Glucose-to-Insulin Ratio Rather than Sex Hormone-Binding Globulin and Adiponectin Levels Is the Best Predictor of Insulin Resistance in Nonobese Women with Polycystic Ovary Syndrome

Abstract

Polycystic ovary syndrome (PCOS), the main androgen disorder in women, has been suggested to be associated with a high risk of developing cardiovascular disease and type 2 diabetes. In many PCOS patients, overweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance, and has been identified as a target for new therapeutic strategy, including early change in lifestyle. Early biochemical marker(s) for identifying at-risk patients will be useful for prevention studies. The main goal of the present study was to search for such tool(s). We investigated 16 nonobese PCOS women by performing euglycemic hyperinsulinemic clamp and measuring insulin levels during fasting and oral glucose tolerance test, as well as the serum concentrations of SHBG, leptin, and adiponectin, the newly identified adipose factors. Eight of the 16 patients had a steady-state glucose disposal rate less than 8.5 mg/kg.min, the lowest normal value for nonobese control women. These insulin-resistant patients had significant higher body mass index (BMI) and waist-to-hip ratio (WHR), and lower high-density lipoprotein cholesterol and SHBG levels. As expected, glucose disposal correlated negatively with BMI (P = 0.01), WHR (P = 0.01), and fasting insulin level (P = 0.003). On stepwise regression analysis, however, the glucose-to-insulin ratio (GIR) emerged as the strongest independent parameter to appraise insulin resistance (R(2) = 0.61). SHBG level correlated positively with GIR (P < 0.001) and negatively with BMI (P = 0.003) but did not correlate with either insulin response during the glucose tolerance test or plasma leptin and/or adiponectin levels. In contrast, BMI was the only independent predictive parameter of SHBG (P = 0.003, R(2) = 0.73). Interestingly, plasma adiponectin levels were positively associated with glucose disposal rate (P = 0.043) and negatively with WHR (P = 0.024), waist circumference being the best predictor of adiponectin level (P < 0.01). Leptin level correlated only with BMI (r = 0.62, P = 0.01). This study confirmed that insulin resistance, despite the lack of obesity as such, is clearly present in many PCOS women, and demonstrated that GIR is the best predictor for insulin resistance. It was also shown that adiponectin level is a good indicator of abdominal fat mass and is associated to insulin resistance. Finally, low SHBG levels in PCOS are intimately associated with BMI, suggesting that some signal(s) from the adipose tissue, independent of adiponectin and leptin, may regulate liver production of SHBG.

Novel Associations Between Bioavailable Estradiol and Adipokines in Elderly Women With Different Phenotypes of Obesity

“…Hormonal changes characteristic for centrally obese women versus generally and peripherally obese women included markedly decreased SHBG and increased estradiol levels. The comparable high SHBG of generally and peripherally obese women suggests that signals from PFM stimulate hepatic SHBG release, a notion recently raised by Ducluzeau et al 19 However, high PFM% is also prone to lower plasma estradiol, which could be explained, at least in part, by a contrasting impact of obesity on the 17␤-hydroxysteroid dehydrogenase (17␤-HSD)/aromatase ratio in visceral (increased ratio) and peripheral adipocytes (decreased ratio). 16 High ratio promotes estradiol formation, whereas low ratio facilitates peripheral aromatization and formation of estrone, a 12-fold weaker form of estrogen.…”

Low sex hormone-binding globulin as a predictive marker for insulin resistance in women with hyperandrogenic syndrome

“…Ducluzeau et al (44) reported that the GIR is a better marker for assessing IR than SHBG levels in nonobese women with PCOS. The authors also reported that low SHBG levels in PCOS are associated with the BMI, suggesting that certain signals from adipose tissue may regulate the hepatic production of SHBG.…”

Sex hormone-binding globulin gene expression in the liver: Drugs and the metabolic syndrome

“…In women with polycystic ovary syndrome, low SHBG levels are negatively correlated with body mass index and waist to hip ratio, and are associated with insulin resistance, as shown by glucose clamp studies in patients with the polycystic ovary syndrome (Ducluzeau et al 2003).…”