Agreement among insulin sensitivity indexes on the diagnosis of insulin resistance in polycystic ovary syndrome and ovulatory women

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Abstract

Objective

The objective was to compare agreement on the diagnosis of insulin resistance (IR) among insulin sensitivity indexes in both ovulatory women and those with polycystic ovary syndrome (PCOS).

Study design

In an observational study, the 75-g oral glucose tolerance test was performed in 105 women with PCOS and 51 ovulatory women. The insulin sensitivity indexes used were insulin quantitative sensitivity check index (QUICKI), 1/homeostasis model assessment-insulin resistance (1/HOMA-IR), area under curve for insulin (AUC-I), and the Matsuda insulin sensitivity index (COMP). For the IR diagnosis we used cut-off values described in recent publications (insulin >12 μIU/ml, 1/HOMA-IR <0.47, QUICKI ≤0.333, AUC-I ≥7000 μIU/ml 120 min, and COMP <4.75.

Results

Excellent agreement was assessed among insulin, QUICKI, and 1/HOMA-IR. However, the rate of IR detected by these indexes in the PCOS group (44.8–51.4%) was lower than expected. New cut-offs were then determined based on COMP results. Using these values, 1/HOMA-IR and QUICKI showed excellent agreement (κ = 0.83) with COMP.

Conclusion

The observed agreements among insulin, QUICKI and 1/HOMA-IR were higher than 93%. Therefore, clinicians may choose any of those obtaining similar results. For clinicians who prefer COMP, but are looking for a simpler test to detect IR in PCOS women, the use of QUICKI and 1/HOMA-IR with the new cut-offs seems reasonable.

Introduction

Polycystic ovary syndrome (PCOS) is the most common hormonal disorder among women of reproductive age, affecting 2.6–6.6% of the population [1], [2]. A relationship between insulin resistance (IR) and PCOS was shown in 1980 [3] and later studies have demonstrated that IR is a feature of PCOS [4], with prevalence estimated at 64–79% of a population with a diagnosis of PCOS [5], [6]. Obesity is highly prevalent in PCOS, reaching 67% [1], and worsens the plasma insulin levels [7], [8]. Women with a diagnosis of PCOS are at increased risk of dyslipidemia, hypertension, and type 2 diabetes mellitus [1]. These features lead to an 11-fold increase in the prevalence of metabolic syndrome [9] and endothelial dysfunction [10], which are all well established risk factors for cardiovascular disease [11].

The method considered “the gold standard” for measuring insulin resistance is the euglycemic insulin clamp, described by DeFronzo et al. [12]. This method can be used to assess accurately the rate of whole-body glucose disposal during steady-state hyperinsulinemia. A clamp study takes at least 2 h; the patient receives a continuous, steady infusion of insulin and a variable infusion of glucose; every 5 min blood is drawn to determine glucose level; and monitoring of plasma insulin is also required. Based on the oral glucose tolerance test (OGTT), a number of insulin sensitivity indexes (ISI) have been developed to assess insulin resistance [13], [14], [15]. They are less expensive and invasive. However, these indexes take at least two hours, the patient receives an oral glucose overload and blood is drawn every 30 min (five samples) for the determination of glucose and insulin levels and the ISI values are overestimated when only three samples of blood are collected in the OGTT [16].

Among the insulin sensitivity indexes based on the oral glucose tolerance test, the area under curve for insulin (AUC-I) and the composite ISI by Matsuda and DeFronzo (COMP) [15] have a high positive predictive value (>0.85) compared with the euglycemic insulin clamp in PCOS patients [17]. Other ISIs, based only on fasting plasma glucose and/or insulin are used: fasting plasma insulin (INS), the quantitative sensitivity check index (QUICKI), and the homeostasis model assessment (HOMA) [18], [19], [20]. They are cheaper, simpler to calculate, and require only one blood sample; however, some studies have shown a lower correlation with glucose clamp techniques [13], [21].

In this scenario, uncertainty remains with regard to the use of these methods. For current use in clinical practice the importance of showing the agreement of these tests in the diagnosis of IR for both ovulatory women and those with PCOS has emerged.

Section snippets

Materials and methods

The research protocol was conducted in accordance with the guidelines in The Declaration of Helsinki and it was approved by the Ethics and Research Committee of the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Informed written consent was obtained from all women.

One hundred and five patients with PCOS, aged 21–36 years, whose chief complaints were menstrual disturbances or infertility, from the Hospital das Clínicas da Faculdade de Medicina de

Results

There was considerable variance among the rate of detection of IR by the different methods in the various groups. The highest rate (82.0%) was found by AUC-I in the group PS >25 and the lowest (0.0%) was found in the group OV ≤25 by COMP. There was no significant difference found among the ISI with regard to the IR detection rates in ovulatory women. Table 2 shows the rates of IR detection by all methods and the significant differences among them.

The kappa coefficients obtained to assess the

Discussion

In our study we have demonstrated that the fasting-based ISI (INS, QUICKI, and 1/HOMA-IR) are in excellent agreement with each other (κ = 0.83–0.90). However, the IR detection rate by the fasting-based ISI in the PCOS group of patients (44.8–51.4%) was lower than the 64–79% described in the literature [5], [6]. Higher rates of IR in PCOS patients (67% using fasting plasma insulin, 79.2% using QUICKI, and 77% using 1/HOMA-IR) [6] were described in a PCOS population with a mean BMI (27.6 kg/m2)

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