Impact of glycemic variations on the regulation of androgen metabolism in obese women with polycystic ovary syndrome

Ludwig, A.; Goharian, Lilian G.; Dietze, Thomas; Tauchert, S.; Rudolf, Sebastian; Diedrich, K.; Schweiger, Ulrich; Oltmanns, Kerstin M.

doi:10.1016/j.fertnstert.2008.05.052

Cited by 6 publications

(6 citation statements)

References 16 publications

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“…The basal and incremental glucagon responses to hypoglycemia in our study were also similar to those reported in healthy women in the literature [8, 10, 24, 25]. The findings of lower cortisol levels in PCOS women in previous studies [22, 23], including overweight and obese women, were consistent with our finding of a trend toward decreased steady-state and incremental cortisol levels in PCOS. Most hypoglycemic clamp studies in normal women have been in nonobese, reproductive-age cohorts [7, 8, 9, 25].…”

Section: Discussionsupporting

confidence: 92%

“…Our sample size was relatively small, although similar in size to other studies that assessed sex differences in CRR [7, 8, 9, 10, 11, 22, 24, 25]. The basal and incremental glucagon responses to hypoglycemia in our study were also similar to those reported in healthy women in the literature [8, 10, 24, 25].…”

Section: Discussionsupporting

confidence: 82%

“…Cortisol and other steroid responses to these glycemic changes were reported in a second publication from Ludwig and colleagues [22]. Cortisol levels were lower at baseline and remained lower throughout the study in PCOS compared to control women [22]. …”

Section: Discussionmentioning

confidence: 99%

“…There have been very few studies of responses to hypoglycemia in PCOS [11, 12, 22, 23]. Gennarelli and colleagues [11] reported CRR responses to uncontrolled hypoglycemia after an iv insulin bolus in PCOS and control women stratified by obesity.…”

Section: Discussionmentioning

confidence: 99%

“…However, the study may have been constrained by the independent effect of adiposity on insulin sensitivity since the PCOS women tended (P=0.08) to be heavier, mean BMI 28.0 kg/m 2 , than the control women, mean BMI 21.6 kg/m 2 [12]. Cortisol and other steroid responses to these glycemic changes were reported in a second publication from Ludwig and colleagues [22]. Cortisol levels were lower at baseline and remained lower throughout the study in PCOS compared to control women [22].…”

Section: Discussionmentioning

confidence: 99%

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Exaggerated glucagon responses to hypoglycemia in women with polycystic ovary syndrome

et al. 2017

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Context Premenopausal women have blunted counter-regulatory hormone responses (CRR) to hypoglycemia compared to men. Postmenopausal women have CRR similar to men; the premenopausal pattern can be restored by estrogen. However, glucagon and pancreatic polypeptide (PP) responses remain lower in postmenopausal women than in men. Since hyperandrogenemia contributes to the metabolic phenotype of polycystic ovary syndrome (PCOS), we hypothesize that CRR to hypoglycemia especially of glucagon and PP is exaggerated in premenopausal women with PCOS compared to premenopausal control women. Study Subjects and Methods Ten obese women with PCOS and 9 control women of similar ethnicity, age and BMI underwent determination of CRR in response to hypoglycemia during 180-min 60 mU/m2/min insulin dose hypoglycemic clamp with isotopic assessment of endogenous glucose production (EGP). To assess CRR to hypoglycemia, glucagon, cortisol, growth hormone (GH), epinephrine, norepinephrine, PP, lactate, free fatty acid (FFA), β-hydroxybutyrate, and glycerol levels were sampled at 15-min intervals throughout the clamp. Main Findings Incremental glucagon levels were ~3-fold higher during hypoglycemia (P=0.03) in PCOS. Postabsorptive, steady-state and incremental GH, cortisol, epinephrine, norepinephrine, PP, FFA, glycerol and β-hydroxybutyrate did not differ. At target glucose levels of ~52 mg/dl, insulin mediated glucose disposal (IMGD) was decreased by ~40% (P=0.02) in PCOS, compared to control women, despite ~20% higher steady-state insulin levels (P=0.03). Neither postabsorptive nor steady-state EGP differed. However, postabsorptive lactate levels were ~50% higher (P=0.02). PCOS status (P=0.038) and IMGD (P=0.024) predicted the differential glucagon response to hypoglycemia in separate regression models, however, neither parameter remained an independent predictor in a combined model. Principal Conclusions Glucagon responses were increased in PCOS, whereas other CRR did not differ. Women with PCOS were insulin resistant under hypoglycemic conditions and higher postabsorptive lactate levels in PCOS were consistent with this finding. Insulin resistance may have contributed to exaggerated glucagon response to hypoglycemia in PCOS.

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