Use of national data sources in diabetes epidemiology
Authors: Mark Woodward
Journal: The Lancet Diabetes & Endocrinology (2014)

Health authorities worldwide have been collecting vast quantities of data for many years. Historically, such data—generally obtained for administrative, financial, and clinical reasons—have rarely been used for research because of problems with access, scale, and linkages. However, things are changing, with a move towards open data access, improved computing power, and a realisation by governments that routine data might be able to answer important health questions efficiently and cost-effectively if records are appropriately linked while maintaining anonymity. The UK, where patients can be traced from primary care consultations to death, offers one of the world's most promising sources of routine data in terms of research potential. The key issue is whether such data can be used to produce good-quality research that is similar to, or even enhances, bespoke data collection. Up to now, evidence of this type of data being used in such a way to study diabetes has been scant, but this gap has now been addressed by Anoop Dinesh Shah and colleagues1Shah AD Langenberg C Rapsomaniki E et al.Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people.Lancet Diabetes Endocrinol. 2014; (published online Nov 11.)http://dx.doi.org/10.1016/S2213-8587(14)70219-0Google Scholar in The Lancet Diabetes & Endocrinology.The investigators have linked longitudinal data for almost 2 million people aged 30 years or older without previous cardiovascular disease, across general practices, hospitals, the national register of acute coronary syndromes, and death registrations in the CALIBER study.2Denaxas SC George J Herrett E et al.Data resource profile: cardiovascular disease research using linked bespoke studies and electronic health records (CALIBER).Int J Epidemiol. 2012; 41: 1625-1638Crossref PubMed Scopus (152) Google Scholar They analysed the relation between type 2 diabetes status (recorded as positive in 34 198 individuals in the cohort) and twelve initial manifestations of incident cardiovascular disease. This study is the first, of which I am aware, to look at subtypes of cardiovascular disease outcomes in such fine detail. They report that peripheral arterial disease is the most common first presentation of cardiovascular disease for people with type 2 diabetes (reported in 992 [16%] of 6137 who had a cardiovascular event), and people with diabetes were almost three times as likely to have peripheral arterial disease as an initial presentation than were those without diabetes (10 074 [9%] of 107 501; adjusted HR 2·98 [95% CI 2·76–3·22]; p<0·0001). However, diabetes was not associated with sudden death, and was negatively associated with subarachnoid haemorrhage and abdominal aortic aneurysm, which provide intriguing contrasts with the other nine initial manifestations of cardiovascular disease analysed, all of which showed positive associations with diabetes. Importantly, the hazard ratios reported for other types of cardiovascular disease that are often analysed in clinical trials and observational epidemiology (ie, myocardial infarction and stroke) are broadly consistent with past cohort studies.3Woodward M Zhang X Barzi F et al.The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region.Diabetes Care. 2003; 26: 360-366Crossref PubMed Scopus (252) Google Scholar, 4The Emerging Risk Factors CollaborationDiabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies.Lancet. 2010; 375: 2215-2222Summary Full Text Full Text PDF PubMed Scopus (2929) Google Scholar Furthermore, the investigators' data suggest that diabetes has more of an effect on cardiovascular disease in young women than in young men, consistent with results of the most recent large meta-analyses.5Peters SAE Huxley RR Woodward M Diabetes as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 64 cohorts, including 775 385 individuals and 12 539 strokes.Lancet. 2014; 383: 1973-1980Summary Full Text Full Text PDF PubMed Scopus (457) Google Scholar, 6Peters SAE Huxley RR Woodward M Diabetes as risk factor for incident coronary heart disease in women compared with men: a systematic review and meta-analysis of 64 cohorts including 858 507 individuals and 28 203 coronary events.Diabetologia. 2014; 57: 1542-1551Crossref PubMed Scopus (353) Google Scholar Finally, in line with large epidemiological studies,3Woodward M Zhang X Barzi F et al.The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region.Diabetes Care. 2003; 26: 360-366Crossref PubMed Scopus (252) Google Scholar, 4The Emerging Risk Factors CollaborationDiabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies.Lancet. 2010; 375: 2215-2222Summary Full Text Full Text PDF PubMed Scopus (2929) Google Scholar Shah and colleagues' results show attenuation of the effects of diabetes on cardiovascular disease with age. So the study not only shows that use of routine data can give sensible results, but also adds value in terms of fine detail and precision (narrow confidence intervals).The study's results should be interpreted with caution. Unusually, the investigators analysed initial presentations rather than all manifestations of, for example, peripheral arterial disease. Most researchers would include, in presentations of risk and relative risk, peripheral arterial disease events that came after other cardiovascular disease events. This limitation makes direct comparisons with earlier studies, including those in the preceding paragraph, approximate. However, since the risk of having several cardiovascular disease events is not high, the approximation should be quite accurate. Whether or not this method gives a more reasonable estimate of the true effect of diabetes, unencumbered by intervention after another cardiovascular disease event, is debatable—hazard ratios for diabetes might be expected to be lower than with the usual all-events method, because of the greater risk of most competing cardiovascular disease events in individuals with diabetes.Shah and colleagues have shown that careful processing of routinely obtained linked national health data, and not a little hard labour,2Denaxas SC George J Herrett E et al.Data resource profile: cardiovascular disease research using linked bespoke studies and electronic health records (CALIBER).Int J Epidemiol. 2012; 41: 1625-1638Crossref PubMed Scopus (152) Google Scholar can produce an excellent basis for aetiological research.7CALIBERWelcome page.https://www.caliberresearch.org/Google Scholar Their study suggests that the limited quality of routine data—including incomplete event ascertainment and missing data—can be overcome in observational analyses. The question remains as to how the new epidemiological results on subsets of cardiovascular disease outcomes in diabetes might affect practice. As the investigators imply, new clinical trials in diabetes should now consider including (at least) peripheral arterial disease as part of any composite cardiovascular disease outcome, as should cardiovascular disease risk scores for people with diabetes.8van Dieren S Beulens JW Kengne AP et al.Prediction models for the risk of cardiovascular disease in patients with type 2 diabetes: a systematic review.Heart. 2012; 98: 360-369Crossref PubMed Scopus (160) Google Scholar The varying levels and directions of association for different initial manifestations of cardiovascular disease might well prompt readers to instigate new research.I declare no competing interests. Health authorities worldwide have been collecting vast quantities of data for many years. Historically, such data—generally obtained for administrative, financial, and clinical reasons—have rarely been used for research because of problems with access, scale, and linkages. However, things are changing, with a move towards open data access, improved computing power, and a realisation by governments that routine data might be able to answer important health questions efficiently and cost-effectively if records are appropriately linked while maintaining anonymity. The UK, where patients can be traced from primary care consultations to death, offers one of the world's most promising sources of routine data in terms of research potential. The key issue is whether such data can be used to produce good-quality research that is similar to, or even enhances, bespoke data collection. Up to now, evidence of this type of data being used in such a way to study diabetes has been scant, but this gap has now been addressed by Anoop Dinesh Shah and colleagues1Shah AD Langenberg C Rapsomaniki E et al.Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people.Lancet Diabetes Endocrinol. 2014; (published online Nov 11.)http://dx.doi.org/10.1016/S2213-8587(14)70219-0Google Scholar in The Lancet Diabetes & Endocrinology. The investigators have linked longitudinal data for almost 2 million people aged 30 years or older without previous cardiovascular disease, across general practices, hospitals, the national register of acute coronary syndromes, and death registrations in the CALIBER study.2Denaxas SC George J Herrett E et al.Data resource profile: cardiovascular disease research using linked bespoke studies and electronic health records (CALIBER).Int J Epidemiol. 2012; 41: 1625-1638Crossref PubMed Scopus (152) Google Scholar They analysed the relation between type 2 diabetes status (recorded as positive in 34 198 individuals in the cohort) and twelve initial manifestations of incident cardiovascular disease. This study is the first, of which I am aware, to look at subtypes of cardiovascular disease outcomes in such fine detail. They report that peripheral arterial disease is the most common first presentation of cardiovascular disease for people with type 2 diabetes (reported in 992 [16%] of 6137 who had a cardiovascular event), and people with diabetes were almost three times as likely to have peripheral arterial disease as an initial presentation than were those without diabetes (10 074 [9%] of 107 501; adjusted HR 2·98 [95% CI 2·76–3·22]; p<0·0001). However, diabetes was not associated with sudden death, and was negatively associated with subarachnoid haemorrhage and abdominal aortic aneurysm, which provide intriguing contrasts with the other nine initial manifestations of cardiovascular disease analysed, all of which showed positive associations with diabetes. Importantly, the hazard ratios reported for other types of cardiovascular disease that are often analysed in clinical trials and observational epidemiology (ie, myocardial infarction and stroke) are broadly consistent with past cohort studies.3Woodward M Zhang X Barzi F et al.The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region.Diabetes Care. 2003; 26: 360-366Crossref PubMed Scopus (252) Google Scholar, 4The Emerging Risk Factors CollaborationDiabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies.Lancet. 2010; 375: 2215-2222Summary Full Text Full Text PDF PubMed Scopus (2929) Google Scholar Furthermore, the investigators' data suggest that diabetes has more of an effect on cardiovascular disease in young women than in young men, consistent with results of the most recent large meta-analyses.5Peters SAE Huxley RR Woodward M Diabetes as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 64 cohorts, including 775 385 individuals and 12 539 strokes.Lancet. 2014; 383: 1973-1980Summary Full Text Full Text PDF PubMed Scopus (457) Google Scholar, 6Peters SAE Huxley RR Woodward M Diabetes as risk factor for incident coronary heart disease in women compared with men: a systematic review and meta-analysis of 64 cohorts including 858 507 individuals and 28 203 coronary events.Diabetologia. 2014; 57: 1542-1551Crossref PubMed Scopus (353) Google Scholar Finally, in line with large epidemiological studies,3Woodward M Zhang X Barzi F et al.The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region.Diabetes Care. 2003; 26: 360-366Crossref PubMed Scopus (252) Google Scholar, 4The Emerging Risk Factors CollaborationDiabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies.Lancet. 2010; 375: 2215-2222Summary Full Text Full Text PDF PubMed Scopus (2929) Google Scholar Shah and colleagues' results show attenuation of the effects of diabetes on cardiovascular disease with age. So the study not only shows that use of routine data can give sensible results, but also adds value in terms of fine detail and precision (narrow confidence intervals). The study's results should be interpreted with caution. Unusually, the investigators analysed initial presentations rather than all manifestations of, for example, peripheral arterial disease. Most researchers would include, in presentations of risk and relative risk, peripheral arterial disease events that came after other cardiovascular disease events. This limitation makes direct comparisons with earlier studies, including those in the preceding paragraph, approximate. However, since the risk of having several cardiovascular disease events is not high, the approximation should be quite accurate. Whether or not this method gives a more reasonable estimate of the true effect of diabetes, unencumbered by intervention after another cardiovascular disease event, is debatable—hazard ratios for diabetes might be expected to be lower than with the usual all-events method, because of the greater risk of most competing cardiovascular disease events in individuals with diabetes. Shah and colleagues have shown that careful processing of routinely obtained linked national health data, and not a little hard labour,2Denaxas SC George J Herrett E et al.Data resource profile: cardiovascular disease research using linked bespoke studies and electronic health records (CALIBER).Int J Epidemiol. 2012; 41: 1625-1638Crossref PubMed Scopus (152) Google Scholar can produce an excellent basis for aetiological research.7CALIBERWelcome page.https://www.caliberresearch.org/Google Scholar Their study suggests that the limited quality of routine data—including incomplete event ascertainment and missing data—can be overcome in observational analyses. The question remains as to how the new epidemiological results on subsets of cardiovascular disease outcomes in diabetes might affect practice. As the investigators imply, new clinical trials in diabetes should now consider including (at least) peripheral arterial disease as part of any composite cardiovascular disease outcome, as should cardiovascular disease risk scores for people with diabetes.8van Dieren S Beulens JW Kengne AP et al.Prediction models for the risk of cardiovascular disease in patients with type 2 diabetes: a systematic review.Heart. 2012; 98: 360-369Crossref PubMed Scopus (160) Google Scholar The varying levels and directions of association for different initial manifestations of cardiovascular disease might well prompt readers to instigate new research. I declare no competing interests. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million peopleHeart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The differences between relative risks of different cardiovascular diseases in patients with type 2 diabetes have implications for clinical risk assessment and trial design. Full-Text PDF Open Access