The
n e w e ng l a n d j o u r na l
of
m e dic i n e
c or r e sp ondence
Bariatric Surgery versus Intensive Medical Therapy for Diabetes To the Editor: Emerging evidence links the gut microbiota and type 2 diabetes. As compared with controls, patients with type 2 diabetes have a lower abundance of firmicutes and clostridia, and the ratio of bacteroidetes to firmicutes is positively associated with the plasma glucose concentration.1,2 In addition, the microbiome is implicated in obesity and associated with Roux-en-Y gastric bypass surgery.3,4 Beyond these associations, in a small, randomized, controlled trial involving 18 patients with the metabolic syndrome, those receiving fecal microbiota transplants from a lean donor had a significant improvement in peripheral insulin sensitivity 6 weeks later as compared with recipients of autologous fecal microbiota transplants.5 Because it is uncertain whether the microbiome is a cause or an effect of type 2 diabetes and obesity, trials with longitudinal follow-up, such as the study by Schauer and colleagues (May 22 issue),6 are rare opportunities to deeply examine the microbiome. Given the challenge of conducting long-term studies and the potential mechanistic insights from low-cost microbiome sequencing, we hope that future studies of type 2 diabetes will include standard microbial characterization. this week’s letters
680
680
Bariatric Surgery versus Intensive Medical Therapy for Diabetes
683
Aortic Dilatation with Bicuspid Aortic Valve
683
Lyme Disease
685
Activated Protein C Resistance Assay and Factor V Leiden
Zain Kassam, M.D., M.P.H. Mark Smith, Ph.D. Eric Alm, Ph.D. Massachusetts Institute of Technology Cambridge, MA
[email protected] No potential conflict of interest relevant to this letter was reported. 1. Larsen N, Vogensen FK, van den Berg FW, et al. Gut micro-
biota in human adults with type 2 diabetes differs from nondiabetic adults. PLoS One 2010;5(2):e9085. 2. Karlsson FH, Tremaroll V, Nookaew I, et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 2013;498:99-103. 3. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature 2006;444: 1022-3. 4. Kong LC, Tap J, Aron-Wisnewsky J, et al. Gut microbiota after gastric bypass in human obesity: increased richness and associations of bacterial genera with adipose tissue genes. Am J Clin Nutr 2013;98:16-24. 5. Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 2012; 143(4):913.e7-916.e7. [Erratum, Gastroenterology 2013;144:250.] 6. Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric surgery versus intensive medical therapy for diabetes — 3-year outcomes. N Engl J Med 2014;370:2002-13. DOI: 10.1056/NEJMc1407393
To the Editor: In reporting 3-year outcomes of patients undergoing bariatric surgery in the STAMPEDE (Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently) trial, Schauer et al. found a significant improvement in the albumin-to-creatinine ratio with surgery as compared with medical therapy. However, the incidence of nephropathy (defined as a doubling of the serum creatinine level, >20% reduction in the estimated glomerular filtration rate, new macroalbuminuria, or the need for renal-replacement therapy) was increased in the surgical groups, particularly in the gastric-bypass group.
n engl j med 371;7 nejm.org august 14, 2014
The New England Journal of Medicine Downloaded from nejm.org at AUSTRALIAN NATL UNIV on January 29, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
correspondence
The increased rate of nephropathy, despite impressive improvements in the glycated hemoglobin level and body-mass index, suggests other deleterious effects of bariatric surgery on renal function. Gastric bypass surgery is associated with a long-term increase in urinary oxalate excretion1 and in the risk of urolithiasis.2 Increased oxalate absorption, probably due to fat malabsorption and subsequent reductions in the intraluminal free calcium concentration,3 may provide one mechanism for renal injury after gastric bypass surgery. Nasr et al.4 described the devastating consequences of oxalate nephropathy after bypass surgery in a case series of 11 patients. Although bariatric surgery represents a valuable treatment to combat the epidemic of obesity and its complications, unintended consequences of this gross distortion of gut physiology should not be overlooked. Matthew Sypek, M.B., B.S.
of low-density lipoprotein cholesterol and blood pressure were not significantly reduced in the surgical groups, findings that are at variance with those in previous reports from us and others.3,4 This is probably due to discontinuation of statins and antihypertensive medication, which seems a questionable step that is not consonant with current guidelines.5 Hence, it may be premature to conclude that bariatric surgery is superior to intensive medical therapy for type 2 diabetes, and we would recommend continuing pharmacologic cardiovascular prophylaxis. Hanne Løvdal Gulseth, M.D., Ph.D. Hilde Risstad, M.D. Kåre I. Birkeland, M.D., Ph.D.
Oxford University Hospitals National Health Service Trust Oxford, United Kingdom
hyperglycaemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Dia betologia 2012;55:1577-96. [Erratum, Diabetologia 2013;56:680.] 2. Riddle MC, Rosenstock J, Gerich J. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003;26:3080-6. 3. Aftab H, Risstad H, Søvik TT, et al. Five-year outcome after gastric bypass for morbid obesity in a Norwegian cohort. Surg Obes Relat Dis 2014;10:71-8. 4. Adams TD, Davidson LE, Litwin SE, et al. Health benefits of gastric bypass surgery after 6 years. JAMA 2012;308:1122-31. 5. Buse JB, Caprio S, Cefalu WT, et al. How do we define cure of diabetes? Diabetes Care 2009;32:2133-5.
[email protected] No potential conflict of interest relevant to this letter was reported. 1. Duffey BG, Alanee S, Pedro RN, et al. Hyperoxaluria is a
long-term consequence of Roux-en-Y gastric bypass: a 2-year prospective longitudinal study. J Am Coll Surg 2010;211:8-15. 2. Matlaga BR, Shore AD, Magnuson T, Clark JM, Johns R, Makary MA. Effect of gastric bypass surgery on kidney stone disease. J Urol 2009;181:2573-7. 3. Kumar R, Lieske JC, Collazo-Clavell ML, et al. Fat malabsorption and increased intestinal oxalate absorption are common after Roux-en-Y gastric bypass surgery. Surgery 2011;149:654-61. 4. Nasr SH, D’Agati VD, Said SM, et al. Oxalate nephropathy complicating Roux-en-Y gastric bypass: an underrecognized cause of irreversible renal failure. Clin J Am Soc Nephrol 2008;3:1676-83. DOI: 10.1056/NEJMc1407393
To the Editor: Schauer et al. report that, after 3 years, bariatric surgery was superior to intensive medical therapy in the control of glycemia in patients with type 2 diabetes. We have some concerns about the conduct and interpretation of this study. First, we question whether the medicaltherapy group did receive intensive glucose-lowering therapy. After 3 years, the mean (±SD) glycated hemoglobin level was 8.4±2.2%, the number of glucose-lowering drugs was 2.6±1.1, and only 55% of patients used insulin. Hence, although not reaching protocol targets, medical therapy was not intensified according to published guidelines.1 Nearly half the patients did not use insulin despite ample evidence that it can improve glycemic control.2 Second, it is surprising that levels
Oslo University Hospital Oslo, Norway [email protected] No potential conflict of interest relevant to this letter was reported. 1. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of
DOI: 10.1056/NEJMc1407393
To the Editor: The findings by Schauer et al. are in line with a growing body of evidence showing the benefit of bariatric surgery. Despite convincing data, the question remains whether surgery can provide the solution to the obesity epidemic. In the past 20 years, rates of severe obesity tripled in the United States.1 Concurrently, bariatric-surgery volumes grew by a factor of more than 10 without substantially affecting this overall trend.2 According to current projections, 50% of the adult population will be obese by 2030.1 Thus, do we need more bariatric surgery? At an estimated cost of about $25,000 per surgery,3 operating on only severely obese persons would consume 15 to 20% of annual health care expenditures. Expenditures do not stop with the surgical procedure, as prior studies have shown persistently high health care utilization and costs for at least 6 years after surgery.3 Truly overcom-
n engl j med 371;7 nejm.org august 14, 2014
The New England Journal of Medicine Downloaded from nejm.org at AUSTRALIAN NATL UNIV on January 29, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
681
The
n e w e ng l a n d j o u r na l
ing this epidemic will require different strategies that have proved affordable and effective in dealing with the devastating effects of unhealthy food.4 Klaus Bielefeldt, M.D., Ph.D. University of Pittsburgh Medical Center Pittsburgh, PA
[email protected] No potential conflict of interest relevant to this letter was reported. 1. Finkelstein EA, Khavjou OA, Thompson H, et al. Obesity and
severe obesity forecasts through 2030. Am J Prev Med 2012;42: 563-70. 2. Kohn GP, Galanko JA, Overby DW, Farrell TM. Recent trends in bariatric surgery case volume in the United States. Surgery 2009;146:375-80. 3. Neovius M, Narbro K, Keating C, et al. Health care use during 20 years following bariatric surgery. JAMA 2012;308:1132-41. 4. Wagstaff DJ. Public health and food safety: a historical association. Public Health Rep 1986;101:624-31. DOI: 10.1056/NEJMc1407393
of
m e dic i n e
benefits beyond cholesterol reduction, but this hypothesis currently remains unproved. Similarly, the benefit of blood-pressure medications appears to be due to their effects on achieving sustained blood-pressure reduction without inducing unacceptable side effects. Bielefeldt brings up issues of cost containment. The approach to obesity and diabetes needs to start with public health efforts on a population level, with targeted lifestyle and medical therapy for at-risk persons and bariatric surgery reserved for those who, despite medical attempts to control their weight and diabetes, continue to have uncontrolled glucose levels. This stepped approach to the intensity of treatment is common in medicine, as with the treatment of coronary artery disease with lifestyle management, medications, percutaneous coronary intervention, and coronary-artery bypass grafting depending on the extent and severity of disease. Perhaps a similar tiered approach is needed in the management of obesity and diabetes. Given that the lifetime medical costs of treating type 2 diabetes and its complications are in the range of $124,000 to $130,000 (with an age at onset of 25 to 44 years), bariatric surgery — which has been shown to be cost-effective and possibly cost-saving — seems reasonable for patients whose condition is not well controlled with medical management alone.4,5 Philip R. Schauer, M.D.
The authors reply: Kassam et al. note the emerging relationships between the microbiome and obesity (as well as diabetes), which are certainly interesting. We agree that future studies of bariatric surgery ideally should try to examine these potential links. Sypek raises concerns regarding nephropathy. The rates of kidney injury events in our study were low, and there were no significant differences among the treatment groups. We did not observe any oxalate nephropathy in our study. Diabetic nephropathy is a serious consequence of uncontrolled diabetes, and better glycemic Cleveland Clinic control through bariatric surgery may reduce its Cleveland, OH incidence, though a larger study with a longer [email protected] follow-up period would be necessary to explore Deepak L. Bhatt, M.D., M.P.H. Brigham and Women’s Hospital Heart and Vascular Center that possibility. Gulseth et al. raise questions about the medi- Boston, MA cal care of the participating patients, a difficult- Sangeeta R. Kashyap, M.D. to-treat diabetic population, and we would em- Cleveland Clinic Cleveland, OH phasize that their care was optimized to every Since publication of their article, the authors report no furextent possible. Table 2 in our article showed the ther potential conflict of interest. number of medications that patients were taking, 1. Roussel R, Travert F, Pasquet B, et al. Metformin use and not the number that had been tried but discontin- mortality among patients with diabetes and atherothrombosis. ued owing to side effects or a lack of efficacy. Not Arch Intern Med 2010;170:1892-9. all patients are willing to use an injectable drug 2. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. such as insulin. Furthermore, other than, possi- N Engl J Med 2013;369:1317-26. bly, metformin, it is not clear whether any cur- 3. Gerstein HC, Bosch J, Dagenais GR, et al. Basal insulin and and other outcomes in dysglycemia. N Engl J Med rent diabetes medications reduce cardiovascular cardiovascular 2012;367:319-28. 1-3 events. 4. Zhuo X, Zhang P, Hoerger TJ. Lifetime direct medical costs The lack of a greater effect of bariatric sur- of treating type 2 diabetes and diabetic complications. Am J Prev Med 2013;45:253-61. gery on lipid or blood-pressure measures almost 5. Chang SH, Stoll CR, Colditz GA. Cost-effectiveness of barcertainly is due to a reduced need for these iatric surgery: should it be universally available? Maturitas medications after bariatric surgery. It is possible 2011;69:230-8. that medicines such as statins have pleiotropic DOI: 10.1056/NEJMc1407393 682
n engl j med 371;7 nejm.org august 14, 2014
The New England Journal of Medicine Downloaded from nejm.org at AUSTRALIAN NATL UNIV on January 29, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
n e w e ng l a n d j o u r na l
of
m e dic i n e
c or r e sp ondence
Bariatric Surgery versus Intensive Medical Therapy for Diabetes To the Editor: Emerging evidence links the gut microbiota and type 2 diabetes. As compared with controls, patients with type 2 diabetes have a lower abundance of firmicutes and clostridia, and the ratio of bacteroidetes to firmicutes is positively associated with the plasma glucose concentration.1,2 In addition, the microbiome is implicated in obesity and associated with Roux-en-Y gastric bypass surgery.3,4 Beyond these associations, in a small, randomized, controlled trial involving 18 patients with the metabolic syndrome, those receiving fecal microbiota transplants from a lean donor had a significant improvement in peripheral insulin sensitivity 6 weeks later as compared with recipients of autologous fecal microbiota transplants.5 Because it is uncertain whether the microbiome is a cause or an effect of type 2 diabetes and obesity, trials with longitudinal follow-up, such as the study by Schauer and colleagues (May 22 issue),6 are rare opportunities to deeply examine the microbiome. Given the challenge of conducting long-term studies and the potential mechanistic insights from low-cost microbiome sequencing, we hope that future studies of type 2 diabetes will include standard microbial characterization. this week’s letters
680
680
Bariatric Surgery versus Intensive Medical Therapy for Diabetes
683
Aortic Dilatation with Bicuspid Aortic Valve
683
Lyme Disease
685
Activated Protein C Resistance Assay and Factor V Leiden
Zain Kassam, M.D., M.P.H. Mark Smith, Ph.D. Eric Alm, Ph.D. Massachusetts Institute of Technology Cambridge, MA
[email protected] No potential conflict of interest relevant to this letter was reported. 1. Larsen N, Vogensen FK, van den Berg FW, et al. Gut micro-
biota in human adults with type 2 diabetes differs from nondiabetic adults. PLoS One 2010;5(2):e9085. 2. Karlsson FH, Tremaroll V, Nookaew I, et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 2013;498:99-103. 3. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature 2006;444: 1022-3. 4. Kong LC, Tap J, Aron-Wisnewsky J, et al. Gut microbiota after gastric bypass in human obesity: increased richness and associations of bacterial genera with adipose tissue genes. Am J Clin Nutr 2013;98:16-24. 5. Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 2012; 143(4):913.e7-916.e7. [Erratum, Gastroenterology 2013;144:250.] 6. Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric surgery versus intensive medical therapy for diabetes — 3-year outcomes. N Engl J Med 2014;370:2002-13. DOI: 10.1056/NEJMc1407393
To the Editor: In reporting 3-year outcomes of patients undergoing bariatric surgery in the STAMPEDE (Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently) trial, Schauer et al. found a significant improvement in the albumin-to-creatinine ratio with surgery as compared with medical therapy. However, the incidence of nephropathy (defined as a doubling of the serum creatinine level, >20% reduction in the estimated glomerular filtration rate, new macroalbuminuria, or the need for renal-replacement therapy) was increased in the surgical groups, particularly in the gastric-bypass group.
n engl j med 371;7 nejm.org august 14, 2014
The New England Journal of Medicine Downloaded from nejm.org at AUSTRALIAN NATL UNIV on January 29, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
correspondence
The increased rate of nephropathy, despite impressive improvements in the glycated hemoglobin level and body-mass index, suggests other deleterious effects of bariatric surgery on renal function. Gastric bypass surgery is associated with a long-term increase in urinary oxalate excretion1 and in the risk of urolithiasis.2 Increased oxalate absorption, probably due to fat malabsorption and subsequent reductions in the intraluminal free calcium concentration,3 may provide one mechanism for renal injury after gastric bypass surgery. Nasr et al.4 described the devastating consequences of oxalate nephropathy after bypass surgery in a case series of 11 patients. Although bariatric surgery represents a valuable treatment to combat the epidemic of obesity and its complications, unintended consequences of this gross distortion of gut physiology should not be overlooked. Matthew Sypek, M.B., B.S.
of low-density lipoprotein cholesterol and blood pressure were not significantly reduced in the surgical groups, findings that are at variance with those in previous reports from us and others.3,4 This is probably due to discontinuation of statins and antihypertensive medication, which seems a questionable step that is not consonant with current guidelines.5 Hence, it may be premature to conclude that bariatric surgery is superior to intensive medical therapy for type 2 diabetes, and we would recommend continuing pharmacologic cardiovascular prophylaxis. Hanne Løvdal Gulseth, M.D., Ph.D. Hilde Risstad, M.D. Kåre I. Birkeland, M.D., Ph.D.
Oxford University Hospitals National Health Service Trust Oxford, United Kingdom
hyperglycaemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Dia betologia 2012;55:1577-96. [Erratum, Diabetologia 2013;56:680.] 2. Riddle MC, Rosenstock J, Gerich J. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003;26:3080-6. 3. Aftab H, Risstad H, Søvik TT, et al. Five-year outcome after gastric bypass for morbid obesity in a Norwegian cohort. Surg Obes Relat Dis 2014;10:71-8. 4. Adams TD, Davidson LE, Litwin SE, et al. Health benefits of gastric bypass surgery after 6 years. JAMA 2012;308:1122-31. 5. Buse JB, Caprio S, Cefalu WT, et al. How do we define cure of diabetes? Diabetes Care 2009;32:2133-5.
[email protected] No potential conflict of interest relevant to this letter was reported. 1. Duffey BG, Alanee S, Pedro RN, et al. Hyperoxaluria is a
long-term consequence of Roux-en-Y gastric bypass: a 2-year prospective longitudinal study. J Am Coll Surg 2010;211:8-15. 2. Matlaga BR, Shore AD, Magnuson T, Clark JM, Johns R, Makary MA. Effect of gastric bypass surgery on kidney stone disease. J Urol 2009;181:2573-7. 3. Kumar R, Lieske JC, Collazo-Clavell ML, et al. Fat malabsorption and increased intestinal oxalate absorption are common after Roux-en-Y gastric bypass surgery. Surgery 2011;149:654-61. 4. Nasr SH, D’Agati VD, Said SM, et al. Oxalate nephropathy complicating Roux-en-Y gastric bypass: an underrecognized cause of irreversible renal failure. Clin J Am Soc Nephrol 2008;3:1676-83. DOI: 10.1056/NEJMc1407393
To the Editor: Schauer et al. report that, after 3 years, bariatric surgery was superior to intensive medical therapy in the control of glycemia in patients with type 2 diabetes. We have some concerns about the conduct and interpretation of this study. First, we question whether the medicaltherapy group did receive intensive glucose-lowering therapy. After 3 years, the mean (±SD) glycated hemoglobin level was 8.4±2.2%, the number of glucose-lowering drugs was 2.6±1.1, and only 55% of patients used insulin. Hence, although not reaching protocol targets, medical therapy was not intensified according to published guidelines.1 Nearly half the patients did not use insulin despite ample evidence that it can improve glycemic control.2 Second, it is surprising that levels
Oslo University Hospital Oslo, Norway [email protected] No potential conflict of interest relevant to this letter was reported. 1. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of
DOI: 10.1056/NEJMc1407393
To the Editor: The findings by Schauer et al. are in line with a growing body of evidence showing the benefit of bariatric surgery. Despite convincing data, the question remains whether surgery can provide the solution to the obesity epidemic. In the past 20 years, rates of severe obesity tripled in the United States.1 Concurrently, bariatric-surgery volumes grew by a factor of more than 10 without substantially affecting this overall trend.2 According to current projections, 50% of the adult population will be obese by 2030.1 Thus, do we need more bariatric surgery? At an estimated cost of about $25,000 per surgery,3 operating on only severely obese persons would consume 15 to 20% of annual health care expenditures. Expenditures do not stop with the surgical procedure, as prior studies have shown persistently high health care utilization and costs for at least 6 years after surgery.3 Truly overcom-
n engl j med 371;7 nejm.org august 14, 2014
The New England Journal of Medicine Downloaded from nejm.org at AUSTRALIAN NATL UNIV on January 29, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
681
The
n e w e ng l a n d j o u r na l
ing this epidemic will require different strategies that have proved affordable and effective in dealing with the devastating effects of unhealthy food.4 Klaus Bielefeldt, M.D., Ph.D. University of Pittsburgh Medical Center Pittsburgh, PA
[email protected] No potential conflict of interest relevant to this letter was reported. 1. Finkelstein EA, Khavjou OA, Thompson H, et al. Obesity and
severe obesity forecasts through 2030. Am J Prev Med 2012;42: 563-70. 2. Kohn GP, Galanko JA, Overby DW, Farrell TM. Recent trends in bariatric surgery case volume in the United States. Surgery 2009;146:375-80. 3. Neovius M, Narbro K, Keating C, et al. Health care use during 20 years following bariatric surgery. JAMA 2012;308:1132-41. 4. Wagstaff DJ. Public health and food safety: a historical association. Public Health Rep 1986;101:624-31. DOI: 10.1056/NEJMc1407393
of
m e dic i n e
benefits beyond cholesterol reduction, but this hypothesis currently remains unproved. Similarly, the benefit of blood-pressure medications appears to be due to their effects on achieving sustained blood-pressure reduction without inducing unacceptable side effects. Bielefeldt brings up issues of cost containment. The approach to obesity and diabetes needs to start with public health efforts on a population level, with targeted lifestyle and medical therapy for at-risk persons and bariatric surgery reserved for those who, despite medical attempts to control their weight and diabetes, continue to have uncontrolled glucose levels. This stepped approach to the intensity of treatment is common in medicine, as with the treatment of coronary artery disease with lifestyle management, medications, percutaneous coronary intervention, and coronary-artery bypass grafting depending on the extent and severity of disease. Perhaps a similar tiered approach is needed in the management of obesity and diabetes. Given that the lifetime medical costs of treating type 2 diabetes and its complications are in the range of $124,000 to $130,000 (with an age at onset of 25 to 44 years), bariatric surgery — which has been shown to be cost-effective and possibly cost-saving — seems reasonable for patients whose condition is not well controlled with medical management alone.4,5 Philip R. Schauer, M.D.
The authors reply: Kassam et al. note the emerging relationships between the microbiome and obesity (as well as diabetes), which are certainly interesting. We agree that future studies of bariatric surgery ideally should try to examine these potential links. Sypek raises concerns regarding nephropathy. The rates of kidney injury events in our study were low, and there were no significant differences among the treatment groups. We did not observe any oxalate nephropathy in our study. Diabetic nephropathy is a serious consequence of uncontrolled diabetes, and better glycemic Cleveland Clinic control through bariatric surgery may reduce its Cleveland, OH incidence, though a larger study with a longer [email protected] follow-up period would be necessary to explore Deepak L. Bhatt, M.D., M.P.H. Brigham and Women’s Hospital Heart and Vascular Center that possibility. Gulseth et al. raise questions about the medi- Boston, MA cal care of the participating patients, a difficult- Sangeeta R. Kashyap, M.D. to-treat diabetic population, and we would em- Cleveland Clinic Cleveland, OH phasize that their care was optimized to every Since publication of their article, the authors report no furextent possible. Table 2 in our article showed the ther potential conflict of interest. number of medications that patients were taking, 1. Roussel R, Travert F, Pasquet B, et al. Metformin use and not the number that had been tried but discontin- mortality among patients with diabetes and atherothrombosis. ued owing to side effects or a lack of efficacy. Not Arch Intern Med 2010;170:1892-9. all patients are willing to use an injectable drug 2. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. such as insulin. Furthermore, other than, possi- N Engl J Med 2013;369:1317-26. bly, metformin, it is not clear whether any cur- 3. Gerstein HC, Bosch J, Dagenais GR, et al. Basal insulin and and other outcomes in dysglycemia. N Engl J Med rent diabetes medications reduce cardiovascular cardiovascular 2012;367:319-28. 1-3 events. 4. Zhuo X, Zhang P, Hoerger TJ. Lifetime direct medical costs The lack of a greater effect of bariatric sur- of treating type 2 diabetes and diabetic complications. Am J Prev Med 2013;45:253-61. gery on lipid or blood-pressure measures almost 5. Chang SH, Stoll CR, Colditz GA. Cost-effectiveness of barcertainly is due to a reduced need for these iatric surgery: should it be universally available? Maturitas medications after bariatric surgery. It is possible 2011;69:230-8. that medicines such as statins have pleiotropic DOI: 10.1056/NEJMc1407393 682
n engl j med 371;7 nejm.org august 14, 2014
The New England Journal of Medicine Downloaded from nejm.org at AUSTRALIAN NATL UNIV on January 29, 2015. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
