Syndrome W: A new model of hyperinsulinemia, hypertension and midlife weight gain in healthy women with normal glucose tolerance

Harriette R. Mogul, Bernard I. Weinstein, Douglas B. Mogul, Stephen J. Peterson, Shaochun Zhang, Michael Frey, Steven R. Gambert, A. Louis Southren

Research output: Contribution to journalArticlepeer-review


To characterize a new insulin resistance syndrome in euglycemic midlife women and the relationship of its features (including hypertension and dyslipidemia), with hyperinsulinemia (AUC insulin ≥100 μU/mL), retrospective cohort analysis was conducted in 278 consecutive women who presented to a Menopausal Health Program. Of 67 women with midlife weight gain "greater than 20 pounds since their twenties" and body mass indices (BMIs) between 25 and 32 kg/m2, none of the subjects met criteria for Type 2 diabetes, 5 women had impaired glucose tolerance, and 36 women were hyperinsulinemic. Hyperinsulinemia was a highly statistically significant determinant of hypertension, dyslipidemia, and truncal obesity (Odds Ratios 10.6, 4.0, and 13.7; P values ≤ 0.0001, ≤ 0.007, and ≤ 0.0001) in cross-tabulations. AUC insulin was the best predictor variable of hypertension and dyslipidemia in univariate and multivariate logistic regression models (univariate P values 0.0004 and 0.0088). After adjustment for BMI, age, and estrogen use, the final models, correctly classified, respectively, 74% and 69% of all cases in the dataset (model P values: ≤ 0.0001 and ≤ 0.0067) and AUC insulin had a log-linear (i.e., dose-dependent) relationship with hypertension and dyslipidemia, which suggests causality. We propose that the constellation of symptoms that includes midlife weight gain, "waist-gain," hypertension, dyslipidemia, and appetite dysregulation in euglycemic women with hyperinsulinemia be titled Syndrome W and suggest that the highly statistically significant relationship of hyperinsulinemia with the characteristic features are evidence of a causal role for insulin in its etiology. The identification of Syndrome W before the onset of overt impaired glucose tolerance, diabetes, or manifestations of coronary artery disease could have important clinical and public health implications for midlife women.

Original languageEnglish (US)
Pages (from-to)78-85
Number of pages8
JournalHeart Disease
Issue number2
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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