The Effect of Bariatric Surgery on Insulin Sensitivity and Energy Metabolism (Bariatrix)

Study Description

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Brief Summary:

The purpose of this study is:

1. To explore to what extent insulin sensitivity, energy metabolism and ectopic lipid storage can be improved by bariatric surgery
2. To explore to what extent hepatic and muscular disorders of energy metabolism occur in patients with obesity (degree 2-3)
3. To explore whether the steato liver occurring in patients with obesity (degree 2-3) is associated with the degree of liver inflammation

Condition or disease	Intervention/treatment	Phase
Obesity; Diabetes Mellitus, Non-Insulin-Dependent	Procedure: surgery	Not Applicable

Detailed Description:

Insulin resistance strongly relates to ectopic lipid deposition in skeletal muscle and the liver, which correlate with insulin resistance. Lipid metabolites accumulating in skeletal muscle and the liver are thought to impair insulin signalling and thereby reduce glucose uptake and glycogen storage. Insulin resistant humans frequently present with decreased mitochondrial function in skeletal muscle which might contribute to lipid accumulation and the development of insulin resistance. Non-alcoholic liver disease (NAFLD) comprise fatty liver, steatohepatitis and cirrhosis. NAFLD correlate with insulin resistance increased risk for cardiovascular diseases, type 2 diabetes and hepatocellular. The mechanisms leading from fatty liver to steatohepatitis and insulin resistance in the liver are yet unclear. Bariatric surgery relates to surgery for the reduction of body weight. Bariatric surgery frequently leads to normalization of glucose tolerance in previously diabetic humans even before the onset of body weight reduction. The underlying mechanisms are yet unclear. In this study we aim to explore the mechanisms underlying the onset of insulin resistance and steatohepatitis in patients with fatty liver and to identify the mechanisms leading to improved glucose tolerance in humans after bariatric surgery. We test the following hypotheses: increased lipid availability leads to (i) increased lipid oxidation and oxidative stress (ii) accumulation of lipid metabolites that impair insulin signalling (iii) bariatric surgery improves insulin sensitivity by increasing lipid oxidation.

This study will contribute to the understanding of NAFLD and will help to identify new targets for the therapy of diabetes.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	250 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	Assessment of the Effect of Bariatric Surgery on Insulin Sensitivity and Energy Metabolism
Study Start Date :	September 2012
Estimated Primary Completion Date :	December 2021
Estimated Study Completion Date :	December 2021

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: Surgery; bariatric surgery	Procedure: surgery; biliopancreatic diversion, gastric banding, gastric sleeve resection; Other Name: bariatric surgery

Outcome Measures

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Primary Outcome Measures :

1. Energy metabolism [ Time Frame: 4 years ]
   whole body substrate oxidation, ex vivo mitochondrial function via measurement of high resolution respirometry and in vivo mitochondrial function via measurement of ATP production

Secondary Outcome Measures :

1. weight loss [ Time Frame: four year ]
   body weight and body composition before and after bariatric surgery
2. Insulin sensitivity [ Time Frame: four years ]
   Whole body glucose uptake and enfogenous glucose production as measure of skeletal muscle and hepatic insulin sensitivity

Eligibility Criteria

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Ages Eligible for Study:	30 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

• Aged ≥ 30 years- ≤ 70 years
• Balanced sex (50: 50)
• BMI 20- 25 kg/m 2 normal- weight group
• BMI 35- 39,9 kg/m 2 (Obese type II)
• BMI >40 kg/m 2 (Obese type III)

Exclusion Criteria:

• Acute illness 2 weeks before start of examination
• Autoimmune or Immune disorder diseases (Leukozyten < 5000/µl
• Renal insufficiency (Kreatin > 1,5 mg/dl)
• Heart disease, condition after heart attack
• Anemia (Hb <12g/l, controlled before every day of examination) or blood donations 4weeks before examination.
• Participation in another trial within the last 2 weeks
• Pharmacological- immunotherapy (Cortisol, Antihistaminika, ASS)
• Thyroid disorders
• Glitazone or Insulin- Therapy
• Pregnancy, Lactation, Menstruation
• Smoking cigarettes, Alcohol- and drug abuse
• Psychiatric disorders
• Risk for/ or diagnosed HIV/ AIDS or Hepatitis B/C
• Liver disease, which are not caused by non- alcoholic steato- hepatitis
• Working on night shifts or irregular rhythm of night- day
• Impaired wound healing or clotting disorders
• Allergic reaction to local anesthetics
• Malignant cancer

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Germany
DDZ (Deutsches Diabetes Zentrum)	Recruiting
Düsseldorf, NRW, Germany, 40225
Contact: Michael Roden, Prof. med. 49(0) 2 11-33 82-201 roden@ddz.uni-duesseldorf.de
Contact: Julia Szendrödi, Dr. med Ph.D 0211/3382-203 julia.Szendroedi@ddz.uni-duesseldorf.de

Sponsors and Collaborators

German Diabetes Center

Dep.of General-, Visceral- and Pediatric Surgery, HHU, Duesseldorf

Dep.for Metabolic Diseases, HHU, Duesseldorf

Investigators

Principal Investigator:	Julia Szendrödi, MD, PhD	German Diabetes Center

More Information

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Additional Information:

Homepage 

Publications of Results:

Koliaki C, Szendroedi J, Kaul K, Jelenik T, Nowotny P, Jankowiak F, Herder C, Carstensen M, Krausch M, Knoefel WT, Schlensak M, Roden M. Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis. Cell Metab. 2015 May 5;21(5):739-46. doi: 10.1016/j.cmet.2015.04.004.

Responsible Party:	julia szendrödi, Dr PhD, German Diabetes Center
ClinicalTrials.gov Identifier:	NCT01477957 History of Changes
Other Study ID Numbers:	Bariatrix
First Posted:	November 23, 2011
Last Update Posted:	September 14, 2017
Last Verified:	September 2017

Keywords provided by julia szendrödi, German Diabetes Center:

weight loss after bariatric surgery; Insulin sensitivity; insulin resistance

Additional relevant MeSH terms:

Diabetes Mellitus; Hypersensitivity; Insulin Resistance; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases	Immune System Diseases; Hyperinsulinism; Insulin, Globin Zinc; Insulin; Hypoglycemic Agents; Physiological Effects of Drugs