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A blast from the past: lessons learned from a 40-year-old surgical randomized, controlled trial
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Surgery for Obesity and Related Diseases ] (2016) 00–00
Paired editorial
A blast from the past: lessons learned from a 40-year-old surgical randomized, controlled trial Buchwald et al. report a unique study that is not only fascinating, but also provides very useful insight regarding the effect of the gut on glucose metabolism [1]. The Program on the Surgical Control of the Hyperlipidemias’ randomized, controlled trial compared partial ileal bypass with no surgery in patients who had experienced myocardial infarction [2]. The study was designed to address whether the reduction in plasma levels of total and LDL cholesterol and the increase in plasma level of HDL cholesterol induced by the surgery would favorably affect overall mortality and morbidity due to coronary heart disease [2]. Participants at baseline were aged 30 to 64 years and had survived 1 myocardial infarction as documented by changes in the electrocardiogram and cardiac enzymes. They had total plasma cholesterol levels of Z220 mg/dL, or LDL cholesterol of Z140 mg/dL if total plasma cholesterol was between 200 and 219 mg/dL after a minimum of 6 weeks of dietary fat and cholesterol restriction [2]. Diabetes and overweight status (weight 40% above ideal weight, according to the Metropolitan Life Insurance Company weight tables) were exclusion criteria, as they were considered potentially confounding major risk factors for atherosclerosis [2]. The rationale for the design of the procedure was based on animal and human data suggesting that ileal exclusion was associated with lower cholesterol absorption and circulating cholesterol levels [3]. This is a different procedure from jejunoileal bypass in terms of technique, bypassed length, outcomes, complications, rationale, and intent [4]. Partial ileal bypass offered a sustained improvement in the lipid profile in an era when pharmacotherapy was not yet available; the Program on the Surgical Control of the Hyperlipidemias investigators provided evidence that this modulation was beneficial for patients [3]. Randomization commenced in September 1975 and ended in July 1983 with enrollment of 838 participants (421 surgery, 417 no surgery). The authors previously reported follow-up data at 25 years. These demonstrated improvements in overall survival, cardiovascular disease– free survival, and life expectancy in the surgery group compared with the no-surgery group [5].
In the latest report, the authors investigated the incidence of type 2 diabetes at 430 years follow-up. Fewer than 1 in 5 of 838 patients were still alive and contactable, comprising 80 surgery patients and 66 no-surgery patients. Eight in the surgery group had developed type 2 diabetes, compared with 17 in the no-surgery group (P ¼ .015). Including patients with borderline diabetes, the totals were 10 in the surgery group and 22 in the no-surgery group (P o .004). The authors concluded that partial ileal bypass showed a protective effect for development of type 2 diabetes. This is a very important finding, as there is a shift in the diabetes and obesity epidemic paradigm from treatment of established disease to disease modification, deceleration of disease progression, and disease prevention. In addition to possibly representing the longest follow-up of metabolic surgery, the work by Buchwald et al. complements the available evidence showing that bariatric surgery has a protective effect on diabetes incidence. This has so far only been found in a nonrandomized, prospective cohort design —the Swedish Obese Subjects Study [6]. The study highlights the key role the gastrointestinal tract has in glucose metabolism with regard to health and disease and the potential it has as a therapeutic target. Furthermore, it encourages surgeons, physicians, and scientists interested in diabetes and obesity to continue gut-related investigative work. Finally, this inspirational work supports the need for well-designed randomized, controlled trials with long-term follow-up, as they can still provide valuable lessons well beyond their “sell by” date. Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article. Richard Welbourn, M.D., F.R.C.S., Department of Bariatric Surgery, Musgrove Park Hospital, Taunton,UK Dimitri Pournaras, Ph.D., F.R.C.S. The Cambridge Oesophago-Gastric Centre, Addenbrooke’s Hospital, Cambridge, UK
http://dx.doi.org/10.1016/j.soard.2016.02.025 1550-7289/r 2016 American Society for Metabolic and Bariatric Surgery. All rights reserved.
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R. Welbourn et al. / Surgery for Obesity and Related Diseases ] (2016) 00–00
References [1] Buchwald H, Oien DM, Schieber DJ, Bantle JP, Connett JE. Partial ileal bypass affords protection from onset of Type 2 diabetes In press. Surg Obes Relat Dis. 2016. [2] Buchwald H, Varco RL, Matts JP, et al. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N Engl J Med 1990;323(14):946–55. [3] Buchwald H. Lowering of cholesterol absorption and blood levels by ileal exclusion. Experimental basis and preliminary clinical report. Circulation 1964;29:713–20.
[4] Buchwald H, Varco RL, Moore RB, Schwartz MZ. Intestinal bypass procedures. Partial ileal bypass for hyperlipidemia and jejunoileal bypass for obesity. Curr Probl Surg 1975:1–51. [5] Buchwald H, Rudser KD, Williams SE, Michalek VN, Vagasky J, Connett JE. Overall mortality, incremental life expectancy, and cause of death at 25 years in the program on the surgical control of the hyperlipidemias. Ann Surg 2010;251(6):1034–40. [6] Carlsson LM, Peltonen M, Ahlin S, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. New Engl J Med 2012;367(8):695–704.
122 123 124 125 126 127 128 129 130 131 132
Surgery for Obesity and Related Diseases ] (2016) 00–00
Paired editorial
A blast from the past: lessons learned from a 40-year-old surgical randomized, controlled trial Buchwald et al. report a unique study that is not only fascinating, but also provides very useful insight regarding the effect of the gut on glucose metabolism [1]. The Program on the Surgical Control of the Hyperlipidemias’ randomized, controlled trial compared partial ileal bypass with no surgery in patients who had experienced myocardial infarction [2]. The study was designed to address whether the reduction in plasma levels of total and LDL cholesterol and the increase in plasma level of HDL cholesterol induced by the surgery would favorably affect overall mortality and morbidity due to coronary heart disease [2]. Participants at baseline were aged 30 to 64 years and had survived 1 myocardial infarction as documented by changes in the electrocardiogram and cardiac enzymes. They had total plasma cholesterol levels of Z220 mg/dL, or LDL cholesterol of Z140 mg/dL if total plasma cholesterol was between 200 and 219 mg/dL after a minimum of 6 weeks of dietary fat and cholesterol restriction [2]. Diabetes and overweight status (weight 40% above ideal weight, according to the Metropolitan Life Insurance Company weight tables) were exclusion criteria, as they were considered potentially confounding major risk factors for atherosclerosis [2]. The rationale for the design of the procedure was based on animal and human data suggesting that ileal exclusion was associated with lower cholesterol absorption and circulating cholesterol levels [3]. This is a different procedure from jejunoileal bypass in terms of technique, bypassed length, outcomes, complications, rationale, and intent [4]. Partial ileal bypass offered a sustained improvement in the lipid profile in an era when pharmacotherapy was not yet available; the Program on the Surgical Control of the Hyperlipidemias investigators provided evidence that this modulation was beneficial for patients [3]. Randomization commenced in September 1975 and ended in July 1983 with enrollment of 838 participants (421 surgery, 417 no surgery). The authors previously reported follow-up data at 25 years. These demonstrated improvements in overall survival, cardiovascular disease– free survival, and life expectancy in the surgery group compared with the no-surgery group [5].
In the latest report, the authors investigated the incidence of type 2 diabetes at 430 years follow-up. Fewer than 1 in 5 of 838 patients were still alive and contactable, comprising 80 surgery patients and 66 no-surgery patients. Eight in the surgery group had developed type 2 diabetes, compared with 17 in the no-surgery group (P ¼ .015). Including patients with borderline diabetes, the totals were 10 in the surgery group and 22 in the no-surgery group (P o .004). The authors concluded that partial ileal bypass showed a protective effect for development of type 2 diabetes. This is a very important finding, as there is a shift in the diabetes and obesity epidemic paradigm from treatment of established disease to disease modification, deceleration of disease progression, and disease prevention. In addition to possibly representing the longest follow-up of metabolic surgery, the work by Buchwald et al. complements the available evidence showing that bariatric surgery has a protective effect on diabetes incidence. This has so far only been found in a nonrandomized, prospective cohort design —the Swedish Obese Subjects Study [6]. The study highlights the key role the gastrointestinal tract has in glucose metabolism with regard to health and disease and the potential it has as a therapeutic target. Furthermore, it encourages surgeons, physicians, and scientists interested in diabetes and obesity to continue gut-related investigative work. Finally, this inspirational work supports the need for well-designed randomized, controlled trials with long-term follow-up, as they can still provide valuable lessons well beyond their “sell by” date. Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article. Richard Welbourn, M.D., F.R.C.S., Department of Bariatric Surgery, Musgrove Park Hospital, Taunton,UK Dimitri Pournaras, Ph.D., F.R.C.S. The Cambridge Oesophago-Gastric Centre, Addenbrooke’s Hospital, Cambridge, UK
http://dx.doi.org/10.1016/j.soard.2016.02.025 1550-7289/r 2016 American Society for Metabolic and Bariatric Surgery. All rights reserved.
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111 112 113 Q3 114 115 116 117 118 119 120 121
R. Welbourn et al. / Surgery for Obesity and Related Diseases ] (2016) 00–00
References [1] Buchwald H, Oien DM, Schieber DJ, Bantle JP, Connett JE. Partial ileal bypass affords protection from onset of Type 2 diabetes In press. Surg Obes Relat Dis. 2016. [2] Buchwald H, Varco RL, Matts JP, et al. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N Engl J Med 1990;323(14):946–55. [3] Buchwald H. Lowering of cholesterol absorption and blood levels by ileal exclusion. Experimental basis and preliminary clinical report. Circulation 1964;29:713–20.
[4] Buchwald H, Varco RL, Moore RB, Schwartz MZ. Intestinal bypass procedures. Partial ileal bypass for hyperlipidemia and jejunoileal bypass for obesity. Curr Probl Surg 1975:1–51. [5] Buchwald H, Rudser KD, Williams SE, Michalek VN, Vagasky J, Connett JE. Overall mortality, incremental life expectancy, and cause of death at 25 years in the program on the surgical control of the hyperlipidemias. Ann Surg 2010;251(6):1034–40. [6] Carlsson LM, Peltonen M, Ahlin S, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. New Engl J Med 2012;367(8):695–704.
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