Prediabetes and Fracture Risk Among Middle-Aged Women in the Nationwide Women’s Health Study
Key points Is prediabetes associated with an increased risk of fractures among middle-aged women? Findings In this cohort study of 1,690 middle-aged women without diabetes from the Nationwide Women’s Health Study cohort, relative to not having prediabetes at any visit before the menopausal transition (MT), having Prediabetes at each visit prior to TM was associated with a statistically significant 120% increased risk of fracture during TM and after menopause. This association was independent of bone mineral density at the start of MT. Meaning This study suggests that, for middle-aged women, prediabetes may be a risk factor for future fractures. |
“Diabetic bone disease” and fractures are increasingly recognized as end-organ complications of diabetes. At present, it is not known whether prediabetes is also a risk factor for fractures. Such an association is plausible; Recently published data show that prediabetes is associated with lower bone turnover and worse trabecular bone microarchitecture. Furthermore, at levels seen in individuals without type 2 diabetes, greater insulin resistance is associated with lower bone mineral density (BMD), lower trabecular bone score, lower indices of hip strength, and bone contraction. more rapid loss, all fracture risk factors.
Clarifying whether prediabetes increases the risk of fractures is a step to understanding its clinical relevance. Although prediabetes is a risk factor for developing diabetes, doctors disagree about how aggressively to treat it. Not all people with prediabetes develop type 2 diabetes, and prediabetes itself has not been definitively associated with end-organ complications. With respect to bone health, it is unknown whether prediabetes is associated with fractures in the absence of prior or future progression to type 2 diabetes.
The first objective of this study was to examine whether prediabetes among midlife women is associated with subsequent fracture in the absence of type 2 diabetes. We focused on midlife, when women undergo the menopausal transition (MT) and the risk of fracture accelerates. Because prediabetes can affect BMD, our second objective was to evaluate whether the possible association of prediabetes with fracture was independent of BMD.
Importance
It is not known whether prediabetes is associated with fractures.
Aim
To evaluate whether prediabetes before the menopausal transition (MT) is associated with incident fracture during and after MT.
Design, environment and participants
This cohort study used data collected between January 6, 1996 and February 28, 2018 in the Study of Women’s Health Across the Nation cohort study , an ongoing, multicenter, US-based longitudinal study. in various ambulatory women.
The study included 1,690 middle-aged women in premenopause or early perimenopause at baseline (who have since transitioned to postmenopause) who did not have type 2 diabetes before the menopausal transition (MT) and who were not taking beneficial medications. the bones before TM. The onset of menopausal transition (MT) was defined as the first visit in late perimenopause (or the first postmenopausal visit if participants transitioned directly from premenopause or early perimenopause to postmenopause). The mean (SD) follow-up was 12 (6) years . The statistical analysis was carried out from January to May 2022.
Exposure
Proportion of visits before the menopausal transition (MT) in which women had prediabetes (fasting glucose, 100-125 mg/dL [to convert to millimoles per liter, multiply by 0.0555]), with values that They range from 0 (prediabetes without visits) to 1 (prediabetes at all visits).
Main results and measures
Time to first fracture after onset of menopausal transition (MT) with exclusion at first diagnosis of type 2 diabetes, initiation of bone-beneficial medication, or last follow-up. Cox proportional hazards regression was used to examine the association (before and after adjustment for bone mineral density) of prediabetes before MT with fracture during MT and after menopause.
Results
This analysis included 1690 women (mean [SD] age, 49.7 [3.1] years; 437 black women [25.9%], 197 Chinese women [11.7%], 215 Japanese women [12.7 %] and 841 white women [49.8%]; mean [SD] body mass index [BMI] at initiation of MT, 27.6 [6.6]).
A total of 225 women (13.3%) had prediabetes at one or more study visits before MT and 1465 women (86.7%) did not have prediabetes before MT. Of the 225 women with prediabetes, 25 (11.1%) suffered a fracture, while 111 of the 1465 women without prediabetes (7.6%) suffered a fracture.
After adjustment for age, BMI, and cigarette use at the beginning of the menopause transition (MT); fracture before MT; use of medications that are harmful to bones; race and ethnicity; and study site, prediabetes before MT was associated with more subsequent fractures (fracture hazard ratio with prediabetes at all vs no pre-MT visit, 2.p = 0.02). This association was essentially unchanged after controlling for BMD at the start of MT.
Conclusions and relevance In this cohort study of middle-aged women, prediabetes before MT was associated with an increased risk of subsequent fractures during the menopausal transition (MT) and after menopause, independent of BMD. Because fractures in midlife are associated with subsequent fractures in old age, future research could examine whether treating prediabetes before MT reduces the risk of different fracture outcomes (e.g., hip, vertebral , non-vertebral, major osteoporotic) in adulthood. |
