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Potential PCOS biomarkers could improve detection, clinical care
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Circulating irisin and glucose-dependent insulinotropic peptide may play roles in the development of polycystic ovary syndrome, according to research published in The Journal of Clinical Endocrinology & Metabolism.
The findings could offer novel biomarkers to improve detection of polycystic ovary syndrome (PCOS), according to the study by Chia Lin Chang, MD, of Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University, Taoyuan, Taiwan, and colleagues.
“Aberrant regulation of brown adipose-differentiation irisin and white adipose stimulating glucose-dependent insulinotropic peptide (GIP) from the gut may represent early events in PCOS development and contribute to the manifestation of metabolic syndrome-like phenotypes,” the researchers wrote.
The team recruited 202 patients (mean age, 25 years) with PCOS and 47 healthy women (mean age, 27 years). Based on definitions by the National Cholesterol Education Program in its Adult Treatment Panel III report — ATPIII (+) and ATPIII (–) or BMI (healthy weight and overweight) — participants were stratified by presence or absence of metabolic syndrome risk factors.
Serum hormone levels for irisin, GIP, luteinizing hormone (LH), anti-Mullerian hormone (AMH) and androgens were evaluated; metabolic indices including HOMA-IR, ISI Matsuda and QUICKI were also measured.
Patients with PCOS exhibited hyperandrogenism, dyslipidemia and hyperinsulinism; they also demonstrated elevated LH and AMH levels. Compared with the healthy women, patients with PCOS had elevated fasting irisin level (P<.001) and glucose-induced GIP response (P=.013); the levels of both remained elevated in ATPIII (–) and healthy weight patients vs. controls.
Both fasting irisin and glucose-induced GIP response remained significant risk factors for PCOS (OR=6.63 and OR=4.21, respectively) when analyzed for effect size.
“These findings also hinted at how endocrine factors from muscle, gut and ovarian tissues interact to maintain normal ovarian physiology,” the researchers wrote.
Disclosures: The study was supported by Chang Gung Memorial Hospital.
Perspective
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Stéphanie B. Mayer, MD, MHSc
This observational study measured baseline metabolic parameters including irisin and glucose-dependent insulinotropic peptide (GIP) and stratified participants by BMI and presence of at least one Adult Treatment Panel III (ATPIII) risk factor, followed by 3-hour oral glucose tolerance testing. The women with PCOS, regardless of BMI or presence of ATPIII risk factor, were more insulin resistant and had higher fasting irisin and 1-hour GIP levels.
Irisin is thought to regulate glucose homeostasis by converting white to brown adipose tissue, inducing thermogenesis. Similarly to insulin and leptin, irisin levels rise with increased fat mass, but perhaps as compensation for hyperglycemia that accompanies insulin resistance. GIP is in the Secretin-glucagon family of gastric incretins and regulates insulin mediated uptake of glucose into white adipose tissue.
This study solidifies the theory that PCOS carries an inherent risk of insulin resistance regardless of BMI/ATP III status. This is critical for practitioners treating women with PCOS to keep in mind and should prompt early screening for metabolic risk and glucose intolerance. It remains to be determined if irisin and GIP are co-variate markers that parallel the insulin resistance inherent to PCOS, or if their regulation is implicated in the genesis of PCOS. Irisin and GIP may prove useful to identify insulin resistance in PCOS.
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