Elevated insulin levels in two-hour glucose challenge tests are associated with adverse metabolic traits in patients with polycystic ovarian syndrome (PCOS)

Abstract

Insulin resistance (IR) is central in the pathophysiology of PCOS. Fasting and 2-hour post-glucose challenge insulin levels are frequently assessed in women with PCOS, but their clinical significance is uncertain. We sought to characterize clinical and biochemical traits of PCOS patients in groups categorized by results of these tests. Prospective cross-sectional. 113 women with PCOS-Rotterdam were systematically evaluated in a multidisciplinary clinic. IR was evaluated by fasting and 2-hour insulin values following 75g oral glucose tolerance test, with cutoffs of 12 and 50 mU/L, respectively. Patients were subdivided into four groups based on results of these tests: G1) both tests normal G2) 2-hour insulin elevated G3) fasting insulin elevated, and G4) both tests elevated. Clinical and metabolic features were compared across groups with the non-parametric test for trend or Fisher’s exact as indicated. 41% of PCOS patients had normal insulin tests, while 22%, 6% and 31% had abnormal tests categorized into Groups 2, 3 and 4, respectively. Significant differences were noted between BMI, waist circumference, fasting triglycerides and HDL. Acanthosis and MFG scores were highest in Groups 3 and 4.Tabled 1Patient CharacteristicsMean (SD)G1 (N=46)G2 (N=25)G3 (N=7)G4 (N=35)P for trendBMI, kg/m225.5 (5.4)28.2 (7.6)33.6 (7.0)35.0 (7.9)0.000Age, yrs28.5 (5.2)26.9 (7.5)27.0 (6.0)28.8 (7.4)0.931Waist, cm30.9 (4.8)32.6 (7.1)36.6 (8.2)38.6 (10.2)0.000SHBG, nmol/L57.2 (28.3)62.0 (55.6)55.2 (34.3)30.1 (16.4)0.000Total cholesterol, mg/dL177.5 (29.7)185.4 (44.1)185.0 (29.8)179.3 (28.6)0.765Triglycerides75.8 (37.3)93.5 (60.1)106.2 (64.6)142.6 (91.7)0.000HDL64.0 (14.9)59.3 (18.1)52.2 (14.4)46.3 (9.5)0.000Total testosterone, ng/dL52.8 (20.6)46.9 (13.9)50.3 (28.5)52.5 (34.5)0.236Androstenedione164.9 (94.7)151.5 (66.5)131.7 (51.2)185.0 (78.2)0.359Acanthosis (% present)26.732.083.377.10.000MFG Score6.1 (4.4)8.0 (6.4)11.1 (4.6)10.1 (5.5)0.000G1: Both tests normal; G2: 2-hour insulin abnormal; G3: Fasting insulin abnormal; G4: Both tests abnormal; SHBG: sex hormone-binding globulin; MFG: Modified Ferriman Gallway Open table in a new tab G1: Both tests normal; G2: 2-hour insulin abnormal; G3: Fasting insulin abnormal; G4: Both tests abnormal; SHBG: sex hormone-binding globulin; MFG: Modified Ferriman Gallway Elevated insulin levels on glucose challenge tests are associated with multiple adverse health indices in PCOS and indicate a more severe metabolic phenotype. Patients with isolated abnormal fasting insulin had slightly worse clinical and metabolic abnormalities than those with isolated 2-hour insulin elevations, while patients with both tests abnormal had the most severe derangements.