Population-based diabetes screening programs may not pay off in terms of overall mortality or cardiovascular outcomes, but individuals who are found to have diabetes via screening do appear to benefit, new research suggests.
Results of two analyses from the Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Denmark, along with a separate report from the Västerbotten Intervention Program, were published August 23 in Diabetologia.
In the post hoc evaluation from the Danish arm of the 2012 ADDITION study, population-based, stepwise screening for type 2 diabetes and cardiovascular risk factors among all middle-aged adults in Denmark was not associated with a reduction in mortality or cardiovascular events during 2001–2012. The finding mirrored the overall results of ADDITION, one of two studies that informed the United States Preventive Services Task Force (USPSTF) to focus its 2015 guidelines on screening for prediabetes rather than diabetes.
However, the ADDITION-Denmark data set also revealed that a single round of diabetes screening and cardiovascular-risk assessment in middle-aged adults in general practice was associated with a significant reduction in risk of all-cause mortality and CVD events among those who were diagnosed with diabetes.
Both of those analyses were conducted by Rebecca K Simmons, PhD, of the Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, United Kingdom, and colleagues.
In the third study, from a large Swedish cohort, data showed that individuals with screen-detected diabetes were diagnosed earlier than those who were clinically detected and had reduced all-cause mortality, CVD, renal disease, and retinopathy. However, it’s not clear that this benefit is completely the result of earlier treatment rather than various study biases, according to the authors Adina L Feldman, PhD, also of the Cambridge MRC Unit, and colleagues.
Two separate editorials that accompany the three papers both conclude that the data support the use of opportunistic screening in clinical settings rather than community-based or other general screenings in non-healthcare settings, at least in developed countries where opportunistic screening is already widely practiced.
“Community screening programs, such as those that have been established for colon and breast cancer, cannot be justified for type 2 diabetes in countries where opportunistic diabetes screening is functioning well and management of cardiovascular risk factors is good. The large amounts of public money required for such screening programs would be better spent on treating those with clinically diagnosed disease,” Jonathan E Shaw, MD, of the Baker IDI Heart and Diabetes Institute, Melbourne, Australia, writes in one editorial.
The question remains open in less-developed healthcare systems where the prevalence of undiagnosed diabetes is high, Dr Shaw adds.
Indeed, in the other editorial, David Simmons, MD, professor of medicine at Western Sydney University, Campbelltown, Australia, and Janice C Zgibor, PhD, of the College of Public Health, University of South Florida, Tampa, Florida, point out that trials of screening for undiagnosed diabetes among asymptomatic people may no longer be feasible or ethical in many countries.
Thus, Dr Simmons and Dr Zgibor say that “the most efficient recommendation may be opportunistic screening” in which patients seen in routine primary care for any reason are tested for diabetes or prediabetes “and that focus should now shift to trials of how to screen, methods for implementing treatment earlier, and better risk-factor control in those at highest risk.”
No Benefit of Population-Based Stepwise Screening
The Danish arm of the nonrandomized, controlled ADDITION trial included a total of 1,912,392 adult men and women aged 40 to 69 years without known diabetes who were registered with general practices in Denmark between 2001 and 2006. Of those, 153,107 were screened via risk-score questionnaire while the other 1,759,285 were not.
Of those screened, 18% (27,177) presented for in-person diabetes and cardiovascular risk testing via random capillary blood glucose, cholesterol, and HbA1c. Of those, 1533 were diagnosed with diabetes.
Over a median 9.5 years of follow-up, there were 11,826 deaths in the screening group and 141,719 in the no-screening group; the mortality rates were not significantly different after adjustment (hazard ratio [HR], 0.99; P = .66). Similarly, there were 17,941 first cardiovascular events in the screening group and 208,476 in the no-screening group, also not significantly different (HR, 0.99; P = .49).
Those With Screen-Detected Diabetes Fare Better
The second ADDITION-Denmark post hoc analysis compared mortality and CVD outcomes through 2012 in 13,992 individuals diagnosed with diabetes following screening with 125,083 nonscreened individuals diagnosed with diabetes via clinical practice during 2001–2009.
In a median 6.2 years of follow-up, there were 1775 deaths among those with diabetes who had been screened (12.7%) and 19,739 deaths among the nonscreened group with diabetes (15.8%), a significant difference (HR, 0.79; P < .0001). Interestingly, the most common cause of death was not cardiovascular disease but cancer (38.2%).
There were 2854 first CVD events among those with diabetes who had been screened (20.4%) vs 28,487 among the nonscreened with diabetes (22.8%), again a significant difference (HR, 0.84).
The Swedish study also found benefit for 1403 individuals in whom diabetes was detected via screening in a public-health program that invites residents of a single county for screening by oral glucose tolerance test at 10-year intervals, compared with 8642 people diagnosed clinically who were identified through several registries.
Average follow-up time was 8.7 years for those with screen-detected diabetes, vs 7.2 years for those diagnosed clinically. Average age at diabetes diagnosis was 4.6 years lower for the screen-detected vs clinically diagnosed individuals.
Those with clinically detected diabetes had worse overall outcomes than did those detected via screening, including all-cause mortality (HR, 2.07), CVD events (HR, 1.55), renal disease (HR, 2.26), and retinopathy (HR, 1.66), all statistically significant.
Outcomes Depend on Treatment Approach
In their editorial, Dr Simmons and Dr Zgibor list several flaws of the ADDITION analyses, including that the original trial was not randomized, doesn’t examine benefit of identifying people with impaired glucose tolerance or impaired fasting glucose (prediabetes), and is subject to selection bias in that patients of clinicians who chose to participate may be more likely to have better outcomes.
And of course, they add, “Once diagnosed, a key factor determining mortality among those with diabetes is the intensity of the management received.”
Indeed, Dr Shaw notes, “Currently available therapies for type 2 diabetes are, at best, of modest efficacy. However, if the impressive effects of sodium-glucose cotransporter-2 [SGLT2] inhibitors on cardiovascular outcomes among people with diabetes who are at very high cardiovascular risk were also shown to apply to those at lower cardiovascular risk, this might influence the screening argument.”
Dr Shaw also notes that “although the evidence for community screening is not strong, it is necessary to recognize that the success of screening programs is very sensitive to the circumstances in which they are set.…The question of community screening for diabetes needs to be reassessed according to local settings and over time, and not as a one-off decision based on a single study.”
ADDITION-Denmark was supported by the National Health Services in the participating Danish counties, the Danish Council for Strategic Research, the Danish Research Foundation for General Practice, Novo Nordisk Foundation, the Danish Center for Evaluation and Health Technology Assessment, the diabetes fund of the National Board of Health, the Danish Medical Research Council, and the Aarhus University Research Foundation. The trial has been supported by unrestricted grants from Novo Nordisk, Novo Nordisk Scandinavia, Novo Nordisk UK, ASTRA Denmark, Pfizer Denmark, GlaxoSmithKline Pharma Denmark, Servier Denmark, and HemoCue Denmark. Dr Rebecca K Simmons was supported by the European Foundation for the Study of Diabetes. Disclosures for the coauthors are listed in the paper. The Swedish study was supported by the Medical Research Council, the Swedish Council for Working Life and Social Research, and the Swedish Research Council. Dr Feldman reports no relevant financial relationships. Disclosures for the coauthors are listed in the paper. Dr Shaw is supported by a National Health and Medical Research Council Fellowship. Dr David Simmons and Dr Zgibor have no relevant financial relationships.
Diabetologia. Published August 23, 2017. Simmons study 1, Simmons study 2, Feldman study, David Simmons editorial, Shaw editorial
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