Ethnicity and Insulin Resistance

Abstract & Commentary

Synopsis: Insulin resistance increases with increasing body weight and is most prevalent in Mexican-Americans.

Source: Park YW, et al. Arch Intern Med. 2003;163: 427-436.

The prevalence of the metabolic syndrome was assessed in the Third National Health and Nutrition Survey. Overall, the metabolic syndrome was present in 22.6% of American women. The prevalence increases with increasing body weight, from about 5% in normal weight individuals to 60% in obese men and women. The prevalence is highest in Mexican-Americans and lowest in Blacks.

Comment By Leon Speroff, MD

Insulin resistance is defined as a reduced glucose response to a given amount of insulin. Resistance to insulin-stimulated glucose uptake is a relatively common phenomenon, but only 1 component of a condition referred to in the past as syndrome X, now called metabolic syndrome. In addition to insulin resistance, the metabolic syndrome includes at least 2 of the following: hypertension, elevated triglyceride levels, reduced HDL-cholesterol levels, abdominal or overall obesity, and albuminuria. The prevalence of metabolic syndrome in Finland and Sweden has been estimated to be approximately 10% of people with normal glucose tolerance, 40% of people with impaired glucose tolerance, and 85% of people with type 2 diabetes mellitus.1 In the United States, the overall prevalence was previously estimated to be 24%, higher in women and increasing with age.2

Do all anovulatory patients require testing for hyperinsulinemia? Both lean and obese women with polycystic ovaries can be found to have hyperinsulinemia, but not all hyperandrogenic women with polycystic ovaries (lean and obese) have hyperinsulinemia. However, hyperinsulinemia is more common and severe in overweight women and androgenic effects are more intense. Furthermore, lean women with hyperinsulinemia do not appear to have the same risk of future diabetes mellitus, although clinical follow-up may in time document an onset later in life of noninsulin-dependent diabetes mellitus compared to an earlier onset in obese women.

Young women with irregular menses are very likely to be anovulatory and should be evaluated for hyperinsulinemia. Because of the probable inherited susceptibility for anovulation and insulin resistance, consideration should be given to a glucose tolerance and insulin evaluation for family members of already diagnosed patients. Both brothers and sisters of anovulatory, hyperandrogenism women can be insulin resistant. What about those women who are ovulatory and have no clinical complaints, yet supposedly have an underlying hyperinsulinemic disorder? In my view, if this is real, it is a homeostatic compensatory state, and until appropriate data reveal adverse outcomes in these women, diagnostic and therapeutic interventions are not indicated.

Teenagers who present with persistent anovulation (oligomenorrhea at least 2 years after menarche) are good candidates for hyperinsulinemia testing. During puberty, insulin resistance develops, probably because of the increase in sex steroids and growth hormone, resulting in a secondary increase in insulin and IGF-I. The increase in insulin leads to a decrease in SHBG, which would allow greater sex steroid activity for pubertal development. There is reason to believe that some teenagers fail to normalize the hyperinsulinemia associated with the growth hormone increase in early puberty. It would be important to identify these teenagers who are at an increased risk for the development of diabetes mellitus and are destined to struggle with all of the problems associated with anovulation and polycystic ovaries. All anovulatory adolescents with polycystic ovaries, especially those who are overweight, should undergo periodic screening for abnormal glucose tolerance,3 but there is a particular group associated with premature adrenarche that deserves special attention.

Premature adrenarche can be due to hyperinsulinemia, and these patients go on to develop the full characteristics of anovulation, hyperandrogenism, and polycystic ovaries. A marker for this unique teenage problem is low birth weight. Furthermore, these individuals are not overweight and insulin resistance and dyslipidemia are present during childhood, indicating that the basic problem is hyperinsulinemia beginning in fetal life, present in childhood, and worse after puberty. Most importantly, treatment with metformin returns the metabolic parameters to normal, and ovulatory menstrual function is initiated.4 Long-term metformin treatment, therefore, offers the opportunity to prevent cardiovascular disease and the early onset of diabetes mellitus.

Unfortunately, it is not certain what levels of insulin in the fasting state or in response to an oral glucose tolerance test are correlated with clinical outcome. The most accurate assessment, the euglycemic clamp technique, is not practical, requiring considerable time, an experienced technician, intravenous access, and/or multiple venipunctures. Several quick methods based upon the fasting values for glucose and insulin are available, but all are subject to the variability associated with insulin levels. Because there is considerable overlap between normal women and patients with anovulation and polycystic ovaries, it is reasonable to assume that all overweight, anovulatory women with polycystic ovaries are hyperinsulinemic. The measurement of the ratio of fasting glucose to fasting insulin has been advocated in order to provide evidence that lends credence and importance to counseling efforts, with a ratio of less than 4.5 being consistent with insulin resistance.5

An important disadvantage of the ratio method is variability among different ethnic groups, and even among populations living in different regions of the United States. In one study from Texas, a ratio less than 7.2 indicated insulin resistance in white women compared with a ratio less than 4.0 in Mexican-American women.6 In addition to Mexican-American women, insulin resistance appears to be more severe in Black women and Asian women.7,8 Because of the variability, the fasting glucose to fasting insulin ratio is no longer recommended; a 2-hour oral glucose tolerance test is now the preferred method of assessment.

All anovulatory women who are hyperandrogenic should be assessed for glucose tolerance and insulin resistance with measurement of 2-hour glucose and insulin levels after a 75 g glucose load (see Table, below).

Dr. Speroff is Professor of Obstetrics and Gynecology at Oregon Health Sciences University in Portland and editor of Ob/Gyn Clinical Alert.

References

1. Groop L, et al. Diabetes. 1996;45:1585-1593.

2. Ford ES, et al. JAMA. 2002;287:356-359.

3. Palmert MR, et al. J Clin Endocrinol Metab. 2002;87:1017-1023.

4. Ibanez L, et al. J Clin Endocrinol Metab. 2001;86:3595-3598.

5. Legro RS, et al. J Clin Endocrinol Metab. 1998;83:2694-2698.

6. Kauffman RP, et al. Am J Obstet Gynecol. 2002;187:1362-1369.

7. Palaniappan LP, et al. Diabetes Care. 2002;25: 1351-1357.

8. Wijeyaratne CN, et al. Clin Endocrinol. 2002;57: 343-503.