The Effect of Bariatric Surgery on Insulin Sensitivity and Energy Metabolism (BARIA-DDZ)

Assessment of the Effect of Bariatric Surgery on Insulin Sensitivity and Energy Metabolism

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

Study Overview

• Status: Recruiting
• Conditions: Obesity; Diabetes Mellitus, Type 2
• Intervention / Treatment: Procedure: surgery

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 Type: Observational
• Enrollment (Estimated): 450

Contacts and Locations

• Study Contact: Name: Sabine Kahl, MD; Phone Number: 698 0049211-3382; Email: sabine.kahl@ddz.de

Study Locations

• Germany
  • NRW
    • Düsseldorf, NRW, Germany, 40225
      • Recruiting
      • German Diabetes Center
      • Contact: Sabine Kahl, MD; Phone Number: 698 0049211-3382; Email: sabine.kahl@ddz.de
      • Contact: Michael Roden, Prof., MD; Phone Number: 201 0049211-3382; Email: michael.roden@ddz.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

People with obesity and various stages of NAFLD, that qualify for bariatric surgery.

Description

Inclusion Criteria:

• Aged ≥ 20 years- ≤ 70 years
• BMI 20- 25 kg/m 2 normal- weight group
• BMI 35- 39,9 kg/m 2 (Obesity grade 2)
• BMI >40 kg/m 2 (Obesity grade 3)

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 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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Surgery; bariatric surgery	Procedure: surgery; biliopancreatic diversion, gastric banding, gastric sleeve resection; Other Names: bariatric surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Energy metabolism	whole body substrate oxidation, ex vivo mitochondrial function via measurement of high resolution respirometry and in vivo mitochondrial function via measurement of ATP production	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
weight loss	body weight and body composition before and after bariatric surgery	5 years
Insulin sensitivity	Whole body glucose uptake and endogenous glucose production as measure of skeletal muscle and hepatic insulin sensitivity	5 years

Collaborators and Investigators

• Sponsor: German Diabetes Center
• Collaborators: Dep.of General-, Visceral- and Pediatric Surgery, HHU, Duesseldorf; Dep.for Metabolic Diseases, HHU, Duesseldorf
• Investigators: Principal Investigator: Michael Roden, Prof., MD, German Diabetes Center

Publications and helpful links

General Publications

• 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.
• Pafili K, Kahl S, Mastrototaro L, Strassburger K, Pesta D, Herder C, Putzer J, Dewidar B, Hendlinger M, Granata C, Saatmann N, Yavas A, Gancheva S, Heilmann G, Esposito I, Schlensak M, Roden M. Mitochondrial respiration is decreased in visceral but not subcutaneous adipose tissue in obese individuals with fatty liver disease. J Hepatol. 2022 Dec;77(6):1504-1514. doi: 10.1016/j.jhep.2022.08.010. Epub 2022 Aug 19.
• Apostolopoulou M, Gordillo R, Koliaki C, Gancheva S, Jelenik T, De Filippo E, Herder C, Markgraf D, Jankowiak F, Esposito I, Schlensak M, Scherer PE, Roden M. Specific Hepatic Sphingolipids Relate to Insulin Resistance, Oxidative Stress, and Inflammation in Nonalcoholic Steatohepatitis. Diabetes Care. 2018 Jun;41(6):1235-1243. doi: 10.2337/dc17-1318. Epub 2018 Mar 30.

Helpful Links

• Homepage

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 13, 2011
• First Submitted That Met QC Criteria: November 22, 2011
• First Posted (Estimated): November 23, 2011

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: insulin resistance; Insulin sensitivity; weight loss after bariatric surgery
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperinsulinism; Hypersensitivity; Diabetes Mellitus, Type 2; Insulin Resistance
• Other Study ID Numbers: BARIA-DDZ