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Reviews |2 June 2015

Screening for Type 2 Diabetes Mellitus: A Systematic Review for the U.S. Preventive Services Task Force Free

Shelley Selph, MD, MPH; Tracy Dana, MLS; Ian Blazina, MPH; Christina Bougatsos, MPH; Hetal Patel, MD; Roger Chou, MD

Shelley Selph, MD, MPH
From Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon.

Tracy Dana, MLS
From Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon.

Ian Blazina, MPH
From Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon.

Christina Bougatsos, MPH
From Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon.

Hetal Patel, MD
From Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon.

Roger Chou, MD
From Pacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, Oregon.

Article, Author, and Disclosure Information
Author, Article, and Disclosure Information
This article was published online first at www.annals.org on 14 April 2015.
  • 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.

    Requests for Single Reprints: Shelley Selph, MD, MPH, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Mail Code BICC, Portland, OR 97239; e-mail, selphs@ohsu.edu.

    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.

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Abstract

Background:

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.

Purpose:

To update the 2008 U.S. Preventive Services Task Force review on diabetes screening in adults.

Data Sources:

Cochrane databases and MEDLINE (2007 through October 2014) and relevant studies from previous Task Force reviews.

Study Selection:

Randomized, controlled trials; controlled, observational studies; and systematic reviews.

Data Extraction:

Data were abstracted by 1 investigator and checked by a second; 2 investigators independently assessed study quality.

Data Synthesis:

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.

Limitation:

The review was restricted to English-language articles, and few studies were conducted in screen-detected populations.

Conclusion:

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.

Methods

Scope of the Review

We developed a review protocol and analytic framework (Appendix Figure 1) that included the following key questions:
Appendix Figure 1.

Analytic framework.

DM = diabetes mellitus; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; KQ = key question; MI = myocardial infarction.

Image: 5ff1_Appendix_Figure 1_Analytic_framework
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.

Study Selection

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.
Appendix Figure 2.

Inclusion and exclusion criteria per KQ.

BP = blood pressure; DM = diabetes mellitus; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; KQ = key question; MI = myocardial infarction.

Image: 5ff2_Appendix_Figure 2_Inclusion_and_exclusion_criteria_per_KQ
Appendix Figure 3.

Summary of evidence search and selection.

KQ = key question.

* Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews.

† Other sources include previous reports, reference lists of relevant articles, and systematic reviews.

‡ An additional 27 publications are included in the full report (23). Some studies have several publications and some are included for more than 1 KQ.

Image: 5ff3_Appendix_Figure 3_Summary_of_evidence_search_and_selection

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.

Results

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] [32], rated good-quality, and a trial conducted in Ely, United Kingdom [n = 4936] [33], 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.

Appendix Table 1. Effect of Screening for Diabetes on Health Outcomes

Image: 5tt2_Appendix_Table_1_Effect_of_Screening_for_Diabetes_on_Health_Outcomes
Appendix Table 1. Effect of Screening for Diabetes on Health Outcomes
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).

Appendix Table 2. Health Outcomes in Studies of Interventions for Screen-Detected/Early DM, IFG, or IGT

Image: 5tt3_Appendix_Table_2_Health_Outcomes_in_Studies_of_Interventions_for_Screen-Detected_Early_DM_I
Appendix Table 2. Health Outcomes in Studies of Interventions for Screen-Detected/Early DM, IFG, or IGT
Trials of pharmacologic interventions (alone [28–30, 45–49] or in combination with lifestyle modification [50] 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).
Appendix Figure 4.

Meta-analysis of the effect of pharmacologic interventions on all-cause mortality.

M-H = Mantel–Haenszel fixed-effects model; OR = odds ratio.

* Included in the 2008 report (22).

Image: 5ff4_Appendix_Figure 4_Meta-analysis_of_the_effect_of_pharmacologic_interventions_on_all-cause_m
Appendix Figure 5.

Meta-analysis of the effect of pharmacologic interventions on cardiovascular mortality.

M-H = Mantel–Haenszel fixed-effects model; OR = odds ratio.

* Included in the 2008 report (22).

Image: 5ff5_Appendix_Figure 5_Meta-analysis_of_the_effect_of_pharmacologic_interventions_on_cardiovascu

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).

Appendix Table 3. Good-Quality Systematic Reviews of Intensive Versus Standard Glucose Control in People With DM Reporting Health Outcomes and Harms

Image: 5tt4_Appendix_Table_3_Good-Quality_Systematic_Reviews_of_Intensive_Versus_Standard_Glucose_Contr
Appendix Table 3. Good-Quality Systematic Reviews of Intensive Versus Standard Glucose Control in People With DM Reporting Health Outcomes and Harms
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).

Appendix Table 4. Trials of Variably Defined Intensive Versus Standard BP Control in People With DM

Image: 5tt5_Appendix_Table_4_Trials_of_Variably_Defined_Intensive_Versus_Standard_BP_Control_in_People
Appendix Table 4. Trials of Variably Defined Intensive Versus Standard BP Control in People With DM

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).

Appendix Table 5. Studies of Interventions to Prevent or Delay Progression to DM

Image: 5tt6_Appendix_Table_5_Studies_of_Interventions_to_Prevent_or_Delay_Progression_to_DM
Appendix Table 5. Studies of Interventions to Prevent or Delay Progression to DM

Lifestyle Interventions

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%).
Appendix Figure 6.

Meta-analysis of the effect of lifestyle interventions on incidence of progression to DM.

DM = diabetes mellitus; D+L = DerSimonian–Laird random-effects model; PL = profile likelihood model.

* Included in the 2008 report (22).

Image: 5ff6_Appendix_Figure 6_Meta-analysis_of_the_effect_of_lifestyle_interventions_on_incidence_of_pr

Pharmacologic Interventions

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.
Appendix Figure 7.

Meta-analysis of the effect of thiazolidinediones on incidence of progression to DM.

DM = diabetes mellitus; D+L = DerSimonian–Laird random-effects model; PL = profile likelihood model.

* Included in the 2008 report (22).

Image: 5ff7_Appendix_Figure 7_Meta-analysis_of_the_effect_of_thiazolidinediones_on_incidence_of_progres
Appendix Figure 8.

Meta-analysis of the effect of α-glucosidase inhibitors on incidence of progression to DM.

DM = diabetes mellitus; D+L = DerSimonian–Laird random-effects model; PL = profile likelihood model.

* Included in the 2008 report (22).

† Included in the 2003 report (21).

Image: 5ff8_Appendix_Figure 8_Meta-analysis_of_the_effect_of_-glucosidase_inhibitors_on_incidence_of_pr

Multifactorial Interventions

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).

Discussion

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).

Table. Summary of Evidence

Image: 5tt1_Table_Summary_of_Evidence
Table. Summary of Evidence
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 [24]), 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.

References

  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.
  2. American Diabetes Association
    Diagnosis and classification of diabetes mellitus.
    Diabetes Care
    2013
    36 Suppl 1
    S67
    74
    PubMed
    PubMed
  3. 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
    PubMed
    PubMed
  4. Harris
    MI
    Eastman
    RC
    Early detection of undiagnosed diabetes mellitus: a U.S. perspective.
    Diabetes Metab Res Rev
    2000
    16
    230
    6
    PubMed
    CrossRef
    PubMed
  5. 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
    PubMed
    CrossRef
    PubMed
  6. American Diabetes Association
    Standards of medical care in diabetes—2014.
    Diabetes Care
    2014
    37 Suppl 1
    S14
    80
    PubMed
    PubMed
  7. 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
    PubMed
    CrossRef
    PubMed
  8. 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
    PubMed
    CrossRef
    PubMed
  9. 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
    PubMed
    CrossRef
    PubMed
  10. 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
    PubMed
    CrossRef
    PubMed
  11. 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
    PubMed
    CrossRef
    PubMed
  12. 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
    PubMed
    CrossRef
    PubMed
  13. 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
    PubMed
    CrossRef
    PubMed
  14. 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
    PubMed
    CrossRef
    PubMed
  15. American Diabetes Association
    Standards of medical care in diabetes—2015.
    Diabetes Care
    2015
    38 Suppl 1
    S1
    94
  16. 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
    PubMed
    CrossRef
    PubMed
  17. American Academy of Family Physicians
    Summary of Recommendations for Clinical Preventive Services.
    Leawood, KS
    American Acad Family Physicians
    2012
    19
    .
  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.
  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.
  20. 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
    PubMed
    CrossRef
    PubMed
  21. 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
    CrossRef
    PubMed
  22. 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
  23. 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
    CrossRef
    PubMed
  24. 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
  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.
  26. Higgins
    JP
    Thompson
    SG
    Deeks
    JJ
    Altman
    DG
    Measuring inconsistency in meta-analyses.
    BMJ
    2003
    327
    557
    60
    PubMed
    CrossRef
    PubMed
  27. 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
    CrossRef
    PubMed
  28. 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
    PubMed
    CrossRef
    PubMed
  29. 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
    PubMed
    CrossRef
    PubMed
  30. 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
    PubMed
    CrossRef
    PubMed
  31. 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
    PubMed
    CrossRef
    PubMed
  32. 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
    PubMed
    CrossRef
    PubMed
  33. 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
    PubMed
    CrossRef
    PubMed
  34. 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
    PubMed
    CrossRef
    PubMed
  35. 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
    .
    PubMed
    CrossRef
    PubMed
  36. 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
    PubMed
    CrossRef
    PubMed
  37. 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
    PubMed
    CrossRef
    PubMed
  38. 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
    PubMed
    CrossRef
    PubMed
  39. 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
    PubMed
    CrossRef
    PubMed
  40. 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
    PubMed
    CrossRef
    PubMed
  41. 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
    .
    PubMed
    CrossRef
    PubMed
  42. 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
    PubMed
    CrossRef
    PubMed
  43. 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
    PubMed
    CrossRef
    PubMed
  44. 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
    .
    PubMed
    CrossRef
    PubMed
  45. 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
    PubMed
    CrossRef
    PubMed
  46. 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
    PubMed
    CrossRef
    PubMed
  47. 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
    PubMed
    CrossRef
    PubMed
  48. 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
    PubMed
    CrossRef
    PubMed
  49. 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
    PubMed
    CrossRef
    PubMed
  50. 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
    PubMed
    CrossRef
    PubMed
  51. 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
    PubMed
    CrossRef
    PubMed
  52. 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
    PubMed
    CrossRef
    PubMed
  53. 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
    PubMed
    CrossRef
    PubMed
  54. 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
    PubMed
    CrossRef
    PubMed
  55. 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
    PubMed
    CrossRef
    PubMed
  56. 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
    PubMed
    CrossRef
    PubMed
  57. 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
    PubMed
  58. 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
    PubMed
    CrossRef
    PubMed
  59. 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
    .
    PubMed
    PubMed
  60. 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
    .
    PubMed
    CrossRef
    PubMed
  61. 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
    .
    PubMed
    CrossRef
    PubMed
  62. 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
    PubMed
    PubMed
  63. 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
    CrossRef
    PubMed
  64. 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
    PubMed
    CrossRef
    PubMed
  65. 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
    PubMed
    CrossRef
    PubMed
  66. 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
    PubMed
    CrossRef
    PubMed
  67. Gerstein
    HC
    Miller
    ME
    Byington
    RP
    Goff
    DC
    Jr
    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
    PubMed
    CrossRef
    PubMed
  68. 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
    PubMed
    CrossRef
    PubMed
  69. 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
    PubMed
    CrossRef
    PubMed
  70. 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
    PubMed
    CrossRef
    PubMed
  71. Cushman
    WC
    Evans
    GW
    Byington
    RP
    Goff
    DC
    Jr
    Grimm
    RH
    Jr
    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
    PubMed
    CrossRef
    PubMed
  72. 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
    PubMed
    CrossRef
    PubMed
  73. Poulter
    NR
    Blood pressure and glucose control in subjects with diabetes: new analyses from ADVANCE.
    J Hypertens Suppl
    2009
    27
    S3
    8
    PubMed
    CrossRef
    PubMed
  74. 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
    PubMed
    CrossRef
    PubMed
  75. 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
    PubMed
    CrossRef
    PubMed
  76. 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
    PubMed
    CrossRef
    PubMed
  77. 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
    PubMed
    CrossRef
    PubMed
  78. 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
    PubMed
    CrossRef
    PubMed
  79. 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
    PubMed
    CrossRef
    PubMed
  80. 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
    PubMed
    CrossRef
    PubMed
  81. 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
    PubMed
    CrossRef
    PubMed
  82. 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
    PubMed
    CrossRef
    PubMed
  83. 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
    PubMed
    CrossRef
    PubMed
  84. 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
    .
    PubMed
    CrossRef
    PubMed
  85. 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
    PubMed
    CrossRef
    PubMed
  86. 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
    .
    PubMed
    CrossRef
    PubMed
  87. 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
    PubMed
    CrossRef
    PubMed
  88. 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
    PubMed
    CrossRef
    PubMed
  89. 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
    PubMed
    CrossRef
    PubMed
  90. 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
    PubMed
    CrossRef
    PubMed
  91. 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
    PubMed
    CrossRef
    PubMed
  92. 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
    .
    PubMed
  93. 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
    PubMed
    CrossRef
    PubMed
Appendix Figure 1.

Analytic framework.

DM = diabetes mellitus; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; KQ = key question; MI = myocardial infarction.

Image: 5ff1_Appendix_Figure 1_Analytic_framework
Appendix Figure 2.

Inclusion and exclusion criteria per KQ.

BP = blood pressure; DM = diabetes mellitus; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; KQ = key question; MI = myocardial infarction.

Image: 5ff2_Appendix_Figure 2_Inclusion_and_exclusion_criteria_per_KQ
Appendix Figure 3.

Summary of evidence search and selection.

KQ = key question.

* Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews.

† Other sources include previous reports, reference lists of relevant articles, and systematic reviews.

‡ An additional 27 publications are included in the full report (23). Some studies have several publications and some are included for more than 1 KQ.

Image: 5ff3_Appendix_Figure 3_Summary_of_evidence_search_and_selection
Appendix Figure 4.

Meta-analysis of the effect of pharmacologic interventions on all-cause mortality.

M-H = Mantel–Haenszel fixed-effects model; OR = odds ratio.

* Included in the 2008 report (22).

Image: 5ff4_Appendix_Figure 4_Meta-analysis_of_the_effect_of_pharmacologic_interventions_on_all-cause_m
Appendix Figure 5.

Meta-analysis of the effect of pharmacologic interventions on cardiovascular mortality.

M-H = Mantel–Haenszel fixed-effects model; OR = odds ratio.

* Included in the 2008 report (22).

Image: 5ff5_Appendix_Figure 5_Meta-analysis_of_the_effect_of_pharmacologic_interventions_on_cardiovascu
Appendix Figure 6.

Meta-analysis of the effect of lifestyle interventions on incidence of progression to DM.

DM = diabetes mellitus; D+L = DerSimonian–Laird random-effects model; PL = profile likelihood model.

* Included in the 2008 report (22).

Image: 5ff6_Appendix_Figure 6_Meta-analysis_of_the_effect_of_lifestyle_interventions_on_incidence_of_pr
Appendix Figure 7.

Meta-analysis of the effect of thiazolidinediones on incidence of progression to DM.

DM = diabetes mellitus; D+L = DerSimonian–Laird random-effects model; PL = profile likelihood model.

* Included in the 2008 report (22).

Image: 5ff7_Appendix_Figure 7_Meta-analysis_of_the_effect_of_thiazolidinediones_on_incidence_of_progres
Appendix Figure 8.

Meta-analysis of the effect of α-glucosidase inhibitors on incidence of progression to DM.

DM = diabetes mellitus; D+L = DerSimonian–Laird random-effects model; PL = profile likelihood model.

* Included in the 2008 report (22).

† Included in the 2003 report (21).

Image: 5ff8_Appendix_Figure 8_Meta-analysis_of_the_effect_of_-glucosidase_inhibitors_on_incidence_of_pr

Appendix Table 1. Effect of Screening for Diabetes on Health Outcomes

Image: 5tt2_Appendix_Table_1_Effect_of_Screening_for_Diabetes_on_Health_Outcomes
Appendix Table 1. Effect of Screening for Diabetes on Health Outcomes

Appendix Table 2. Health Outcomes in Studies of Interventions for Screen-Detected/Early DM, IFG, or IGT

Image: 5tt3_Appendix_Table_2_Health_Outcomes_in_Studies_of_Interventions_for_Screen-Detected_Early_DM_I
Appendix Table 2. Health Outcomes in Studies of Interventions for Screen-Detected/Early DM, IFG, or IGT

Appendix Table 3. Good-Quality Systematic Reviews of Intensive Versus Standard Glucose Control in People With DM Reporting Health Outcomes and Harms

Image: 5tt4_Appendix_Table_3_Good-Quality_Systematic_Reviews_of_Intensive_Versus_Standard_Glucose_Contr
Appendix Table 3. Good-Quality Systematic Reviews of Intensive Versus Standard Glucose Control in People With DM Reporting Health Outcomes and Harms

Appendix Table 4. Trials of Variably Defined Intensive Versus Standard BP Control in People With DM

Image: 5tt5_Appendix_Table_4_Trials_of_Variably_Defined_Intensive_Versus_Standard_BP_Control_in_People
Appendix Table 4. Trials of Variably Defined Intensive Versus Standard BP Control in People With DM

Appendix Table 5. Studies of Interventions to Prevent or Delay Progression to DM

Image: 5tt6_Appendix_Table_5_Studies_of_Interventions_to_Prevent_or_Delay_Progression_to_DM
Appendix Table 5. Studies of Interventions to Prevent or Delay Progression to DM

Table. Summary of Evidence

Image: 5tt1_Table_Summary_of_Evidence
Table. Summary of Evidence

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3 Comments

Gauranga Dhar

Bangladesh Institute of Family Medicine and Reserach

April 30, 2015

Earliest detection of T2DM in asymptomatic individuals is vital

What is the “take home message” for a physician as a result of current systemic review on screening for type 2 diabetes of U.S. Preventive Services Task Force?
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.

Ebrahim Barkoudah, MD, MPH, FACP 1 3, Larry A Weinrauch, MD 2 3

1 Department of Medicine Brigham and Women’s Hospital, Boston; 2 Department of Medicine, Mount Auburn Hospital, Cambridge and 3 Harvard Medical School, Boston, all in MA

June 19, 2015

Screening Cannot Improve Outcomes Unless Treatment is Effective

In an attempt to update the 2008 U.S. Preventive Services Task Force review on diabetes screening in adults a recent meta-analysis was conducted . The question asked was whether screening for type 2 diabetes (T2D), impaired fasting glucose or impaired glucose tolerance among asymptomatic adults improved health care outcomes. Unfortunately, the authors appear to have lost focus in their selection of a title and provide an unbalanced assessment on the troubling consequences of T2D that is associated with an excess of morbid/mortal events, disability and shortened lifespan . Pervasive in such unbalanced analyses is the formulaic conception that no true observation exists except for recent controlled and randomized trials.

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.

References:

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.

Shelley Selph, Ian Blazina, Roger Chou

Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University

July 22, 2015

In response to Drs Barkoudah and Weinrauch

Our review used rigorous methods and a structured approach to evaluate the effectiveness of screening asymptomatic persons for diabetes in improving health outcomes. Evaluating the appropriateness of treatment in persons diagnosed with diabetes due to the presence of symptoms was outside the scope of our review. In order to better understand the risks and benefits of screening, we evaluated direct evidence on benefits and harms of screening as well as indirect evidence, including effects of treatment for screen-detected and early diabetes and the effects of more-intensive versus less-intensive treatments. As described in our results, we found that treatment for impaired fasting glucose or impaired glucose tolerance can reduce or delay the progression to diabetes. In terms of duration of follow-up, our analysis was not restricted to short-term trials. Our review included a well-conducted randomized trial of screening that found no mortality benefit of screening asymptomatic persons after 10 years and a trial that found treatment with lifestyle interventions associated with reduced risk of all-cause and cardiovascular mortality in persons with impaired glucose tolerance after 23 years. Neither of these trials reported effects on microvascular outcomes, such as blindness or end stage renal disease. Studies on the effects of treatment for diabetes on microvascular outcomes were not conducted in asymptomatic persons with screen-detected diabetes; symptomatic populations and are outside the scope of our review. Epidemiological evidence on the association between diabetes and adverse health outcomes and uncontrolled observational studies on the effects of treatments are limited in their ability to demonstrate causality and highly susceptible to bias, and such studies cannot supersede well-designed and well-conducted trials on the effectiveness of early treatments. Rather, longer-term, well-conducted trials that evaluate macrovascular and microvascular outcomes are needed to better understand the effects of early treatment.

Shelley Selph, MD, MPH
Blazina I, MPH
Roger Chou, MD

References:
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.

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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;162:765–776. doi: 10.7326/M14-2221

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Published: Ann Intern Med. 2015;162(11):765-776.

DOI: 10.7326/M14-2221

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