The Effect of Roux-en-Y Gastric Bypass on Insulin Sensitivity in Type 2 Diabetes

Study Overview
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Brief Summary
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Gastric bypass surgery induces remission of diabetes within days after surgery, before significant weight loss. The aim of the study is to examine whether improved insulin sensitivity of muscle and liver contributes to the immediate diabetes resolution.

Detailed Description
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Obesity has become a severe epidemic globally. With the rapid increase in obesity comes a pronounced rise in obesity-related disorders, especially type 2 diabetes. Weight loss achieved through lifestyle changes improves diabetes, but is very difficult to maintain over time. In contrast, Roux-en-Y gastric bypass (RYGB) surgery can induce long-term weight loss and remission of diabetes. Surprisingly, the resolution of type 2 diabetes occurs within days after surgery and before significant weight loss. The resolution of diabetes must therefore be explained by a response to the surgical alterations of the stomach and intestines: restriction in gastric volume and bypass of the stomach, duodenum and proximal jejunum. Severe insulin resistance in muscle and liver is the common defect in obesity and type 2 diabetes and may be improved or even reversed shortly after the operation. The aim of this study is to examine the acute changes in insulin sensitivity of muscle and liver by using hyperinsulinaemic euglycaemic clamp combined with glucose tracer to assess hepatic glucose production. Insulin signaling pathways will be studied in biopsies from muscle and subcutaneous fat as to explain the molecular basis of the changes in insulin sensitivity after RYGB. Insulin secretion will be evaluated in response to oral glucose as well as iv glucose-glucagon.

Conditions
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Type 2 Diabetes, Obesity

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients eligible for gastric bypass surgery Verified type 2 diabetes or normal glucose tolerance by oral glucose tolerance test (OGTT) Exclusion Criteria: Treatment for Hyperthyroidism

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| RYGB patients with type 2 diabetes<br>Morbid obese patients with type 2 diabetes undergoing gastric bypass surgery | |
| RYGB patients without type 2 diabetes<br>Morbid obese patients with normal glucose tolerance undergoing gastric bypass surgery | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in insulin sensitivity after RYGB |  | 1 week, 3 months, 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in insulin secretion in response to oral glucose after RYGB |  | 3 months, 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin resistance, Gastric bypass