a
decrease in incidence of T2DM.
Key question 4: adverse effects of screening
8 studies Cohort and cross-sectional
studies (98–100, 103–105, 107,
All observational studies; predominantly
white; study samples composed of
volunteers; short follow-up.
It is difficult to compare results across studies because of
heterogeneous outcome measures and comparison
groups; however, no serious adverse effects were
Key question 5: adverse effects of treatment
24 studies Systematic reviews (111–113,
Reviews were almost entirely based on trials
of short to moderate duration; long-term
data were lacking.
Not applicable; different drugs were examined in each
* ACE-I ? angiotensin-converting enzyme inhibitor; BP ? blood pressure; CVD ? cardiovascular disease; NSD ? no significant difference; RCT ? randomized, controlled
trial; T2DM ? type 2 diabetes mellitus.
Screening Adults for Type 2 Diabetes
860 3 June 2008 Annals of Internal Medicine Volume 148 • Number 11
persons with prediabetes versus those with normoglycemia.
The ALLHAT (51) examined various antihypertensive
therapies among persons with diabetes, impaired fasting
glucose, and normoglycemia and failed to demonstrate su-
periority for an angiotensin-converting enzyme inhibitor or
a calcium-channel blocker compared with a thiazide-type
diuretic across the 3 glycemic strata for the composite out-
come of coronary heart disease death and nonfatal myocar-
Modeling studies have been used to examine the treat-
ment of prediabetes (35, 87–94). The health technology
assessment by Waugh and colleagues (35) recommended
screening for glucose intolerance because strategies for re-
ducing cholesterol and blood pressure are effective and be-
cause type 2 diabetes can be prevented. Waugh and col-
leagues seem to assume that the effects of treating persons
with screening-detected diabetes are the same as those of
treating persons with clinically detected diabetes and that
there are proven linkages between treating dysglycemia and
final health outcomes. They also systematically reviewed
published economic models and noted that, despite the
variable quality, structure, and assumptions of the models,
all predicted that delaying the onset of diabetes would sub-
stantially reduce the incidence of vascular complications,
improve quality of life, and avoid future medical costs.
They concluded that if a screening program was imple-
mented to target persons at risk for diabetes, subsequent
treatment for persons with impaired glucose tolerance with
lifestyle or pharmacologic interventions was a good use of
Herman and associates (90) examined the lifetime util-
ity and cost-effectiveness of the DPP lifestyle intervention
(36) and found the intervention to be relatively cost-effec-
tive (cost per quality-adjusted life-year, $8800 [from a so-
Primary Care Applicability Overall
Summary of Findings
Case–control study was representative of a primary
care population, but results did not represent
population-level results from a screening program.
Fair-quality cross-sectional study was a non-U.S.
population in an area of high screening rates and
national registries; however, an unknown percentage
was clinically detected.
PoorBoth fair-quality studies demonstrated no benefit for screening:
Case–control study: Patients with ?1 glucose screening event in 10
years had a 13% reduction in risk for severe microvascular T2DM
Cross-sectional study: No significant differences between T2DM
population and general Swedish population (where there is a high
level of screening for T2DM) in most measures of visual acuity.
One poor-quality study showed NSD.
Studies were representative of a primary care population,
but results did not represent population-level results
from a screening program.
FairPersons with T2DM without known CVD seem to benefit from aggressive
lipid-lowering treatment as much as persons without T2DM with
known CVD. There is little strong evidence that specific
antihypertensive drugs benefit persons with T2DM more than those
without. Persons with T2DM seem to benefit from a lower BP target
than persons without. Fair evidence suggests a marginal benefit of
aspirin for primary prevention of CVD, although no clear evidence
suggests that those with diabetes benefit more than other subgroups at
high risk for CVD.
Trials consisted of highly selected participants.FairIntensive lifestyle and pharmacotherapeutic interventions reduce the
progression of prediabetes to T2DM at follow-up up to 7 years. Few
data exist on the effect of these interventions on cardiovascular events,
death, or other long-term health outcomes.
Studies included persons at high risk for T2DM, so
results may not be applicable to primary care
Fair to poor Data were sparse on the psychological effects of screening for T2DM,
and no available data suggested significant adverse effects at up to
1-year follow-up. No study reported serious, long-term, adverse effects
of a new diagnosis of T2DM.
Included studies were largely trials of selected
populations with limited applicability to real-world,
primary care populations.
Fair Acarbose: NSD in death from placebo; gastrointestinal side effects
Metformin: NSD in death, hypoglycemia, lactic acidosis vs. placebo or
ACE-I: significant increase in cough vs. placebo.
?-Blockers: increase in withdrawals secondary to adverse events vs.
placebo; NSD in total deaths.
Rosiglitazone: new data on potential for increased risk for cardiac events
and heart failure.
Screening Adults for Type 2 Diabetes
3 June 2008 Annals of Internal Medicine Volume 148 • Number 11 861
cietal perspective]), with a 0.5-year gain in life expectancy
and 20% decrease in diabetes incidence. Results were
somewhat less marked with metformin, which was still rel-
Eddy and colleagues (87, 88) examined the DPP in-
terventions and also predicted large absolute reductions in
the proportion of persons developing type 2 diabetes and a
delay of 7 to 8 years in onset of diabetes, as well as that the
DPP lifestyle intervention will lead to fewer complications
and improved quality-adjusted life-years (95). They, how-
ever, estimated much higher marginal cost-effectiveness ra-
tios than did Herman and associates (96).
Several other models recently evaluated primary pre-
vention of type 2 diabetes among persons with impaired
glucose tolerance (91, 92, 94, 97), and all demonstrated
relative cost-effectiveness of lifestyle interventions. Two
models examined metformin and found it to be cost-saving
under many conditions (92, 97).
Key Question 4
What adverse effects result from screening a person for
type 2 diabetes, impaired fasting glucose, or impaired glucose
Data are sparse on the psychological effects of screen-
ing for type 2 diabetes, and none of the data that we iden-
tified suggested significant adverse effects at up to 1-year
follow-up (98–110). In the ADDITION study (103),
stepwise screening had limited effects on anxiety levels at
up to 1-year follow-up. In a cross-sectional study, Skinner
and colleagues (109) did not find that screening high-risk
patients for type 2 diabetes with an oral glucose tolerance
test was associated with significant anxiety. Other included
studies also did not report any serious psychological effects
of a new diagnosis of type 2 diabetes (98–104, 107, 108,
Several studies compared persons with screening-
detected diabetes with persons without diabetes. Using
Hoorn observational data, Adriaanse and colleagues (100)
found no significant differences in well-being and health-
related quality of life between patients with newly diag-
nosed diabetes and those at high risk but without diabetes
at 2-week and 1-year follow-ups. Poorer quality-of-life
scores at 6-month follow-up in the group with diabetes
may suggest a temporary effect. Similar results were found
in several other studies (98, 104, 107). In the ADDITION
study (102, 103, 110), persons with screening-detected di-
abetes generally reported low emotional distress, with some
differences in distress and self-efficacy noted between
groups treated intensively compared with usual care.
We identified no studies that addressed the effects of a
false-positive result from any of the tests used to screen for
dysglycemia. We identified no studies that directly ad-
dressed labeling of persons with screening-detected diabe-
tes and no studies that examined the effect of a diagnosis of
Key Question 5
What adverse effects result from treating a person with
type 2 diabetes, impaired fasting glucose, or impaired glucose
tolerance detected by screening?
Recent systematic reviews of the adverse effects of
drugs used in treating type 2 diabetes and prediabetes
(111–136) reveal some important new data related to the
zone and increased risk for myocardial infarction (134,
137) and heart failure (134) was noted recently. For other
drugs examined in the studies included in this review, we
identified no new data on severe adverse effects compared
with data available at the time of the previous USPSTF
review (29). Intensive glucose control in the UKPDS was
not associated with high rates of hypoglycemia (0.55% an-
nual incidence of major hypoglycemia) (138). Relatively
common side effects, such as cough with angiotensin-con-
verting enzyme inhibitors and gastrointestinal effects with
acarbose, should be considered when prescribing these
drugs, but they are not associated with increased deaths or
adverse cardiovascular outcomes.
No direct evidence clearly determines whether screen-
ing asymptomatic individuals for diabetes or prediabetes
alters health outcomes (Table 1). Evidence shows that per-
sons with diabetes benefit from control of blood pressure
and lipid levels, but studies have not included persons with
screening-detected diabetes. Persons with hypertension and
type 2 diabetes benefit from lower blood pressure targets
than persons with hypertension but without diabetes (66).
Persons with newly diagnosed, largely clinically detected,
diabetes benefit from intensive glycemic control, largely
because of a reduction in microvascular events (62). Evi-
dence shows that intensive lifestyle modification in persons
with prediabetes—an implicitly screening-detected popula-
tion—delays the progression to clinical diabetes, but
whether treatment alters final health outcomes is unknown
because studies were not powered for those outcomes or
were not of sufficient duration.
Tables 2 and 3 show the numbers needed to screen to
prevent an outcome of interest in different theoretical pop-
ulations. These outcomes have not changed from the esti-
mates of the previous USPSTF review (29) because we
identified no new data on the effectiveness of these inter-
ventions. As noted elsewhere (29), interventions that target
cardiovascular events produce greater effects than those
that target microvascular complications occurring later in
the disease process.
On the basis of the DPP (36) and the Finnish Diabe-
tes Prevention Study (76), screening 1000 persons with
prediabetes will delay 44 cases of type 2 diabetes over 3.0
years. Pharmacotherapy with metformin (on the basis of
DPP data ) produced a somewhat less favorable num-
ber needed to screen. Many important assumptions under-
Screening Adults for Type 2 Diabetes
862 3 June 2008 Annals of Internal Medicine Volume 148 • Number 11
lying number-needed-to-screen estimates remain, includ-
ing length of the asymptomatic period, prevalence of
undiagnosed diabetes or prediabetes, incidence rates of di-
abetes complications, and treatment effect.
Screening targeted to populations at risk for diabetes
would probably increase the yield and economic efficiency
of screening, and risk scores have been developed to iden-
tify those at high risk for diabetes (139–144). In the DPP,
older age and higher body mass index increased the yield of
screening across ethnic groups (145). On the other hand,
the prevalence of diagnosed diabetes in certain high-risk
groups, such as non-Hispanic black persons and Mexican-
American persons, has increased, whereas the proportion of
persons with undiagnosed disease in those groups has de-
creased, suggesting that opportunistic screening targeted to
populations at high risk may already be occurring. This
trend reduces the prevalence of undiagnosed diabetes and
increases the number needed to screen to prevent adverse
events in the remaining unscreened group (1).
A diabetes population of significant interest to a
screening program would be individuals who would benefit
from aggressive interventions to reduce macrovascular
complications in persons who would not have been other-
wise identified through recommended hypertension and
hyperlipidemia screening (31). Many persons with diabetes
are hypertensive or have additional cardiovascular disease
risk factors, and those with the highest cardiovascular risk
profiles are likely to benefit most from treatment (57, 62,
146–148). As shown in the Heart Protection Study (63),
elevated low-density lipoprotein cholesterol levels alone
Table 2. Number Needed to Screen for Type 2 Diabetes to Prevent 1 Adverse Event after 5 Years of Additional Treatment*
Patient Population Tight Glycemic Control to Prevent 1 Case
of Blindness in 1 Eye (Screening
1000 People with Given Prevalence)
Tight Blood Pressure Control to Prevent 1 CVD
Event (Screening 1000 Hypertensive People
with Given Prevalence)
Increase in Persons
with Tight Glycemic
NNS Increase in Persons with
Tight Blood Pressure
prevalence in U.S.
500.06 16 42050 0.53 1905
90 0.11 9122900.95 1058
50 0.08 12 771 500.681481
90 0.14709590 1.22823
50 0.13 7663 501.13 889
90 0.23 425790 2.03494
* CVD ? cardiovascular disease; NNS ? number needed to screen.
† Relative risk reduction, 0.29 over 5 years; rate of blindness in no-treatment group, 1.5% over 5 years. Data on incidence of retinal photocoagulation in 1 eye from the
United Kingdom Prospective Diabetes Study (62).
‡ Relative risk reduction of 0.50 over 5 years; 5-year incidence in usual treatment group, 7.5%. Data from the Hypertension Optimal Treatment trial (66).
Table 3. Number Needed to Screen for Prediabetes to Prevent 1 Case of Diabetes after 3 Years*
IGT or IFG
Patient PopulationLifestyle Intervention to Prevent 1
Case of Diabetes (Screening 1000 People with
Metformin to Prevent 1 Case of
Diabetes (Screening 1000 People with
Increase in Persons
NNS Increase in Persons
15.0% IGT only, total U.S.
IFG only, total U.S.
Estimate IFG and/or
* IFG ? impaired fasting glucose; IGT ? impaired glucose tolerance; NNS ? number needed to screen.
† Relative risk reduction, 58%; 38% achieved weight loss goal of 7% at end of 3-year follow-up (intention-to-treat analysis); control rate, 11%. Data from the Diabetes
Prevention Program (36).
‡ Relative risk reduction, 31% with adherence rates (?80% of medications taken); 77% in control group; 72% in intervention group. Data from the Diabetes Prevention
§ Based on National Health and Nutrition Examination Survey, 1994 data (2).
? Prevalence data from National Health and Nutrition Examination Survey, 2002 (1): IFG, 5.5–6.93 mmol/L (100–126 mg/dL).
¶ From National Institute of Diabetes and Digestive and Kidney Diseases, 1994 data (http://diabetes.niddk.nih.gov/dm/pubs/statistics).
Screening Adults for Type 2 Diabetes
3 June 2008 Annals of Internal Medicine Volume 148 • Number 11 863
may not identify many persons with diabetes and dyslipi-
demia who might benefit from lipid-lowering treatment,
but this population had higher-than-average cardiovascular
risk profiles. The benefit of identifying and treating asymp-
tomatic diabetes in normotensive, nondyslipidemic persons
at average cardiovascular risk is unclear.
The potential yield of diabetes and prediabetes screen-
ing must be weighed carefully against the potential harms
of screening and diagnosis. We did not identify evidence
suggesting serious adverse effects of screening for type 2
diabetes. The literature does, however, have important lim-
itations. Included studies examined persons at high risk for
diabetes, and thus the results may not be applicable to mass
screening programs that are not targeted (98–100). Theo-
retical concerns include the effects of labeling (149) on
anxiety and insurability, but available evidence is insuffi-
cient to support or refute these concerns.
Several limitations deserve mention. First, we re-
stricted our review of diabetes treatment to studies with
mean diabetes duration of 1 year or less, because we felt
that these patient populations would most closely resemble
screening-detected populations. Individuals with long-
standing type 2 diabetes will likely show greater benefits
from treatment, so focusing on treatment of early disease,
in the absence of trials with extended follow-up, may un-
derestimate the effectiveness of treatment and therefore
screening interventions. For studies comparing a given
treatment among persons with and persons without type 2
diabetes, we included studies of any duration of disease,
and the applicability of these data to populations with
screening-detected disease is uncertain. Second, attempts to
divide patients with diagnosed diabetes into those with a
“clinical diagnosis” based on symptoms and those deemed
to be “screened” because of alleged asymptomatic status
does not truly compare “not screened” with “screened”
patients. Third, participants with prediabetes in studies of
intensive lifestyle interventions may not be representative
of general prediabetic populations. For example, the level
of physical inactivity in the DPP cohort was less than that
reported in the Third National Health and Nutrition Ex-
amination Survey (150). Fourth, most of the data on dia-
betes treatment were from prespecified subgroup analyses
of large trials that included both diabetic and nondiabetic
populations. The diabetes and nondiabetes subgroups had
important differences, and subgroup analyses were often
underpowered to demonstrate significant changes in pri-
mary outcomes. Prevention trials among persons with pre-
diabetes were powered to examine the primary outcome of
new cases of diabetes and not to examine long-term health
outcomes, such as cardiovascular events.
Models rely on data from trials and observational stud-
ies and are only as good as the data and assumptions un-
derlying them. All 7 models that we identified that exam-
ined the effect of screening interventions (35, 43–48) lack
transparency to some degree, and all have had 1 or more of
their important underlying assumptions criticized (35).
Further research is needed to define the benefits and
harms of screening average-risk individuals for type 2 dia-
betes. We must learn whether early, aggressive glycemic
control in persons with diabetes produces improvements in
clinical outcomes after many years of follow-up (151). An
extension of the largest study of an initial strategy of sus-
tained tight glycemic control in type 1 diabetes (152) sug-
gested that participants originally randomly assigned to
tight glycemic control had a significant reduction in car-
diovascular events at long-term follow-up despite similar
glycemic control in the control group during the post-
randomization period (153). To date, similar data are un-
available for type 2 diabetes. We also need studies to define
the duration of the prediabetes phase and identify measur-
able risk factors for progression to diabetes and its compli-
cations, particularly cardiovascular disease.
The cost-effectiveness of diabetes screening programs
is considered to be mainly determined by the long-term
health benefits rather than the cost of detection and treat-
ment of diabetes (154). Thus, intervention research needs
to continue focusing on long-term, sustainable interven-
tions that affect health outcomes in real-world settings.
Further work is also needed to examine the effect of screen-
ing and diagnosis on patient self-efficacy, motivation for
lifestyle change, and the potential psychological effects of
Direct evidence is lacking on the health benefits of
detecting type 2 diabetes by either targeted or mass screen-
ing, and indirect evidence also fails to demonstrate health
benefits for screening general populations or persons at
high risk for diabetes complications without hypertension.
Persons with hypertension do benefit from knowing their
diagnosis of diabetes, because blood pressure targets are
lower than for nondiabetic persons. Although intensive
lifestyle interventions delay or prevent diabetes onset in
persons with prediabetes, positive effects of this delay on
long-term health outcomes have not been adequately dem-
From the Oregon Evidence-based Practice Center of the Oregon Health
& Science University and Portland Veterans Administration Medical
Center, Portland, Oregon.
Acknowledgment: The following people provided valuable guidance
and insights: Mark Helfand, MD, MPH, Evelyn Whitlock, MD, MPH,
and Peggy Nygren, MA, of the Oregon Evidence-based Practice Center;
Tracy Wolff, MD, MPH, and Mary Barton, MD, MPP, at the Agency
for Healthcare Research and Quality; and the U.S. Preventive Services
Task Force members Ned Calonge, MD, Russ Harris, MD, MPH,
George Isham, MD, MS, and Virginia Moyer, MD, MPH. The authors
thank Andrew Hamilton, MLS, MS, for assistance in developing and
running search strategies; Peggy Nygren, MA, and Tracy Dana, MLS, for
assistance with data abstraction; and Sarah Baird, MS, for technical as-
Grant Support: This report was conducted by the Oregon Evidence-
based Practice Center under contract to the Agency for Healthcare Re-
search and Quality (contract no. 290-02-0024, Task Order no. 2 for the
U.S. Preventive Services Task Force).
Screening Adults for Type 2 Diabetes
864 3 June 2008 Annals of Internal Medicine Volume 148 • Number 11
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Susan L. Norris, MD, MPH, Depart-
ment of Medical Informatics and Clinical Epidemiology, Oregon Health
& Science University, 3181 SW Sam Jackson Park Road, Mail Stop
B1CC, Portland, OR 97239.
Current author addresses are available at www.annals.org.
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Appendix Figure 1. Analytic framework.
Fasting blood glucose
Oral glucose tolerance test
Blood pressure control
Treatment interventions in
screening-detected persons or persons
with diabetes duration ≤1 y
Quality of life
Severe visual impairment
Stage IV and V chronic kidney
KQ ? key question.
W-188 3 June 2008 Annals of Internal Medicine Volume 148 • Number 11