The Effect of Bariatric Surgery on Insulin Sensitivity and Energy Metabolism

Conditions

Diabetes Mellitus, Type 2, Obesity

Keywords

weight loss after bariatric surgery, Insulin sensitivity, insulin resistance

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

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. 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.

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.

2026-08-02

10.1016/j.diabres.2026.113481

Dysglycemia and liver lipid content determine the relationship of insulin resistance with hepatic OXPHOS capacity in obesity

S. Kahl, Klaus Straßburger, Giovanni Pacini, Nina Trinks, Kalliopi Pafili et al. (13 authors)

Journal of Hepatology2024-08-3112 citations

10.1016/j.jhep.2024.08.012

Loss of mitochondrial adaptation associates with deterioration of mitochondrial turnover and structure in metabolic dysfunction-associated steatotic liver disease.

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.

2023-12-196 citations

10.1016/j.metabol.2023.155762

Mitochondrial respiration is decreased in visceral but not subcutaneous adipose tissue in obese individuals with fatty liver disease.

Pafili K, Kahl S, Mastrototaro L, Strassburger K, Pesta D, Herder C, Pützer J, Dewidar B, Hendlinger M, Granata C, Saatmann N, Yavas A, Gancheva S, Heilmann G, Esposito I, Schlensak M, Roden M.

2022-08-1944 citations

10.1016/j.jhep.2022.08.010

Interventions

PROCEDUREsurgery

biliopancreatic diversion, gastric banding, gastric sleeve resection

Study design

Observational model

CASE_CONTROL

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

20 Years to 70 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Energy metabolism	5 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

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

Countries

Germany

Contacts

Primary ContactSabine Kahl, MD

sabine.kahl@ddz.de0049211-3382

Outcome results

None listed