The Effect of Bariatric Surgery on Insulin Sensitivity and Energy Metabolism

Официальное название

The Effect of Bariatric Surgery on Insulin Sensitivity and Energy Metabolism in Obesity Grade 2 -3

Обзор

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

Подробное описание

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. Metabolic dysfunction-associated steatotic liver disease comprises steatosis, steatohepatitis and cirrhosis. MASLD correlates with insulin resistance, increased risk for cardiovascular diseases and type 2 diabetes. The mechanisms leading from steatosis to steatohepatitis and insulin resistance in the liver are yet unclear. Bariatric surgery aims at profound reduction of body weight. Also, it frequently and rapidly leads to normalization of glucose tolerance 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 steatosis 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 MASLD and will help to identify new targets for the therapy of diabetes.

Вмешательства

• Процедура surgery
  biliopancreatic diversion, gastric banding, gastric sleeve resection

Первичные конечные точки

• Energy metabolism [Срок оценки: 5 years]

Вторичные конечные точки (2)

• weight loss [Срок оценки: 5 years]
• Insulin sensitivity [Срок оценки: 5 years]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Германия · 1 центр

• German Diabetes Center — Düsseldorf

Публикации

• 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. PMID 25955209
• Miya A, Tura A, Shokouhmehr A, Esposito I, Yavas A, Granderath FA, Schlensak M, Huttasch M, Xourafa G, Heilmann G, Kahl S, Roden M, Schrauwen P. Insulin resistance, not hepatic histological features, is the dominant correlate of insulin clearance in class 3 obesity. Diabetes Res Clin Pract. 2026 Aug 2:113481. doi: 10.1016/j.diabres.2026.113481. Online ahead of print. PMID 42543084
• Kahl S, Strassburger K, Pacini G, Trinks N, Pafili K, Mastrototaro L, Dewidar B, Sarabhai T, Trenkamp S, Esposito I, Schlensak M, Granderath FA, Roden M. Dysglycemia and liver lipid content determine the relationship of insulin resistance with hepatic OXPHOS capacity in obesity. J Hepatol. 2025 Mar;82(3):417-426. doi: 10.1016/j.jhep.2024.08.012. Epub 2024 Aug 31. PMID 39218222
• Kovac L, Gancheva S, Jahnert M, Sehgal R, Mastrototaro L, Schlensak M, Granderath FA, Rittig K, Roden M, Schurmann A, Kahl S, Ouni M. Different effects of bariatric surgery on epigenetic plasticity in skeletal muscle of individuals with and without type 2 diabetes. Diabetes Metab. 2024 Sep;50(5):101561. doi: 10.1016/j.diabet.2024.101561. Epub 2024 Jul 6. PMID 38977261
• Sarabhai T, Kahl S, Gancheva S, Mastrototaro L, Dewidar B, Pesta D, Ratter-Rieck JM, Bobrov P, Jeruschke K, Esposito I, Schlensak M, Roden M. Loss of mitochondrial adaptation associates with deterioration of mitochondrial turnover and structure in metabolic dysfunction-associated steatotic liver disease. Metabolism. 2024 Feb;151:155762. doi: 10.1016/j.metabol.2023.155762. Epub 2023 Dec 19. PMID 38122893
• 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. Ep PMID 35988689
• 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. PMID 29602794

Идентификаторы

NCT: NCT01477957 · BARIA-DDZ

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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