LETTER TO THE EDITOR From Bariatric to Pure Metabolic Surgery: New Concepts on the Rise To the Editor: Dr Carlson’s1 recent Editorial suggests that there is a misplaced emphasis on innovations in bariatric surgery. I cannot agree. Bariatric surgery was developed on the basis of mechanical restriction and malabsorption, and new concepts are rising. They demand a change in the way we do things, because they change why we do them. Here, I list some of them.
Mechanical Restriction and Functional Restriction All of us present restrictive mechanisms to stop eating, but they are functional. After meals, food is sent to the gut because hunger, a life-threatening condition, is resolved in the gut and not in the stomach. Just after eating a considerable amount of food, gut signals slow down the gastric emptying (like a sink with a clogged drain) so that the next (not the previous) portions can be stored there. As the storage capacity is limited, at a certain point, gastric pressure is high and the meal has to be finished. Observe that restriction appears only later in the eating process and not after the first bite. This is a functional restriction. A mechanical restriction is static and is an obstacle for the passage of food after the very first spoonful. A narrow anastomosis, a ring, and a band are mechanical restrictions and not physiological. Mechanical restrictions limit ingestion; functional restrictions limit stocking. Metabolic surgery can provoke an earlier functional restriction and avoid a mechanical restriction. This is a major difference, a significant progress, and it demands changes.
Intestinal Satiety and Gastric Satiety As an immediate consequence of the previous concept, it becomes clear that one
Disclosure: The author declares no conflicts of interest. C 2014 Wolters Kluwer Health, Inc. All Copyright rights reserved. ISSN: 0003-4932/14/26202-e0079 DOI: 10.1097/SLA.0000000000000590
must obtain intestinal signals of satiety before the size of the stomach and its internal pressure become a limiting issue. Therefore, one must obtain the intestinal satiety before the beginning of the stocking process and then the gastric satiety, which finishes the meal.
A Physiological Definition for Hunger and Gluttony Foraging is moved by hunger, a necessity. You eat quickly and your stomach empties rapidly until intestinal satiety appears, slowing the gastric emptying. Then, the typical hunger is gone, but if there is available food that does not demand significant energy or risk to obtain, we keep on eating until gastric satiety stops us. Intestinal satiety first interrupts hunger and then gastric satiety interrupts gluttony. In this didactic scenario, the amount of food we eat moved by hunger is related to the capacity of our gut to receive, process, and absorb food and send signals. The size of the stomach is only related to the amount we eat later due to gluttony. If gut signals are too weak or come too late, one may eat too much with a very small functional stomach or even none.
The Cautious Gut and The Reliable Gut To trigger a strong insulinic response, with the interruption of endogenous glucose production, is very risky. Severe hypoglycemia is a fast killer. It is very reasonable that animals carefully check the amount and the quality of ingested food before triggering such a dangerous response. GIP (glucose-dependent insulinotropic polypeptide), a typical proximal gut hormone, produces an insulinic response, but instead of diminishing secretion of glucagon, it enhances it!2 And this is quite logical. In the proximal gut, food is not well quantified and it is still too early to stop endogenous glucose production, too early to cause strong satiety, and too soon to block gastric emptying (unless there is an acute hyperglycemia). The proximal gut is cautious. It would even be logical from a evolutionary point of view that duodenal-jejunal products could induce some insulinic resistance, as previously suggested by Rubino and Marescaux.3 Food in the distal gut means a lot more; it means you are fairly well fed. It is safe for the distal gut to trigger an intense response that aims at reducing glycemia and at inducing satiety. Distal gut signals strongly potenti-
Annals of Surgery r Volume 262, Number 2, August 2015
ate insulinic responses,4 but, differently from the proximal gut, it has the authority to block glucagon secretion,5 to interrupt endogenous glucose production and the supply of fat to the circulation (clearance of triglycerides),6 to cause strong satiety,7 and to stop gastric emptying.8 The distal gut is reliable.
The Gut Imbalance Theory The strong connection between the type of food and its abundance with obesity and the metabolic syndrome (MS) is clear. The fast rise in the incidence of these conditions is coincident with the introduction of an abundant processed diet. This “unnatural” food has concentrated highly absorbable nutrients (refined sugar and refined flour) and progressively less fiber and residues. Processed nutrients indeed suffer an “external digestion.” Duodenum is very permeable, a lot more than the distal gut. Indeed, the presence of fully digested nutrients is not expected there. In face of “unnatural” high glycemic index food that is rapidly absorbed, this “excessive” permeability allows a fast invasion of nutrients in the blood, faster than what naturally occurs. Obviously, the proximal gut would be overstimulated in this scenario whereas the distal gut less stimulated, as nutritive absorption occurs more proximally than what is “naturally” expected: an imbalance. Indeed, the obese and the diabetic patients present abnormally high GIP9 (mainly a proximal gut product). If they eat less, on a diet, GIP falls.10 GIP is obesogenic and insulinotropic (contributing to hyperinsulinemia), and the therapeutic blockage of GIP is beneficial for these patients.11,12 The opposite is also very clear. Therapeutic additions of the distal gut products [GLP-1 (glucagon-like peptide-1), PYY (peptide tyrosine-tyrosine), oxyntomodulin] or their agonists are beneficial in MS patients. Drugs and hormones that interfere in this balance, by enhancing the distal gut activity or blocking the proximal gut activity, help MS patients. Surgical procedures support this observation. The more you shift food from proximal to distal, the better the results in obesity and MS are, despite worse nutritional results when this is obtained by excluding segments. There is an imbalance in gut activity, and the introduction of easily absorbed food can justify that. Epidemiology, physiology, drugs, and surgical procedures point at the same direction. The proximal-distal imbalance makes sense. www.annalsofsurgery.com | e79
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Letter to the Editor
Abandoning The Term “Bariatric” “Bariatric” has become an inadequate term. Bariatric refers to weight. Weight itself is not the problem, obesity and MS are. They are metabolic problems. If we call the surgery “bariatric,” it means we are targeting weight; surgical indication is guided by the weight, and the promise is weight loss. Bariatric surgery uses mechanical restriction and malabsorption. Both are diseases, classified in the International Classification of Diseases (K.90 code indicates malabsorption), and they are not physiological at all. If we call it metabolic, it changes a lot. The objective is to adjust the metabolic response to food ingestion. The surgical indication is metabolically driven and therefore the surgical goal is not primarily weight loss, even because the weight does not depend on the surgery alone. The promise is a metabolic change, which will help patients obtain better results for their efforts in maintaining good health and body composition. Also, fortunately, we can produce major metabolic changes without any significant mechanical restriction or malabsorption. Possibly, it is the birth of pure metabolic surgery, which is not bariatric, not mechanically restrictive, and not malabsorptive. It works through functional restriction and a correction of a gut activity imbalance, caused mainly by human interventions on the quality and quantity of food. New surgical procedures and some other innovations may take us toward more physiological solutions. Ideally, pure metabolic surgery does not bring new diseases (mechanical restriction, malabsorption, and excluded segments) with the purpose to treat old ones.
Annals of Surgery r Volume 262, Number 2, August 2015
Urgent help in the treatment of the epidemic obesity and MS is needed. New understandings demand new attitudes. There are many uncertainties, but no doubt that there were mistakes in the initial concepts of bariatric surgery. The abundant literature in the field, therefore, is precious. There is a very well-placed emphasis on this search for innovations. Sergio Santoro, MD Hospital Israelita Albert Einstein Sao Paulo, Brazil [email protected]
9.
10.
11.
12.
REFERENCES 1. Carlson MA. Research priorities in bariatric surgery: misplaced emphasis on innovation? Ann Surg. 2015;261:e58–e59. 2. Meier JJ, Gallwitz B, Siepmann N, et al. Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Diabetologia. 2003;46:798– 801. 3. Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a nonobese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg. 2004;239:1–11. 4. Holst JJ, Gromada J. Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am J Physiol Endocrinol Metab. 2004;287:E199–E206. 5. Hare KJ, Knop FK, Asmar M, et al. Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2009;94:4679–4687. 6. Meier JJ, Gethmann A, Gotze O, et al. Glucagonlike peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans. Diabetologia. 2006;49:452–458. 7. Batterham RL, Cohen MA, Ellis SM, et al. Inhibition of food intake in obese subjects by peptide YY3–36. N Engl J Med. 2003;349:941–948. 8. Nauck MA, Niedereichholz U, Ettler R, et al. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in
healthy humans. Am J Physiol Endocrinol Metab. 1997;273:E981–E988. Vilsboll T, Krarup T, Sonne J, et al. Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab. 2003;88:2706–2713. Deschamps I, Heptner W, Desjeux JF, et al. Effects of diet on insulin and gastric inhibitory polypeptide levels in obese children. Pediatr Res. 1980;14:300–303. Miyawaki K, Yamada Y, Ban N, et al. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med. 2002;8:738–742. Irwin N, Flatt PR. Evidence for beneficial effects of compromised gastric inhibitory polypeptide action in obesity-related diabetes and possible therapeutic implications. Diabetologia. 2009;52: 1724–1731.
Reply: would like to thank Dr Santoro for writing a response to my recent editorial.1 In this response, Dr Santoro provided a summary of recent advances in bariatric and metabolic surgery and related physiology. Dr Santoro did not, however, address the concerns that I raised in that editorial about bariatric procedure and device development, which seems to be outpacing our knowledge of gastrointestinal physiology. The concerns that I raised in that editorial still stand.
I
Mark A. Carlson, MD University of Nebraska Medical Center Omaha, NE [email protected]
REFERENCE 1. Carlson MA. Research priorities in bariatric surgery: misplaced emphasis on innovation? Ann Surg. 2015;261:e58–e59.
Disclosure: The author declares no conflicts of interest. 10.1097/SLA.0000000000000591
e80 | www.annalsofsurgery.com
C 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Mechanical Restriction and Functional Restriction All of us present restrictive mechanisms to stop eating, but they are functional. After meals, food is sent to the gut because hunger, a life-threatening condition, is resolved in the gut and not in the stomach. Just after eating a considerable amount of food, gut signals slow down the gastric emptying (like a sink with a clogged drain) so that the next (not the previous) portions can be stored there. As the storage capacity is limited, at a certain point, gastric pressure is high and the meal has to be finished. Observe that restriction appears only later in the eating process and not after the first bite. This is a functional restriction. A mechanical restriction is static and is an obstacle for the passage of food after the very first spoonful. A narrow anastomosis, a ring, and a band are mechanical restrictions and not physiological. Mechanical restrictions limit ingestion; functional restrictions limit stocking. Metabolic surgery can provoke an earlier functional restriction and avoid a mechanical restriction. This is a major difference, a significant progress, and it demands changes.
Intestinal Satiety and Gastric Satiety As an immediate consequence of the previous concept, it becomes clear that one
Disclosure: The author declares no conflicts of interest. C 2014 Wolters Kluwer Health, Inc. All Copyright rights reserved. ISSN: 0003-4932/14/26202-e0079 DOI: 10.1097/SLA.0000000000000590
must obtain intestinal signals of satiety before the size of the stomach and its internal pressure become a limiting issue. Therefore, one must obtain the intestinal satiety before the beginning of the stocking process and then the gastric satiety, which finishes the meal.
A Physiological Definition for Hunger and Gluttony Foraging is moved by hunger, a necessity. You eat quickly and your stomach empties rapidly until intestinal satiety appears, slowing the gastric emptying. Then, the typical hunger is gone, but if there is available food that does not demand significant energy or risk to obtain, we keep on eating until gastric satiety stops us. Intestinal satiety first interrupts hunger and then gastric satiety interrupts gluttony. In this didactic scenario, the amount of food we eat moved by hunger is related to the capacity of our gut to receive, process, and absorb food and send signals. The size of the stomach is only related to the amount we eat later due to gluttony. If gut signals are too weak or come too late, one may eat too much with a very small functional stomach or even none.
The Cautious Gut and The Reliable Gut To trigger a strong insulinic response, with the interruption of endogenous glucose production, is very risky. Severe hypoglycemia is a fast killer. It is very reasonable that animals carefully check the amount and the quality of ingested food before triggering such a dangerous response. GIP (glucose-dependent insulinotropic polypeptide), a typical proximal gut hormone, produces an insulinic response, but instead of diminishing secretion of glucagon, it enhances it!2 And this is quite logical. In the proximal gut, food is not well quantified and it is still too early to stop endogenous glucose production, too early to cause strong satiety, and too soon to block gastric emptying (unless there is an acute hyperglycemia). The proximal gut is cautious. It would even be logical from a evolutionary point of view that duodenal-jejunal products could induce some insulinic resistance, as previously suggested by Rubino and Marescaux.3 Food in the distal gut means a lot more; it means you are fairly well fed. It is safe for the distal gut to trigger an intense response that aims at reducing glycemia and at inducing satiety. Distal gut signals strongly potenti-
Annals of Surgery r Volume 262, Number 2, August 2015
ate insulinic responses,4 but, differently from the proximal gut, it has the authority to block glucagon secretion,5 to interrupt endogenous glucose production and the supply of fat to the circulation (clearance of triglycerides),6 to cause strong satiety,7 and to stop gastric emptying.8 The distal gut is reliable.
The Gut Imbalance Theory The strong connection between the type of food and its abundance with obesity and the metabolic syndrome (MS) is clear. The fast rise in the incidence of these conditions is coincident with the introduction of an abundant processed diet. This “unnatural” food has concentrated highly absorbable nutrients (refined sugar and refined flour) and progressively less fiber and residues. Processed nutrients indeed suffer an “external digestion.” Duodenum is very permeable, a lot more than the distal gut. Indeed, the presence of fully digested nutrients is not expected there. In face of “unnatural” high glycemic index food that is rapidly absorbed, this “excessive” permeability allows a fast invasion of nutrients in the blood, faster than what naturally occurs. Obviously, the proximal gut would be overstimulated in this scenario whereas the distal gut less stimulated, as nutritive absorption occurs more proximally than what is “naturally” expected: an imbalance. Indeed, the obese and the diabetic patients present abnormally high GIP9 (mainly a proximal gut product). If they eat less, on a diet, GIP falls.10 GIP is obesogenic and insulinotropic (contributing to hyperinsulinemia), and the therapeutic blockage of GIP is beneficial for these patients.11,12 The opposite is also very clear. Therapeutic additions of the distal gut products [GLP-1 (glucagon-like peptide-1), PYY (peptide tyrosine-tyrosine), oxyntomodulin] or their agonists are beneficial in MS patients. Drugs and hormones that interfere in this balance, by enhancing the distal gut activity or blocking the proximal gut activity, help MS patients. Surgical procedures support this observation. The more you shift food from proximal to distal, the better the results in obesity and MS are, despite worse nutritional results when this is obtained by excluding segments. There is an imbalance in gut activity, and the introduction of easily absorbed food can justify that. Epidemiology, physiology, drugs, and surgical procedures point at the same direction. The proximal-distal imbalance makes sense. www.annalsofsurgery.com | e79
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Letter to the Editor
Abandoning The Term “Bariatric” “Bariatric” has become an inadequate term. Bariatric refers to weight. Weight itself is not the problem, obesity and MS are. They are metabolic problems. If we call the surgery “bariatric,” it means we are targeting weight; surgical indication is guided by the weight, and the promise is weight loss. Bariatric surgery uses mechanical restriction and malabsorption. Both are diseases, classified in the International Classification of Diseases (K.90 code indicates malabsorption), and they are not physiological at all. If we call it metabolic, it changes a lot. The objective is to adjust the metabolic response to food ingestion. The surgical indication is metabolically driven and therefore the surgical goal is not primarily weight loss, even because the weight does not depend on the surgery alone. The promise is a metabolic change, which will help patients obtain better results for their efforts in maintaining good health and body composition. Also, fortunately, we can produce major metabolic changes without any significant mechanical restriction or malabsorption. Possibly, it is the birth of pure metabolic surgery, which is not bariatric, not mechanically restrictive, and not malabsorptive. It works through functional restriction and a correction of a gut activity imbalance, caused mainly by human interventions on the quality and quantity of food. New surgical procedures and some other innovations may take us toward more physiological solutions. Ideally, pure metabolic surgery does not bring new diseases (mechanical restriction, malabsorption, and excluded segments) with the purpose to treat old ones.
Annals of Surgery r Volume 262, Number 2, August 2015
Urgent help in the treatment of the epidemic obesity and MS is needed. New understandings demand new attitudes. There are many uncertainties, but no doubt that there were mistakes in the initial concepts of bariatric surgery. The abundant literature in the field, therefore, is precious. There is a very well-placed emphasis on this search for innovations. Sergio Santoro, MD Hospital Israelita Albert Einstein Sao Paulo, Brazil [email protected]
9.
10.
11.
12.
REFERENCES 1. Carlson MA. Research priorities in bariatric surgery: misplaced emphasis on innovation? Ann Surg. 2015;261:e58–e59. 2. Meier JJ, Gallwitz B, Siepmann N, et al. Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Diabetologia. 2003;46:798– 801. 3. Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a nonobese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg. 2004;239:1–11. 4. Holst JJ, Gromada J. Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am J Physiol Endocrinol Metab. 2004;287:E199–E206. 5. Hare KJ, Knop FK, Asmar M, et al. Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2009;94:4679–4687. 6. Meier JJ, Gethmann A, Gotze O, et al. Glucagonlike peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans. Diabetologia. 2006;49:452–458. 7. Batterham RL, Cohen MA, Ellis SM, et al. Inhibition of food intake in obese subjects by peptide YY3–36. N Engl J Med. 2003;349:941–948. 8. Nauck MA, Niedereichholz U, Ettler R, et al. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in
healthy humans. Am J Physiol Endocrinol Metab. 1997;273:E981–E988. Vilsboll T, Krarup T, Sonne J, et al. Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab. 2003;88:2706–2713. Deschamps I, Heptner W, Desjeux JF, et al. Effects of diet on insulin and gastric inhibitory polypeptide levels in obese children. Pediatr Res. 1980;14:300–303. Miyawaki K, Yamada Y, Ban N, et al. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med. 2002;8:738–742. Irwin N, Flatt PR. Evidence for beneficial effects of compromised gastric inhibitory polypeptide action in obesity-related diabetes and possible therapeutic implications. Diabetologia. 2009;52: 1724–1731.
Reply: would like to thank Dr Santoro for writing a response to my recent editorial.1 In this response, Dr Santoro provided a summary of recent advances in bariatric and metabolic surgery and related physiology. Dr Santoro did not, however, address the concerns that I raised in that editorial about bariatric procedure and device development, which seems to be outpacing our knowledge of gastrointestinal physiology. The concerns that I raised in that editorial still stand.
I
Mark A. Carlson, MD University of Nebraska Medical Center Omaha, NE [email protected]
REFERENCE 1. Carlson MA. Research priorities in bariatric surgery: misplaced emphasis on innovation? Ann Surg. 2015;261:e58–e59.
Disclosure: The author declares no conflicts of interest. 10.1097/SLA.0000000000000591
e80 | www.annalsofsurgery.com
C 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
