We have previously shown that women with polycystic ovary syndrome (PCOS) have increased urinary clearance of d-chiro-inositol (uClDCI), which was positively associated with hyperinsulinemia. The objective of this study was thus to determine if such relationship also exists in men with a large range of insulin sensitivity and levels. A cross-sectional study was performed on 11 brothers of women with PCOS and 21 control men. In this study, brothers served as a model of insulin resistance. We assessed uClDCI, urinary clearance of myo-inositol, and insulin levels with a standard 75-g oral glucose tolerance test, a 2-hour euglycemic-hyperinsulinemic clamp, and a 24-hour urine collection. Our results showed in all men together that low uClDCI was strongly associated (P < .001) with hyperinsulinemia, for which uClDCI was a significant predictor independent of other classic factors. Brothers were heavier than controls (P = .02), with increased glucose-stimulated glucose (P < .001) and insulin levels (P < .001) and reduced insulin sensitivity (P = .001). In this group, plasma DCI was increased by 3-fold (P = .02), with a 3-fold decrease in the uClDCI to urinary clearance of myo-inositol ratio, which was almost significant (P = .07). Low uClDCI is strongly associated with hyperinsulinemia in all men, and brothers of PCOS women who are more insulin resistant display increased plasma DCI and borderline decreased uClDCI. Thus, compensatory hyperinsulinemia might suppress renal clearance of DCI to increase plasma DCI levels and partially compensate for insulin resistance by improving DCI availability in men. The apparent discrepancy with PCOS women might be explained by higher insulin levels in men as compared with women and requires confirmation.