Effects of Hepatic Insulin Resistance on Type 2 Diabetes Mellitus in Morbidly Obese Subjects Following Roux-en-Y Gastric Bypass Surgery or Gastric Sleeve Surgery
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Aarhus
- Enrollment
- 30
- Locations
- 2
- Primary Endpoint
- Change from baseline diabetes status at 1 month after surgery
Study Overview
Brief Summary
Roux-en-Y Gastric Bypass surgery (RYGB) ameliorates type 2 diabetes within days after surgery. Studies indicate that the gastric sleeve procedure has comparable effect on type 2 diabetes, but to what extent and how is not fully elucidated. This study investigates the effect of the surgeries on incretin levels, glucose effectiveness and hepatic insulin sensitivity.
Detailed Description
Introduction This study comprises of a series of studies in morbidly obese subjects with type 2 diabetes before and after Roux-en-Y Gastric Bypass surgery (RYGB) and the gastric sleeve procedure, investigating the effect of these surgeries on incretin levels and hepatic insulin sensitivity. The method study (study 2) seeks to validate a better and physiological method to investigate insulin sensitivity in morbidly obese patients.
RYGB is considered the most effective treatment for obesity. The procedure improves glycemic control, and patients with type 2 diabetes may experience reductions in antidiabetic medication within days after surgery.
The improvement in glucose tolerance is associated with enhanced insulin action in muscle and adipose tissues. Recent reports indicate that hepatic insulin resistance also is improved, but the contribution of increased hepatic insulin action on glucose tolerance is controversial and remains to be thoroughly investigated. Studies indicate that RYGB reduces basal glucose production, and at 1 week following surgery hepatic insulin resistance is improved and insulin clearance increased. In contrast, insulin sensitivity in extra-hepatic tissues is not increased until 3 months after surgery. These observations imply that the liver plays an important role for early improvements in carbohydrate metabolism after RYBG, while increased insulin sensitivity in extra-hepatic tissues (muscle and adipose tissues) is delayed and more closely related to weight loss.
Effects of hepatic insulin sensitivity on glucose tolerance in obese subjects has in previous studies been addressed. However, dose response curves that determines time-dependent changes in hepatic insulin action are important for understanding the pathophysiology of glucose intolerance in obese subjects after RYGB, have not yet been conducted.
The development of a valid easy procedure that estimates insulin sensitivity at the same time the effect of the incretin hormones can be studied is of great value in especially RYGB operated patients where the secretion of hormones has been altered by the procedure. Understanding the impact of incretin hormones and hepatic insulin resistance on glucose intolerance may have implications for the medical treatment of obese patients, and may potentially predict which subset of patients are likely to experience the greatest benefits of RYGB or gastric sleeve surgery.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •BMI > 35 kg/m2
- •Diabetes Mellitus, type 2
Exclusion Criteria
- •Diabetes Mellitus, type 1
- •Chronic obstructive lung disease
- •Heart failure or other cardiac disease
- •Chronic inflammatory diseases
- •Hepatitis or HIV
- •Abnormal kidney or liver function
- •Metabolic disease
- •Prescription of prednisolone as pill or injection in the study period or 3 months prior to study start
- •Alcoholism or abuse of other substances
- •Pregnancy or planning to get pregnant within the study period
Outcomes
Primary Outcomes
Change from baseline diabetes status at 1 month after surgery
Time Frame: Baseline and 1 month
fasting plasma glucose \< 7.0 mmol/l
Change from baseline diabetes status at 12 months after surgery
Time Frame: Baseline and 12 months
fasting plasma glucose \< 7.0 mmol/l
Secondary Outcomes
- Estimates of changes in endogen glucose production from baseline(Baseline to 12 months)
- Estimates of changes in insulin sensitivity from baseline(Baseline to 12 months)
- Weight loss from baseline(Baseline to 1 month)
- Estimates of changes in Insulin secretion from baseline(Baseline to 12 months)
- Estimates of changes in insulin clearance from baseline(Baseline to 12 months)
- Estimates of changes in glucose effectiveness from baseline(Baseline to 12 months)
- Assessment og changes in fat and fat free mass from baseline(Baseline to 12 months)
- Assessment of changes in glucagon-like peptide-1 from baseline(Baseline to 12 months)
- Assessment of changes in gastric inhibitor polypeptide from baseline(Baseline to 12 months)
- Assessment of changes in liver function from baseline(Baseline to 12 months)
- Assessment of changes in Leptin from baseline(Baseline to 12 months)
- Assessment of Liver steatosis(4 months)
- Estimates of changes in Non-oxidative glucose-disposal from baseline(Baseline to 12 months)
- Estimates of changes in insulin secretion from baseline(Baseline to 12 months)
- Assessment of changes in Ghrelin from baseline(Baseline to 12 months)
- Assessment of the role of FGF21 in type 2 diabetes and obesity from baseline(Baseline to 12 months)
- Assessment of changes in Glucagon levels from baseline(Baseline to 12 months)