Shelley Selph, MD, MPH; Tracy Dana, MLS; Ian Blazina, MPH; Christina Bougatsos, MPH; Hetal Patel, MD; Roger Chou, MD
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, firstname.lastname@example.org.
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.
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.
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.
Agency for Healthcare Research and Quality.
DM = diabetes mellitus; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; KQ = key question; MI = myocardial infarction.
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.
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.
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
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).
Meta-analysis of the effect of pharmacologic interventions on cardiovascular mortality.
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
Appendix Table 5. Studies of Interventions to Prevent or Delay Progression to DM
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.
Meta-analysis of the effect of thiazolidinediones on incidence of progression to DM.
Meta-analysis of the effect of α-glucosidase inhibitors on incidence of progression to DM.
† Included in the 2003 report (21).
Table. Summary of Evidence
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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, MPHBlazina I, MPHRoger Chou, MDReferences: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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