Dietary intervention
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All the eligible subjects were randomly allocated to the VLCKD (treatment) or HBD (active comparator) group. Each nutritional program lasted 24 weeks. VLCKD is a restricted multiple-steps dietary regimen including nutritional supplements and replacement meals. In the first step (four weeks), four or five replacement meals per day, according to patients’ specific nutritional needs, were used. In the second step (four weeks), one and subsequently two replacement meals were replaced with conventional food containing proteins (meat, fish, eggs, soy) at lunch and/or dinner. During the first two steps, diet provided a minimum protein content based on a Population Reference Intake for protein adjusted for people with overweight and obesity (75–105 g/day), carbohydrate intake was drastically restricted (30–50 g/day) and lipid intake was very low and mostly derived from olive oil (20 g per day, linoleic acid 11 g/day, alpha-linoleic acid 1.4 g/day), according to the European Food Safety Authority (EFSA) [In the following four weeks (LCD phase), carbohydrates were gradually reintroduced, starting from foods with the lowest glycemic index (fruit, dairy products), followed by foods with moderate and high glycemic index (legumes, bread, pasta and cereals). The goal was to achieve a hypocaloric balanced diet (HBD), that was the same of the control group. From week 12 week to week 24 all subjects enrolled continued the study following HBD.The HBD group followed a hypocaloric balanced diet for 24 weeks. Total daily average energy intake was 1500–1600 kcal/day and macronutrients composition was based on the Mediterranean Diet [lipid: 30% of total daily energy (10% MUFA, 10% PUFA, 10% SFA); carbohydrates: 55% of total daily intake; daily protein intake was approximately 0.8–1.5 g/kg of ideal body weight].The summary of timeline of visits is shown in Fig. Emiketo: visits’ timeline