Surgery for Obesity and Related Diseases ] (2014) 00–00
Editorial comment
Comment on: Roux-en-Y gastric bypass increases hepatic and peripheral insulin sensitivity in rats with type 2 diabetes mellitus Since first reported nearly half a century ago, gastric bypass has become a mainstay in the repertoire of the bariatric surgeon. The efficacy of gastric bypass in achieving body mass reduction was evident from the earliest experience [1]. The deleterious effects of excess weight had been recognized, and the prevailing hypothesis was that health improvement would result from weight loss. While this may indeed be true, surgeons began to identify improvement in co-morbid diseases and realize that some conditions, most notably type II diabetes mellitus, exhibited significant recovery independent of loss of body mass [2]. As these discoveries were coalescing, the report of laparoscopic Roux-en-Y gastric bypass (RYGB) [3] ignited a surge in the number of patients who have undergone bariatric surgery over the past 2 decades. During this period, evidence for the weight loss-independent effects of RYGB on restoring metabolic regulation has increased, prompting a name change for the major bariatric surgery professional society and innumerable research efforts to biochemically describe these changes. In this issue of SOARD, He et al. have sought to enhance our understanding of the return of insulin sensitivity after RYGB by conducting an elegant study in rats. The experimental outcomes corroborated the clinical experience of bariatric surgeons. Namely, diabetic rats regained normoglycemia and exhibited a significant drop in free fatty acids at 2 weeks postRYGB, while diabetes in the sham surgery group remained comparable to that in diabetic controls. The similarities between these experimental findings and clinical observations in humans indicate relevance of the surgical response in this animal model to patient care. Although these data are descriptive and not novel, the authors used this foundation to report a set of interesting experimental findings. First, the RYGB rats showed a dramatic reduction in fat mass within 1 week of surgery and quickly reached equivalency with nondiabetic controls. In contrast, diabetic rats that underwent sham surgery maintained fat mass equivalent to diabetic controls. Interestingly, there was no difference in lean mass. Second, muscle and hepatic insulin sensitivity, which were impaired in diabetic rats, improved postRYGB. Hepatic insulin sensitivity recovered at 2 weeks after surgery. Muscle insulin
sensitivity was improved at 2 weeks but did not become significant until 4 weeks. Finally, RYGB resulted in decreased hepatic (2 weeks) and muscle (4 weeks) triglyceride and total cholesterol content. The authors analyzed these changes and found that the decrease in triglyceride content correlated with measures of improved insulin sensitivity in both tissues. The results of this study are focused and do not directly address possible mechanisms for diabetes remission after RYGB. From a wide mechanistic perspective, the remarkable effects of RYGB on improvement or remission of type II diabetes have been hypothetically attributed to manipulation of the gastrointestinal tract [4]. Such findings are compelling to the clinician, because they seem to imply that a single treatment can be effective in all patients. However, there is considerable biologic variability among patients, and it is precisely this variability that mandates a more dissecting assessment of metabolic recovery after RYGB. This paper does just that; we now have another piece of information in this puzzle. In reality, we are not much closer to discovering the single pathway that leads from RYGB to diabetes remission, but, at this point, it is probably naïve to even consider that the answers will lie in any single biologic process. Thus, He et al. have enhanced our knowledge by showing that improvement in hepatic insulin sensitivity precedes that of the muscle after RYGB. They have also shown that reduction in the lipid content of liver and muscle cells correlates with improvements in insulin sensitivity. This study adds to the body of literature and inches us yet closer to understanding the significant metabolic changes that follow RYGB, and we are grateful to the authors. Mohamed R. Ali, M.D. Chief, Bariatric Surgery Director, Minimally Invasive and Robotic Surgery University of California, Davis Sacramento, CA 95817 References [1] Mason EE, Ito C. Gastric bypass. Ann Surg 1969;170:329–39.
1550-7289/13/$ – see front matter r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved. http://dx.doi.org/10.1016/j.soard.2013.11.003
2
M. Ali / Surgery for Obesity and Related Diseases ] (2014) 00–00
[2] Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg 1995;222: 339–50; discussion 350–2.
[3] Wittgrove AC, Clark GW, Tremblay LJ. Laparoscopic gastric bypass, Roux-en-Y: preliminary report of five cases. Obes Surg 1994;4:353–7. [4] Rubino F. Bariatric surgery: effects on glucose homeostasis. Curr Opin Clin Nutr Metab Care 2006;9:497–507.
Editorial comment
Comment on: Roux-en-Y gastric bypass increases hepatic and peripheral insulin sensitivity in rats with type 2 diabetes mellitus Since first reported nearly half a century ago, gastric bypass has become a mainstay in the repertoire of the bariatric surgeon. The efficacy of gastric bypass in achieving body mass reduction was evident from the earliest experience [1]. The deleterious effects of excess weight had been recognized, and the prevailing hypothesis was that health improvement would result from weight loss. While this may indeed be true, surgeons began to identify improvement in co-morbid diseases and realize that some conditions, most notably type II diabetes mellitus, exhibited significant recovery independent of loss of body mass [2]. As these discoveries were coalescing, the report of laparoscopic Roux-en-Y gastric bypass (RYGB) [3] ignited a surge in the number of patients who have undergone bariatric surgery over the past 2 decades. During this period, evidence for the weight loss-independent effects of RYGB on restoring metabolic regulation has increased, prompting a name change for the major bariatric surgery professional society and innumerable research efforts to biochemically describe these changes. In this issue of SOARD, He et al. have sought to enhance our understanding of the return of insulin sensitivity after RYGB by conducting an elegant study in rats. The experimental outcomes corroborated the clinical experience of bariatric surgeons. Namely, diabetic rats regained normoglycemia and exhibited a significant drop in free fatty acids at 2 weeks postRYGB, while diabetes in the sham surgery group remained comparable to that in diabetic controls. The similarities between these experimental findings and clinical observations in humans indicate relevance of the surgical response in this animal model to patient care. Although these data are descriptive and not novel, the authors used this foundation to report a set of interesting experimental findings. First, the RYGB rats showed a dramatic reduction in fat mass within 1 week of surgery and quickly reached equivalency with nondiabetic controls. In contrast, diabetic rats that underwent sham surgery maintained fat mass equivalent to diabetic controls. Interestingly, there was no difference in lean mass. Second, muscle and hepatic insulin sensitivity, which were impaired in diabetic rats, improved postRYGB. Hepatic insulin sensitivity recovered at 2 weeks after surgery. Muscle insulin
sensitivity was improved at 2 weeks but did not become significant until 4 weeks. Finally, RYGB resulted in decreased hepatic (2 weeks) and muscle (4 weeks) triglyceride and total cholesterol content. The authors analyzed these changes and found that the decrease in triglyceride content correlated with measures of improved insulin sensitivity in both tissues. The results of this study are focused and do not directly address possible mechanisms for diabetes remission after RYGB. From a wide mechanistic perspective, the remarkable effects of RYGB on improvement or remission of type II diabetes have been hypothetically attributed to manipulation of the gastrointestinal tract [4]. Such findings are compelling to the clinician, because they seem to imply that a single treatment can be effective in all patients. However, there is considerable biologic variability among patients, and it is precisely this variability that mandates a more dissecting assessment of metabolic recovery after RYGB. This paper does just that; we now have another piece of information in this puzzle. In reality, we are not much closer to discovering the single pathway that leads from RYGB to diabetes remission, but, at this point, it is probably naïve to even consider that the answers will lie in any single biologic process. Thus, He et al. have enhanced our knowledge by showing that improvement in hepatic insulin sensitivity precedes that of the muscle after RYGB. They have also shown that reduction in the lipid content of liver and muscle cells correlates with improvements in insulin sensitivity. This study adds to the body of literature and inches us yet closer to understanding the significant metabolic changes that follow RYGB, and we are grateful to the authors. Mohamed R. Ali, M.D. Chief, Bariatric Surgery Director, Minimally Invasive and Robotic Surgery University of California, Davis Sacramento, CA 95817 References [1] Mason EE, Ito C. Gastric bypass. Ann Surg 1969;170:329–39.
1550-7289/13/$ – see front matter r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved. http://dx.doi.org/10.1016/j.soard.2013.11.003
2
M. Ali / Surgery for Obesity and Related Diseases ] (2014) 00–00
[2] Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg 1995;222: 339–50; discussion 350–2.
[3] Wittgrove AC, Clark GW, Tremblay LJ. Laparoscopic gastric bypass, Roux-en-Y: preliminary report of five cases. Obes Surg 1994;4:353–7. [4] Rubino F. Bariatric surgery: effects on glucose homeostasis. Curr Opin Clin Nutr Metab Care 2006;9:497–507.
