Patients with overweight or obesity are in need to loose weight and represent a particularly challenging medical condition. Undoubtedly, any intervention achieving a negative energy balance over an extended time period will result in weight loss. Although several treatment modalities are available, currently the most extended approaches are lifestyle changes, pharmacotherapy, and bariatric surgery. Given the limited approved anti-obesity drugs, the main therapeutic strategies involve either conventional treatment or bariatric surgery. Conventional weight-reduction programs pursue a safe weight loss rate of 0,5-1,0 kg per week. The main modifiable factors affecting energy balance are dietary energy intake and energy expended through physical activity. In spite of the difficulty in achieving relevant and sustained weight loss via the conventional approach, some patients are successful in reducing weight and obesity-associated complications. Bariatric surgery has proved to be the most effective long-term treatment for weight loss and comorbidity improvement. While some of the surgery-induced benefits are directly dependent on adipose tissue reduction, others are due to specific gastrointestinal changes that take place early on and before any significant effects on body weight are observed. The present study contemplates the determination and comparison of the anthropometric and metabolic changes produced by the conventional and surgery-induced treatment modalities. Particular emphasis will be placed on the potential differential effects between conventional and surgical weight loss on body composition changes, circulating adipokines and gastrointestinal hormones together with their subsequent impact on cardiometabolic risk factors.

In spite of the recognition of obesity as a serious public health problem due to its well-known increased risk for the development of type 2 diabetes hypertension, coronary heart disease, sleep-breathing disorders, and certain forms of cancer, among others, it is proving extraordinarily difficult to halt this pandemia. Strictly speaking obesity does not refer to an excess weight or weight to height ratio. In fact, the World Health Organization defines obesity as a state of increased adipose tissue of sufficient magnitude to produce adverse health consequences. Thus, in order to better define the effects and benefits of weight loss it is important to address the impact on body fat changes. Given the limited approved anti-obesity drugs, the main therapeutic strategies involve either conventional treatment or bariatric surgery. The main modifiable factors affecting energy balance are dietary energy intake and energy expended through physical activity. In spite of the difficulty in achieving relevant and sustained weight loss via the conventional approach, some patients are successful in reducing weight and obesity-associated complications. Bariatric surgery has proved to be the most effective long-term treatment for weight loss and comorbidity improvement. While some of the surgery-induced benefits are directly dependent on adipose tissue reduction, others are due to specific gastrointestinal changes that take place early on and before any significant effects on body weight are observed. Noteworthy, currently available bariatric procedures differ on their impact on these aspects. The present study contemplates the determination and comparison of the anthropometric and metabolic changes produced by the conventional and surgery-induced treatment modalities. Particular emphasis will be placed on the potential differential effects between conventional and surgical weight loss on energy intake, energy expenditure, body composition changes, circulating adipokines and gastrointestinal hormones together with their subsequent impact on cardiometabolic risk factors. The conventional weight-reduction program (CONV) will pursue a safe weight loss rate of 0,5-1,0 kg per week. The surgery-induced weight loss will be achieved by two of the most frequently used bariatric operations, the sleeve gastrectomy [SG (which implies a restrictive component)] and the Roux-en-Y gastric bypass [RYGB (which combines a restrictive and a malabsorptive component)].

The purpose of the study is to determine the effect of three weight loss procedures that differ on their manipulation of the anatomical and functional characteristics of the gastrointestinal tract. While in the conventional treatment the gastrointestinal system remains intact, in the SG only the stomach is manipulated as opposed to the RYGB, where both the stomach and the small intestine are operated on. Since bariatric surgery is well known to induce partial or total remission of type 2 diabetes mellitus, the effects of the three different weight loss procedures will be assessed separately in obese normoglycemic and obese type 2 diabetic individuals.

Inclusion Criteria:

• Age between 21 and 65 years.
• Obesity as defined by World Health Organization criteria.
• For bariatric surgery patients: qualified for obesity surgery by the -Multidisciplinary Obesity Team of the Clinica Universidad de Navarra
• For type 2 diabetic patients: T2D diagnosis confirmed by either fasting plasma glucose ≥126 mg/dL on two separate occasions, or fasting plasma glucose ≥126 mg/dL and plasma glucose ≥140 mg/dL 2 h after OGTT, or treatment with anti-diabetic medication in accordance with good clinical practice with and well-documented information on diagnosis, history, treatment(s) and HbA1c data.
• No major organ disease unrelated to excess body weight.
• Mentally able to understand the study and willingness to participate in the study.

Exclusion Criteria:

• Pregnancy/lactation
• Poor overall general health
• Drug and/or alcohol addiction
• Prior bariatric or gastrointestinal surgery
• Active gastric or intestinal tract disease
• Thyroid disease
• Type 1 diabetes mellitus
• Portal hypertension and/or cirrhosis
• Malignancies
• History of eating disorders or major psychiatric illness
• Unable to communicate with study staff