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Survival as a function of HbA1c in people with type 2 diabetes
Correspondence
Craig Currie and colleagues (Feb 6, p 481)1 report that the ideal glycosylated haemoglobin (HbA1c) concentration for patients with type 2 diabetes is 7·5% and that revised recommendations should target such a value. In this retrospective study, increased mortality was seen with high HbA1c, as expected, but also with low values, especially in patients on insulin. However, the inclusion period extended from November, 1986, to November, 2008, raising questions about the homogeneity of the populations and strategies studied. The guidelines for treatment of diabetes have changed strikingly since the 1980s. The demonstration of the benefits of intensive glycaemic control by the UK Prospective Diabetes Study (UKPDS) in 19982 and the introduction of new molecules, especially insulin analogues, possibly translated into better management of patients with type 2 diabetes. And basal insulin analogues resulted in a lower incidence of hypoglycaemia than did neutral protamine hagedorn insulin.3 This is an important issue since hypoglycaemia was suspected of being responsible for the higher mortality rates in patients achieving the lowest mean HbA1c, although this hypothesis was not supported by a subanalysis of the ACCORD study.4 Furthermore, the introduction and subsequent widespread use of other drugs, such as statins, in cardiovascular prevention could have positively affected mortality.5 Thus we would be interested in the mortality rate of patients with HbA1c below 7% and treated in the post-UKPDS era. Is the same U-shaped relation between HbA1c and mortality seen in these more recently included patients? This issue should be addressed before considering any modification of current guidelines. www.thelancet.com Vol 375 April 24, 2010
We declare that we have no conflicts of interest.
*Jean-Pierre Riveline, Ronan Roussel, Kamel Mohammedi [email protected] Centre Hospitalier Sud-Francilien, 91106 Corbeil-Essonnes, France (JPR); Centre de Recherche des Cordeliers, INSERM UMRS 872, Paris, France (JPR); and Hôpital Bichat-Claude Bernard, Assistance Publique Hôpitaux de Paris, Paris, France (RR, KM) 1
2
3
4
5
Currie CJ, Peters JR, Tynan A, et al. Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study. Lancet 2010; 375: 481–89. 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: 837–53. Riddle MC, Rosenstock J, Gerich J, et al, for the insulin Glargine 4002 Study Investigators. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003; 26: 3080–86. Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 2010; 340: b4909. Colhoun HM, Betteridge DJ, Durrington PN, et al, on behalf of the CARDS investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004; 364: 685–96.
Although Craig Currie and colleagues1 report that both low and high concentrations of glycosylated haemoglobin (HbA1c) are associated with increased risks of all-cause mortality and cardiac events, the optimum HbA1c seems to vary between patients. To show this variability, the ACCORD trial2 and the VADT trial3 showed that intensive glucose control in type 2 diabetes is associated with higher mortality than is conventional glucose control. However, UKPDS 344 indicated that intensive treatment might significantly reduce cardiovascular events and mortality. How can we explain the discrepancy between these results, which might jeopardise the validity of current therapeutic guidelines? The answer to the question is the difference in the length of diabetic periods. The diabetic periods at the
inception of ACCORD and VADT were 8·0–10·5 years, but UKPDS 34 recruited newly diagnosed patients. In Currie and colleagues’ report,1 the hazard ratios for HbA1c of less than 7·0% were higher in cohort 2 than in cohort 1, which corresponds to progression of atherosclerosis with age. Moreover, a retrospective analysis5 of ACCORD showed that hypoglycaemia cannot explain the difference in mortality between the intensive and conventional treatments. In conclusion, diabetic patients with a disease history of about 8 years or more should aim for a concentration of HbA1c of 7·5–8·5%.
Science Photo Library
Survival as a function of HbA1c in people with type 2 diabetes
We declare that we have no conflicts of interest.
*Eishu Nango, Takeo Saio [email protected] Department of General Medicine, Tokyo-kita Social Insurance Hospital, Tokyo 115-0053, Japan (EN); and Fuji-Toranomon Health Promotion Center, Shizuoka, Japan (TS) 1
2
3
4
5
Currie CJ, Peters JR, Tynan A, et al. Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study. Lancet 2010; 375: 481–89. Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358: 2545–59. Duckworth W, Abraira C, Moritz T, et al, for the VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009; 360: 129–39. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854–65. Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 2010; 340: b4909.
Craig Currie and colleagues1 report a U-shaped relation between achieved glycosylated haemoglobin (HbA1c) and mortality in type 2 diabetes. Increased mortality at the very low, near-normal HbA1c range would help to explain the findings from the ACCORD trial,2 in which those assigned intensive treatment, striving for HbA1c values below 6·0%, encountered a higher risk of mortality than did those assigned standard treatment. However, three
Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/
1433
Craig Currie and colleagues (Feb 6, p 481)1 report that the ideal glycosylated haemoglobin (HbA1c) concentration for patients with type 2 diabetes is 7·5% and that revised recommendations should target such a value. In this retrospective study, increased mortality was seen with high HbA1c, as expected, but also with low values, especially in patients on insulin. However, the inclusion period extended from November, 1986, to November, 2008, raising questions about the homogeneity of the populations and strategies studied. The guidelines for treatment of diabetes have changed strikingly since the 1980s. The demonstration of the benefits of intensive glycaemic control by the UK Prospective Diabetes Study (UKPDS) in 19982 and the introduction of new molecules, especially insulin analogues, possibly translated into better management of patients with type 2 diabetes. And basal insulin analogues resulted in a lower incidence of hypoglycaemia than did neutral protamine hagedorn insulin.3 This is an important issue since hypoglycaemia was suspected of being responsible for the higher mortality rates in patients achieving the lowest mean HbA1c, although this hypothesis was not supported by a subanalysis of the ACCORD study.4 Furthermore, the introduction and subsequent widespread use of other drugs, such as statins, in cardiovascular prevention could have positively affected mortality.5 Thus we would be interested in the mortality rate of patients with HbA1c below 7% and treated in the post-UKPDS era. Is the same U-shaped relation between HbA1c and mortality seen in these more recently included patients? This issue should be addressed before considering any modification of current guidelines. www.thelancet.com Vol 375 April 24, 2010
We declare that we have no conflicts of interest.
*Jean-Pierre Riveline, Ronan Roussel, Kamel Mohammedi [email protected] Centre Hospitalier Sud-Francilien, 91106 Corbeil-Essonnes, France (JPR); Centre de Recherche des Cordeliers, INSERM UMRS 872, Paris, France (JPR); and Hôpital Bichat-Claude Bernard, Assistance Publique Hôpitaux de Paris, Paris, France (RR, KM) 1
2
3
4
5
Currie CJ, Peters JR, Tynan A, et al. Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study. Lancet 2010; 375: 481–89. 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: 837–53. Riddle MC, Rosenstock J, Gerich J, et al, for the insulin Glargine 4002 Study Investigators. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003; 26: 3080–86. Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 2010; 340: b4909. Colhoun HM, Betteridge DJ, Durrington PN, et al, on behalf of the CARDS investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004; 364: 685–96.
Although Craig Currie and colleagues1 report that both low and high concentrations of glycosylated haemoglobin (HbA1c) are associated with increased risks of all-cause mortality and cardiac events, the optimum HbA1c seems to vary between patients. To show this variability, the ACCORD trial2 and the VADT trial3 showed that intensive glucose control in type 2 diabetes is associated with higher mortality than is conventional glucose control. However, UKPDS 344 indicated that intensive treatment might significantly reduce cardiovascular events and mortality. How can we explain the discrepancy between these results, which might jeopardise the validity of current therapeutic guidelines? The answer to the question is the difference in the length of diabetic periods. The diabetic periods at the
inception of ACCORD and VADT were 8·0–10·5 years, but UKPDS 34 recruited newly diagnosed patients. In Currie and colleagues’ report,1 the hazard ratios for HbA1c of less than 7·0% were higher in cohort 2 than in cohort 1, which corresponds to progression of atherosclerosis with age. Moreover, a retrospective analysis5 of ACCORD showed that hypoglycaemia cannot explain the difference in mortality between the intensive and conventional treatments. In conclusion, diabetic patients with a disease history of about 8 years or more should aim for a concentration of HbA1c of 7·5–8·5%.
Science Photo Library
Survival as a function of HbA1c in people with type 2 diabetes
We declare that we have no conflicts of interest.
*Eishu Nango, Takeo Saio [email protected] Department of General Medicine, Tokyo-kita Social Insurance Hospital, Tokyo 115-0053, Japan (EN); and Fuji-Toranomon Health Promotion Center, Shizuoka, Japan (TS) 1
2
3
4
5
Currie CJ, Peters JR, Tynan A, et al. Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study. Lancet 2010; 375: 481–89. Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358: 2545–59. Duckworth W, Abraira C, Moritz T, et al, for the VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009; 360: 129–39. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854–65. Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 2010; 340: b4909.
Craig Currie and colleagues1 report a U-shaped relation between achieved glycosylated haemoglobin (HbA1c) and mortality in type 2 diabetes. Increased mortality at the very low, near-normal HbA1c range would help to explain the findings from the ACCORD trial,2 in which those assigned intensive treatment, striving for HbA1c values below 6·0%, encountered a higher risk of mortality than did those assigned standard treatment. However, three
Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/
1433