Polycystic ovary syndrome: How are obesity and insulin resistance involved?

OBG Management. 2012 October;24(10):1e-5e

October 1, 2012|OBG Management

Leah Whigham, PhD;Steven R. Lindheim, MD, MMM

Which of my patients with PCOS do I screen for insulin sensitivity? What screening tests are available, and which are most appropriate? Two experts continue to tackle a long list of questions that your clinician–colleagues have been posing.

IN THIS ARTICLE

Hyperandrogenism and insulin resistance
Direct and indirect assessments for insulin resistance
What about HbA_1c?

Glucose/insulin ratio

The glucose/insulin (G/I) ratio has become very popular since its first description in 1998 as an accurate index of insulin sensitivity in women with PCOS. The ratio of glucose to insulin is easy to calculate, with lower values depicting higher degrees of insulin resistance. A G/I ratio of less than 4.5 has been shown to be sensitive (95%) and specific (84%) for insulin resistance in women with PCOS, compared with a control group. The normal range for G/I ratios may vary in different ethnic groups and have not been fully validated in nonobese patients.^22-25

Homeostatic model assessment

First described in 1985, homeostatic model assessment (HOMA) has been used widely in clinical research to assess insulin sensitivity. Rather than using fasting insulin or a G/I ratio, the product of the fasting values of glucose (expressed as mg/dL) and insulin (expressed as μU/mL) is divided by a constant: I0 x G0 ÷ 405.

The constant 405 should be replaced by 22.5 if glucose is expressed in SI units (mmol/L). Unlike fasting insulin and the G/I ratio, the HOMA calculation compensates for fasting hyperglycemia. The HOMA value correlates well with clamp techniques and has been used frequently to assess changes in insulin sensitivity after treatment. HOMA also has been used to study insulin resistance among PCOS patients of differing ethnic origins.^12,24-26

Quantitative insulin sensitivity check index

Like HOMA, quantitative insulin sensitivity check index (QUICKI) can be applied to normoglycemic and hyperglycemic patients. It is derived by calculating the inverse of the sum of logarithmically expressed values of fasting glucose and insulin: 1 ÷ [log(I0) + log(G0)].

Many investigators believe that QUICKI is superior to HOMA as a way of determining insulin sensitivity, although the two values correlate well. As the SI decreases, QUICKI values decrease.²⁷

Oral glucose tolerance test

As OGTT does not require IV access, it is the current standard in practice for diagnosis of IGT and DM. It provides a better assessment of IGT and DM than fasting techniques because these patients may have normal fasting glucose values despite abnormal 2-hour fasting levels. The OGTT uses a 50-, 75-, or 100-g glucose load and measures glucose and insulin at various intervals over 1 to 3 hours. The WHO currently recommends a 75-g oral dose in all adults. A 50-g dose is used to screen for gestational diabetes over an hour, and the 100-g load over 3 hours if abnormal.²⁸ See TABLE for normal and abnormal values. Insulin sensitivity has been assessed by calculating insulin area under the curve (AUC insulin), AUC glucose/AUC insulin, and by an insulin sensitivity index (ISI) that applies only the glucose and insulin values from 0 and 120 minutes into a complex mathematical formula.^13,25,29-31

Criteria for diagnosis of diabetes

	Venous plasma glucose (mg/dL)
	Fasting Level*	2-hour postglucose load**
Normal/Low risk	≤99	≤139
Prediabetes/Increased risk	100–125	140–199
Diabetes	≥126	≥200
Fasting is defined as no caloric intake for at least 8 h *OGTT using a glucose load or 75 g as described by the World Health Organization SOURCE: American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care. 2012;35 (suppl 1):s11–s63. doi:10.2337/dc12-s011.

Test for glycosylated hemoglobin

Tests for blood levels of glycosylated hemoglobin, also known as hemoglobin A_1c (HbA_1c) are not currently used for an initial diagnosis because normal HbA_1c levels do not necessarily rule out diabetes, but they are strongly associated with complications of diabetes. The test is not affected by food intake so it can be taken at any time. A normal HbA_1c level is below 7%.

In the next installment: The authors begin by addressing recent data that have drawn attention to the long-term metabolic risks of PCOS by answering:

“What is metabolic syndrome and what are the current diagnostic criteria?”
“We know metformin is used to treat insulin resistance…but what about hyperandrogenism, anovulation, infertility, weight loss, and early pregnancy loss?”

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