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PCOS + Obesity Leads to Severe Insulin Resistance in Adolescent Girls

Severe insulin resistance, seen only through more extreme measurements, was identified in adolescent girls with and obesity…. 

The treatment for these girls should be with metformin no matter their HbA1c, according to a presenter at the Pediatric Academic Societies annual meeting.

Melanie Cree Green, MD, PhD, of the University of Colorado, Denver added that, "Almost any obese girl with PCOS (polycystic ovary syndrome) should be put on metformin, especially if they have a family history of type 2 diabetes, because the measures that we do to assess insulin resistance just aren’t good enough." "In a way, this is confirmation that physical measures for insulin measures are inadequate, but in these obese girls with PCOS, we really need to consider them all insulin resistant."

Green’s study looked at 60 adolescent girls with obesity (23 without PCOS, 37 with PCOS), similarly matched for age, BMI (>95th percentile) and HbA1c; exclusion criteria included diagnosed diabetes and weight >250 lb. The researchers used standard clinical measures: fasting glucose, fasting insulin, HbA1c, and a 2-hour oral glucose tolerance test, with sampling every 15 and 30 minutes in the beginning to look at pancreatic function and then every 30 minutes after that to look at glucose area under the curve. They then completed a three-stage hyperinsulinemic-euglycemic clamp to look at adipose insulin sensitivity, hepatic insulin sensitivity and muscle insulin sensitivity.

The traditional fasting measures produced similar results for both groups of girls. The OGTT showed that approximately 30% of the patients with PCOS and obesity had impaired glucose tolerance (105 ± 4 mg/dL vs. 135 ± 8 mg/dL, obese vs. obese with PCOS; P=.002) and insulin resistance (136 ± 13 IU/mL vs. 294 ± 42 IU/mL, obese vs. obese with PCOS; P=.01).

Glucose clearance during the clamp testing was lower in PCOS (16.3 ± 2.4 mg/kg/min vs. 9.9 ± 0.6 mg/kg/min, obese vs. obese with PCOS), and insulin concentration required to suppress 50% of endogenous glucose release was greater (52 ± 9 IU/mL vs. 102 ± 12 IU/mL, obese vs. obese with PCOS; P=.006).

"Their hepatic insulin sensitivity is also significantly reduced so that even when their serum insulin concentration is over 200, their liver is still putting out glucose. We could not shut off their endogenous hepatic glucose secretions," Green said. "These are not the sickest girls that I have in clinic, and yet their muscle and liver insulin sensitivity is really severe and you don’t pick it up in your standard clinical measures."

Green said the Endocrine Society’s guidelines suggest metformin in insulin-resistant adolescents, but all adolescent females with obesity and PCOS should be considered insulin resistant and receive metformin, sometimes in addition to oral contraceptives if necessary.

There is a disconnect in that, "People need to be more cognizant of the severe underlying insulin resistance and that if you have an HbA1c of 5.2, it does not mean that they’re not insulin resistant. Your HbA1c is just reflecting beta-cell function.

Practice Pearls:
  • The treatment for PCOS and obesity should be with metformin no matter what their HbA1c is
  • An HbA1c of 5.2, does not mean that the patient is not insulin resistant

Cree Green M. Platform presentation #2865.2. Presented at: Pediatric Academic Societies and Asian Society for Pediatric Research joint meeting; May 3-6, 2014; Vancouver, British Columbia.