- Email: [email protected]
Should we still screen for type 2 diabetes after ADDITION-Cambridge? A low-income world perspective
diabetes research and clinical practice 100 (2013) 282–284
Contents available at Sciverse ScienceDirect
Diabetes Research and Clinical Practice jou rnal hom ep ag e: w ww.e l s e v i er . c om/ loca te / d i ab r es
Commentary
Should we still screen for type 2 diabetes after ADDITION-Cambridge? A low-income world perspective Simeon-Pierre Choukem a, Jean-Claude Mbanya b,* a b
Department of Clinical Sciences, Faculty of Health Sciences, University of Buea, Buea, Cameroon Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences, University of Yaounde´ I, Yaounde´, Cameroon
article info
abstract
Article history:
The worldwide growing epidemic of diabetes is driven by the increase in type 2 diabetes. The
Received 24 December 2012
very insidious natural history of type 2 diabetes and the availability of simple means to
Received in revised form
detect it as well as its preceding silent stages make type 2 diabetes and ideal disease for
16 January 2013
screening. Although public policies for type 2 diabetes screening do exist in many developed
Accepted 25 January 2013
countries, issues related to its benefits on disease outcomes and its cost-effectiveness have
Published on line 22 February 2013
been a concern. Recent results from the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Cambridge show that
Keywords:
screening for type 2 diabetes is not associated with a reduction in mortality, either all-cause,
Type 2 diabetes
cardiovascular or diabetes-related, after 10 years of follow-up. It seems crucial to raise the
Screening
awareness of the medical community on the high risk of misinterpretation of these results
ADDITION-Cambridge
as the death knell of type 2 diabetes screening. To that end, we discuss here some potential
Low-income countries
explanations of the lack of benefit, and we suggest a cautious uptake of the results, especially in low-income countries where type 2 diabetes screening is by far more likely to yield substantial health benefits. # 2013 Elsevier Ireland Ltd. All rights reserved.
The number of people with diabetes in 2012 is estimated at 371 million worldwide, more than 90% of which are attributed to type 2 diabetes [1]. This estimate is projected to increase by 50.7% to reach 552 million in 2030; the greatest increase (91%) being in sub-Saharan Africa (SSA) [2]. The relationship between hyperglycaemia, either diabetic or prediabetic, and mortality has been established in many major ethnic groups in the world by observational studies [3,4]. Current knowledge on the natural history of type 2 diabetes, the existing precocious and detectable phases of the disease, and the availability of simple tests to detect abnormal glucose levels amongst others make type 2 diabetes a chronic disease eligible to screening [5,6].
In the recent years, many developed countries have built national policies and guidelines for type 2 diabetes screening, and there have been increasing advocacy for large-scale screening as a critical mean to tackle diabetes epidemic [7]. Although it seems apparently logical that screening for type 2 diabetes would certainly yield long term benefits, one of the major challenges has been the evidence to support it, along with the confirmation of its cost-effectiveness. Previous findings have ruled out some pertinent potential risks associated with screening, like serious negative psychological impact [8]. The Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care
* Corresponding author at: Department of Internal Medicine and Specialities, Faculty of Medicine and Biomedical Sciences, University of Yaounde´ I, PO Box 8046, Yaounde´, Cameroon. Tel.: +237 2231 5235. E-mail addresses: [email protected] (S.-P. Choukem), [email protected] (J.-C. Mbanya). 0168-8227/$ – see front matter # 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.diabres.2013.01.025
diabetes research and clinical practice 100 (2013) 282–284
(ADDITION)-Cambridge investigated whether a populationbased screening for diabetes would improve the risk of allcause mortality, by comparing screen-detected and managed with non-screened participants [9]. The results show that screening is not associated with a reduction in mortality, either all-cause, cardiovascular or diabetes-related, after 10 years of follow-up. The main question arising is what explains the lack of difference in outcome? The authors have explored potential answers including a dilution effect attributable to the current public health screening policy for diabetes in UK; to our view, the optimal standard of patients management in the UK also contributes to that effect, as it narrows the gap between research-related findings and real-world setting facts. Another major issue raised is whether mortality is a good indicator of the effectiveness of an intervention at such an early stage of the disease. The answer is certainly yes for cancers as were shown in studies assessing the benefits of screening for prostate [10] and cervical [11] cancers on mortality outcome. Indeed, the link between cancer and mortality is a direct one. The case is different for diabetes, a metabolic disease that leads to chronic specific microvascular complications, and non-specific cardiovascular diseases, the later accounting for about 65% of all diabetes-attributable deaths [12]. In other words, ‘‘diabetes-related mortality is most often indirectly related to diabetes’’. This is substantiated by the very late-occurring benefits in cardiovascular morbidity as well as all-cause deaths in the intensively managed group, observed only after 20 years from randomisation in the United Kingdom Prospective Diabetes Study [13]. Also, a recent metaanalysis including major clinical trials showed that more-intensive glucose control as compared with less-intensive did not decrease all-cause (OR 1.04; 95% CI 0.90–1.20) or cardiovascular (OR 1.10; 95% CI 0.84–1.42) mortality [14]. In our opinion, microvascular complications such as retinopathy or nephropathy, and the ensuing impairment of the quality of life should be used as better measures of efficacy for interventions set at the level of diabetes screening, the length of time needed to reach significant mortality being too long to be ascertained by a randomised trial. Should the findings of ADDITION-Cambridge be applied elsewhere? An uncritical approach in the uptake of the results might lead to the hasty and unwanted conclusion that there is no benefit in screening for type 2 diabetes. The authors have purposefully recommended a cautious generalisation, especially in socioeconomically disadvantaged communities [9]. Here we focus on the case of SSA. Although SSA is has one of the highest growing burden of the diabetes epidemic [2], the socioeconomic context is paradoxically unprepared to cope with. Numerous specific factors leading to worsening of the prevalence, detection and management of diabetes in SSA exist [15]. While the average rate of undiagnosed diabetes is 51% worldwide, it is 81% in SSA [1]. We recently reported a high, yet underestimated rate of screen-detected diabetes and impaired fasting glucose in urban dwellers in Cameroon [16]. The rationale, challenges and opportunities of screening for diabetes in the developing world have also been recently reviewed with an analysis of the cost-effectiveness [6]. In the absence of studies on the impact of type 2 diabetes screening in SSA, how can we predict its potential benefits on
283
morbidity and mortality? Inference can be done from longitudinal observational studies that showed a gradually crescendo risk of mortality from IGT through newly diagnosed diabetes to known diabetes [3,4,17] or, more interestingly, from the tendency to a benefit after four years in ADDITIONEurope [18]. What guidelines should be used to set screening policy? The International Diabetes Federation guidelines on type 2 diabetes screening using fasting glucose seem more universal, are easy to implement and might be used as a template to draw local recommendations [19]. We therefore deliver an opposite message to the developing world, to claim that they should develop and continue more screening for type 2 diabetes. Not only does it have a highly potential benefit in the quality of life and life-saving, but moreover, screening sessions are opportunities for global health education, assessment of other basic cardiovascular risk factors like blood pressure, body mass index and waist circumference, and raising the general awareness on health. Should the screening be routine or opportunistic? How helpful are the available risk scores to improve the efficiency and costeffectiveness? Is it definitely useful to detect diabetes in people with meagre resources? Answers would be possible only at the cost of a reorientation and redeployment of health care resources and an increase in research funding in that area of the world. The consensual agreement by the World Health Organization member states of the Global Monitoring Framework for diabetes and other NCDs on November 7, 2012 [20] was timely and will certainly be a pivotal driving force for progress to be made.
Conflicts of interest The authors declare that they have no conflict of interest.
references
[1] Guariguata L. By the numbers: New estimates from the IDF Diabetes Atlas Update for 2012. Diabetes Res Clin Pract 2012;98:524–5. [2] Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011;94(3):311–21. [3] Nakagami T. Hyperglycaemia and mortality from all causes and from cardiovascular disease in five populations of Asian origin. Diabetologia 2004;47:385–94. [4] Saydah SH, Loria CM, Eberhardt MS, Brancati FL. Subclinical states of glucose intolerance and risk of death in the U.S. Diabetes Care 2001;24:447–53. [5] Gerstein HC, Santaguida P, Raina P, Morrison KM, Balion C, Hunt D, et al. Annual incidence and relative risk of diabetes in people with various categories of dysglycemia: a systematic overview and meta-analysis of prospective studies. Diabetes Res Clin Pract 2007;78:305–12. [6] Echouffo-Tcheugui JB, Mayige M, Ogbera AO, Sobngwi E, Kengne AP. Screening for hyperglycemia in the developing world: Rationale, challenges and opportunities. Diabetes Res Clin Pract 2012;98:199–208. [7] Stephens JW, Williams R. Time to stop talking about screening for diabetes? Diabet Med 2006;23:1163–4. [8] Eborall HC, Griffin SJ, Prevost AT, Kinmonth AL, French DP, Sutton S. Psychological impact of screening for type 2
284
[9]
[10]
[11]
[12]
[13]
[14]
diabetes research and clinical practice 100 (2013) 282–284
diabetes: controlled trial and comparative study embedded in the ADDITION (Cambridge) randomised controlled trial. BMJ 2007;335:486. 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. Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320–8. Sankaranarayanan R, Nene BM, Shastri SS, Jayant K, Muwonge R, Budukh AM, et al. HPV screening for cervical cancer in rural India. N Engl J Med 2009;360:1385–94. Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 1999;100:1134–46. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577–89. Turnbull FM, Abraira C, Anderson RJ, Byington RP, Chalmers JP, Duckworth WC, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 2009;52:2288–98.
[15] Mbanya JC, Motala AA, Sobngwi E, Assah FK, Enoru ST. Diabetes in sub-Saharan Africa. Lancet 2010;375:2254–66. [16] Echouffo-Tcheugui JB, Dzudie A, Epacka ME, Choukem SP, Doualla MS, Luma H, et al. Prevalence and determinants of undiagnosed diabetes in an urban sub-Saharan African population. Prim Care Diabetes 2012;6(3):229–34. [17] Barr EL, Zimmet PZ, Welborn TA, Jolley D, Magliano DJ, Dunstan DW, et al. Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). Circulation 2007;116:151–7. [18] Griffin SJ, Borch-Johnsen K, Davies MJ, Khunti K, Rutten GE, Sandbaek A, et al. Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITIONEurope): a cluster-randomised trial. Lancet 2011;378:156–67. [19] International Diabetes Federation. Clinical Guideline Task Force. Global guideline for type 2 diabetes. Brussels: International Diabetes Federation; 2012. [20] Announcement of the adoption by the World Health Organization member states of the Global Monitoring Framework for diabetes and other NCDs. http:// www.who.int/mediacentre/news/notes/2012/ ncd_20121109/en/index.html (accessed on 11.11.12).
Contents available at Sciverse ScienceDirect
Diabetes Research and Clinical Practice jou rnal hom ep ag e: w ww.e l s e v i er . c om/ loca te / d i ab r es
Commentary
Should we still screen for type 2 diabetes after ADDITION-Cambridge? A low-income world perspective Simeon-Pierre Choukem a, Jean-Claude Mbanya b,* a b
Department of Clinical Sciences, Faculty of Health Sciences, University of Buea, Buea, Cameroon Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences, University of Yaounde´ I, Yaounde´, Cameroon
article info
abstract
Article history:
The worldwide growing epidemic of diabetes is driven by the increase in type 2 diabetes. The
Received 24 December 2012
very insidious natural history of type 2 diabetes and the availability of simple means to
Received in revised form
detect it as well as its preceding silent stages make type 2 diabetes and ideal disease for
16 January 2013
screening. Although public policies for type 2 diabetes screening do exist in many developed
Accepted 25 January 2013
countries, issues related to its benefits on disease outcomes and its cost-effectiveness have
Published on line 22 February 2013
been a concern. Recent results from the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Cambridge show that
Keywords:
screening for type 2 diabetes is not associated with a reduction in mortality, either all-cause,
Type 2 diabetes
cardiovascular or diabetes-related, after 10 years of follow-up. It seems crucial to raise the
Screening
awareness of the medical community on the high risk of misinterpretation of these results
ADDITION-Cambridge
as the death knell of type 2 diabetes screening. To that end, we discuss here some potential
Low-income countries
explanations of the lack of benefit, and we suggest a cautious uptake of the results, especially in low-income countries where type 2 diabetes screening is by far more likely to yield substantial health benefits. # 2013 Elsevier Ireland Ltd. All rights reserved.
The number of people with diabetes in 2012 is estimated at 371 million worldwide, more than 90% of which are attributed to type 2 diabetes [1]. This estimate is projected to increase by 50.7% to reach 552 million in 2030; the greatest increase (91%) being in sub-Saharan Africa (SSA) [2]. The relationship between hyperglycaemia, either diabetic or prediabetic, and mortality has been established in many major ethnic groups in the world by observational studies [3,4]. Current knowledge on the natural history of type 2 diabetes, the existing precocious and detectable phases of the disease, and the availability of simple tests to detect abnormal glucose levels amongst others make type 2 diabetes a chronic disease eligible to screening [5,6].
In the recent years, many developed countries have built national policies and guidelines for type 2 diabetes screening, and there have been increasing advocacy for large-scale screening as a critical mean to tackle diabetes epidemic [7]. Although it seems apparently logical that screening for type 2 diabetes would certainly yield long term benefits, one of the major challenges has been the evidence to support it, along with the confirmation of its cost-effectiveness. Previous findings have ruled out some pertinent potential risks associated with screening, like serious negative psychological impact [8]. The Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care
* Corresponding author at: Department of Internal Medicine and Specialities, Faculty of Medicine and Biomedical Sciences, University of Yaounde´ I, PO Box 8046, Yaounde´, Cameroon. Tel.: +237 2231 5235. E-mail addresses: [email protected] (S.-P. Choukem), [email protected] (J.-C. Mbanya). 0168-8227/$ – see front matter # 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.diabres.2013.01.025
diabetes research and clinical practice 100 (2013) 282–284
(ADDITION)-Cambridge investigated whether a populationbased screening for diabetes would improve the risk of allcause mortality, by comparing screen-detected and managed with non-screened participants [9]. The results show that screening is not associated with a reduction in mortality, either all-cause, cardiovascular or diabetes-related, after 10 years of follow-up. The main question arising is what explains the lack of difference in outcome? The authors have explored potential answers including a dilution effect attributable to the current public health screening policy for diabetes in UK; to our view, the optimal standard of patients management in the UK also contributes to that effect, as it narrows the gap between research-related findings and real-world setting facts. Another major issue raised is whether mortality is a good indicator of the effectiveness of an intervention at such an early stage of the disease. The answer is certainly yes for cancers as were shown in studies assessing the benefits of screening for prostate [10] and cervical [11] cancers on mortality outcome. Indeed, the link between cancer and mortality is a direct one. The case is different for diabetes, a metabolic disease that leads to chronic specific microvascular complications, and non-specific cardiovascular diseases, the later accounting for about 65% of all diabetes-attributable deaths [12]. In other words, ‘‘diabetes-related mortality is most often indirectly related to diabetes’’. This is substantiated by the very late-occurring benefits in cardiovascular morbidity as well as all-cause deaths in the intensively managed group, observed only after 20 years from randomisation in the United Kingdom Prospective Diabetes Study [13]. Also, a recent metaanalysis including major clinical trials showed that more-intensive glucose control as compared with less-intensive did not decrease all-cause (OR 1.04; 95% CI 0.90–1.20) or cardiovascular (OR 1.10; 95% CI 0.84–1.42) mortality [14]. In our opinion, microvascular complications such as retinopathy or nephropathy, and the ensuing impairment of the quality of life should be used as better measures of efficacy for interventions set at the level of diabetes screening, the length of time needed to reach significant mortality being too long to be ascertained by a randomised trial. Should the findings of ADDITION-Cambridge be applied elsewhere? An uncritical approach in the uptake of the results might lead to the hasty and unwanted conclusion that there is no benefit in screening for type 2 diabetes. The authors have purposefully recommended a cautious generalisation, especially in socioeconomically disadvantaged communities [9]. Here we focus on the case of SSA. Although SSA is has one of the highest growing burden of the diabetes epidemic [2], the socioeconomic context is paradoxically unprepared to cope with. Numerous specific factors leading to worsening of the prevalence, detection and management of diabetes in SSA exist [15]. While the average rate of undiagnosed diabetes is 51% worldwide, it is 81% in SSA [1]. We recently reported a high, yet underestimated rate of screen-detected diabetes and impaired fasting glucose in urban dwellers in Cameroon [16]. The rationale, challenges and opportunities of screening for diabetes in the developing world have also been recently reviewed with an analysis of the cost-effectiveness [6]. In the absence of studies on the impact of type 2 diabetes screening in SSA, how can we predict its potential benefits on
283
morbidity and mortality? Inference can be done from longitudinal observational studies that showed a gradually crescendo risk of mortality from IGT through newly diagnosed diabetes to known diabetes [3,4,17] or, more interestingly, from the tendency to a benefit after four years in ADDITIONEurope [18]. What guidelines should be used to set screening policy? The International Diabetes Federation guidelines on type 2 diabetes screening using fasting glucose seem more universal, are easy to implement and might be used as a template to draw local recommendations [19]. We therefore deliver an opposite message to the developing world, to claim that they should develop and continue more screening for type 2 diabetes. Not only does it have a highly potential benefit in the quality of life and life-saving, but moreover, screening sessions are opportunities for global health education, assessment of other basic cardiovascular risk factors like blood pressure, body mass index and waist circumference, and raising the general awareness on health. Should the screening be routine or opportunistic? How helpful are the available risk scores to improve the efficiency and costeffectiveness? Is it definitely useful to detect diabetes in people with meagre resources? Answers would be possible only at the cost of a reorientation and redeployment of health care resources and an increase in research funding in that area of the world. The consensual agreement by the World Health Organization member states of the Global Monitoring Framework for diabetes and other NCDs on November 7, 2012 [20] was timely and will certainly be a pivotal driving force for progress to be made.
Conflicts of interest The authors declare that they have no conflict of interest.
references
[1] Guariguata L. By the numbers: New estimates from the IDF Diabetes Atlas Update for 2012. Diabetes Res Clin Pract 2012;98:524–5. [2] Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011;94(3):311–21. [3] Nakagami T. Hyperglycaemia and mortality from all causes and from cardiovascular disease in five populations of Asian origin. Diabetologia 2004;47:385–94. [4] Saydah SH, Loria CM, Eberhardt MS, Brancati FL. Subclinical states of glucose intolerance and risk of death in the U.S. Diabetes Care 2001;24:447–53. [5] Gerstein HC, Santaguida P, Raina P, Morrison KM, Balion C, Hunt D, et al. Annual incidence and relative risk of diabetes in people with various categories of dysglycemia: a systematic overview and meta-analysis of prospective studies. Diabetes Res Clin Pract 2007;78:305–12. [6] Echouffo-Tcheugui JB, Mayige M, Ogbera AO, Sobngwi E, Kengne AP. Screening for hyperglycemia in the developing world: Rationale, challenges and opportunities. Diabetes Res Clin Pract 2012;98:199–208. [7] Stephens JW, Williams R. Time to stop talking about screening for diabetes? Diabet Med 2006;23:1163–4. [8] Eborall HC, Griffin SJ, Prevost AT, Kinmonth AL, French DP, Sutton S. Psychological impact of screening for type 2
284
[9]
[10]
[11]
[12]
[13]
[14]
diabetes research and clinical practice 100 (2013) 282–284
diabetes: controlled trial and comparative study embedded in the ADDITION (Cambridge) randomised controlled trial. BMJ 2007;335:486. 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. Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320–8. Sankaranarayanan R, Nene BM, Shastri SS, Jayant K, Muwonge R, Budukh AM, et al. HPV screening for cervical cancer in rural India. N Engl J Med 2009;360:1385–94. Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 1999;100:1134–46. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577–89. Turnbull FM, Abraira C, Anderson RJ, Byington RP, Chalmers JP, Duckworth WC, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 2009;52:2288–98.
[15] Mbanya JC, Motala AA, Sobngwi E, Assah FK, Enoru ST. Diabetes in sub-Saharan Africa. Lancet 2010;375:2254–66. [16] Echouffo-Tcheugui JB, Dzudie A, Epacka ME, Choukem SP, Doualla MS, Luma H, et al. Prevalence and determinants of undiagnosed diabetes in an urban sub-Saharan African population. Prim Care Diabetes 2012;6(3):229–34. [17] Barr EL, Zimmet PZ, Welborn TA, Jolley D, Magliano DJ, Dunstan DW, et al. Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). Circulation 2007;116:151–7. [18] Griffin SJ, Borch-Johnsen K, Davies MJ, Khunti K, Rutten GE, Sandbaek A, et al. Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITIONEurope): a cluster-randomised trial. Lancet 2011;378:156–67. [19] International Diabetes Federation. Clinical Guideline Task Force. Global guideline for type 2 diabetes. Brussels: International Diabetes Federation; 2012. [20] Announcement of the adoption by the World Health Organization member states of the Global Monitoring Framework for diabetes and other NCDs. http:// www.who.int/mediacentre/news/notes/2012/ ncd_20121109/en/index.html (accessed on 11.11.12).