Bariatric Surgery and HDL-cholesterol
Condition: Morbid Obesity
MeSH terms: Obesity, Morbid
Study type: Interventional

Summary: 
      Objective: to assess the effect of gastric bypass on HDL-cholesterol concentration and its
      Apolipoprotein A4 content at 1 year following bariatric surgery in comparison with a
      hypocaloric diet. Secondary aim was to measure total cholesterol and triglycerides levels as
      well as insulin sensitivity after interventions.

      Summary Background Data: Very few prospective uncontrolled studies have investigated the
      effects of Roux-en-Y gastric bypass (RYGB) on cardiovascular risk factors. No controlled
      studies had as primary goal the changes in HDL-cholesterol after gastric bypass.

      Methods: Forty subjects with a BMI>40 or ≥35 kg/m2 in the presence of diabetes were enrolled.

      Twenty of them were operated of RYGB while 20 received lifestyle modification suggestions and
      medical therapy for obesity complications (diabetes, hypertension and hyperlipidemia).
    

Detailed description: 
      Study design The study was an unblinded, prospective, non randomized clinical trial.
      Participants were recruited from referrals for treatment of morbid obesity between September
      2008 and July 2009. One year follow-up was completed in September 2011.

      The aim of the study related to the changes in HDL-cholesterol at 1 year after the
      intervention. Secondary aims were the changes in Apolipoprotein 4 (Apo4) and insulin
      sensitivity after the interventions.

      Twenty morbidly-obese subjects (11 women and 9 men), whose 14 with normal glucose tolerance
      and 6 with type 2 diabetes mellitus (T2DM), have been studied before and 1, 2, 3, 6, 9 and 12
      months after bariatric surgery.

      Twenty morbidly-obese subjects (12 women and 8 men), 15 with normal glucose tolerance and 5
      with T2DM, in the waiting list for bariatric surgery were enrolled in the protocol and
      underwent medical therapy for obesity complications (diabetes, hypertension and
      hyperlipidemia) and lifestyle modification suggestions.

      Participants were eligible for inclusion if they had a BMI of 40 kg/m2 or >35 kg/m2 in
      presence of type 2 diabetes, were aged 30 to 60 years, and had not sustained weight loss in
      the previous 1 year. Exclusion criteria were a history of major abdominal or bariatric
      surgery, disabling cardiac or pulmonary diseases, cancer, long-term treatment with oral
      corticosteroids, and mental illness.

      Roux-&-Y Gastric Bypass (RYGB) involves the use of a surgical stapler to create a small and
      vertically oriented gastric pouch with a volume usually < 30 ml. The upper pouch is
      completely divided by the gastric remnant and is anastomosed to the jejunum, 75 cm distally
      to the Treitz's ligament , through a narrow gastrojejunal anastomosis in a Roux-en-Y fashion.
      Bowel continuity is restored by an entero-entero anastomosis, between the excluded biliary
      limb and the alimentary limb, performed at 150 cm from the gastrojejunostomy.

      Lifestyle modifications A hypocaloric diet (15 kcal/kgbw containing 55% carbohydrates, 30%
      lipids and 15% proteins) was prescribed together with the indications to perform 30 minutes
      brisk walk each day. Patients had open access to a diabetologist every 3 months. Medical
      therapies, including pharmaceutical agents, were assigned on an individual basis.

      Anthropometric measures Body weight was measured to the nearest 0.1 kg with a beam scale and
      height to the nearest 0.5 cm using a stadiometer (Holatin, Crosswell, Wales, U.K.).

      Blood pressure Blood pressure was measured 3 times with an appropriately sized cuff after the
      participant had rested for 5 minutes, and the last 2 measurements were averaged.

      Oral glucose tolerance test A standard 75-g oral glucose tolerance test (OGTT) was performed
      after an overnight fasting with blood sampling at 0, 30, 60, 90, 120, and 180 min. Samples
      were placed in chilled tubes, and plasma was separated within 20 min and stored at -80°C.

      Analytical methods Blood was drawn in the morning after an overnight fast. The sera and
      plasma were immediately separated by centrifugation at 4°C and stored at -80°C until assay.

      Plasma glucose was measured by the glucose-oxidase method (Beckman, Fullerton, CA). Plasma
      insulin was assayed by microparticle-enzyme immunoassay (Abbott, Pasadena, CA) with a
      sensitivity of 1 μU/ml and an intra-assay CV of 6.6%.

      Total cholesterol and triglycerides were measured enzymatically. HDL-cholesterol was measured
      after precipitating apolipoprotein B-containing lipoproteins with dextran sulfate and
      magnesium chloride.

      HbA1c serum levels were measured by high-performance liquid-chromatography (normal range
      3.5-6.5%) Apo A4 was assessed by ELISA (Cusabio Biotech, Wuhan, Hubei, China); the detection
      range is from 15.62 μg/l to 1000 μg/l and the minimum detectable concentration is 4 μg/l.

      Insulin Sensitivity Models

      The OGTT and fasting plasma glucose and insulin were used to compute the insulin sensitivity.
      Insulin resistance was assessed using the homeostasis model assessment (HOMA-IR) originally
      described by Mathew et al. HOMA-IR was calculated using the following equation:

      HOMA-IR(μU/ml∙mg/dl)=fasting insulin(μU/ml)∙(fasting glucose (mg/dl))/405 Peripheral insulin
      sensitivity was assessed by the Oral Glucose Insulin Sensitivity (OGIS) model. OGIS is an
      index of insulin sensitivity calculated in this case from the 3 hours OGTT and it is an
      estimate of the glucose clearance during a hyperinsulinemic euglycemic glucose clamp
      expressed in ml/min per square meter of body surface area.

      Statistics All of the data are expressed as means ± SD unless otherwise specified. The
      Wilcoxon paired-sample test was used for intragroup comparisons. Two-sided P < 0.05 was
      considered significant. Nonparametric Spearman correlations were used to assess linear
      relationships between single variables.

      We calculated that a total of 30 participants would give 80% power to detect a significant (P
      < 0.05) difference between the groups. To allow for possible dropouts and add power for
      analysis of secondary outcomes, we decided to enroll 40 participants.
    

Intervention name(s): Roux-en-Y gastric bypass; diet and lifestyle modifications
Intervention type(s): Procedure; Behavioral
Intervention description(s): Active Comparator: Roux-en-Y gastric bypass; Active Comparator: diet and lifestyle modifications
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment