Effects of Sex and Hormone Replacement Therapy Use on the Prevalence of Isolated Impaired Fasting Glucose and Isolated Impaired Glucose Tolerance in Subjects With a Family History of Type 2 Diabetes

Abstract

Impaired fasting glucose (IFG) is more prevalent in men and impaired glucose tolerance (IGT) more prevalent in women. To explore whether this sex difference is related to female sex hormones, we performed a cross-sectional analysis of data from 2,164 (1,329 women and 835 men) firstdegree relatives of individuals with type 2 diabetes. Subjects were categorized based on a 75-g oral glucose tolerance test. Sex and hormone replacement therapy (HRT) effects on the distribution of glucose tolerance were assessed using multinomial logistic regression corrected for familial clustering. T he reclassification of glucose tolerance in 1997 included the subdivision of impaired glucose regulation into both impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) (1). When first defined, these both were expected to represent states of increased risk for developing type 2 diabetes and thus frequently have been referred to as pre-diabetes. Since that time, it has become clear that these two states do not always occur in the same individuals and that their pathogenesis may be different (2-6).In line with the fact that IFG and IGT may independently occur and may differ in their etiology, it has been reported that the prevalence of IFG and IGT differs by sex, with IFG being more prevalent in men and IGT more prevalent in women (6 -12). The reason(s) for this sex difference in glucose metabolism has not been explored, but some studies suggest that female sex hormones may contribute. In the Women's Health Initiative, when compared with placebo, the combination of estrogen and progesterone was associated with a decreased incidence of diabetes (13) and there was a trend for a decreased incidence of diabetes in the estrogen-only arm (P ϭ 0.07) (14). After the 1st year of treatment, both the combination of estrogen plus progesterone and the estrogen-alone groups demonstrated decreased fasting plasma glucose (FPG) and decreased insulin resistance, as measured by the homeostasis model assessment of insulin resistance (13,14). Similarly, the Heart and Estrogen/Progestin Replacement Study showed a lower incidence of diabetes in women using combination hormone replacement therapy (HRT) (15). However, neither the Women's Health Initiative nor the Heart and Estrogen/Progestin Replacement Study performed oral glucose tolerance tests (OGTTs) to determine the effect of treatment on postchallenge plasma glucose. Studies that have measured both fasting and 2-h plasma glucose levels have shown that the beneficial effects of HRT on the fasting glucose were accompanied by adverse effects on the 2-h glucose (16 -18), while others failed to see an effect on glucose metabolism (19 -21).While IFG and IGT both are known to increase the risk of developing diabetes, there are a number of other factors that also influence progression to hyperglycemia, including a family history of type 2 diabetes (22,23). As the

Effects of Gender and Height on the Oral Glucose Tolerance Test: The Isfahan Diabetes Prevention Study

“…Other studies suggested that the observed gender differences in the glucose metabolism may be mediated by female sex hormones [29]. Estrogen may be influencing fasting glucose levels by impacting insulin sensitivity.…”

Diabetes and Impaired Glucose Regulation in First-Degree Relatives of Patients with Type 2 Diabetes in Isfahan, Iran: Prevalence and Risk Factors

“…The potential reason or reasons for this gender difference in glucose metabolism has not been explored, but some studies suggest that female sex hormones may contribute [26][27][28][29][30], while others failed to see any effect on glucose metabolism [31][32][33].…”

Sex and Gender Differences in Endocrinology

“…4 Postmenopausal women with a family history of T2DM on hormone replacement therapy have an even higher rate of isolated impaired glucose tolerance. 5 Accordingly, postprandial/postload hyperglycemia is more commonly found in females than males and may in part be ascribed to lower height. 6 Recently, a study in healthy, glucose-tolerant subjects showed different gut glucose absorption rates during OGTT in women and men and a negative relationship between body height and gut glucose half-life.…”