The Effect of Bariatric Surgery on Insulin Sensitivity and Energy Metabolism

Obesity Clinical Trial

— BARIA-DDZ  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01477957
• Other study ID #: BARIA-DDZ
• Status: Recruiting
• Start date: September 2012
• Est. completion date: December 2028

Study information

• Verified date: November 2023
• Source: German Diabetes Center
• Contact: Sabine Kahl, MD
• Phone: 0049211-3382
• Email: sabine.kahl[@]ddz.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: December 2028
• Est. primary completion date: December 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Hypersensitivity
• Insulin Resistance
• Obesity

Intervention

Procedure:
• surgery
biliopancreatic diversion, gastric banding, gastric sleeve resection

Locations

Country	Name	City	State
Germany	German Diabetes Center	Düsseldorf	NRW

Sponsors (3)

Lead Sponsor	Collaborator
German Diabetes Center	Dep.for Metabolic Diseases, HHU, Duesseldorf, Dep.of General-, Visceral- and Pediatric Surgery, HHU, Duesseldorf

Country where clinical trial is conducted

Germany, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	weight loss	body weight and body composition before and after bariatric surgery	5 years
Secondary	Insulin sensitivity	Whole body glucose uptake and endogenous glucose production as measure of skeletal muscle and hepatic insulin sensitivity	5 years

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