This non-randomized controlled trial aimed to compare the effect of the 5:2 diet on insulin levels as a primary outcome and markers of insulin secretion (connecting peptide (C-peptide) and insulin-like growth factor binding protein-1 (IGFBP-1)) and sensitivity (Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)), as well as body composition as secondary outcomes in overweight/obese individuals with and without type 2 diabetes (T2D). Ninety-seven participants (62% women), 35 with T2D and 62 BMI- and waist-matched controls without T2D, followed the 5:2 diet (two days per week of fasting) for six months with a 12-month follow-up. At six months, there was no loss to follow-up in the T2D group, whereas four controls discontinued this study. Overall, 82% attended the 12-month follow-up. After the intervention, insulin levels decreased in the control group and glucose decreased in the T2D group, while C-peptide, HOMA-IR, waist circumference, BMI, trunk, and total fat% decreased in both groups. Furthermore, low IGFBP-1, indicating hyperinsulinemia, improved in the T2D group. The changes in fasting glucose and waist measurement were significantly more improved in the T2D group than in the controls. Persistent positive effects were observed at the 12-month follow-up. The 5:2 diet for six months was feasible and efficient to reduce markers of insulin secretion and resistance and therefore holds promise as management of overweight/obesity in subjects with and without T2D.

Women with polycystic ovary syndrome (PCOS) have varying difficulties in achieving weight loss by lifestyle intervention, which may depend on adipose tissue metabolism. The objective was to study baseline subcutaneous adipose tissue gene expression as a prediction of weight loss by lifestyle intervention in obese/overweight women with PCOS. This is a secondary analysis of a randomized controlled trial where women with PCOS, aged 18–40 and body mass index (BMI) ≥ 27 were initially randomized to either a 4-month behavioral modification program or minimal intervention according to standard care. Baseline subcutaneous adipose tissue gene expression was related to weight change after the lifestyle intervention. A total of 55 obese/overweight women provided subcutaneous adipose samples at study entry. Weight loss was significant after behavioral modification (−2.2%, p = 0.0014), while there was no significant weight loss in the control group (−1.1%, p = 0.12). In microarray analysis of adipose samples, expression of 40 genes differed significantly between subgroups of those with the greatest weight loss or weight gain. 10 genes were involved in metabolic pathways including glutathione metabolism, gluconeogenesis, and pyruvate metabolism. Results were confirmed by real-time polymerase chain reaction (RT-PCR) in all 55 subjects. Expressions of GSTM5, ANLN, and H3C2 correlated with weight change (R = −0.41, p = 0.002; R = −0.31, p = 0.023 and R = −0.32, p = 0.016, respectively). GSTM5, involved in glutathione metabolism, was the strongest predictor of weight loss, and together with baseline waist-hip ratio (WHR) explained 31% of the variation in body weight change. This study shows that baseline subcutaneous adipose tissue genes play a role for body weight outcome in response to lifestyle intervention in overweight/obese women with PCOS.

This is a secondary analysis of a non-randomized controlled six-month trial concerning the effects of the 5:2 diet on cardiovascular risk factors (blood pressure, blood lipids, adipokines and inflammatory markers) in overweight or obese individuals with and without type 2 diabetes (T2D). Ninety-seven individuals were recruited, 35 with T2D and 62 without (controls). Ninety-three completed six months of the 5:2 diet, consisting of 2 days of fasting (500 kilocalories (kcal) for women and 600 kcal for men) and five days of their regular diet. A total of 82 participants (31 with T2D and 51 controls) attended the 12-month follow-up. After the six-month intervention, both groups lost body weight (−6.3% in the T2D group and −5.0% among controls). There were significant improvements in waist circumference, blood pressure, high-density lipoprotein cholesterol (HDLchol), low-density lipoprotein cholesterol (LDLchol) and serum levels of adiponectin. In addition, participants with T2D had decreased alanine transferase (ALT) and high-sensitive C-reactive protein (hsCRP), which were significantly different from the control group. The control group had significant decreases in triglycerides and leptin concentrations. At the 12-month follow-up, improvements remained for HDLchol and adiponectin in both groups. In addition, the T2D group had significantly decreased hsCRP and leptin concentrations and the control group showed a significant decrease in ALT. In conclusion, a six-month 5:2 diet resulted in significant improvements in cardiovascular risk factors in overweight or obese participants with and without T2D, with several improvements persisting at 12 months. Individuals with T2D appeared to gain somewhat greater metabolic benefits from the intervention than the control group.