The Influence Of GIP (Glucose-Dependent Insulinotropic Polypeptide) Infusion On Human Adipose Tissue: An In Vivo Study

The Influence Of GIP (Glucose-Dependent Insulinotropic Polypeptide) Infusion On Hormone Sensitive Lipase, Lipoprotein Lipase And Adipokine Expression In Human Subcutaneous Adipose Tissue: An In Vivo Study

Study part-1

GIP (glucose-dependent insulinotropic polypeptide) is one of the two main incretin hormones secreted by specialized cells of the gastrointestinal tract in response to ingestion of nutrients. Data emerging from studies in animal models and cultured human fat cells support a physiological role for GIP in the adipose tissue metabolism which may contribute to the pathogenesis of obesity.

The proposed study will shed more light on the interactions between gut hormones and adipose tissue. For this pilot study, male subjects fulfilling the inclusion criteria will be given GIP or placebo infusions in a randomized manner. Fat tissue biopsies will be obtained from all subjects during both visits, once in the basal state (before the start of the peptide/placebo infusion) and then repeated at the end of the period of infusion.

Study part-2

Surgery represents the most effective therapeutic modality for morbid obesity. Resolution of type 2 diabetes mellitus (T2DM) has been consistently observed as an additional benefit of surgical treatment of obesity. The mechanisms underlying the dramatic effects of surgery on insulin sensitivity and β-cell function are poorly understood. Bariatric surgery (gastric bypass) promotes changes in the enteroendocrine system as a result of nutrient diversion from the physiological intestinal routes with subsequent profound modification of gut hormone secretion

We hypothesize that restoration of GIP action after bariatric procedures plays a cardinal role in the improvement and/or restoration of diabetes, we propose to study patients (both sex)with morbid obesity and T2DM within 3 months after their surgery. Their responses will be compared to those of BMI matched control subjects with normal glucose tolerance

Study Overview

• Status: Unknown
• Conditions: Adipose Tissue
• Intervention / Treatment: Other: GIP (glucose dependent insulinotropic peptide) infusion

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: CHRISTINA DAOUSI, MD FRCP; Phone Number: +44 (0) 151 529 5920; Email: cdaousi@liverpool.ac.uk
• Study Contact Backup: Name: Sravan K Thondam, MBBS MRCP; Phone Number: +44 (0) 151 529 6464; Email: s.thondam@liverpool.ac.uk

Study Locations

• United Kingdom
  • Liverpool, United Kingdom, L9 7AL
    • Recruiting
    • University Hospital Aintree
    • Contact: Christina Daousi, MD FRCP; Phone Number: +44 (0) 151 5295885; Email: cdaousi@liverpool.ac.uk
    • Contact: Sravan K Thondam, MBBS MRCP; Phone Number: 44 (0) 151 5296464; Email: s.thondam@liverpool.ac.uk
    • Principal Investigator: Christina Daousi, MD FRCP
    • Sub-Investigator: Sravan K Thondam, MBBS MRCP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Lean (BMI 20-25 kg/m2) subjects with normal glucose tolerance
• Obese (BMI >30 kg/m2) subjects also with normal glucose tolerance.
• Obese with impaired glucose tolerance
• Obese with diet controlled diabetes mellitus
• Morbid obesity, type diabetes and post bariatric surgery (study part 2)

Exclusion Criteria:

• History of severe cardiac, hepatic or renal disease
• Thyroid dysfunction (hyper-or hypothyroidism), or other endocrine disturbance (acromegaly, growth hormone deficiency, hypoadrenalism or cortisol overproduction)
• Current malignant disease
• Known alcohol misuse
• Major psychiatric disease (including current use of antidepressants)
• History of major eating disorder (anorexia or bulimia nervosa)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To measure Lipoprotein lipase (LPL) and Hormone sensitive Lipase (HSL) activity in adipose tissue	Before and after 4 hours of infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the role of GIP in adipocytokine gene expression and secretion from human subcutaneous adipose tissue	Baseline and after 4 hours of continuous infusion

Collaborators and Investigators

• Sponsor: Liverpool University Hospitals NHS Foundation Trust
• Investigators: Principal Investigator: CHRISTINA DAOUSI, MD FRCP, UNIVERSITY HOSPITAL AINTREE NHS TRUST

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: December 15, 2008
• First Submitted That Met QC Criteria: December 15, 2008
• First Posted (Estimate): December 16, 2008

Study Record Updates

• Last Update Posted (Estimate): December 21, 2011
• Last Update Submitted That Met QC Criteria: December 20, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: GIP; HSL; OBESITY; LPL; ADIPOCYTOKINES; BARIATRIC SURGERY
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Gastric Inhibitory Polypeptide
• Other Study ID Numbers: 08/H1001/20; 08DE001