Unexpected effects of treating insulin-resistant obese women with highdose D-chiro-inositol: opening Pandora's box

Sabrina Basciani ^1* Maurizio Nordio ² Maria Letizia Spizzichini ² Lucio Gnessi ²

• ¹ Division of Medical Pathophysiology, Food Science and Endocrinology, Department of Experimental Medicine, Faculty of Medicine and Dentistry, Sapienza University of Rome, Rome, Italy
• ² Sapienza University of Rome, Rome, Lazio, Italy

Purpose: the combination of lifestyle changes and nutraceuticals, such as inositols, can reduce excess weight, leading to a reduction in insulin resistance and a normalization of the metabolic profile. As such, this study investigated the metabolic and hormonal changes observed in women with insulin resistance and were overweight/obese undergoing a hypocaloric Mediterranean diet combined with high dose D-chiro-inositol (DCI) treatment. Methods: 48 insulin resistant women between 25 and 40, with a BMI between 26 and 32 were divided into two groups: both groups followed a hypocaloric Mediterranean diet for four months, and patients in the treated group also underwent treatment with 2400 mg/day of DCI for the same period. We evaluated HOMA index, body weight, BMI, blood glucose, fasting insulin, lipid profile (cholesterol, LDL, HDL and triglycerides) and hormonal profile (total testosterone, androstenedione, DHEAS, SHBG, estradiol, FSH, LH and menstrual length) at baseline and at the end of treatment. Results: after four months, both groups displayed a significant improvement in insulin sensitivity, as reflected by a reduction in HOMA index, blood glucose, fasting insulin levels and lipid profile. Furthermore, we observed a significant decrease in body weight and BMI in both groups. However, the evaluation of hormonal profile revealed unexpected findings, with the DCIsupplemented group exhibiting hyperandrogenism and menstrual irregularity, as demonstrated by the significant increase of total testosterone, androstenedione, LH and menstrual length. Conclusion: the study strengthens the evidence regarding the metabolic benefits of the hypocaloric Mediterranean diet, independently from the association with DCI, on women with insulin resistance and weight excess, while also acknowledging the complex hormonal impact of high-dose DCI supplementation for medium-to-long periods.