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Erschienen in: Surgery Today 3/2016

01.03.2016 | Review Article

Potential mechanisms mediating improved glycemic control after bariatric/metabolic surgery

verfasst von: Hiroshi Yamamoto, Sachiko Kaida, Tsuyoshi Yamaguchi, Satoshi Murata, Masaji Tani, Tohru Tani

Erschienen in: Surgery Today | Ausgabe 3/2016

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Abstract

Conservative medical treatment for morbid obesity generally fails to sustain weight loss. On the other hand, surgical operations, so-called bariatric surgery, have evolved due to their long-term effects. The global increase in the overweight population and the introduction of laparoscopic surgery have resulted in the use of bariatric surgery spreading quickly worldwide in recent years. Recent clinical evidence suggests that bariatric surgery not only reduces body weight, but also improves secondary serious diseases, including type 2 diabetes mellitus, in so-called metabolic surgery. Moreover, several potential mechanisms mediating the improvement in glycemic control after bariatric/metabolic surgery have been proposed based on the animal and human studies. These mechanisms include changes in the levels of gastrointestinal hormones, bacterial flora, bile acids, intestinal gluconeogenesis and gastrointestinal motility as well as adipose tissue and inflammatory mediators after surgery. The mechanisms underlying improved glycemic control are expected to accelerate the promotion of both metabolic and bariatric surgery. This article describes the current status of bariatric surgery worldwide and in Japan, reviews the accumulated data for weight loss and diabetic improvements after surgery and discusses the potential mechanisms mediating improved glycemic control.
Literatur
1.
Zurück zum Zitat Karra E, Yousseif A, Batterham RL. Mechanisms facilitating weight loss and resolution of type 2 diabetes following bariatric surgery. Trends Endocrinol Metab. 2010;21(6):337–44.CrossRefPubMed Karra E, Yousseif A, Batterham RL. Mechanisms facilitating weight loss and resolution of type 2 diabetes following bariatric surgery. Trends Endocrinol Metab. 2010;21(6):337–44.CrossRefPubMed
2.
3.
Zurück zum Zitat Kasama K. Dr. Isao Kawamura, a pioneer in morbid obesity treatment in Japan. Obes Surg. 2012;22:1143.CrossRef Kasama K. Dr. Isao Kawamura, a pioneer in morbid obesity treatment in Japan. Obes Surg. 2012;22:1143.CrossRef
4.
Zurück zum Zitat Kasama K, Tagaya N, Kanahira E, Umezawa A, Kurosaki T, Oshiro T, et al. Has laparoscopic bariatric surgery been accepted in Japan? The experience of a single surgeon. Obes Surg. 2008;18(11):1473–8.CrossRefPubMed Kasama K, Tagaya N, Kanahira E, Umezawa A, Kurosaki T, Oshiro T, et al. Has laparoscopic bariatric surgery been accepted in Japan? The experience of a single surgeon. Obes Surg. 2008;18(11):1473–8.CrossRefPubMed
5.
Zurück zum Zitat Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292(14):1724–37.CrossRefPubMed Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292(14):1724–37.CrossRefPubMed
6.
Zurück zum Zitat Sjöström L, Narbro K, Sjöström CD, Karason K, Larsson B, Wede H, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741–52.CrossRefPubMed Sjöström L, Narbro K, Sjöström CD, Karason K, Larsson B, Wede H, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741–52.CrossRefPubMed
7.
Zurück zum Zitat Trastulli S, Desiderio J, Guarino S, Cirocchi R, Scalercio V, Noya G, et al. Laparoscopic sleeve gastrectomy compared with other bariatric surgical procedures: a systematic review of randomized trials. Surg Obes Relat Dis. 2013;9(5):816–29.CrossRefPubMed Trastulli S, Desiderio J, Guarino S, Cirocchi R, Scalercio V, Noya G, et al. Laparoscopic sleeve gastrectomy compared with other bariatric surgical procedures: a systematic review of randomized trials. Surg Obes Relat Dis. 2013;9(5):816–29.CrossRefPubMed
8.
Zurück zum Zitat Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366(17):1567–76.PubMedCentralCrossRefPubMed Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366(17):1567–76.PubMedCentralCrossRefPubMed
9.
Zurück zum Zitat Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366(17):1577–85.CrossRefPubMed Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366(17):1577–85.CrossRefPubMed
10.
Zurück zum Zitat Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Brethauer SA, Navaneethan SD, et al. Bariatric surgery versus intensive medical therapy for diabetes–3-year outcomes. N Engl J Med. 2014;370(21):2002–13.CrossRefPubMed Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Brethauer SA, Navaneethan SD, et al. Bariatric surgery versus intensive medical therapy for diabetes–3-year outcomes. N Engl J Med. 2014;370(21):2002–13.CrossRefPubMed
11.
Zurück zum Zitat Trung VN, Yamamoto H, Yamaguchi T, Murata S, Akabori H, Ugi S, et al. J Surg Res. 2013;185:159–65.CrossRefPubMed Trung VN, Yamamoto H, Yamaguchi T, Murata S, Akabori H, Ugi S, et al. J Surg Res. 2013;185:159–65.CrossRefPubMed
12.
Zurück zum Zitat Lee WJ, Chong K, Ser KH, Lee YC, Chen SC, Chen JC, et al. Gastric bypass vs sleeve gastrectomy for type 2 diabetes mellitus: a randomized controlled trial. Arch Surg. 2011;146(2):143–8.CrossRefPubMed Lee WJ, Chong K, Ser KH, Lee YC, Chen SC, Chen JC, et al. Gastric bypass vs sleeve gastrectomy for type 2 diabetes mellitus: a randomized controlled trial. Arch Surg. 2011;146(2):143–8.CrossRefPubMed
13.
Zurück zum Zitat DuPree CE, Blair K, Steele SR, Martin MJ. Laparoscopic sleeve gastrectomy in patients with preexisting gastroesophageal reflux disease: a national analysis. JAMA Surg. 2014;149(4):328–34.CrossRefPubMed DuPree CE, Blair K, Steele SR, Martin MJ. Laparoscopic sleeve gastrectomy in patients with preexisting gastroesophageal reflux disease: a national analysis. JAMA Surg. 2014;149(4):328–34.CrossRefPubMed
14.
Zurück zum Zitat Rosenthal RJ, Diaz AA, Arvidsson D, Baker RS, Basso N, Bellanger D, International Sleeve Gastrectomy Expert Panel, et al. International Sleeve Gastrectomy Expert Panel Consensus Statement: best practice guidelines based on experience of >1,2000 cases. Surg Obes Relat Dis. 2012;8(1):8–19.CrossRefPubMed Rosenthal RJ, Diaz AA, Arvidsson D, Baker RS, Basso N, Bellanger D, International Sleeve Gastrectomy Expert Panel, et al. International Sleeve Gastrectomy Expert Panel Consensus Statement: best practice guidelines based on experience of >1,2000 cases. Surg Obes Relat Dis. 2012;8(1):8–19.CrossRefPubMed
15.
Zurück zum Zitat Mittermair R, Sucher R, Perathoner A. Results and complications after laparoscopic sleeve gastrectomy. Surg Today. 2014;44(7):1307–12.CrossRefPubMed Mittermair R, Sucher R, Perathoner A. Results and complications after laparoscopic sleeve gastrectomy. Surg Today. 2014;44(7):1307–12.CrossRefPubMed
16.
Zurück zum Zitat Ribaric G, Buchwald JN, McGlennon TW. Diabetes and weight in comparative studies of bariatric surgery vs. conventional medical therapy: a systematic review and meta-analysis. Obes Surg. 2014;24:437–55.PubMedCentralCrossRefPubMed Ribaric G, Buchwald JN, McGlennon TW. Diabetes and weight in comparative studies of bariatric surgery vs. conventional medical therapy: a systematic review and meta-analysis. Obes Surg. 2014;24:437–55.PubMedCentralCrossRefPubMed
18.
Zurück zum Zitat Knop FK. Resolution of type 2 diabetes following gastric bypass surgery: involvement of gut-derived glucagon and glucagonotropic signaling? Diabetologia. 2009;52(11):2270–6.CrossRefPubMed Knop FK. Resolution of type 2 diabetes following gastric bypass surgery: involvement of gut-derived glucagon and glucagonotropic signaling? Diabetologia. 2009;52(11):2270–6.CrossRefPubMed
19.
Zurück zum Zitat Silecchia G, Boru C, Pecchia A, Rizzello M, Casella G, Leonetti F, et al. Effectiveness of laparoscopic sleeve gastrectomy (first stage of biliopancreatic diversion with duodenal switch) on co-morbidities in super-obese high-risk patients. Obes Surg. 2006;16:1138–44.CrossRefPubMed Silecchia G, Boru C, Pecchia A, Rizzello M, Casella G, Leonetti F, et al. Effectiveness of laparoscopic sleeve gastrectomy (first stage of biliopancreatic diversion with duodenal switch) on co-morbidities in super-obese high-risk patients. Obes Surg. 2006;16:1138–44.CrossRefPubMed
20.
Zurück zum Zitat Vidal J, Ibarzabal A, Romero F, Delgado S, Momblán D, Flores L, et al. Type 2 diabetes mellitus and the metabolic syndrome following sleeve gastrectomy in severely obese subjects. Obes Surg. 2008;18:1077–82.CrossRefPubMed Vidal J, Ibarzabal A, Romero F, Delgado S, Momblán D, Flores L, et al. Type 2 diabetes mellitus and the metabolic syndrome following sleeve gastrectomy in severely obese subjects. Obes Surg. 2008;18:1077–82.CrossRefPubMed
21.
Zurück zum Zitat Sasaki A, Wakabayashi G, Yonei Y. Current status of bariatric surgery in Japan and effectiveness in obesity and diabetes. J Gastroenterol. 2010;49(1):57–63.CrossRef Sasaki A, Wakabayashi G, Yonei Y. Current status of bariatric surgery in Japan and effectiveness in obesity and diabetes. J Gastroenterol. 2010;49(1):57–63.CrossRef
22.
Zurück zum Zitat Deitel M, Crosby RD, Gagner M. The first international consensus summit for sleeve gastrectomy (SG), New York City, October 25–27, 2007. Obes Surg. 2008;18:487–96.CrossRefPubMed Deitel M, Crosby RD, Gagner M. The first international consensus summit for sleeve gastrectomy (SG), New York City, October 25–27, 2007. Obes Surg. 2008;18:487–96.CrossRefPubMed
23.
Zurück zum Zitat Karamanakos SN, Vagenas K, Kalfarentzos F, Alexandrides TK, et al. Weight loss, appetite suppression, and changes in fasting and postprandial ghrelin and peptide-YY levels after Roux-en-Y gastric bypass and sleeve gastrectomy: a prospective, double blind study. Ann Surg. 2008;247:401–7.CrossRefPubMed Karamanakos SN, Vagenas K, Kalfarentzos F, Alexandrides TK, et al. Weight loss, appetite suppression, and changes in fasting and postprandial ghrelin and peptide-YY levels after Roux-en-Y gastric bypass and sleeve gastrectomy: a prospective, double blind study. Ann Surg. 2008;247:401–7.CrossRefPubMed
24.
Zurück zum Zitat Langer FB, Reza Hoda MA, Bohdjalian A, Felberbauer FX, Zacherl J, Wenzl E, et al. Sleeve gastrectomy and gastric banding: effects on plasma ghrelin levels. Obes Surg. 2005;15(7):1024–9.CrossRefPubMed Langer FB, Reza Hoda MA, Bohdjalian A, Felberbauer FX, Zacherl J, Wenzl E, et al. Sleeve gastrectomy and gastric banding: effects on plasma ghrelin levels. Obes Surg. 2005;15(7):1024–9.CrossRefPubMed
25.
Zurück zum Zitat Peterli R, Wölnerhanssen B, Peters T, Devaux N, Kern B, Christoffel-Courtin C, et al. Improvement in glucose metabolism after bariatric surgery: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: a prospective randomized trial. Ann Surg. 2009;250(2):234–41.CrossRefPubMed Peterli R, Wölnerhanssen B, Peters T, Devaux N, Kern B, Christoffel-Courtin C, et al. Improvement in glucose metabolism after bariatric surgery: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: a prospective randomized trial. Ann Surg. 2009;250(2):234–41.CrossRefPubMed
26.
Zurück zum Zitat Takiguchi S, Murakami K, Yanagimoto Y, Takata A, Miyazaki Y, Mori M et al., Clinical application of ghrelin in the field of surgery. Surg Today. 2014 [Epub ahead of print]. Takiguchi S, Murakami K, Yanagimoto Y, Takata A, Miyazaki Y, Mori M et al., Clinical application of ghrelin in the field of surgery. Surg Today. 2014 [Epub ahead of print].
27.
Zurück zum Zitat Ugi S, Yamamoto H, Kusunoki C, Kamo A, Ikeda K, Hashimoto T, et al. Laparoscopic sleeve gastrectomy leads to rapid improvement of glucose tolerance and insulin secretion with enhanced glucagon-like peptide (GLP-1) secretion. Diabetol Int. 2010;1(2):99–103.CrossRef Ugi S, Yamamoto H, Kusunoki C, Kamo A, Ikeda K, Hashimoto T, et al. Laparoscopic sleeve gastrectomy leads to rapid improvement of glucose tolerance and insulin secretion with enhanced glucagon-like peptide (GLP-1) secretion. Diabetol Int. 2010;1(2):99–103.CrossRef
28.
Zurück zum Zitat Trung VN, Yamamoto H, Furukawa A, Yamaguchi T, Murata S, Yoshimura M, et al. Enhanced intestinal motility during oral glucose tolerance test after laparoscopic sleeve gastrectomy : preliminary results using cine magnetic resonance imaging. PLoS One. 2013;8(6):e65739.PubMedCentralCrossRefPubMed Trung VN, Yamamoto H, Furukawa A, Yamaguchi T, Murata S, Yoshimura M, et al. Enhanced intestinal motility during oral glucose tolerance test after laparoscopic sleeve gastrectomy : preliminary results using cine magnetic resonance imaging. PLoS One. 2013;8(6):e65739.PubMedCentralCrossRefPubMed
29.
Zurück zum Zitat Melissas J, Koukouraki S, Askoxylakis J, Stathaki M, Daskalakis M, Perisinakis K, et al. Sleeve gastrectomy: a restrictive procedure? Obes Surg. 2007;17:57–62.CrossRefPubMed Melissas J, Koukouraki S, Askoxylakis J, Stathaki M, Daskalakis M, Perisinakis K, et al. Sleeve gastrectomy: a restrictive procedure? Obes Surg. 2007;17:57–62.CrossRefPubMed
30.
Zurück zum Zitat Braghetto I, Davanzo C, Korn O, Csendes A, Valladares H, Herrera E, et al. Scintigraphic evaluation of gastric emptying in obese patients submitted to sleeve gastrectomy compared to normal subjects. Obes Surg. 2009;19:1515–21.CrossRefPubMed Braghetto I, Davanzo C, Korn O, Csendes A, Valladares H, Herrera E, et al. Scintigraphic evaluation of gastric emptying in obese patients submitted to sleeve gastrectomy compared to normal subjects. Obes Surg. 2009;19:1515–21.CrossRefPubMed
31.
Zurück zum Zitat Wilson-Pérez HE, Chambers AP, Ryan KK, Li B, Sandoval DA, Stoffers D, Drucker DJ, et al. Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon-like Peptide 1 receptor deficiency. Diabetes. 2013;62(7):2380–6.PubMedCentralCrossRefPubMed Wilson-Pérez HE, Chambers AP, Ryan KK, Li B, Sandoval DA, Stoffers D, Drucker DJ, et al. Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon-like Peptide 1 receptor deficiency. Diabetes. 2013;62(7):2380–6.PubMedCentralCrossRefPubMed
32.
Zurück zum Zitat Chambers AP, Kirchner H, Wilson-Perez HE, Willency JA, Hale JE, Gaylinn BD, et al. The effects of vertical sleeve gastrectomy in rodents are ghrelin independent. Gastroenterology. 2013;144(1):50–2.PubMedCentralCrossRefPubMed Chambers AP, Kirchner H, Wilson-Perez HE, Willency JA, Hale JE, Gaylinn BD, et al. The effects of vertical sleeve gastrectomy in rodents are ghrelin independent. Gastroenterology. 2013;144(1):50–2.PubMedCentralCrossRefPubMed
33.
Zurück zum Zitat Tremaroli V, Bäckhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489(7415):242–9.CrossRefPubMed Tremaroli V, Bäckhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489(7415):242–9.CrossRefPubMed
34.
Zurück zum Zitat Vrieze A, Van Nood E, Holleman F, Salojärvi J, Kootte RS, Bartelsman JF, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143:913–6.CrossRefPubMed Vrieze A, Van Nood E, Holleman F, Salojärvi J, Kootte RS, Bartelsman JF, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143:913–6.CrossRefPubMed
35.
Zurück zum Zitat Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci USA. 2009;106(7):2365–70.PubMedCentralCrossRefPubMed Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci USA. 2009;106(7):2365–70.PubMedCentralCrossRefPubMed
36.
Zurück zum Zitat Ryan KK, Tremaroli V, Clemmensen C, Kovatcheva-Datchary P, Myronovych A, Karns R, et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature. 2014;509(7499):183–8.PubMedCentralCrossRefPubMed Ryan KK, Tremaroli V, Clemmensen C, Kovatcheva-Datchary P, Myronovych A, Karns R, et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature. 2014;509(7499):183–8.PubMedCentralCrossRefPubMed
37.
Zurück zum Zitat Mudaliar S, Henry RR, Sanyal AJ, Morrow L, Marschall HU, Kipnes M, et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology. 2013;145(3):574–82.CrossRefPubMed Mudaliar S, Henry RR, Sanyal AJ, Morrow L, Marschall HU, Kipnes M, et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology. 2013;145(3):574–82.CrossRefPubMed
38.
Zurück zum Zitat Troy S, Soty M, Ribeiro L, Laval L, Migrenne S, Fioramonti X, et al. Intestinal gluconeogenesis is a key factor for early metabolic changes after gastric bypass but not after gastric lap-band in mice. Cell Metab. 2008;8(3):2001–211.CrossRef Troy S, Soty M, Ribeiro L, Laval L, Migrenne S, Fioramonti X, et al. Intestinal gluconeogenesis is a key factor for early metabolic changes after gastric bypass but not after gastric lap-band in mice. Cell Metab. 2008;8(3):2001–211.CrossRef
39.
Zurück zum Zitat Breen DM, Rasmussen BA, Kokorovic A, Wang R, Cheung GW, Lam TK. Jejunal nutrient sensing is required for duodenal–jejunal bypass surgery to rapidly lower glucose concentrations in uncontrolled diabetes. Nat Med. 2012;18(6):950–5.CrossRefPubMed Breen DM, Rasmussen BA, Kokorovic A, Wang R, Cheung GW, Lam TK. Jejunal nutrient sensing is required for duodenal–jejunal bypass surgery to rapidly lower glucose concentrations in uncontrolled diabetes. Nat Med. 2012;18(6):950–5.CrossRefPubMed
Metadaten
Titel
Potential mechanisms mediating improved glycemic control after bariatric/metabolic surgery
verfasst von
Hiroshi Yamamoto
Sachiko Kaida
Tsuyoshi Yamaguchi
Satoshi Murata
Masaji Tani
Tohru Tani
Publikationsdatum
01.03.2016
Verlag
Springer Japan
Erschienen in
Surgery Today / Ausgabe 3/2016
Print ISSN: 0941-1291
Elektronische ISSN: 1436-2813
DOI
https://doi.org/10.1007/s00595-015-1134-2

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