Diet and Medical Therapy Versus Bariatric Surgery in Type 2 Diabetes - Full Text View

Purpose

It is generally held that ß-cell function is irreversibly lost already at the time the disease manifests itself and thereafter continues to decline linearly with time. Several studies, however, have documented the possibility that ß-cell function may be restored, at least partially, in type 2 diabetes. Of major relevance to the issue of ß-cell recovery in diabetes are the following findings:

bariatric surgery in morbidly obese patients with type 2 diabetes can restore euglycaemia, the acute insulin response to glucose and insulin sensitivity;
recent studies have reported that diabetic subjects return to euglycaemia and normal insulin levels within days after surgery, long before a significant weight loss has occurred; and
whereas gastric bypass (GBP) improves insulin sensitivity in proportion to weight loss, bilio-pancreatic diversion (BPD) improves insulin action out of proportion to weight loss, i.e., it normalizes it at a time when patients are still markedly obese. Because RYGB is a predominantly restrictive procedure involving the foregut, whereas BPD is a predominantly malabsorptive procedure involving the distal gastro-intestinal (GI) tract, these findings suggest that the control of both insulin action and ß-cell function is influenced by signals originating from the GI tract.

The principal aim of this study is to verify the effect on type 2 diabetes mellitus (T2DM) of GBP and BPD, the two operations which have shown specific actions on glucose homeostasis control, in type 2 diabetic patients with BMI > 35 kg/m2, and to compare this effect with matched T2DM control patients receiving the standard of medical care.

Condition	Intervention	Phase
Type 2 Diabetes	Procedure: Gastric bypass Procedure: Bilio-pancreatic diversion Behavioral: anti-diabetic drugs and behavioral suggestions	Phase 2 Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Prospective Randomized Controlled Trial on the Effect of Gastric Bypass and Biliopancreatic Diversion on Type 2 Diabetes Mellitus in Patients With BMI > 35 vs. Medical Therapy

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines Diabetes Type 2 Weight Loss Surgery

U.S. FDA Resources

Further study details as provided by Catholic University of the Sacred Heart:

Primary Outcome Measures:

To assess the efficacy of bariatric surgery in inducing partial or total remission of type 2 diabetes mellitus, as compared to standard medical anti-diabetic care (STC). [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Secondary endpoints include percentage change of fasting plasma glucose levels, glycated hemoglobin, weight, waist circumference, blood pressure, cholesterol, HDL-cholesterol and triglycerides, hard cardiovascular risk and quality of life. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
We aim at measuring in the long term (5 years after enrollment) by the glycemic holter the degree of glucose control in the patients belonging to the 3 arms of our randomized, controlled study comparing conventional medical therapy with bilio-pancreatic diversion and Roux-en-Y gastric bypass. To this end, the patients will wear the glycemic holter over 24-48 hours and the results recorded. The patients are already recording periodical 7 points glucose self monitoring.

Quality of life will be investigated at 5 years from enrollment by the RAND 36-Item Health Survey. It taps 8 health concepts: physical functioning, bodily pain, role of limitations deriving from physical health problems, limitations due to physical or emotional problems, emotional well being, social functioning, energy/fatigue, and general health perception. It also includes a single item that provides an indication of perceived change in health. The questionnaire will be administered by the physician.


Enrollment:	60
Study Start Date:	April 2009
Study Completion Date:	November 2011
Primary Completion Date:	October 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: GBP Type 2 diabetic subjects with BMI ≥ 35, poor glycemic control (HbA1c ≥ 7.0%) and diabetes duration ≥ 5 years undergo gastric bypass	Procedure: Gastric bypass Gastric bypass (GBP): A subcardial gastric pouch with a 30±10 ml capacity will be created on a naso-gastric 36F calibrating tube by sectioning the stomach with a linear stapler 3-4 cm horizontally on the lesser curve, 4 cm distal to the e-g junction, and then vertically until attainment of the angle of Hiss. After identification of the Treitz ligament, the jejunum will be transected at 100 cm from the ligament of Treitz and the two stumps will be closed. The distal stump will be anastomosed to the distal end of the gastric pouch. The preferred gastro-jejunal anastomosis is the totally hand-sewn one, but it can be performed using any other the technique the surgeon is more familiar with. Finally, the proximal stump of the transacted bowel will be joined end-to-side to the jejunum 150 cm distal to the gastroenterostomy.
Active Comparator: BPD 2 Type 2 diabetic subjects with BMI ≥ 35, poor glycemic control (HbA1c ≥ 7.0%) and diabetes duration ≥ 5 years undergo bilio-pancreatic diversion	Procedure: Bilio-pancreatic diversion Biliopancreatic diversion (BPD): A distal two-third gastrectomy will be carried out aiming at leaving an about 400 ml gastric remnant. The gastrointestinal continuity will be re-established by sectioning the small bowel 300 cm proximal to the ileocecal valve, closing the intestinal stumps, and joining the proximal one end-to-side to the distal ileum at 50 cm from the ligament of Treitz. The distal stump of the transacted bowel will be anastomosed to the left corner of the gastric stump, preferably in a totally hand-sewn fashion.
Active Comparator: Med Ter3 Type 2 diabetic subjects with BMI ≥ 35, poor glycemic control (HbA1c ≥ 7.0%) and diabetes duration ≥ 5 yearsundergo medical therapy	Behavioral: anti-diabetic drugs and behavioral suggestions Medical therapies (oral hypoglycemic agents and insulin) are optimized on an individual basis. Lifestyle modification programs, including reduced energy and fat (<30% total fat and <10% saturated fat, high fibre content) intake and increased physical exercise (suggested at least 30 minutes of brisk walking every day possibly associated with a moderate intensity aerobic activity twice a week), are tailor made by an experienced diabetologist assisted by a dietitian. After the two years, the patients in control group will be offered the choice to undergo one of the two surgical procedures.

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Eligibility


Ages Eligible for Study:	30 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

patients with type 2 diabetes and BMI ≥35 kg.m-2
age between 30 and 60 years
duration of diabetes ≥ 5 years
poor glycemic control (i.e., HbA1c ≥ 7.0%) in spite a medical antidiabetic therapy in accordance with good clinical practice (GCP)

Exclusion Criteria:

pregnancy
medical conditions requiring acute hospitalisation
severe diabetes complications or associated medical conditions (such as blindness, end-stage renal failure, liver cirrhosis, malignancy, chronic congestive heart failure)
recent (within preceding 12 months) myocardial infarction, stroke or TIA
unstable angina pectoris
psychological conditions which may hamper patient's cooperation
geographic inaccessibility
any condition which, in the judgement of the Investigator, may make risky the participation in the study or bias the results

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00888836

Locations


Italy
Catholic University, Faculty of Medicine
Rome, Italy, 00168

Sponsors and Collaborators

Catholic University of the Sacred Heart

Investigators


Principal Investigator:	Geltrude Mingrone, MD, PhD	Catholic University Hospital
Study Chair:	Giuseppe Nanni, MD	Catholic University Hospital

More Information

Publications:

Ferrannini E. Insulin resistance versus insulin deficiency in non-insulin-dependent diabetes mellitus: problems and prospects. Endocr Rev. 1998 Aug;19(4):477-90. Review.

Weyer C, Tataranni PA, Bogardus C, Pratley RE. Insulin resistance and insulin secretory dysfunction are independent predictors of worsening of glucose tolerance during each stage of type 2 diabetes development. Diabetes Care. 2001 Jan;24(1):89-94.

Ferrannini E, Gastaldelli A, Miyazaki Y, Matsuda M, Pettiti M, Natali A, Mari A, DeFronzo RA. Predominant role of reduced beta-cell sensitivity to glucose over insulin resistance in impaired glucose tolerance. Diabetologia. 2003 Sep;46(9):1211-9. Epub 2003 Jul 23.

Rossetti L, Giaccari A, DeFronzo RA. Glucose toxicity. Diabetes Care. 1990 Jun;13(6):610-30. Review.

Grill V, Björklund A. Dysfunctional insulin secretion in type 2 diabetes: role of metabolic abnormalities. Cell Mol Life Sci. 2000 Mar;57(3):429-40. Review.

Ferrannini E, Gastaldelli A, Miyazaki Y, Matsuda M, Mari A, DeFronzo RA. beta-Cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis. J Clin Endocrinol Metab. 2005 Jan;90(1):493-500. Epub 2004 Oct 13.

Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW, Neifing JL, Ward WK, Beard JC, Palmer JP, et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes. 1993 Nov;42(11):1663-72.

Ilkova H, Glaser B, Tunçkale A, Bagriaçik N, Cerasi E. Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients by transient intensive insulin treatment. Diabetes Care. 1997 Sep;20(9):1353-6.

Kärvestedt L, Andersson G, Efendic S, Grill V. A rapid increase in beta-cell function by multiple insulin injections in type 2 diabetic patients is not further enhanced by prolonging treatment. J Intern Med. 2002 Apr;251(4):307-16.

Alvarsson M, Sundkvist G, Lager I, Henricsson M, Berntorp K, Fernqvist-Forbes E, Steen L, Westermark G, Westermark P, Orn T, Grill V. Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients. Diabetes Care. 2003 Aug;26(8):2231-7.

Ryan EA, Imes S, Wallace C. Short-term intensive insulin therapy in newly diagnosed type 2 diabetes. Diabetes Care. 2004 May;27(5):1028-32.

Salinari S, Bertuzzi A, Asnaghi S, Guidone C, Manco M, Mingrone G. First-phase insulin secretion restoration and differential response to glucose load depending on the route of administration in type 2 diabetic subjects after bariatric surgery. Diabetes Care. 2009 Mar;32(3):375-80. doi: 10.2337/dc08-1314. Epub 2008 Nov 25.

Cowan GS Jr, Buffington CK. Significant changes in blood pressure, glucose, and lipids with gastric bypass surgery. World J Surg. 1998 Sep;22(9):987-92.

Marceau P, Hould FS, Simard S, Lebel S, Bourque RA, Potvin M, Biron S. Biliopancreatic diversion with duodenal switch. World J Surg. 1998 Sep;22(9):947-54.

Scopinaro N, Adami GF, Marinari GM, Gianetta E, Traverso E, Friedman D, Camerini G, Baschieri G, Simonelli A. Biliopancreatic diversion. World J Surg. 1998 Sep;22(9):936-46.

Greco AV, Mingrone G, Giancaterini A, Manco M, Morroni M, Cinti S, Granzotto M, Vettor R, Camastra S, Ferrannini E. Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion. Diabetes. 2002 Jan;51(1):144-51.

Hickey MS, Pories WJ, MacDonald KG Jr, Cory KA, Dohm GL, Swanson MS, Israel RG, Barakat HA, Considine RV, Caro JF, Houmard JA. A new paradigm for type 2 diabetes mellitus: could it be a disease of the foregut? Ann Surg. 1998 May;227(5):637-43; discussion 643-4.

Mari A, Manco M, Guidone C, Nanni G, Castagneto M, Mingrone G, Ferrannini E. Restoration of normal glucose tolerance in severely obese patients after bilio-pancreatic diversion: role of insulin sensitivity and beta cell function. Diabetologia. 2006 Sep;49(9):2136-43. Epub 2006 Jul 4.

Muscelli E, Mingrone G, Camastra S, Manco M, Pereira JA, Pareja JC, Ferrannini E. Differential effect of weight loss on insulin resistance in surgically treated obese patients. Am J Med. 2005 Jan;118(1):51-7.

Rubino F, Gagner M, Gentileschi P, Kini S, Fukuyama S, Feng J, Diamond E. The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg. 2004 Aug;240(2):236-42.

Näslund E, Backman L, Holst JJ, Theodorsson E, Hellström PM. Importance of small bowel peptides for the improved glucose metabolism 20 years after jejunoileal bypass for obesity. Obes Surg. 1998 Jun;8(3):253-60.

le Roux CW, Aylwin SJ, Batterham RL, Borg CM, Coyle F, Prasad V, Shurey S, Ghatei MA, Patel AG, Bloom SR. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg. 2006 Jan;243(1):108-14.

Clements RH, Gonzalez QH, Long CI, Wittert G, Laws HL. Hormonal changes after Roux-en Y gastric bypass for morbid obesity and the control of type-II diabetes mellitus. Am Surg. 2004 Jan;70(1):1-4; discussion 4-5.

Lauritsen KB, Christensen KC, Stokholm KH. Gastric inhibitory polypeptide (GIP) release and incretin effect after oral glucose in obesity and after jejunoileal bypass. Scand J Gastroenterol. 1980;15(4):489-95.

Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg. 2004 Jan;239(1):1-11.

Sirinek KR, O'Dorisio TM, Hill D, McFee AS. Hyperinsulinism, glucose-dependent insulinotropic polypeptide, and the enteroinsular axis in morbidly obese patients before and after gastric bypass. Surgery. 1986 Oct;100(4):781-7.

Morínigo R, Moizé V, Musri M, Lacy AM, Navarro S, Marín JL, Delgado S, Casamitjana R, Vidal J. Glucagon-like peptide-1, peptide YY, hunger, and satiety after gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab. 2006 May;91(5):1735-40. Epub 2006 Feb 14.

Valverde I, Puente J, Martín-Duce A, Molina L, Lozano O, Sancho V, Malaisse WJ, Villanueva-Peñacarrillo ML. Changes in glucagon-like peptide-1 (GLP-1) secretion after biliopancreatic diversion or vertical banded gastroplasty in obese subjects. Obes Surg. 2005 Mar;15(3):387-97.

Jorde R, Burhol PG, Johnson JA. The effect of jejunoileal bypass on postprandial release of plasma gastric inhibitory polypeptide (GIP). Scand J Gastroenterol. 1981;16(2):313-9.

Sarson DL, Scopinaro N, Bloom SR. Gut hormone changes after jejunoileal (JIB) or biliopancreatic (BPB) bypass surgery for morbid obesity. Int J Obes. 1981;5(5):471-80.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, Nanni G, Pomp A, Castagneto M, Ghirlanda G, Rubino F. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012 Apr 26;366(17):1577-85. doi: 10.1056/NEJMoa1200111. Epub 2012 Mar 26.


Responsible Party:	Geltrude Mingrone, Assistant Professor of Internal Medicine, Catholic University of the Sacred Heart
ClinicalTrials.gov Identifier:	NCT00888836 History of Changes
Other Study ID Numbers:	UCSC-2009-1
Study First Received:	April 27, 2009
Last Updated:	July 28, 2014
Health Authority:	Italy: Ministry of Health

Keywords provided by Catholic University of the Sacred Heart:


bariatric surgery GBP BPD type 2 diabetes

Additional relevant MeSH terms:


Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases

ClinicalTrials.gov processed this record on February 27, 2015

Diet and Medical Therapy Versus Bariatric Surgery in Type 2 Diabetes (DIBASY)