In the Journals

Insulin resistance observed in girls with PCOS, regardless of BMI

Normal-weight adolescents with polycystic ovary syndrome show peripheral insulin resistance, changes in postprandial glucose disposal and post-exercise muscle mitochondrial dysfunction when compared with normal-weight adolescents without the syndrome, according to published findings.

“Even if teen girls with PCOS are normal weight, they have mild insulin resistance in their muscle, mild muscle mitochondrial dysfunction, and an increase in liver fat relative to their weight-similar peers with normal menstrual cycles,” Melanie Cree-Green, MD, PhD, assistant professor of pediatric endocrinology and director of the adolescent PCOS multidisciplinary clinic at the University of Colorado, Anschutz and Children’s Hospital Colorado, told Endocrine Today. “As clinicians, we need to monitor the metabolic health of all girls with PCOS, not just those who are overweight or obese.”

Melanie Cree-Green
Melanie Cree-Green

Cree-Green and colleagues analyzed data from 18 normal-weight girls with PCOS (mean age, 16 years; mean BMI, 22.7 kg/m²) and 20 normal-weight controls (mean age, 15 years; mean BMI, 21.3 kg/m²). All girls underwent a four-phase, hyperinsulinemic-euglycemic clamp with isotope trackers to assess tissue-specific insulin sensitivity, as well as a standard 2-hour, 75-g oral glucose tolerance test; hepatic fat was determined via MRI, and body composition was measured via DXA. Researchers also measured post-exercise muscle mitochondrial function. Participants completed food frequency questionnaires and wore an accelerometer for 7 days to track habitual physical activity.

When assessing biochemical measurements, researchers found no between-group differences for serum estradiol, sex hormone-binding globulin, leptin, adiponectin, HbA1c, fasting glucose and insulin; inflammatory markers and serum lipids were also similar. Girls with PCOS has higher levels of total testosterone and dehydroepiandrosterone sulfate.

When undergoing the hyperinsulinemic-euglycemic clamp, peripheral insulin sensitivity was lower in girls with PCOS compared with controls without PCOS (mean, 10.9 mg/kg per minute vs. 13.5 mg/kg per minute; P = .02). OGTT insulin levels at 2 hours were also higher in girls with PCOS vs. girls without PCOS (mean, 114 uIU/mL vs. 41 uIU/mL; P < .001) as was 2-hour glucose (mean, 119 mg/dL vs. 85 mg/dL, P = .01).

Girls with PCOS also showed muscle mitochondrial dysfunction, according to the researchers; adenosine diphosphate and phosphocreatine time constants were slower vs. girls without PCOS (mean, 22.8 seconds vs. 17.7 seconds; 0.16 mmol/L per second vs. 0.21 mmol/L per second, respectively). Girls with PCOS also had higher levels of liver fat percentage vs. controls, although still in the normal range. There were no between-group differences for hepatic insulin resistance or adipose insulin resistance.

“These findings indicate that certain aspects of metabolic alterations in PCOS, particularly in the muscle, occur regardless of adiposity, and this are likely related to PCOS status alone,” the researchers wrote.

The findings suggest that future medical interventions to improve metabolic disease must also be studied in normal-weight girls with PCOS, Cree-Green said. – by Regina Schaffer

For more information:

Melanie Cree-Green, MD, PhD, can be reached at the University of Colorado Anschutz Medical Campus, PO Box 265, 13123 E. 16th Ave., Aurora, CO 80045; email: melanie.green@childrenscolorado.org.

Disclosure: The researchers report no relevant financial disclosures.

Normal-weight adolescents with polycystic ovary syndrome show peripheral insulin resistance, changes in postprandial glucose disposal and post-exercise muscle mitochondrial dysfunction when compared with normal-weight adolescents without the syndrome, according to published findings.

“Even if teen girls with PCOS are normal weight, they have mild insulin resistance in their muscle, mild muscle mitochondrial dysfunction, and an increase in liver fat relative to their weight-similar peers with normal menstrual cycles,” Melanie Cree-Green, MD, PhD, assistant professor of pediatric endocrinology and director of the adolescent PCOS multidisciplinary clinic at the University of Colorado, Anschutz and Children’s Hospital Colorado, told Endocrine Today. “As clinicians, we need to monitor the metabolic health of all girls with PCOS, not just those who are overweight or obese.”

Melanie Cree-Green
Melanie Cree-Green

Cree-Green and colleagues analyzed data from 18 normal-weight girls with PCOS (mean age, 16 years; mean BMI, 22.7 kg/m²) and 20 normal-weight controls (mean age, 15 years; mean BMI, 21.3 kg/m²). All girls underwent a four-phase, hyperinsulinemic-euglycemic clamp with isotope trackers to assess tissue-specific insulin sensitivity, as well as a standard 2-hour, 75-g oral glucose tolerance test; hepatic fat was determined via MRI, and body composition was measured via DXA. Researchers also measured post-exercise muscle mitochondrial function. Participants completed food frequency questionnaires and wore an accelerometer for 7 days to track habitual physical activity.

When assessing biochemical measurements, researchers found no between-group differences for serum estradiol, sex hormone-binding globulin, leptin, adiponectin, HbA1c, fasting glucose and insulin; inflammatory markers and serum lipids were also similar. Girls with PCOS has higher levels of total testosterone and dehydroepiandrosterone sulfate.

When undergoing the hyperinsulinemic-euglycemic clamp, peripheral insulin sensitivity was lower in girls with PCOS compared with controls without PCOS (mean, 10.9 mg/kg per minute vs. 13.5 mg/kg per minute; P = .02). OGTT insulin levels at 2 hours were also higher in girls with PCOS vs. girls without PCOS (mean, 114 uIU/mL vs. 41 uIU/mL; P < .001) as was 2-hour glucose (mean, 119 mg/dL vs. 85 mg/dL, P = .01).

Girls with PCOS also showed muscle mitochondrial dysfunction, according to the researchers; adenosine diphosphate and phosphocreatine time constants were slower vs. girls without PCOS (mean, 22.8 seconds vs. 17.7 seconds; 0.16 mmol/L per second vs. 0.21 mmol/L per second, respectively). Girls with PCOS also had higher levels of liver fat percentage vs. controls, although still in the normal range. There were no between-group differences for hepatic insulin resistance or adipose insulin resistance.

“These findings indicate that certain aspects of metabolic alterations in PCOS, particularly in the muscle, occur regardless of adiposity, and this are likely related to PCOS status alone,” the researchers wrote.

The findings suggest that future medical interventions to improve metabolic disease must also be studied in normal-weight girls with PCOS, Cree-Green said. – by Regina Schaffer

For more information:

Melanie Cree-Green, MD, PhD, can be reached at the University of Colorado Anschutz Medical Campus, PO Box 265, 13123 E. 16th Ave., Aurora, CO 80045; email: melanie.green@childrenscolorado.org.

Disclosure: The researchers report no relevant financial disclosures.