- Email: [email protected]
New-onset diabetes after transplantation
Correspondence
range of specific disease outcomes including cardiovascular disease (ie, coronary heart disease and stroke), external causes of death, and lung cancer. We believe consideration should be given to the role of intelligence (cognitive ability) in these associations: it may be that education is acting as a partial mediator of, or a surrogate for, intelligence differences. With regard to the mediating role of education, it is well established that low early-life intelligence is quite strongly associated with a range of indicators of later socioeconomic disadvantage, including low income, manual occupational social class, and basic-level educational credentials.2 A small number of studies have attempted to disentangle the relation between early-life intelligence quotient (IQ), later-life social disadvantage, and mortality. Some have indicated an attenuating effect after adjustment for markers of socioeconomic position (including education), whereas others have not.3 Recent data indicate an inverse association between childhood intelligence, as assessed with validated IQ-type tests, and several of the health outcomes outlined by Huisman and co-workers,1 suggesting that education may be a surrogate for IQ. Thus, relative to their higher-scoring peers, young people with low IQ scores have increased adult rates of total mortality,4 cardiovascular disease4 (including coronary heart disease), and some cancers (including carcinoma of the lung5). The mechanisms cited to explain these associations3 are similar to those advanced by Huisman and co-workers when education is the exposure of interest,1 including the findings that children with high IQ scores are less likely to develop obesity and continue to smoke as adults.3 In summary, there is now strong evidence linking both early cognitive ability and education with later health outcomes. Understanding the mechanisms of these associations will include inquiring empirically whether education is acting as a part mediator of, or a surrogate for, differences in cognitive ability. 1766
We declare that we have no conflict of interest.
*G David Batty, Ian J Deary [email protected] MRC Social and Public Health Sciences Unit, University of Glasgow, 4 Lilybank Gardens, Glasgow G12 8RZ, UK (GDB); Department of Psychology, University of Edinburgh, Edinburgh, UK (IJD, GDB) 1
2
3 4
5
Huisman M, Kunst AE, Bopp M, et al. Educational inequalities in cause-specific mortality in middle-aged and older men and women in eight western European populations. Lancet 2005; 365: 493–500. Neisser U, Boodoo G, Bouchard Jr T, et al. Intelligence: knowns and unknowns. Am Psychol 1996; 51: 77–101. Batty GD, Deary IJ. Early life intelligence and adult health. BMJ 2004; 329: 585–86. Hart CL, Taylor MD, Davey Smith G, et al. Childhood IQ and cardiovascular disease in adulthood: prospective observational study linking the Scottish Mental Survey 1932 and the Midspan studies. Soc Sci Med 2004; 59: 2131–38. Hart CL, Taylor MD, Davey Smith G, et al. Childhood IQ, social class, deprivation, and their relationships with mortality and morbidity risk in later life: prospective observational study linking the Scottish Mental Survey 1932 and the Midspan studies. Psychosom Med 2003; 65: 877–83.
New-onset diabetes after transplantation In their Comment, Andrew Krentz and David Wheeler (Feb 19, p 640)1 state that new-onset diabetes after transplantation reduces survival rates for both graft and recipient. Therefore, pharmacological interventions, as well as lifestyle measures, should be considered to prevent diabetes in this setting. Statins could prevent new-onset diabetes. In a retrospective study of 314 non-diabetic kidney transplant patients, statin use (atorvastatin, pravastatin, simvastatin, or fluvastatin) was associated with a 76% decrease (p=0·0004) in the incidence of newonset diabetes.2 The difference in diabetes incidence appeared early, was sustained for up to 3 years post-transplantation, and was independent of lipid lowering. Additionally, statins might have a favourable effect on vascular outcome in transplant recipients,3 improve renal function in patients with coronary heart disease,4 and reduce the frequency of rejection after cardiac transplantation.5 Moreover, the use of
angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers is associated with a lower incidence of new diabetes.2 We agree with Krentz and Wheeler that randomised controlled trials for the prevention of new diabetes are needed in the post-transplant population. The administration of statins, angiotensinconverting-enzyme inhibitors, and angiotensin-receptor blockers could reduce the risk of vascular events in these patients. Statins could also reduce the risk of rejection. Some of the authors have attended conferences, given sponsored lectures, and participated in trials funded by various pharmaceutical companies.
Evagelos N Liberopoulos, Vasilios G Athyros, Moses S Elisaf, *Dimitri P Mikhailidis [email protected] Department of Clinical Biochemistry, Royal Free Hospital and University College Medical School, Pond Street, London NW3 2QG, UK (ENL, DPM); Atherosclerosis Unit, Hipocration HospitalAristotelian University, Thessaloniki, Greece (VGA); Department of Internal Medicine, University of Ioannina, Ioannina, Greece (MSE) 1
2
3
4
5
Krentz AJ, Wheeler DC. New-onset diabetes after transplantation: a threat to graft and patient survival. Lancet 2005; 365: 640–42. Prasad GVR, Kim SJ, Huang M, et al. Reduced incidence of new-onset diabetes mellitus after renal transplantation with 3-hydroxy-3methyglutaryl-coenzyme A reductase inhibitors (statins). Am J Transplant 2004; 4: 1897–903. Holdaas H, Fellström B, Jardine AG, et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet 2003; 361: 2024–31. Athyros VG, Mikhailidis DP, Papageorgiou AA, et al. The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease: a subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study. J Clin Pathol 2004; 57: 728–34. Mehra MR, Raval NY. Metaanalysis of statins and survival in de novo cardiac transplantation. Transplant Proc 2004; 36: 1539–41.
Andrew Krentz and David Wheeler1 list several risk factors for post-transplant diabetes mellitus (PTDM) such as obesity, use of calcineurin inhibitors, smoking, hypertension, and dyslipidaemia. However, these are not specific for PTDM, but are common causes of type 2 diabetes as well. Infection with hepatitis C virus (HCV) is a specific risk factor for PTDM. The www.thelancet.com Vol 365 May 21, 2005
range of specific disease outcomes including cardiovascular disease (ie, coronary heart disease and stroke), external causes of death, and lung cancer. We believe consideration should be given to the role of intelligence (cognitive ability) in these associations: it may be that education is acting as a partial mediator of, or a surrogate for, intelligence differences. With regard to the mediating role of education, it is well established that low early-life intelligence is quite strongly associated with a range of indicators of later socioeconomic disadvantage, including low income, manual occupational social class, and basic-level educational credentials.2 A small number of studies have attempted to disentangle the relation between early-life intelligence quotient (IQ), later-life social disadvantage, and mortality. Some have indicated an attenuating effect after adjustment for markers of socioeconomic position (including education), whereas others have not.3 Recent data indicate an inverse association between childhood intelligence, as assessed with validated IQ-type tests, and several of the health outcomes outlined by Huisman and co-workers,1 suggesting that education may be a surrogate for IQ. Thus, relative to their higher-scoring peers, young people with low IQ scores have increased adult rates of total mortality,4 cardiovascular disease4 (including coronary heart disease), and some cancers (including carcinoma of the lung5). The mechanisms cited to explain these associations3 are similar to those advanced by Huisman and co-workers when education is the exposure of interest,1 including the findings that children with high IQ scores are less likely to develop obesity and continue to smoke as adults.3 In summary, there is now strong evidence linking both early cognitive ability and education with later health outcomes. Understanding the mechanisms of these associations will include inquiring empirically whether education is acting as a part mediator of, or a surrogate for, differences in cognitive ability. 1766
We declare that we have no conflict of interest.
*G David Batty, Ian J Deary [email protected] MRC Social and Public Health Sciences Unit, University of Glasgow, 4 Lilybank Gardens, Glasgow G12 8RZ, UK (GDB); Department of Psychology, University of Edinburgh, Edinburgh, UK (IJD, GDB) 1
2
3 4
5
Huisman M, Kunst AE, Bopp M, et al. Educational inequalities in cause-specific mortality in middle-aged and older men and women in eight western European populations. Lancet 2005; 365: 493–500. Neisser U, Boodoo G, Bouchard Jr T, et al. Intelligence: knowns and unknowns. Am Psychol 1996; 51: 77–101. Batty GD, Deary IJ. Early life intelligence and adult health. BMJ 2004; 329: 585–86. Hart CL, Taylor MD, Davey Smith G, et al. Childhood IQ and cardiovascular disease in adulthood: prospective observational study linking the Scottish Mental Survey 1932 and the Midspan studies. Soc Sci Med 2004; 59: 2131–38. Hart CL, Taylor MD, Davey Smith G, et al. Childhood IQ, social class, deprivation, and their relationships with mortality and morbidity risk in later life: prospective observational study linking the Scottish Mental Survey 1932 and the Midspan studies. Psychosom Med 2003; 65: 877–83.
New-onset diabetes after transplantation In their Comment, Andrew Krentz and David Wheeler (Feb 19, p 640)1 state that new-onset diabetes after transplantation reduces survival rates for both graft and recipient. Therefore, pharmacological interventions, as well as lifestyle measures, should be considered to prevent diabetes in this setting. Statins could prevent new-onset diabetes. In a retrospective study of 314 non-diabetic kidney transplant patients, statin use (atorvastatin, pravastatin, simvastatin, or fluvastatin) was associated with a 76% decrease (p=0·0004) in the incidence of newonset diabetes.2 The difference in diabetes incidence appeared early, was sustained for up to 3 years post-transplantation, and was independent of lipid lowering. Additionally, statins might have a favourable effect on vascular outcome in transplant recipients,3 improve renal function in patients with coronary heart disease,4 and reduce the frequency of rejection after cardiac transplantation.5 Moreover, the use of
angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers is associated with a lower incidence of new diabetes.2 We agree with Krentz and Wheeler that randomised controlled trials for the prevention of new diabetes are needed in the post-transplant population. The administration of statins, angiotensinconverting-enzyme inhibitors, and angiotensin-receptor blockers could reduce the risk of vascular events in these patients. Statins could also reduce the risk of rejection. Some of the authors have attended conferences, given sponsored lectures, and participated in trials funded by various pharmaceutical companies.
Evagelos N Liberopoulos, Vasilios G Athyros, Moses S Elisaf, *Dimitri P Mikhailidis [email protected] Department of Clinical Biochemistry, Royal Free Hospital and University College Medical School, Pond Street, London NW3 2QG, UK (ENL, DPM); Atherosclerosis Unit, Hipocration HospitalAristotelian University, Thessaloniki, Greece (VGA); Department of Internal Medicine, University of Ioannina, Ioannina, Greece (MSE) 1
2
3
4
5
Krentz AJ, Wheeler DC. New-onset diabetes after transplantation: a threat to graft and patient survival. Lancet 2005; 365: 640–42. Prasad GVR, Kim SJ, Huang M, et al. Reduced incidence of new-onset diabetes mellitus after renal transplantation with 3-hydroxy-3methyglutaryl-coenzyme A reductase inhibitors (statins). Am J Transplant 2004; 4: 1897–903. Holdaas H, Fellström B, Jardine AG, et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet 2003; 361: 2024–31. Athyros VG, Mikhailidis DP, Papageorgiou AA, et al. The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease: a subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study. J Clin Pathol 2004; 57: 728–34. Mehra MR, Raval NY. Metaanalysis of statins and survival in de novo cardiac transplantation. Transplant Proc 2004; 36: 1539–41.
Andrew Krentz and David Wheeler1 list several risk factors for post-transplant diabetes mellitus (PTDM) such as obesity, use of calcineurin inhibitors, smoking, hypertension, and dyslipidaemia. However, these are not specific for PTDM, but are common causes of type 2 diabetes as well. Infection with hepatitis C virus (HCV) is a specific risk factor for PTDM. The www.thelancet.com Vol 365 May 21, 2005