The Incretin Secretion in the Gut System Related to the Physiological Stimulus

NCT00994435 | Completed

• 1 other identifier: 1082/08
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Insulin secretion and insulin sensitivity are related with an inverse, hyperbolic function, the so called disposition index, that shows the critical importance of the ß-cell dysfunction for the development of T2DM. A consequence of the hyperbolic relationship is that increased insulin resistance is compensated by up-regulation of insulin secretion, as it happens in obesity. However, when a defective insulin secretion in relation to insulin sensitivity takes place (i.e. reduced disposition index) then impaired glucose tolerance or type 2 diabetes develop. The investigators have recently demonstrated that bilio-pancreatic diversion determines a prompt reversibility of T2DM by normalizing peripheral insulin sensitivity and enhancing ß-cell sensitivity to glucose; these changes occur within few days after surgery, largely before changes in body weight occur. This operation may affect the entero-insular axis function, by diverting nutrients away from the proximal gastro-intestinal tract and by delivering incompletely digested nutrients to the ileum, thus abnormally stimulating the secretion of intestinal incretins. It has been shown that male Wistar rats undergoing three different types of small intestinal surgery, namely ileal transposition (either 10 or 20 cm of lower ileum transposed to mid-duodenum) or 85% jejuno-ileal bypass, showed a sustained post-operative reduction in food intake and a significant change in body weight gain. All experimental groups had a large increase in basal and meal-stimulated enteroglucagon, while the area under the curve of plasma levels of gastrin, gastric inhibitory polypeptide (GIP), insulin and blood glucose were significantly reduced. GIP is produced mainly in the duodenum and jejunum as shown in dogs .The aim of the present study is to investigate the intestinal site of production of incretins in response to intraluminal nutrients stimulation in order to establish the relationship between insulin resistance, insulin hypersecretion and different small intestinal segments in insulin resistance conditions, such as obesity and T2DM. To this purpose a mixed test meal will be infused in the duodenum, proximal jejunum or ileum and glucose uptake and insulin secretion studied, in relation to glucagon and incretin response. Studies are carried out in 20 obese subjects of both sexes, 10 of whom with type 2 diabetes and 10 with normal glucose tolerance.

Conditions

Obesity

Keywords

obesity

Outcome Measures

Primary Outcomes (1)

• dosage for glucose, free fatty acids (FFA) insulin, C-peptide, glucagon, GLP-1, GIP

  3 test meals of 360 minutes duration each, taken at a time distance of 7-10 days . Overall duration, approximally 30 days for each patient.

Eligibility Criteria

• Age: 30 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Studies are carried out in 20 obese subjects of both gender sexes, 10 of whom with type 2 diabetics and 10 with normal glucose tolerance.

You may qualify if:

• Males and females
• Women in fertile age should engage themselves in avoiding pregnancy during the study protocol. Before starting each experimental session a pregnancy test will be performed and pregnant women excluded from the investigation. All women will be studied in the follicular phase of their menstrual cycle 30 to 60 years old.
• HbA1c between 6.5 and 8.5% (for patients with T2DM only)
• BMI between 30-40 Kg /m2

You may not qualify if:

• Past or active medical history of major endocrinological, renal, cardiac, respiratory, liver or gastro-intestinal diseases.
• All Diabetic patients must have never been treated with oral hypoglycemic agents or insulin.

Sponsors & Collaborators

• Catholic University of the Sacred Heart: lead

Study Sites (1)

Department of Metabolic Diseases, Institute of Internal Medicine - Catholic University

Rome, Rome, 00168, Italy

Location

Related Publications (1)

• Salinari S, Carr RD, Guidone C, Bertuzzi A, Cercone S, Riccioni ME, Manto A, Ghirlanda G, Mingrone G. Nutrient infusion bypassing duodenum-jejunum improves insulin sensitivity in glucose-tolerant and diabetic obese subjects. Am J Physiol Endocrinol Metab. 2013 Jul 1;305(1):E59-66. doi: 10.1152/ajpendo.00559.2012. Epub 2013 May 7.

  PMID: 23651846 DERIVED

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Giovanni Ghirlanda, MD

  Catholic University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 1, 2009
• First Posted: October 14, 2009
• Study Start: January 1, 2009
• Primary Completion: July 1, 2010
• Study Completion: January 1, 2011
• Last Updated: March 24, 2011

Record last verified: 2009-10

Locations

IT (1)