The aim of the present study was to evaluate the predictive capability of fasting-state measurements of glucose and insulin levels alone for abnormal glucose tolerance in women with polycystic ovary syndrome (PCOS).
In total, 153 Korean women with PCOS were included in this study. The correlations between the 2-hour postload glucose (2-hr PG) level during the 75-g oral glucose tolerance test (OGTT) and other parameters were evaluated using Pearson correlation coefficients and linear regression analysis. The predictive accuracy of fasting glucose and insulin levels and other fasting-state indices for assessing insulin sensitivity derived from glucose and insulin levels for abnormal glucose tolerance was evaluated using receiver operating characteristic (ROC) curve analysis.
Significant correlations were observed between the 2-hr PG level and most fasting-state parameters in women with PCOS. However, the area under the ROC curve values for each fasting-state parameter for predicting abnormal glucose tolerance were all between 0.5 and 0.7 in the study participants, which falls into the “less accurate” category for prediction.
Fasting-state measurements of glucose and insulin alone are not enough to predict abnormal glucose tolerance in women with PCOS. A standard OGTT is needed to screen for impaired glucose tolerance and type 2 diabetes mellitus in women with PCOS.
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women, affecting 5%–10% of women worldwide [
A 2-hour, 75-g oral glucose tolerance test (OGTT) is the standard method used to evaluate glucose tolerance and diagnose diabetes. Recent clinical guidelines have recommended a standard OGTT to screen for IGT and T2DM in women with PCOS [
Insulin sensitivity is a concept that reflects the opposite of insulin resistance [
In the present study, we conducted a receiver operating characteristic (ROC) curve analysis to evaluate how well abnormal glucose tolerance can be predicted by measurements of fasting-state parameters alone, such as fasting glucose and insulin concentrations and other fasting-state ISAIs derived from a combination of glucose and insulin levels, without postload glucose measurements, following an oral glucose challenge in women with PCOS.
South Korean women between the ages of 18 and 35 years who first visited Inje University Haeundae Paik Hospital between January 2010 and December 2013 and were diagnosed with PCOS according to the Rotterdam consensus diagnostic criteria [
This study was approved by the Institutional Review Board of Inje University Haeundae Paik Hospital (IRB No. 129792-2014-035), and patient’s informed consent in this study was waived by the IRB. Clinical anthropometric parameters were evaluated in all patients when they first visited the outpatient department. Body mass index (BMI) was defined by dividing body weight (kg) by the square of the height (m2), and the waist-to-hip ratio (WHR) was calculated by dividing the waist circumference (cm) by the hip circumference (cm).
Blood samples were taken from all study participants following overnight fasting in accordance with the guidelines of the Declaration of Helsinki, and sera were obtained by centrifugation to evaluate biochemical parameters. Fasting glucose levels and levels at 2 hours after 75-g glucose ingestion during a 2-hour OGTT were measured using L-Type GluI (Wako Pure Chemical Industries, Osaka, Japan). Fasting insulin levels were evaluated using an Elecsys Insulin assay (Roche Diagnostics Corp., Basel, Switzerland). The intra- and inter-assay coefficients of variation were <5% for all measurements.
Fasting-state homeostatic ISAIs derived from a combination of fasting glucose and insulin levels were calculated according to the following formulas:
HOMA-IR=glucose (mg/dL)×insulin (μU/mL)/405,
GIR=glucose (mg/dL)/insulin (μU/mL); and,
QUICKI=1/{log [insulin (μU/mL)]+log [glucose (mg/dL)]}.
Abnormal glucose tolerance, which comprises IGT and diabetes [
Values are expressed as the mean±standard deviation (SD). The unpaired t-test was used to compare continuous parameters between two groups created using a 2-hr PG threshold level of 140 mg/dL. The correlations between the 2-hr PG level and other parameters were evaluated using Pearson correlation coefficients and linear regression analysis, and partial correlation coefficients were used after controlling for confounding variables such as BMI and WHR. For the assessment of the prediction accuracy of fasting-state parameters for abnormal glucose tolerance, areas under the ROC curves (AUCs), sensitivity, and specificity were evaluated. Predictive accuracy using AUCs was categorized in the present study as follows [
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It is well established that insulin resistance and compensatory hyperinsulinemia are central components in the pathogenesis of PCOS. Insulin resistance/hyperinsulinemia leads to a high incidence of T2DM and cardiovascular disease in PCOS patients. Up to 35% of women with PCOS exhibit IGT, while up to 10% meet the criteria for T2DM [
Postprandial hyperglycemia and the resulting hyperinsulinemia jointly inhibit hepatic glucose production and stimulate glucose uptake by splanchnic and peripheral (primarily muscle) tissues to dispose of the ingested glucose and restore normoglycemia [
IFG and IGT are intermediate states in glucose metabolism that fall between normal glucose homeostasis and overt diabetes [
In this study, the cutoff value of fasting glucose for predicting abnormal glucose tolerance was calculated as 103.5 mg/dL; despite its low sensitivity (0.417), it was closer to the ADA criterion of 100 mg/dL [
An Endocrine Society Clinical Practice Guideline recommends that HbA1c may be considered for screening for IGT and T2DM in adolescents and adult women with PCOS if a patient is unable or unwilling to complete an OGTT [
In the present study, we merely measured the fasting insulin level, and we did not assess postload insulin levels following the OGTT. The lack of postload insulin data may be the most important drawback of this retrospective study because the 2-hour postload insulin level has been suggested to be a good indicator of insulin resistance [
In conclusion, our results suggest that fasting-state measurements of glucose and insulin measurements alone are not enough to predict abnormal glucose tolerance in women with PCOS; it seems quite difficult to replace the OGTT with only fasting-state measurements of glucose and insulin levels to identify abnormal glucose tolerance in PCOS patients. A standard OGTT is needed to screen for IGT and T2DM in women with PCOS.
No potential conflict of interest relevant to this article was reported.
Receiver operating characteristic curve analysis to assess the predictive accuracy of fasting-state parameters for abnormal glucose tolerance following an oral glucose tolerance test. (A) Fasting glucose (FG), fasting insulin (FI), and homeostasis model assessment of insulin resistance (HOMA-IR). (B) Glucose-to-insulin ratio (GIR) and quantitative insulin sensitivity check index (QUICKI).
Comparison of baseline anthropometric characteristics and laboratory parameters between two groups divided according to 2-hr PG of 140 mg/dL in patients with polycystic ovary syndrome
Variable | 2-hr PG <140 mg/dL (n= 129) | 2-hr PG ≥140 mg/dL (n=24) | |
---|---|---|---|
Age (yr) | 26.35±5.16 | 26.58±5.37 | 0.839 |
Body mass index (kg/m2) | 21.83±5.06 | 24.38±5.71 | 0.029 |
Waist-to-hip ratio | 0.79±0.06 | 0.85±0.10 | 0.009 |
Fasting glucose (mg/dL) | 89.53±6.61 | 103.75±27.74 | 0.020 |
Fasting insulin (μIU/mL) | 8.16±6.79 | 15.09±14.08 | 0.026 |
HOMA-IR (fasting) | 1.80±1.51 | 4.46±4.60 | 0.010 |
GIR (fasting) | 16.83±10.20 | 13.10±9.72 | 0.099 |
QUICKI (fasting) | 0.37±0.04 | 0.34±0.05 | 0.012 |
Values are presented as mean±standard deviation.
2-hr PG, 2-hour postload glucose level; HOMA-IR, homeostasis model assessment of insulin resistance; GIR, glucose-to-insulin ratio; QUICKI, quantitative insulin sensitivity check index.
Correlations of 2-hour postload glucose levels with anthropometric parameters and a variety of fasting-state parameters related to glucose and insulin metabolism
Variable | ||||
---|---|---|---|---|
Age | 0.108 | 0.182 | ||
Body mass index | 0.229 | 0.005 | ||
Waist-to-hip ratio | 0.343 | <0.001 | ||
Fasting glucose | 0.738 | <0.001 | 0.736 | <0.001 |
Fasting insulin | 0.369 | <0.001 | 0.281 | 0.001 |
HOMA-IR (fasting) | 0.474 | <0.001 | 0.442 | <0.001 |
GIR (fasting) | –0.204 | 0.203 | –0.157 | 0.07 |
QUICKI (fasting) | –0.276 | 0.001 | –0.295 | 0.001 |
Partial correlation coefficient adjusted by body mass index and waist-to-hip ratio.
Areas under the receiver operating characteristic curve for a variety of fasting-state
Variable | AUC (95% CI) | Cutoff | Sensitivity | Specificity | |
---|---|---|---|---|---|
Fasting glucose | 0.675 (0.534–0.815) | 0.007 | 103.50 mg/dL | 0.417 | 0.985 |
Fasting insulin | 0.634 (0.497–0.771) | 0.037 | 9.70 μIU/mL | 0.5 | 0.814 |
GIR | 0.612 (0.475–0.750) | 0.081 | 5.975 | 0.915 | 0.417 |
QUICKI | 0.670 (0.535–0.805) | 0.008 | 0.315 | 0.915 | 0.458 |
HOMA-IR | 0.667 (0.529–0.805) | 0.009 | 4.220 | 0.459 | 0.922 |
Parameters related to glucose and insulin metabolism for predicting abnormal glucose tolerance.
AUC, area under the receiver operating characteristic curve; CI, confidence interval; GIR, glucose-to-insulin ratio; QUICKI, quantitative insulin sensitivity check index; HOMA-IR, homeostasis model assessment of insulin resistance.