Screening for Type 2 Diabetes Mellitus: A Systematic Review for the U.S. Preventive Services Task ForceFREE
Screening for type 2 diabetes mellitus could lead to earlier identification and treatment of asymptomatic diabetes, impaired fasting glucose (IFG), or impaired glucose tolerance (IGT), potentially resulting in improved outcomes.
To update the 2008 U.S. Preventive Services Task Force review on diabetes screening in adults.
Cochrane databases and MEDLINE (2007 through October 2014) and relevant studies from previous Task Force reviews.
Randomized, controlled trials; controlled, observational studies; and systematic reviews.
Data were abstracted by 1 investigator and checked by a second; 2 investigators independently assessed study quality.
In 2 trials, screening for diabetes was associated with no 10-year mortality benefit versus no screening (hazard ratio, 1.06 [95% CI, 0.90 to 1.25]). Sixteen trials consistently found that treatment of IFG or IGT was associated with delayed progression to diabetes. Most trials of treatment of IFG or IGT found no effects on all-cause or cardiovascular mortality, although lifestyle modification was associated with decreased risk for both outcomes after 23 years in 1 trial. For screen-detected diabetes, 1 trial found no effect of an intensive multifactorial intervention on risk for all-cause or cardiovascular mortality versus standard control. In diabetes that was not specifically screen-detected, 9 systematic reviews found that intensive glucose control did not reduce risk for all-cause or cardiovascular mortality and results for intensive blood pressure control were inconsistent.
The review was restricted to English-language articles, and few studies were conducted in screen-detected populations.
Screening for diabetes did not improve mortality rates after 10 years of follow-up. More evidence is needed to determine the effectiveness of treatments for screen-detected diabetes. Treatment of IFG or IGT was associated with delayed progression to diabetes.
Primary Funding Source:
Agency for Healthcare Research and Quality.
In the United States, approximately 21 million persons received diabetes diagnoses in 2010, and an estimated 8 million cases were undiagnosed; roughly 90% to 95% of them have type 2 diabetes mellitus (1, 2). Prevalence of diabetes among U.S. adults has increased, from approximately 5% in 1995 to 8% in 2010 (3). Diabetes is the leading cause of kidney failure, nontraumatic lower-limb amputations, and blindness; a major cause of heart disease and stroke; and the seventh-leading cause of death in the United States (1).
Risk factors for diabetes include obesity, physical inactivity, smoking, and older age (1). Diabetes is more common among certain ethnic and racial minorities (1, 3). Type 2 diabetes is caused by insulin resistance and relative insulin deficiency, resulting in the inability to maintain normoglycemia. Diabetes typically develops slowly (4, 5), although microvascular disease, such as retinopathy and neuropathy, may be present at the time of diagnosis due to vascular damage during the subclinical phase (4, 6).
Screening asymptomatic persons (those without signs or symptoms of hyperglycemia and no clinical sequelae) may lead to earlier identification and earlier or more-intensive treatments, potentially improving health outcomes (2). Strategies for screening include routine screening or targeted screening based on the presence of risk factors, such as obesity or hypertension. In 2008, the U.S. Preventive Services Task Force (USPSTF) recommended diabetes screening in asymptomatic adults with sustained blood pressure (BP) (treated or untreated) greater than 135/80 mm Hg (B recommendation). Although direct evidence on benefits and harms of screening was not available, the recommendation was based on the ability of screening to identify persons with diabetes and evidence that more-intensive BP treatment was associated with reduced risk for cardiovascular events, including cardiovascular mortality, in patients with diabetes and hypertension. The USPSTF found insufficient evidence to assess the balance of benefits and harms of screening in adults without elevated BP (I statement). It also found that lifestyle and drug interventions for impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), defined as a hemoglobin A1c level of 5.7% to 6.4% or a fasting blood glucose level between 5.55 and 6.94 mmol/L (100 and 125 mg/dL) (2), were associated with reduced risk for progression to diabetes (7–14). Other groups also recommend screening persons with risk factors (15–20).
This article updates previous USPSTF reviews (21–23) on diabetes screening in nonpregnant adults.
Scope of the Review
We developed a review protocol and analytic framework (Appendix Figure 1) that included the following key questions:
1. Is there direct evidence that screening for type 2 diabetes, IFG, or IGT among asymptomatic adults improves health outcomes?
2. What are the harms of screening for type 2 diabetes, IFG, or IGT?
3. Do interventions for screen-detected or early diabetes, IFG, or IGT provide an incremental benefit in health outcomes compared with no interventions or initiating interventions after clinical diagnosis?
4. What are the harms of interventions for screen-detected or early diabetes, IFG, or IGT?
5. Is there evidence that more-intensive glucose, BP, or lipid control interventions improve health outcomes in adults with type 2 diabetes, IFG, or IGT compared with traditional control? Is there evidence that aspirin use improves health outcomes in these populations compared with nonuse?
6. What are the harms of more-intensive interventions compared with traditional control in adults with type 2 diabetes, IFG, or IGT?
7. Do interventions for IFG or IGT delay or prevent the progression to type 2 diabetes?
The full report (24), on which this article is based, provides detailed methods and data for the review, including search strategies, evidence tables, and quality ratings of individual studies (available at www.uspreventiveservicestaskforce.org). The full report includes an additional key question on whether the effects of screening or interventions for screen-detected or early diabetes, IFG, or IGT vary by subgroup; effects of treatments on microvascular outcomes; and evidence on effects of more- versus less-intensive lipid control and aspirin use (24).
Data Sources and Searches
A research librarian searched the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews and MEDLINE (2007 to October 2014). We supplemented electronic searches by reviewing previous USPSTF reports and reference lists of relevant articles.
At least 2 reviewers independently evaluated each study to determine inclusion eligibility using predefined inclusion and exclusion criteria (Appendix Figure 2). Because of the limited evidence on treatment of screen-detected diabetes (key question 5), we also included studies of treatment of early diabetes (defined as a pharmacologically untreated hemoglobin A1c level <8.5% or diabetes diagnosis in the past year) that was not specifically screen-detected. Appendix Figure 3 summarizes the selection of literature.
Data Abstraction and Quality Rating
One investigator abstracted details about the study design, patient population, setting, screening method, interventions, analysis, follow-up, and results. A second investigator reviewed data abstraction for accuracy. Two investigators independently applied criteria developed by the USPSTF (25) to rate the quality of each study as good, fair, or poor. Discrepancies were resolved through a consensus process.
Data Synthesis and Analysis
We conducted meta-analyses to calculate risk ratios (RRs) on effects of interventions with the DerSimonian–Laird random-effects model using Stata, version 12 (StataCorp). Statistical heterogeneity was assessed using the I2 statistic (26). When statistical heterogeneity was present, we performed sensitivity analyses using the profile likelihood method because the DerSimonian–Laird model results in overly narrow 95% CIs (27). Two studies (28–30) that used a 2 × 2 factorial design reported no interaction between treatments and were analyzed as a 2-group parallel group trial for the comparison of interest. When studies evaluated several lifestyle strategies, we combined the lifestyle groups. We included all studies in meta-analyses, regardless of event rates. For rare events (incidence <1%), we calculated the Peto odds ratio (31). We stratified results by drug class or lifestyle intervention and performed additional sensitivity analyses based on study quality and presence of outlier trials. We assessed the aggregate internal validity (quality) of the body of evidence for each key question (good, fair, or poor) using methods developed by the USPSTF, based on the quality of studies, precision of estimates, consistency of results, and directness of evidence (25).
Role of the Funding Source
This research was funded by the Agency for Healthcare Research and Quality (AHRQ) under a contract to support the work of the USPSTF. Investigators worked with USPSTF members and AHRQ staff to develop and refine the scope, analytic framework, and key questions; resolve issues arising during the project; and finalize the report. The AHRQ had no role in study selection, quality assessment, synthesis, or development of conclusions. The AHRQ provided project oversight; reviewed the draft report; and distributed the draft for peer review, including to representatives of professional societies and federal agencies. It also performed a final review of the manuscript to ensure that the analysis met methodological standards. The investigators are solely responsible for the content and the decision to submit the manuscript for publication.
Benefits of Screening
Two randomized, controlled trials (ADDITION [Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen Detected Diabetes in Primary Care]–Cambridge [Cambridge, United Kingdom] trial [n = 19 226] , rated good-quality, and a trial conducted in Ely, United Kingdom [n = 4936] , rated fair-quality) evaluated effects of diabetes screening versus no screening on mortality (Appendix Table 1). The ongoing ADDITION trial includes sites in Cambridge, the Netherlands, and Denmark on intensive versus standard treatment of screen-detected diabetes; however, only the Cambridge site had a no-screening component (34). Mean age ranged from 51 to 58 years, 36% to 54% of participants were women, and follow-up was 10 years in both studies (32, 33). In ADDITION-Cambridge, persons at high risk for diabetes, based on known risk factors, were randomly assigned in clusters by clinic site to screening or no screening (32). The Ely study randomly enrolled participants (not selected based on high risk for diabetes) to screening or no screening from a single practice site (33). Seventy-eight percent of participants (11 737 of 15 089) invited to screening had screening in the ADDITION trial (32); 68% of participants in the Ely study were screened (33). Methodological shortcomings in the Ely study included unclear randomization and allocation concealment methods, with baseline differences between groups.
Screening was not superior to no screening in reducing risk for all-cause mortality in either the ADDITION (hazard ratio [HR], 1.06 [95% CI, 0.90 to 1.25]) (32) or the Ely (unadjusted HR, 0.96 [CI, 0.77 to 1.20]; adjusted HR, 0.79 [CI, 0.63 to 1.00]) (33) trial, with point estimates close to 1. The ADDITION trial also found that screening was not associated with reduced risk for cardiovascular mortality (HR, 1.02 [CI, 0.75 to 1.38]), cancer-related mortality (HR, 1.08 [CI, 0.90 to 1.30]), or diabetes-related mortality (HR, 1.26 [CI, 0.75 to 2.10]) (32). Neither study reported nonmortality health outcomes.
Harms of Screening
A fair-quality pilot study of 116 persons invited for screening in the ADDITION trial found that a new diagnosis of diabetes was associated with increased short-term anxiety 6 weeks after screening, compared with no new diagnosis, based on short-form Spielberger State-Trait Anxiety Inventory scores (46.7 vs. 37.0; P = 0.031) (35). Studies lasting longer than the ADDITION pilot study (≥1 year) found no negative psychological effects associated with invitation to screening or notification of positive diabetes status (36, 37). We identified no studies estimating the rate of false-positive results, psychological effects, or other harms associated with a diagnosis of IFG or IGT.
Benefits of Treating Screen-Detected or Early Diabetes, IFG, or IGT
A randomized trial conducted in Da Qing, China, of overweight (mean body mass index [BMI], 25.8 kg/m2) persons with IGT found that, compared with usual care, a 6-year lifestyle intervention was associated with reduced risk for all-cause (HR, 0.71 [CI, 0.51 to 0.99]) and cardiovascular (HR, 0.59 [CI, 0.36 to 0.96]) mortality after 23 years of follow-up (38). The trial was rated fair-quality because of unclear randomization and allocation concealment methods. This study had previously reported no difference in these outcomes after 20-year follow-up (39). Other trials of lifestyle interventions in persons with IFG or IGT and elevated BMI (40, 41) or newly diagnosed diabetes (42–44) with shorter follow-up also reported no beneficial effects on all-cause or cardiovascular mortality (Appendix Table 2).
Trials of pharmacologic interventions (alone [28–30, 45–49] or in combination with lifestyle modification  vs. placebo or usual care) for early diabetes, IFG, or IGT found few differences in health outcomes, including all-cause and cardiovascular mortality (Appendix Table 2). Mean age ranged from 45 to 64 years, and studies enrolled persons who were overweight (BMI >25.0 kg/m2) or obese (BMI >30.0 kg/m2). Five studies were rated good-quality and 3 were rated fair-quality; common methodological shortcomings in the fair-quality studies included unclear randomization and allocation concealment methods. Although individual studies were generally underpowered to detect these outcomes and few events were reported in most studies, pooled estimates were close to 1. Based on 8 studies (10, 28, 45–48, 51, 52) of glucose-lowering agents, including 3 (10, 51, 52) from the previous USPSTF review (22), the pooled odds ratio for all-cause mortality was 1.01 (CI, 0.87 to 1.18; I2 = 28%) (Appendix Figure 4). For cardiovascular mortality, the pooled odds ratio was 1.06 (CI, 0.84 to 1.35; I2 = 7%) based on 5 studies (28, 48, 52–54) of glucose-lowering agents, including 3 (52–54) from the previous USPSTF review (22) (Appendix Figure 5).
Harms of Treating Screen-Detected or Early Diabetes, IFG, or IGT
Of 4 good-quality and 5 fair-quality trials that reported harms associated with interventions (28–30, 40, 43–49), 1 study was conducted in persons with screen-detected or early diabetes and the others enrolled persons with IFG or IGT. No study was specifically designed to assess harms. There were few differences between medications or lifestyle modification versus placebo or usual care in risk for harms (Appendix Table 2). One trial found that, compared with placebo, acarbose was associated with greater risk for withdrawal because of adverse events (47). Rosiglitazone was associated with increased congestive heart failure in 1 trial, although the estimate was imprecise (HR, 7.04 [CI, 1.60 to 31]) (30). One study found that nateglinide was associated with increased risk for hypoglycemia versus placebo (RR, 1.73 [CI, 1.57 to 1.92]), and valsartan was associated with increased risk for hypotension-related adverse events (RR, 1.16 [CI, 1.11 to 1.23]) (28, 29).
Benefits of More-Intensive Treatment Versus Standard Treatment
The treatment phase of the ADDITION-Europe trial evaluated effects of more-intensive multifactorial treatment of screen-detected diabetes (55–57). It was rated fair-quality because of unclear methods of randomization and allocation concealment. The mean hemoglobin A1c level was 6.5%, approximately one fourth of participants were smokers, mean BMI was 31.5 kg/m2, and 6% to 7% of participants had a previous myocardial infarction (MI). Participants were randomly assigned to a multifactorial intervention that included use of intensive glucose-, BP-, and lipid-lowering targets (hemoglobin A1c level <7.0%, BP <135/85 mm Hg, and total cholesterol level ≤4.5 to 5.0 mmol/L [≤173.7 to 193.1 mg/dL]) plus a lifestyle education component (n = 1678) versus treatment to standard targets according to local guidelines (n = 1379). Participants were followed for 5 years or until their first cardiovascular event (cardiovascular mortality, nonfatal MI or stroke, revascularization, or [nontraumatic] amputation) (55).
After adjustment for country, intensive treatment was not associated with reduced risk for a first cardiovascular event (HR, 0.83 [CI, 0.65 to 1.05]) (55), all-cause (HR, 0.83 [CI, 0.65 to 1.05]) or cardiovascular (HR, 0.88 [CI, 0.51 to 1.51]) mortality, stroke (HR, 0.98 [CI, 0.57 to 1.71]), MI (HR, 0.70 [CI, 0.41 to 1.21]), or revascularization (HR, 0.79 [CI, 0.52 to 1.18]), although most estimates favored intensive therapy. Mortality and cardiovascular event rates were lower than anticipated, with little difference between groups in final hemoglobin A1c and total cholesterol levels and BP (55). There was also no difference in self-reported measures of general and diabetes-specific quality of life (57).
In persons with diabetes that was not specifically screen-detected, 9 good-quality systematic reviews found consistent evidence that intensive glucose-lowering treatment to a target hemoglobin A1c level less than 6.0% to 7.5% was not associated with decreased risk for all-cause or cardiovascular mortality compared with less-intensive therapy (Appendix Table 3) (58–66). One of the largest and most recent reviews (60) analyzed evidence from 14 trials (n = 28 614), including several large, good-quality trials (67–69) published since the previous USPSTF report. Intensive glucose-lowering therapy was consistently associated with reduced risk for nonfatal MI in 6 reviews (RR range, 0.83 to 0.87) (58, 60, 61, 63, 64, 66).
Intensive BP-lowering therapy was associated with reduced risk for all-cause mortality (RR, 0.90 [CI, 0.82 to 0.98]; I2 = 0%) and stroke (RR, 0.83 [CI, 0.73 to 0.95]; I2 = 27%) in 1 good-quality systematic review (70), but individual trials defined intensive BP control differently and some trials showed inconsistent effects (Appendix Table 4). One recent large trial (n = 4732) (71) found no difference between a systolic BP target of 140 mm Hg and 120 mm Hg in risk for all-cause (RR, 1.11 [CI, 0.89 to 1.38]) or cardiovascular (RR, 1.04 [CI, 0.73 to 1.48]) mortality, whereas another trial (n = 11 140) (72, 73) found that, compared with placebo, the addition of an angiotensin-converting enzyme inhibitor plus a diuretic was associated with decreased risk for all-cause (RR, 0.87 [CI, 0.76 to 0.98]) and cardiovascular (RR, 0.33 [CI, 0.15 to 0.74]) mortality. Results from older studies (22) were also mixed and were characterized by variability in antihypertensive treatments and baseline, target, and achieved BP levels (74–79).
Harms of More-Intensive Treatment Versus Standard Treatment
The ADDITION-Netherlands study found no difference between intensive multifactorial treatment versus standard treatment in risk for severe hypoglycemia after 1 year of follow-up, but the event rate was low and the estimate was imprecise (0.4% vs. 0.0%; RR, 2.86 [CI, 0.12 to 70]) (80).
In persons with diabetes not specifically screen-detected, intensive glucose control was associated with increased risk for severe hypoglycemia and serious nonhypoglycemia adverse events requiring medical intervention (Appendix Table 3) (59, 60, 63, 65). Harms of other interventions, including intensive BP-lowering and intensive multifactorial interventions, were mixed (71, 72, 81, 82).
Benefits of Treatment in IFG or IGT on the Delay or Prevention of Progression to Diabetes
We identified 14 randomized, controlled trials (28, 29, 38–40, 45–47, 49, 83–89), 1 quasi-randomized trial (48), and 1 cohort study (90) on the effects of interventions for IFG or IGT on risk for progression to diabetes (Appendix Table 5) (28, 29, 38–40, 45–49, 83–90). Three trials were rated good-quality (28, 29, 46, 49), and the remainder were fair-quality. Methodological shortcomings in the fair-quality studies included unclear randomization and allocation concealment methods, unblinded design, and lack of intention-to-treat analysis. The studies assessed lifestyle interventions (6 studies) (38, 40, 84, 86–88), pharmacologic interventions (8 studies in 9 publications) (28, 29, 45–49, 89, 90), and multifactorial interventions (2 studies) (83, 85). Treatment duration ranged from 6 months to 6 years, with follow-up extending up to 23 years. Mean age ranged from 45 to 65 years. In all but 1 study (86), participants were overweight or obese. Mean total cholesterol levels ranged from 4.3 to 5.9 mmol/L (166 to 228 mg/dL) (Appendix Table 5).
Lifestyle interventions were associated with decreased risk for progression to diabetes, based on 6 studies (38, 40, 84, 86–88), including 4 (7–10) that were in the previous USPSTF review (22) (pooled RR, 0.55 [CI, 0.43 to 0.70]; I2 = 77%; profile likelihood estimate, 0.57 [CI, 0.43 to 0.70]) (Appendix Figure 6). After exclusion of the Da Qing trial, an outlier study with very long (23-year) follow-up (38), we found similar results (pooled RR, 0.53 [CI, 0.44 to 0.63]; I2 = 25%).
Eight studies published since the previous USPSTF review assessed the effect of pharmacologic interventions (28, 45–49, 89, 90). Thiazolinediones were associated with decreased risk for progression to diabetes (3 studies; pooled RR, 0.50 [CI, 0.28 to 0.92]; I2 = 92%) (Appendix Figure 7) (45, 48, 52). Statistical heterogeneity was substantial, and the estimate was no longer statistically significant using the profile likelihood method (RR, 0.51 [CI, 0.23 to 1.06]). Excluding the Indian Diabetes Prevential Programme-2 trial (48), which was conducted in India among mostly male participants, eliminated much of the heterogeneity (RR, 0.42 [CI, 0.37 to 0.47]; I2 = 36%). A similar effect was found in 4 studies of α-glucosidase inhibitors (RR, 0.64 [CI, 0.45 to 0.90]; I2 = 67%; profile likelihood method, 0.65 [CI, 0.44 to 0.91]) (Appendix Figure 8) (46, 47, 51, 91). Other studies found that valsartan (29) and a combination of low-dose metformin and rosiglitazone (49), but not nateglinide (28) or glimepiride (89), was associated with reduced risk for progression to diabetes.
Two trials examined the multifactorial interventions consisting of intensive glucose, BP, and lipid control, in addition to lifestyle counseling and aspirin (83, 85). The ADDITION-Denmark trial (n = 1510) found that the multifactorial intervention was associated with a decreased risk for progression to diabetes that was nearly statistically significant (RR, 0.89 [CI, 0.78 to 1.02]) (85). Effects were greater in the subgroup that also received motivational interviewing (RR, 0.83 [CI, 0.68 to 1.00]) than in the subgroup that did not (RR, 0.95 [CI, 0.80 to 1.14]). A smaller Chinese study (n = 181) reported a lower incidence of progression to diabetes in the intervention group than in the control group, but the estimate was imprecise (0.0% vs. 5.8%; RR, 0.08 [CI, 0.00 to 1.42]) (83).
The Table summarizes the evidence reviewed for this update. In 2 trials, 1 of which focused on persons at greater risk for diabetes, screening was not associated with decreased risk for mortality versus no screening after 10 years of follow-up (32, 33). Point estimates from both trials were close to 1 and did not indicate a trend toward benefit in the good-quality trial, although the CIs encompass potentially meaningful effects (for example, 10% and 37% reduction in risk for all-cause mortality). Possible explanations for the lack of a mortality effect include limited screening uptake, increased mortality among nonattendees invited to screening (potentially attenuating estimates based on intention-to-treat analyses), increased diabetes screening across groups outside of the study protocol, improved management of cardiovascular disease risk factors and diabetes contributing to decreased mortality, and inadequate length of follow-up to adequately assess mortality. In addition, screening trials did not report nonmortality clinical outcomes, which may require less lengthy follow-up to detect clinically relevant effects. Evidence on harms associated with screening is sparse, although limited evidence showed no clear long-term negative effects on psychological measures (35–37).
Lifestyle and pharmacologic interventions both seem to be effective in delaying or preventing progression from IFG or IGT to diabetes in persons with high BMI (7–10, 39, 40, 45–47, 51, 52, 84, 86, 88, 89, 91). Effects of interventions on long-term clinical outcomes are less clear. The study with the longest follow-up (23 years) found that lifestyle modification for 6 years for early diabetes, IFG, or IGT was associated with a mortality benefit (38). Studies with shorter duration of follow-up found no beneficial effects of treatment on mortality, although evidence for improvement in microvascular outcomes was limited, as discussed in more detail in the full report (24).
Pharmacologic treatment of screen-detected or early diabetes, IFG, or IGT was associated with increased risk for withdrawal because of adverse events versus placebo in 1 study (47), with no clear increased risk for serious adverse events. In general, trials were not designed or powered to specifically assess the risk for serious but uncommon or rare adverse events, although studies not restricted to persons with screen-detected or early diabetes did not show a clear increase in risk for such events, such as lactic acidosis with metformin (92).
Since the previous USPSTF review, there is now evidence from a large, good-quality trial that an intensive multifactorial intervention for screen-detected diabetes aimed at decreasing glucose and lipid levels and BP was not associated with a statistically significant reduction in risk for all-cause or cardiovascular mortality or morbidity versus standard treatment, although estimates favored intensive treatment (56). For diabetes not specifically identified by screening, systematic reviews consistently found no association between intensive versus less-intensive glucose-lowering therapy and reduced risk for all-cause or cardiovascular mortality (58–66). Intensive glucose-lowering therapy was associated with reduced risk for nonfatal MI but increased risk for severe hypoglycemia. Other outcomes, such as retinopathy and neuropathy (discussed in the full report ), were found less frequently in these reviews, and pooled risk estimates were inconsistent, precluding reliable conclusions.
The 2008 USPSTF review (22) found that effects of intensive BP control were greater in persons with diabetes versus those without it, based on subgroup analyses from trials that were generally less successful at achieving lower BP than recent studies (71, 72). Since then, there is more evidence on the benefits of more effective, intensive BP control versus standard therapy, specifically in persons with diabetes. Although a good-quality systematic review found that intensive BP control in persons with diabetes was associated with reduced risk for all-cause mortality versus less-intensive BP control (70), results from individual studies, including those from the recent, large, well-conducted trials (71, 72), were inconsistent.
Our review has limitations. We only included English-language articles, although a recent review found that this limitation did not introduce bias into systematic review findings (93). We identified only 2 screening studies, and only 1 treatment study was conducted in a screen-detected population. We included evidence on intensive treatment from studies of persons with early diabetes that was not specifically screen-detected because studies in screen-detected populations were lacking, which could limit applicability to screening settings.
We identified many important research gaps. Screening studies in U.S. populations, in which the prevalence of undiagnosed diabetes (and IFG or IGT) is likely to be greater than the 3% identified in the ADDITION-Cambridge and Ely studies, would be more applicable for informing U.S. screening decisions. As detailed in the full report, there is also little evidence on the effect of screening on ethnic and racial minorities, in whom the prevalence of diabetes is greater than in persons of white, European ancestry (24). Longer-term follow-up of the treatment phase of the ADDITION trial is needed to determine whether beneficial trends become statistically significant as more events occur (56). Studies of the effect of interventions for early diabetes, IFG, or IGT, particularly studies of lifestyle interventions with long-term (>20 years) follow-up, are needed to confirm the findings of the Da Qing study (38).
In conclusion, screening for diabetes did not improve mortality rates after 10 years of follow-up in 2 trials (32, 33) but was found to decrease mortality rates in a lifestyle intervention study with 23 years of follow-up (38). More evidence is needed to determine the effectiveness of treatments for screen-detected diabetes. Treatment of IFG or IGT was associated with delayed progression to diabetes.
- 1. Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2014. Atlanta, GA: U.S. Dept of Health and Human Services; 2014. Accessed at www.cdc.gov/diabetes/pubs/factsheet11.htm on 20 August 2014. Google Scholar
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2013;36 Suppl 1:S67-74. [PMID: 23264425] doi:10.2337/dc13-S067 CrossrefMedlineGoogle Scholar
Centers for Disease Control and Prevention (CDC). Increasing prevalence of diagnosed diabetes—United States and Puerto Rico, 1995-2010. MMWR Morb Mortal Wkly Rep. 2012;61:918-21. [PMID: 23151951] MedlineGoogle Scholar
Harris MI, Eastman RC. Early detection of undiagnosed diabetes mellitus: a U.S. perspective. Diabetes Metab Res Rev. 2000;16:230-6. [PMID: 10934451] CrossrefMedlineGoogle Scholar
Harris MI, Klein R, Welborn TA, Knuiman MW. Onset of NIDDM occurs at least 4–7 yr before clinical diagnosis. Diabetes Care. 1992;15:815-9. [PMID: 1516497] CrossrefMedlineGoogle Scholar
American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37 Suppl 1:S14-80. [PMID: 24357209] doi:10.2337/dc14-S014 CrossrefMedlineGoogle Scholar
Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403. [PMID: 11832527] CrossrefMedlineGoogle Scholar
Kosaka K, Noda M, Kuzuya T. Prevention of type 2 diabetes by lifestyle intervention: a Japanese trial in IGT males. Diabetes Res Clin Pract. 2005;67:152-62. [PMID: 15649575] CrossrefMedlineGoogle Scholar
Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, et al; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344:1343-50. [PMID: 11333990] CrossrefMedlineGoogle Scholar
Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay V; Indian Diabetes Prevention Programme (IDPP). The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia. 2006;49:289-97. [PMID: 16391903] CrossrefMedlineGoogle Scholar
Watanabe M, Yamaoka K, Yokotsuka M, Tango T. Randomized controlled trial of a new dietary education program to prevent type 2 diabetes in a high-risk group of Japanese male workers. Diabetes Care. 2003;26:3209-14. [PMID: 14633803] CrossrefMedlineGoogle Scholar
Swinburn BA, Metcalf PA, Ley SJ. Long-term (5-year) effects of a reduced-fat diet intervention in individuals with glucose intolerance. Diabetes Care. 2001;24:619-24. [PMID: 11315819] CrossrefMedlineGoogle Scholar
Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care. 1997;20:537-44. [PMID: 9096977] CrossrefMedlineGoogle Scholar
Dyson PA, Hammersley MS, Morris RJ, Holman RR, Turner RC. The Fasting Hyperglycaemia Study: II. Randomized controlled trial of reinforced healthy-living advice in subjects with increased but not diabetic fasting plasma glucose. Metabolism. 1997;46:50-5. [PMID: 9439560] CrossrefMedlineGoogle Scholar
American Diabetes Association. Standards of medical care in diabetes—2015. Diabetes Care. 2015;38 Suppl 1:S1-94. Google Scholar
Handelsman Y, Mechanick JI, Blonde L, Grunberger G, Bloomgarden ZT, Bray GA, et al; AACE Task Force for Developing Diabetes Comprehensive Care Plan. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011;17 Suppl 2:1-53. [PMID: 21474420] CrossrefMedlineGoogle Scholar
American Academy of Family Physicians. Summary of Recommendations for Clinical Preventive Services. Leawood, KS: American Acad Family Physicians; 2012:19. Google Scholar
- 18. Colagiuri S, Davies D, Girgis S, Colagiuri R. National Evidence Based Guideline for Case Detection and Diagnosis of Type 2 Diabetes. Canberra, Australia: National Health and Medical Research Council; 2009. Accessed at www.nhmrc.gov.au/_files_nhmrc/file/publications/synopses/di17-diabetes-detection-diagnosis.pdf on 28 October 2014. Google Scholar
- 19. Diabetes UK. Position statement: Early identification of people with, and at high risk of type 2 diabetes and interventions for those at high risk. 2014. Accessed at www.diabetes.org.uk/Documents/About%20Us/What%20we%20say/diabetes-uk-postition-statement-early-identification-type-2-0914.pdf on 28 October 2014. Google Scholar
Pottie K, Jaramillo A, Lewin G, Dickinson J, Bell N, Brauer P, et al; Canadian Task Force on Preventive Health Care. Recommendations on screening for type 2 diabetes in adults. CMAJ. 2012;184:1687-96. [PMID: 23073674] doi:10.1503/cmaj.120732 CrossrefMedlineGoogle Scholar
Harris R, Donahue K, Rathore SS, Frame P, Woolf SH, Lohr KN. Screening adults for type 2 diabetes: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2003;138:215-29. [PMID: 12558362] LinkGoogle Scholar
Norris SL, Kansagara D, Bougatsos C, Nygren P, Fu R. Screening for Type 2 Diabetes: Update of 2003 Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence synthesis no. 61. AHRQ publication no. 08-05116-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2008. Google Scholar
Norris SL, Kansagara D, Bougatsos C, Fu R; U.S. Preventive Services Task Force. Screening adults for type 2 diabetes: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2008;148:855-68. [PMID: 18519931] LinkGoogle Scholar
Selph S, Dana T, Blazina I, Bougatsos C, Patel H, Chou R. Screening for Type 2 Diabetes Mellitus: Systematic Review to Update the 2008 U.S. Preventive Services Task Force Recommendation. Evidence synthesis no. 117. AHRQ publication no. 3-05190-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2014. Google Scholar
- 25. U.S. Preventive Services Task Force. U.S. Preventive Services Task Force Procedure Manual. AHRQ publication no. 08-05118-EF. Rockville, MD: Agency for Healthcare Research and Quality; 2008. Accessed at www.uspreventiveservicestaskforce.org/uspstf08/methods/procmanual.htm on 28 October 2014. Google Scholar
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557-60. [PMID: 12958120] CrossrefMedlineGoogle Scholar
Cornell JE, Mulrow CD, Localio R, Stack CB, Meibohm AR, Guallar E, et al. Random-effects meta-analysis of inconsistent effects: a time for change. Ann Intern Med. 2014;160:267-70. [PMID: 24727843] LinkGoogle Scholar
Holman RR, Haffner SM, McMurray JJ, Bethel MA, Holzhauer B, Hua TA, et al; NAVIGATOR Study Group. Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010;362:1463-76. [PMID: 20228402] doi:10.1056/NEJMoa1001122 CrossrefMedlineGoogle Scholar
McMurray JJ, Holman RR, Haffner SM, Bethel MA, Holzhauer B, Hua TA, et al; NAVIGATOR Study Group. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010;362:1477-90. [PMID: 20228403] doi:10.1056/NEJMoa1001121 CrossrefMedlineGoogle Scholar
Dagenais GR, Gerstein HC, Holman R, Budaj A, Escalante A, Hedner T, et al; DREAM Trial Investigators. Effects of ramipril and rosiglitazone on cardiovascular and renal outcomes in people with impaired glucose tolerance or impaired fasting glucose: results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial. Diabetes Care. 2008;31:1007-14. [PMID: 18268075] doi:10.2337/dc07-1868 CrossrefMedlineGoogle Scholar
Fu R, Gartlehner G, Grant M, Shamliyan T, Sedrakyan A, Wilt TJ, et al. Conducting quantitative synthesis when comparing medical interventions: AHRQ and the Effective Health Care Program. J Clin Epidemiol. 2011;64:1187-97. [PMID: 21477993] doi:10.1016/j.jclinepi.2010.08.010 CrossrefMedlineGoogle Scholar
Simmons RK, Echouffo-Tcheugui JB, Sharp SJ, Sargeant LA, Williams KM, Prevost AT, et al. Screening for type 2 diabetes and population mortality over 10 years (ADDITION-Cambridge): a cluster-randomised controlled trial. Lancet. 2012;380:1741-8. [PMID: 23040422] doi:10.1016/S0140-6736(12)61422-6 CrossrefMedlineGoogle Scholar
Simmons RK, Rahman M, Jakes RW, Yuyun MF, Niggebrugge AR, Hennings SH, et al. Effect of population screening for type 2 diabetes on mortality: long-term follow-up of the Ely cohort. Diabetologia. 2011;54:312-9. [PMID: 20978739] doi:10.1007/s00125-010-1949-8 CrossrefMedlineGoogle Scholar
Lauritzen T, Griffin S, Borch-Johnsen K, Wareham NJ, Wolffenbuttel BH, Rutten G; Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care. The ADDITION study: proposed trial of the cost-effectiveness of an intensive multifactorial intervention on morbidity and mortality among people with type 2 diabetes detected by screening. Int J Obes Relat Metab Disord. 2000;24 Suppl 3:S6-11. [PMID: 11063279] CrossrefMedlineGoogle Scholar
Park P, Simmons RK, Prevost AT, Griffin SJ. Screening for type 2 diabetes is feasible, acceptable, but associated with increased short-term anxiety: a randomised controlled trial in British general practice. BMC Public Health. 2008;8:350. [PMID: 18840266] doi:10.1186/1471-2458-8-350 CrossrefMedlineGoogle Scholar
Rahman M, Simmons RK, Hennings SH, Wareham NJ, Griffin SJ. Effect of screening for type 2 diabetes on population-level self-rated health outcomes and measures of cardiovascular risk: 13-year follow-up of the Ely cohort. Diabet Med. 2012;29:886-92. [PMID: 22283392] doi:10.1111/j.1464-5491.2012.03570.x CrossrefMedlineGoogle Scholar
Paddison CA, Eborall HC, French DP, Kinmonth AL, Prevost AT, Griffin SJ, et al. Predictors of anxiety and depression among people attending diabetes screening: a prospective cohort study embedded in the ADDITION (Cambridge) randomized control trial. Br J Health Psychol. 2011;16:213-26. [PMID: 21226792] doi:10.1348/135910710X495366 CrossrefMedlineGoogle Scholar
Li G, Zhang P, Wang J, An Y, Gong Q, Gregg EW, et al. Cardiovascular mortality, all-cause mortality, and diabetes incidence after lifestyle intervention for people with impaired glucose tolerance in the Da Qing Diabetes Prevention Study: a 23-year follow-up study. Lancet Diabetes Endocrinol. 2014;2:474-80. [PMID: 24731674] doi:10.1016/S2213-8587(14)70057-9 CrossrefMedlineGoogle Scholar
Li G, Zhang P, Wang J, Gregg EW, Yang W, Gong Q, et al. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet. 2008;371:1783-9. [PMID: 18502303] doi:10.1016/S0140-6736(08)60766-7 CrossrefMedlineGoogle Scholar
Saito T, Watanabe M, Nishida J, Izumi T, Omura M, Takagi T, et al; Zensharen Study for Prevention of Lifestyle Diseases Group. Lifestyle modification and prevention of type 2 diabetes in overweight Japanese with impaired fasting glucose levels: a randomized controlled trial. Arch Intern Med. 2011;171:1352-60. [PMID: 21824948] doi:10.1001/archinternmed.2011.275 CrossrefMedlineGoogle Scholar
Uusitupa M, Peltonen M, Lindström J, Aunola S, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, et al; Finnish Diabetes Prevention Study Group. Ten-year mortality and cardiovascular morbidity in the Finnish Diabetes Prevention Study—secondary analysis of the randomized trial. PLoS One. 2009;4:e5656. [PMID: 19479072] doi:10.1371/journal.pone.0005656 CrossrefMedlineGoogle Scholar
Andrews RC, Cooper AR, Montgomery AA, Norcross AJ, Peters TJ, Sharp DJ, et al. Diet or diet plus physical activity versus usual care in patients with newly diagnosed type 2 diabetes: the Early ACTID randomised controlled trial. Lancet. 2011;378:129-39. [PMID: 21705068] doi:10.1016/S0140-6736(11)60442-X CrossrefMedlineGoogle Scholar
Davies MJ, Heller S, Skinner TC, Campbell MJ, Carey ME, Cradock S, et al; Diabetes Education and Self Management for Ongoing and Newly Diagnosed Collaborative. Effectiveness of the diabetes education and self management for ongoing and newly diagnosed (DESMOND) programme for people with newly diagnosed type 2 diabetes: cluster randomised controlled trial. BMJ. 2008;336:491-5. [PMID: 18276664] doi:10.1136/bmj.39474.922025.BE CrossrefMedlineGoogle Scholar
Khunti K, Gray LJ, Skinner T, Carey ME, Realf K, Dallosso H, et al. Effectiveness of a diabetes education and self management programme (DESMOND) for people with newly diagnosed type 2 diabetes mellitus: three year follow-up of a cluster randomised controlled trial in primary care. BMJ. 2012;344:e2333. [PMID: 22539172] doi:10.1136/bmj.e2333 CrossrefMedlineGoogle Scholar
DeFronzo RA, Tripathy D, Schwenke DC, Banerji M, Bray GA, Buchanan TA, et al; ACT NOW Study. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med. 2011;364:1104-15. [PMID: 21428766] doi:10.1056/NEJMoa1010949 CrossrefMedlineGoogle Scholar
Kawamori R, Tajima N, Iwamoto Y, Kashiwagi A, Shimamoto K, Kaku K; Voglibose Ph-3 Study Group. Voglibose for prevention of type 2 diabetes mellitus: a randomised, double-blind trial in Japanese individuals with impaired glucose tolerance. Lancet. 2009;373:1607-14. [PMID: 19395079] doi:10.1016/S0140-6736(09)60222-1 CrossrefMedlineGoogle Scholar
Nijpels G, Boorsma W, Dekker JM, Kostense PJ, Bouter LM, Heine RJ. A study of the effects of acarbose on glucose metabolism in patients predisposed to developing diabetes: the Dutch acarbose intervention study in persons with impaired glucose tolerance (DAISI). Diabetes Metab Res Rev. 2008;24:611-6. [PMID: 18756586] doi:10.1002/dmrr.839 CrossrefMedlineGoogle Scholar
Ramachandran A, Snehalatha C, Mary S, Selvam S, Kumar CK, Seeli AC, et al. Pioglitazone does not enhance the effectiveness of lifestyle modification in preventing conversion of impaired glucose tolerance to diabetes in Asian Indians: results of the Indian Diabetes Prevention Programme-2 (IDPP-2). Diabetologia. 2009;52:1019-26. [PMID: 19277602] doi:10.1007/s00125-009-1315-x CrossrefMedlineGoogle Scholar
Zinman B, Harris SB, Neuman J, Gerstein HC, Retnakaran RR, Raboud J, et al. Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study. Lancet. 2010;376:103-11. [PMID: 20605202] doi:10.1016/S0140-6736(10)60746-5 CrossrefMedlineGoogle Scholar
Florez H, Pan Q, Ackermann RT, Marrero DG, Barrett-Connor E, Delahanty L, et al; Diabetes Prevention Program Research Group. Impact of lifestyle intervention and metformin on health-related quality of life: the diabetes prevention program randomized trial. J Gen Intern Med. 2012;27:1594-601. [PMID: 22692637] doi:10.1007/s11606-012-2122-5 CrossrefMedlineGoogle Scholar
Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M; STOP-NIDDM Trial Research Group. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet. 2002;359:2072-7. [PMID: 12086760] CrossrefMedlineGoogle Scholar
Gerstein HC, Yusuf S, Bosch J, Pogue J, Sheridan P, Dinccag N, et al; DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006;368:1096-105. [PMID: 16997664] CrossrefMedlineGoogle Scholar
Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M; STOP-NIDDM Trial Research Group. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA. 2003;290:486-94. [PMID: 12876091] CrossrefMedlineGoogle Scholar
Ratner R, Goldberg R, Haffner S, Marcovina S, Orchard T, Fowler S, et al; Diabetes Prevention Program Research Group. Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the diabetes prevention program. Diabetes Care. 2005;28:888-94. [PMID: 15793191] CrossrefMedlineGoogle Scholar
Griffin SJ, Borch-Johnsen K, Davies MJ, Khunti K, Rutten GE, Sandbæk A, et al. Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial. Lancet. 2011;378:156-67. [PMID: 21705063] doi:10.1016/S0140-6736(11)60698-3 CrossrefMedlineGoogle Scholar
Simmons RK, Sharp SJ, Sandbæk A, Borch-Johnsen K, Davies MJ, Khunti K, et al. Does early intensive multifactorial treatment reduce total cardiovascular burden in individuals with screen-detected diabetes? Findings from the ADDITION-Europe cluster-randomized trial. Diabet Med. 2012;29:e409-16. [PMID: 22823477] doi:10.1111/j.1464-5491.2012.03759.x CrossrefMedlineGoogle Scholar
Van den Donk M, Griffin SJ, Stellato RK, Simmons RK, Sandbæk A, Lauritzen T, et al. Effect of early intensive multifactorial therapy compared with routine care on self-reported health status, general well-being, diabetes-specific quality of life and treatment satisfaction in screen-detected type 2 diabetes mellitus patients (ADDITION-Europe): a cluster-randomised trial. Diabetologia. 2013. [PMID: 23959571] MedlineGoogle Scholar
Buehler AM, Cavalcanti AB, Berwanger O, Figueiro M, Laranjeira LN, Zazula AD, et al. Effect of tight blood glucose control versus conventional control in patients with type 2 diabetes mellitus: a systematic review with meta-analysis of randomized controlled trials. Cardiovasc Ther. 2013;31:147-60. [PMID: 52902499] doi:10.1111/j.1755-5922.2011.00308.x CrossrefMedlineGoogle Scholar
Hemmingsen B, Lund SS, Gluud C, Vaag A, Almdal TP, Hemmingsen C, et al. Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2013;11:CD008143. [PMID: 24214280] doi:10.1002/14651858.CD008143.pub3 CrossrefMedlineGoogle Scholar
Hemmingsen B, Lund SS, Gluud C, Vaag A, Almdal T, Hemmingsen C, et al. Intensive glycaemic control for patients with type 2 diabetes: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. BMJ. 2011;343:d6898. [PMID: 22115901] doi:10.1136/bmj.d6898 CrossrefMedlineGoogle Scholar
Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, Lafont S, Bergeonneau C, Kassaï B, et al. Effect of intensive glucose lowering treatment on all-cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ. 2011;343:d4169. [PMID: 21791495] doi:10.1136/bmj.d4169 CrossrefMedlineGoogle Scholar
Wu H, Xu MJ, Zou DJ, Han QJ, Hu X. Intensive glycemic control and macrovascular events in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Chin Med J (Engl). 2010;123:2908-13. [PMID: 21034605] MedlineGoogle Scholar
Kelly TN, Bazzano LA, Fonseca VA, Thethi TK, Reynolds K, He J. Systematic review: glucose control and cardiovascular disease in type 2 diabetes. Ann Intern Med. 2009;151:394-403. [PMID: 19620144] LinkGoogle Scholar
Ray KK, Seshasai SR, Wijesuriya S, Sivakumaran R, Nethercott S, Preiss D, et al. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet. 2009;373:1765-72. [PMID: 19465231] doi:10.1016/S0140-6736(09)60697-8 CrossrefMedlineGoogle Scholar
Ma J, Yang W, Fang N, Zhu W, Wei M. The association between intensive glycemic control and vascular complications in type 2 diabetes mellitus: a meta-analysis. Nutr Metab Cardiovasc Dis. 2009;19:596-603. [PMID: 19819121] doi:10.1016/j.numecd.2009.07.004 CrossrefMedlineGoogle Scholar
Mannucci E, Monami M, Lamanna C, Gori F, Marchionni N. Prevention of cardiovascular disease through glycemic control in type 2 diabetes: a meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis. 2009;19:604-12. [PMID: 19427768] doi:10.1016/j.numecd.2009.03.021 CrossrefMedlineGoogle Scholar
Gerstein HC, Miller ME, Byington RP, Goff DC, Bigger JT, Buse JB, et al; Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-59. [PMID: 18539917] doi:10.1056/NEJMoa0802743 CrossrefMedlineGoogle Scholar
Zoungas S, de Galan BE, Ninomiya T, Grobbee D, Hamet P, Heller S, et al; ADVANCE Collaborative Group. Combined effects of routine blood pressure lowering and intensive glucose control on macrovascular and microvascular outcomes in patients with type 2 diabetes: new results from the ADVANCE trial. Diabetes Care. 2009;32:2068-74. [PMID: 19651921] doi:10.2337/dc09-0959 CrossrefMedlineGoogle Scholar
Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al; VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129-39. [PMID: 19092145] doi:10.1056/NEJMoa0808431 CrossrefMedlineGoogle Scholar
Bangalore S, Kumar S, Lobach I, Messerli FH. Blood pressure targets in subjects with type 2 diabetes mellitus/impaired fasting glucose: observations from traditional and Bayesian random-effects meta-analyses of randomized trials. Circulation. 2011;123:2799-810. [PMID: 21632497] doi:10.1161/CIRCULATIONAHA.110.016337 CrossrefMedlineGoogle Scholar
Cushman WC, Evans GW, Byington RP, Goff DC, Grimm RH, Cutler JA, et al; ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575-85. [PMID: 20228401] doi:10.1056/NEJMoa1001286 CrossrefMedlineGoogle Scholar
Patel A, MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, et al; ADVANCE Collaborative Group. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370:829-40. [PMID: 17765963] CrossrefMedlineGoogle Scholar
Poulter NR. Blood pressure and glucose control in subjects with diabetes: new analyses from ADVANCE. J Hypertens Suppl. 2009;27:S3-8. [PMID: 19483505] doi:10.1097/01.hjh.0000354417.70192.be CrossrefMedlineGoogle Scholar
Hansson L, Zanchetti A, Carruthers SG, Dahlöf B, Elmfeldt D, Julius S, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet. 1998;351:1755-62. [PMID: 9635947] CrossrefMedlineGoogle Scholar
UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317:703-13. [PMID: 9732337] CrossrefMedlineGoogle Scholar
Holman RR, Paul SK, Bethel MA, Neil HA, Matthews DR. Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med. 2008;359:1565-76. [PMID: 18784091] doi:10.1056/NEJMoa0806359 CrossrefMedlineGoogle Scholar
Estacio RO, Jeffers BW, Hiatt WR, Biggerstaff SL, Gifford N, Schrier RW. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non–insulin-dependent diabetes and hypertension. N Engl J Med. 1998;338:645-52. [PMID: 9486993] CrossrefMedlineGoogle Scholar
Schrier RW, Estacio RO, Esler A, Mehler P. Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes. Kidney Int. 2002;61:1086-97. [PMID: 11849464] CrossrefMedlineGoogle Scholar
Schrier RW, Estacio RO, Mehler PS, Hiatt WR. Appropriate blood pressure control in hypertensive and normotensive type 2 diabetes mellitus: a summary of the ABCD trial. Nat Clin Pract Nephrol. 2007;3:428-38. [PMID: 17653121] CrossrefMedlineGoogle Scholar
Janssen PG, Gorter KJ, Stolk RP, Rutten GE. Randomised controlled trial of intensive multifactorial treatment for cardiovascular risk in patients with screen-detected type 2 diabetes: 1-year data from the ADDITION-Netherlands study. Br J Gen Pract. 2009;59:43-8. [PMID: 19105915] doi:10.3399/bjgp09X394851 CrossrefMedlineGoogle Scholar
Howard BV, Roman MJ, Devereux RB, Fleg JL, Galloway JM, Henderson JA, et al. Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes: the SANDS randomized trial. JAMA. 2008;299:1678-89. [PMID: 18398080] doi:10.1001/jama.299.14.1678 CrossrefMedlineGoogle Scholar
Gaede P, Lund-Andersen H. Parving HH. Pedersen O, Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358:580-91. [PMID: 18256393] doi:10.1056/NEJMoa0706245 CrossrefMedlineGoogle Scholar
Lu YH, Lu JM, Wang SY, Li CL, Zheng RP, Tian H, et al. Outcome of intensive integrated intervention in participants with impaired glucose regulation in China. Adv Ther. 2011;28:511-9. [PMID: 21533568] doi:10.1007/s12325-011-0022-4 CrossrefMedlineGoogle Scholar
Penn L, White M, Oldroyd J, Walker M, Alberti KG, Mathers JC. Prevention of type 2 diabetes in adults with impaired glucose tolerance: the European Diabetes Prevention RCT in Newcastle upon Tyne, UK. BMC Public Health. 2009;9:342. [PMID: 19758428] doi:10.1186/1471-2458-9-342 CrossrefMedlineGoogle Scholar
Rasmussen SS, Glümer C, Sandbaek A, Lauritzen T, Borch-Johnsen K. General effect on high-risk persons when general practitioners are trained in intensive treatment of type 2 diabetes. Scand J Prim Health Care. 2008;26:166-73. [PMID: 18677673] doi:10.1080/02813430802264624 CrossrefMedlineGoogle Scholar
Sakane N, Sato J, Tsushita K, Tsujii S, Kotani K, Tsuzaki K, et al; Japan Diabetes Prevention Program (JDPP) Research Group. Prevention of type 2 diabetes in a primary healthcare setting: three-year results of lifestyle intervention in Japanese subjects with impaired glucose tolerance. BMC Public Health. 2011;11:40. [PMID: 21235825] doi:10.1186/1471-2458-11-40 CrossrefMedlineGoogle Scholar
Lindahl B, Nilssön TK, Borch-Johnsen K, Røder ME, Söderberg S, Widman L, et al. A randomized lifestyle intervention with 5-year follow-up in subjects with impaired glucose tolerance: pronounced short-term impact but long-term adherence problems. Scand J Public Health. 2009;37:434-42. [PMID: 19181821] doi:10.1177/1403494808101373 CrossrefMedlineGoogle Scholar
Katula JA, Vitolins MZ, Morgan TM, Lawlor MS, Blackwell CS, Isom SP, et al. The Healthy Living Partnerships to Prevent Diabetes study: 2-year outcomes of a randomized controlled trial. Am J Prev Med. 2013;44:S324-32. [PMID: 23498294] doi:10.1016/j.amepre.2012.12.015 CrossrefMedlineGoogle Scholar
Lindblad U, Lindberg G, Månsson NO, Ranstam J, Tyrberg M, Jansson S, et al. Can sulphonylurea addition to lifestyle changes help to delay diabetes development in subjects with impaired fasting glucose? The Nepi ANtidiabetes StudY (NANSY) [Letter]. Diabetes Obes Metab. 2011;13:185-8. [PMID: 21199271] doi:10.1111/j.1463-1326.2010.01331.x CrossrefMedlineGoogle Scholar
Armato J, DeFronzo RA, Abdul-Ghani M, Ruby R. Successful treatment of prediabetes in clinical practice: targeting insulin resistance and β-cell dysfunction. Endocr Pract. 2012;18:342-50. [PMID: 22068250] doi:10.4158/EP11194.OR CrossrefMedlineGoogle Scholar
Pan CY, Gao Y, Chen JW, Luo BY, Fu ZZ, Lu JM, et al. Efficacy of acarbose in Chinese subjects with impaired glucose tolerance. Diabetes Res Clin Pract. 2003;61:183-90. [PMID: 12965108] CrossrefMedlineGoogle Scholar
Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev. 2010:CD002967. [PMID: 20393934] doi:10.1002/14651858.CD002967.pub4 CrossrefMedlineGoogle Scholar
Morrison A, Polisena J, Husereau D, Moulton K, Clark M, Fiander M, et al. The effect of English-language restriction on systematic review-based meta-analyses: a systematic review of empirical studies. Int J Technol Assess Health Care. 2012;28:138-44. [PMID: 22559755] doi:10.1017/S0266462312000086 CrossrefMedlineGoogle Scholar
Author, Article, and Disclosure Information
From Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon.
Acknowledgment: The authors thank Agency for Healthcare Research and Quality Medical Officer Quyen Ngo-Metzger, MD, MPH.
Grant Support: By the Agency for Healthcare Research and Quality (contract HHSA 290-2007-10057-I, Task Order 13).
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-2221.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Corresponding Author: Shelley Selph, MD, MPH, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Mail Code BICC, Portland, OR 97239; e-mail, [email protected]
Current Author Addresses: Drs. Selph, Patel, and Chou; Ms. Dana; Mr. Blazina; and Ms. Bougatsos: Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Mail Code BICC, Portland, OR 97239.
Author Contributions: Conception and design: S. Selph, T. Dana, R. Chou.
Analysis and interpretation of the data: S. Selph, T. Dana, I. Blazina, H. Patel, R. Chou.
Drafting of the article: S. Selph, T. Dana, I. Blazina, H. Patel, R. Chou.
Critical revision of the article for important intellectual content: S. Selph, T. Dana, I. Blazina, R. Chou.
Final approval of the article: S. Selph, T. Dana, I. Blazina, R. Chou.
Statistical expertise: R. Chou.
Obtaining of funding: R. Chou.
Administrative, technical, or logistic support: T. Dana, I. Blazina, C. Bougatsos.
Collection and assembly of data: S. Selph, T. Dana, I. Blazina, C. Bougatsos, H. Patel, R. Chou.
This article was published online first at www.annals.org on 14 April 2015.
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In response to Drs Barkoudah and Weinrauch
Shelley Selph, MD, MPH
Blazina I, MPH
Roger Chou, MD
Selph S, Dana T, Blazina I, Bougatsos C, Patel H, Chou R. Screening for type 2 diabetes mellitus: a systematic review for the U.S. Preventive services task force. Ann Intern Med. 2015;162(11):765-76.
Simmons R, Echouffo-Tcheugui J, Sharp S, Sargeant L, Williams K, Prevost A, Kinmonth A, Wareham N, Griffin S. Screening for type 2 diabetes and population mortality over 10 years (ADDITION-Cambridge): a cluster-randomized controlled trial. Lancet. 2012;380(9855):1741-1748.
Li P, Zhang P, Wang J, An Y, Gong Q, Gregg W, Yang W, Zhang B, Shaui Y, Hong J, Engelgau M, Li H, Roglic G, Hu Y, Bennett P. Cardiovascular mortality, all-cause mortality, and diabetes incidence after lifestyle intervention for people with impaired glucose tolerance in the Da Qing Diabetes Prevention Study: a 23-year follow-up study. Lancet Diabetes & Endocrinology. 2014;2(6):474-480.
Rossouw J, Anderson G, Prentice R, LaCroix A, Kooperberg C, Stafanick M, Jackson R, Beresford S, Howard B, Johnson K, Kotchen J, Ockene J. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women’s health initiative randomized controlled trial. JAMA. 2002;288(3):321-333.
Screening Cannot Improve Outcomes Unless Treatment is Effective
To date, although there is strong evidence that improved glycemic control in T2D will reduce or delay the progression of microvascular disease, studies of macrovascular events conducted over decades in T2D patients have failed to show the same beneficial effect . The authors presume that a short duration observation looking at cardiovascular events and mortality can answer the question of relative screening benefits. It is clear that treatment of diabetes reduces or prolongs time to blindness and end stage renal disease . While loss of vision or renal function may be considered softer end-points by some, they are far more debilitating for our patients. Failure to screen patients for diabetes even in asymptomatic individuals creates a harm that is not imagined in this paper. It is also clear that treatment of impaired fasting glucose or impaired glucose tolerance prolongs the time until complications of diabetes.
As statistical analyses and meta-analyses become more highly complicated and populations studied and morbid/mortal events more limited, study results may derive lesser benefits and may inadvertently create risk of harm. Such harm may be magnified if results are inappropriately generalized; morbid/mortal events are limited to one system, unfocussed or underpowered. We believe this task force review is one such example.
Selph S, Dana T, Blazina I, Bougatsos C, Patel H, Chou R. Screening for type 2 diabetes mellitus: a systematic review for the U.S. Preventive services task force. Ann Intern Med. 2015;162(11):765-76.
Emerging Risk Factors Collaboration, Seshasai SR, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, Sarwar N, Whincup PH, Mukamal KJ, Gillum RF, Holme I, Njølstad I, Fletcher A, Nilsson P, Lewington S, Collins R, Gudnason V, Thompson SG, Sattar N, Selvin E, Hu FB, Danesh J.Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011;364(9):829-41.
Ray KK, Seshasai SR, Wijesuriya S, Sivakumaran R, Nethercott S, Preiss D, Erqou S, Sattar N. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet. 2009;373(9677):1765-72.
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837-53.
Earliest detection of T2DM in asymptomatic individuals is vital
Firstly, the review concluded that screening and earliest detection of type 2 diabetes in asymptomatic individuals did not have any positive effect in reducing mortality at 10-yeras follow up and more evidence is required for the effectiveness of the treatment of screen-detected diabetic patients. That means that we, the physicians should not screen asymptomatic individuals for hyperglycemia.
I cannot support this component of your conclusion. What is the real picture in my practice setting? I routinely screen at least one test HbA1C for all adult who come to me as a patient for the first time. Around 50% of all adults tested, found HbA1C >7%. A significant number of adults without any signs of hyperglycemia have HbA1C even more than 10%. Repeated testing of HbA1C along with FPG and or glucose challenge tests confirms their diagnosis of T2DM. Most of the patients with hyperglycemia remain asymptomatic unless they are either at hyperosmolar state or hypoglycemic coma; incidences of such states are not so high. Asymptomatic patients with hyperglycemia are at high risk specifically of microvascular complications. Most patients come with peripheral neuropathic pain, change of vision or micro or macro-albuminuria in routine urine testing. Further testing confirms T2DM in most of these patients. I have number of normotensive patients suffering from stable angina, having symptoms of peripheral arterial disease, screening of whom confirms diagnosis of T2DM which means both micro and macrovascular diseases develop before diagnosis of T2DM. Literature show that beta cell dysfunction occur even a decade before the diagnosis of overt T2DM. Earliest detection of T2DM may prevent progression of vascular complications. This review showed that no decrease of mortality was found as a result of earliest detection of T2DM in asymptomatic individuals but we can prevent comorbidities.
Now the question is, once T2DM is detected by screening, how to treat these patients? It depends upon the severity of hyperglycemia and presence of vascular complications. Why we should go for acarbose, rosiglitazone or nateglinide? These agents have well known for adverse effects. According to severity, along with lifestyle modification we can start with metformin, or DPP-4 inhibitors. If required, safer sulfonylureas like glimepiride or even insulin can be administered. I think all adults even in the absence of risk factors should be screened for T2DM preferably by at least HbA1C which may not reduce mortality but definitely will reduce morbidity.
Secondly, the review has given good evidence that treatment of IGT and IFG reduces progression to overt diabetes. Literature shows that lifestyle modification only can reduce progression from prediabetes to overt diabetes by 60%. Number of studies proved that drugs like metformin or even insulin glargine (ORIGIN trial) may prevent progression to overt diabetes. Microvascular comlications are commonly found at this state. To find the population on prediabetic state (either IGT or IFG) we need to screen asymptomatic adults.