Wittert and Grossmann give a critical appraisal for two clinically-important questions, namely: the benefits and limitation of weight (including bariatric surgery) and lifestyle management for obesity/MS/T2DM in reversing low T or hypogonadism; the possible role for TRT in the management of Ob/MS/T2DM including effects on glucose metabolism (insulin sensitivity and glycaemic control) and body fat distribution. This evidence concerns the gene INS and myeloid sarcoma.