title: Type 2 diabetes mellitus: a possible surgically reversible intestinal dysfunction.
abstract: Type 2 diabetes mellitus (T2DM) is a global public health problem often associated with obesity. Bariatric surgery is effective for treating serious obesity, and techniques involving intestinal bypass have metabolic benefits, such as complete and early remission of T2DM. We present a literature review of the possible mechanisms of early normalization of glycemic homeostasis after bariatric surgery, including intestinal gluconeogenesis, increased antidiabetogenic signals from L cells located in the distal small intestine, and impaired secretion of diabetogenic signals in the upper part of the small intestine. Adding to these potential mechanisms, unknown factors that regulate insulin sensitivity may be involved and altered by bariatric surgery. This review discusses the various hypotheses about the mechanisms of glycemic control after bariatric surgery involving intestinal bypass. Further research is essential to better understand these mechanisms and to identify potential new mechanisms that might help in developing less invasive and safer alternatives for the treatment of T2DM and reveal novel pharmaceutical targets for glycemic control.
authors.affiliation: Department of Gastroenterology, Digestive Surgery Discipline, LIM 35, University of São Paulo, Medical School, Av Dr Arnaldo, 455 Cerqueira César, CEP 01246-930 São Paulo, Brazil. priscila_csala@hotmail.com
authors.forename: Priscila C
authors.initials: PC
authors.lastname: Sala
authors.forename: Raquel S
authors.initials: RS
authors.lastname: Torrinhas
authors.forename: Steven B
authors.initials: SB
authors.lastname: Heymsfield
authors.forename: Dan L
authors.initials: DL
authors.lastname: Waitzberg
mesh_terms: D050110:Bariatric Surgery / Q000379:methods; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000601:surgery; D005260:Female; D005943:Gluconeogenesis; D006706:Homeostasis; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism* / Q000601:surgery; D008297:Male; D009767:Obesity, Morbid / Q000378:metabolism* / Q000601:surgery; D016896:Treatment Outcome; D015431:Weight Loss
chemical_list: D001786:Blood Glucose
references.citation: Endocrinology. 2008 Nov;149(11):5670-8
references.pmid: 18669601
references.citation: Diabetes. 2004 Aug;53(8):1949-52
references.pmid: 15277371
references.citation: JAMA. 2008 Jan 23;299(3):316-23
references.pmid: 18212316
references.citation: Curr Opin Clin Nutr Metab Care. 2005 Jul;8(4):445-9
references.pmid: 15930972
references.citation: Endocrinology. 1986 Oct;119(4):1467-75
references.pmid: 3530719
references.citation: Obes Surg. 2010 Sep;20(9):1245-50
references.pmid: 20524158
references.citation: Annu Rev Med. 2006;57:243-64
references.pmid: 16409148
references.citation: Am J Physiol Endocrinol Metab. 2004 Jan;286(1):E129-35
references.pmid: 12824085
references.citation: Diabetes Care. 2004 May;27(5):1047-53
references.pmid: 15111519
references.citation: Mol Endocrinol. 2003 Feb;17(2):161-71
references.pmid: 12554744
references.citation: Surgery. 1996 Mar;119(3):261-8
references.pmid: 8619180
references.citation: Diabetes Metab. 2010 Sep;36(4):257-62
references.pmid: 20561808
references.citation: Cell Metab. 2008 Sep;8(3):201-11
references.pmid: 18762021
references.citation: J Clin Endocrinol Metab. 1992 Feb;74(2):379-84
references.pmid: 1730817
references.citation: J Clin Endocrinol Metab. 2001 Aug;86(8):3717-23
references.pmid: 11502801
references.citation: Trends Endocrinol Metab. 2010 Jun;21(6):337-44
references.pmid: 20133150
references.citation: J Visc Surg. 2010 Oct;147(5 Suppl):e21-9
references.pmid: 20971048
references.citation: Diabetes Care. 2009 Jan;32 Suppl 1:S13-61
references.pmid: 19118286
references.citation: World J Surg. 1998 Sep;22(9):919-24
references.pmid: 9717417
references.citation: J Clin Invest. 1993 Jan;91(1):301-7
references.pmid: 8423228
references.citation: J Clin Endocrinol Metab. 1996 Jun;81(6):2061-8
references.pmid: 8964829
references.citation: Diabetes. 2005 Dec;54 Suppl 2:S79-86
references.pmid: 16306345
references.citation: Ann Surg. 2004 Jan;239(1):1-11
references.pmid: 14685093
references.citation: Obesity (Silver Spring). 2006 Feb;14(2):194-8
references.pmid: 16571843
references.citation: Cad Saude Publica. 2003;19 Suppl 1:S29-36
references.pmid: 12886433
references.citation: Ann Surg. 2004 Aug;240(2):236-42
references.pmid: 15273546
references.citation: Eur J Biochem. 1987 May 4;164(3):553-8
references.pmid: 3569278
references.citation: Diabetes Care. 2005 Oct;28(10):2406-11
references.pmid: 16186271
references.citation: Diabetes Metab. 2009 Dec;35(6 Pt 2):537-43
references.pmid: 20152741
references.citation: Diabetologia. 2009 Nov;52(11):2270-2276
references.pmid: 19727661
references.citation: Obesity (Silver Spring). 2008 Jan;16(1):77-81
references.pmid: 18223616
references.citation: Cell Metab. 2006 Mar;3(3):153-65
references.pmid: 16517403
references.citation: Physiology (Bethesda). 2005 Oct;20:357-65
references.pmid: 16174875
references.citation: Diabetes. 1994 Jul;43(7):871-7
references.pmid: 8013750
references.citation: N Engl J Med. 2005 Jul 21;353(3):249-54
references.pmid: 16034010
references.citation: Obes Surg. 2005 Sep;15(8):1124-8
references.pmid: 16197783
references.citation: J Biol Chem. 1986 Sep 5;261(25):11880-9
references.pmid: 3528148
references.citation: Nutr Clin Pract. 2010 Apr;25(2):175-82
references.pmid: 20413698
references.citation: Am J Physiol Endocrinol Metab. 2005 Feb;288(2):E447-53
references.pmid: 15454396
references.citation: Diabetes Metab. 1996 Apr;22(2):122-31
references.pmid: 8792092
references.citation: J Clin Endocrinol Metab. 2008 Nov;93(11 Suppl 1):S89-96
references.pmid: 18987275
references.citation: Diabetologia. 2006 Sep;49(9):2136-43
references.pmid: 16819611
references.citation: Diabetes Care. 2008 Feb;31 Suppl 2:S290-6
references.pmid: 18227499
references.citation: J Clin Endocrinol Metab. 2000 Mar;85(3):1043-8
references.pmid: 10720037
references.citation: Obes Surg. 2005 Oct;15(9):1258-64
references.pmid: 16259883
references.citation: Physiol Rev. 1998 Oct;78(4):1087-108
references.pmid: 9790570
references.citation: Ann Surg. 2003 Jun;237(6):751-6; discussion 757-8
references.pmid: 12796570
references.citation: Int J Obes (Lond). 2010 Mar;34(3):462-71
references.pmid: 20029383
references.citation: Surg Obes Relat Dis. 2008 Jan-Feb;4(1):55-9
references.pmid: 18201671
references.citation: Dan Med Bull. 2004 Nov;51(4):364-70
references.pmid: 16009062
references.citation: J Clin Endocrinol Metab. 2005 Jan;90(1):359-65
references.pmid: 15483088
references.citation: Ann Surg. 1954 Sep;140(3):439-48
references.pmid: 13198079
references.citation: J Clin Invest. 2000 Jul;106(2):171-6
references.pmid: 10903330
references.citation: J Clin Invest. 2007 Jan;117(1):24-32
references.pmid: 17200703
references.citation: Ann Surg. 1995 Sep;222(3):339-50; discussion 350-2
references.pmid: 7677463
references.citation: J Cell Physiol. 2003 Nov;197(2):189-97
references.pmid: 14502558
references.citation: J Clin Endocrinol Metab. 2004 Jun;89(6):2608-15
references.pmid: 15181031
references.citation: Curr Drug Targets. 2005 Mar;6(2):153-69
references.pmid: 15777186
references.citation: Physiol Genomics. 2004 Jul 08;18(2):206-17
references.pmid: 15150374
references.citation: J Clin Endocrinol Metab. 2010 Aug;95(8):4072-6
references.pmid: 20501690
references.citation: Regul Pept. 1981 May;2(2):139-50
references.pmid: 6894800
references.citation: Comp Biochem Physiol B Biochem Mol Biol. 2005 Feb;140(2):333-40
references.pmid: 15649781
references.citation: Surg Gynecol Obstet. 1983 Oct;157(4):301-8
references.pmid: 6623319
references.citation: Cleve Clin J Med. 2010 Jul;77(7):468-76
references.pmid: 20601620
references.citation: World J Surg. 2009 Oct;33(10):2014-21
references.pmid: 19421812
references.citation: Ann Surg. 2006 Nov;244(5):741-9
references.pmid: 17060767
references.citation: Int J Obes (Lond). 2009 Apr;33 Suppl 1:S33-40
references.pmid: 19363506
references.citation: JAMA. 2004 Oct 13;292(14):1724-37
references.pmid: 15479938
references.citation: Surg Obes Relat Dis. 2006 Sep-Oct;2(5):518-22
references.pmid: 17015204
references.citation: Annu Rev Med. 2010;61:393-411
references.pmid: 20059345
references.citation: Gastroenterology. 2007 May;132(6):2131-57
references.pmid: 17498508
references.citation: Ann Surg. 1987 Sep;206(3):316-23
references.pmid: 3632094
references.citation: Diabetes Metab. 2009 Dec;35(6 Pt 2):518-23
references.pmid: 20152737
references.citation: Obes Surg. 1998 Jun;8(3):267-82
references.pmid: 9678194
references.citation: Obes Surg. 2005 Apr;15(4):474-81
references.pmid: 15946424
references.citation: Digestion. 1978;17(2):168-90
references.pmid: 342323
references.citation: JOP. 2004 Nov 10;5(6):464-75
references.pmid: 15536283
references.citation: Diabetes. 1998 Jun;47(6):882-9
references.pmid: 9604863
references.citation: Metabolism. 1995 Jan;44(1):47-51
references.pmid: 7854165
references.citation: J Clin Endocrinol Metab. 2008 Dec;93(12):4656-63
references.pmid: 18765510
references.citation: Diabetes. 2003 Jul;52(7):1649-54
references.pmid: 12829628
references.citation: Diabetologia. 2003 Jun;46(6):798-801
references.pmid: 12764578
references.citation: Diabetes. 2006 Jul;55(7):2025-31
references.pmid: 16804072
references.citation: Diabetes Care. 2009 Mar;32(3):375-80
references.pmid: 19033407
references.citation: Surgery. 2007 Jul;142(1):74-85
references.pmid: 17630003
references.citation: Diabetologia. 1983 Nov;25(5):396-9
references.pmid: 6653943
references.citation: Obes Surg. 2009 Dec;19(12):1605-11
references.pmid: 19885707
references.citation: J Biol Chem. 1989 Aug 5;264(22):12826-9
references.pmid: 2753890
references.citation: Ann Surg. 2003 Oct;238(4):467-84; discussion 84-5
references.pmid: 14530719
references.citation: Diab Vasc Dis Res. 2007 Jun;4(2):151-3
references.pmid: 17654450
references.citation: Nutrition. 2009 Sep;25(9):881-4
references.pmid: 19647621
references.citation: Diabetologia. 1987 Nov;30(11):874-81
references.pmid: 3446554