Cardiometabolic effect of weight loss in metabolically healthy obese subjects

INTERVENTION: Participants are randomly allocated to one of two groups using a computer‐generated sequence of random numbers. Intervention group: Participants take up a Mediterranean diet for two years, which is based on the use of olive oil as the main source of visible fat and regular consumption of vegetables (=2 servings / day), fruits (=3 servings / day), legumes (=3 servings / week) and fish (=3 times a week), reducing the consumption of red meat or sausage (<2 times a week) and eliminating (or reducing to <1 time / week) the consumption of dairy products, sugary drinks and confectionery. The recommended diet provide a calorie deficit of 600 Kcal/day. Participants are also encouraged to practice daily exercise, with a minimum target walk an average of 150 minutes a week for the two year duration of the study. Participants receive nine medical visits throughout the study (every three months during the first year, then every six months) by the specialist physician and a nurse visit every four weeks during the first semester and then every 3 months until the end of the study (16 visits throughout the study). Checkups include general hygiene and dietary recommendations and clinical assessment. Control group: Participants receive a minimum of four medical consultations and four nursing visits annually, which may be extended at the discretion of the physician or nurse responsible according to the associated pathology presented by the patient, according to standard clinical practice in these cases will be made. Checkups include general recommendations on heart‐healthy diet and exercise, and identical clinical and analytical assessments as in the experimental group. During nursing visits (individual, 10 minutes) participants receive written information about diet and exercise without specific individual recommendations. Participants are followed up at 3, 6, 12, 18 and 24 months for the intervention group and at 12, 18 and 24 months in the control group. CONDITION: Obesity ; Nutritional, Metabolic, Endocrine ; Obesity PRIMARY OUTCOME: Type 2 diabetes and/or prediabetes incidence is determined by measuring:; 1. Fasting plasma glucose levels at baseline, 3, 6, 12, 18 and 24 months; 2. Oral glucose tolerance testat baseline, 12 and 24 months; 3. Glycated hemoglobin (HbA1c) at baseline, 3, 6, 12, 18 and 24 months INCLUSION CRITERIA: 1. Aged 35‐55 years 2. Metabolically healthy obese (MHO)* 3. BMI between 30‐45 kg/m2 *A participant is considered to have MHO status when meeting =1 of these four metabolic syndrome criteria: fasting plasma glucose =100 mg/dL, blood pressure =135/85 mmHg (or use of blood pressure‐lowering agents), HDL‐cholesterol =50 mg/dL, and triglycerides =150 mg/dL (or use of lipid‐lowering therapies). SECONDARY OUTCOME: 1. Anthropometric variables are measured at baseline, 3, 6, 12, 18 and 24 months for the intervention group and at baseline, 12, 18 and 24 months in the control group.; 1.1. Weight measured in kg on a scale; 1.2. Waist circumfrence is measured in cm; 1.3. BMI is calculated as the ratio between weight and height (kg/m2) ; 1.4. Blood pressure is measured using a validated automatic sphygmomanometer (OMRON M4‐I) when the participant is in a sitting position.; 2. Insulin resistance is calculated using the HOMA‐IR index and proinsulin/insulin ratio at baseline, 12, 18 and 24 months; 3. Serum lipid profile (HDL‐cholesterol, LDL‐cholesterol, Triglycerides) is measured using commercial equipment (Dimension®, Dade Behring, Germany) at baseline, 12, 18 and 24 months; 4. Inflammatory parameters (leucocytes, fibrinogen, hs‐CRP, IL‐6, TNF‐a) are measured using an Enzyme‐Linked ImmunoSorbent Assay at baseline, 12, 18 and 24 months; 5. Metabolic hormone (adiponectin and resistin) levels are measured using an Enzyme‐Linked ImmunoSorbent Assay at baseline, 12, 18 and 24 months; 6. Liver function is measured through serum liver function tests (AST, ALT, GGT) and Fatty Liver Index (FLI) at baseline, 12, 18 and 24 months