THE RELATIONSHIP BETWEEN SERUM LEVELS OF INSULIN AND SEX HORMONE-BINDING GLOBULIN IN MEN - THE EFFECT OF WEIGHT-LOSS

It is known that there is an inverse relationship between the serum le vels of insulin and sex hormone-binding globulin (SHBG) in women, but the relationship in men has not been reported. It is not known whether changes in the one cause changes in the other, or whether they change in opposite directions in response to some third factor. Because obes ity raises insulin levels and lowers SHBG levels in both sexes, we pro posed to study the cause-effect question by determining whether the re lationship between changes in SHBG and insulin levels during active we ight loss. We studied 70 healthy weight-stable men with body mass inde x (BMI) from 20.7-94 (normal, 22.5 +/- 2.5) and restudied 17 of them d uring diet-induced weight loss. Fasting serum insulin levels in the we ight-stable men showed a positive linear correlation with BMI, increas ing 1 mu U/mL per unit increase in BMI (P < 0.0001). SHBG levels in th e weight-stable men showed a negative linear correlation with BMI, dec reasing 0.2 nmol/L per unit increase in BMI (P < 0.0002). In the weigh t-stable men, there was an inverse hyperbolic correlation between SHBG and insulin levels; SHBG (nmol/L) = 13.1 +/- [30.1 divided by insulin (mu U/mL)] (P < 0.002). During weight loss, insulin levels decreased at an average rate of 6.1 mu U/mL per unit decrease in BMI, a much hig her slope than the positive slope vs. BMI in weight-stable men. During weight loss, SHBG levels increased at an average slope of 0.43 nmol/L per unit decrease in BMI, much higher than the negative slope of 0.2 nmol/L per unit increase in BMI in weight-stable men. Values for the S HBG vs. insulin coordinates in the weight-losing subjects did not diff er significantly from those expected from the SHBG us. insulin equatio n in weight-stable subjects. The stability of the SHBG-insulin relatio nship during weight loss despite the profoundly altered relationship o f each separate component to BMI strongly suggests a close metabolic l ink between SHBG and insulin. As SHBG is not known to alter the produc tion or metabolism of insulin, whereas insulin has been shown in vitro to decrease the synthesis of SHBG, it seems a reasonable conclusion t hat the predictable inverse relationship between serum insulin and SHB G indicates that insulin controls SHBG synthesis in vivo.