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Vasomotor symptoms, encompassing hot flashes and night sweats, may be associated with diabetes but evidence is limited. We sought to estimate these associations.
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Mean duration of follow-up was VMS are associated with elevated diabetes risk, particularly for women reporting night sweats and postmenopausal symptoms. Vasomotor symptoms VMS encompass hot flashes, a sudden feeling of warmth, and night sweats, which are hot flashes that occur at night typically during sleep and are often accompanied by sweating. VMS may be an indicator of diabetes risk unique to women. Findings from studies examining the relationships between VMS and insulin resistance, a precursor to diabetes, have been mixed. Additionally, separate associations of hot flashes and night sweats with diabetes were not investigated, and the differential effects of these symptoms on CVD risk may also translate to diabetes.
Elucidating relationships between VMS and diabetes is important for several reasons.
First, they may shed light on the mechanisms underlying observed associations. Numerous pathways linking VMS and cardiometabolic outcomes have been proposed, including perturbations in cardiac vagal control, dysfunction in the hypothalamic-pituitary-adrenal HPA axis, alterations in hemostasis, and adiposity, among others. Second, positive associations would underscore the menopausal transition as an effective time to motivate behavior change that reduces both diabetes and CVD risk. Many behavioral strategies to address VMS, including physical activity, smoking cessation, and dietary changes, are also primary CVD and diabetes prevention approaches.
Therefore, we sought to expand on the limited knowledge base and evaluate the association between VMS and incident diabetes using multiple dimensions of VMS, including symptom presence, severity, type, timing, and duration.
Participants were recruited from 40 clinical centers across the U. Data collection for the Main Study occurred between andafter which consenting participants were followed up between and in Extension Study 1 and between and in Extension Study 2. Data collection for the Main Study involved clinical measurements, interviews, and self-administered questionnaires.
Institutional Review Boards from all sites approved the study, and all participants provided written informed consent. Information on incident diabetes was available through August Flow diagram for study inclusion and exclusion.
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Participants with prevalent diabetes at baseline, without data on vasomotor symptoms VMSor lacking follow-up data on diabetes were excluded from main analyses. WHI collected data on current postmenopausal hot flashes and night sweats at study baseline. Therefore, we could not separate menopausal symptoms from those due to other causes. We created several variables to characterize VMS, including presence, severity, type, timing, and duration see Table, Supplemental Digital Content 1which shows variable descriptions and classifications.
To identify the presence of VMS, we created a single dichotomous variable reflecting no symptoms versus mild, moderate, or severe hot flashes or night sweats. We classified VMS severity as none, mild, moderate, and severe, which was based on the symptom with the highest reported severity e.
Although hot flashes and night sweats likely reflect the same underlying pathophysiology, these symptoms may be experienced differently by women and could have differential effects on long-term outcomes. Furthermore, WHI participants could report one symptom but not the other.
Therefore, we created two dichotomous variables to reflect symptom type: one for any hot flashes and one for any night sweats. Women were asked if they had ever had menopausal symptoms such as hot flashes or night sweats single question and, if yes, the ages at first and last symptom. Women were classified as having pre- or perimenopausal VMS if the age at first symptom was less than or equal to the age at menopause, and as having postmenopausal VMS if the age at first symptom was greater than the age at menopause or they reported current symptoms at baseline.
For women reporting current symptoms at baseline, VMS duration was defined as time from age at first symptom to age at study baseline; for those reporting only past symptoms, duration was defined as time from age at first symptom to age at last symptom. Diabetes was defined as first report of pills or insulin injections for diabetes.
This definition was found to have acceptable validity when compared with medical records. BMI was calculated based on measured height and weight at baseline. We first examined the baseline demographic, health behavior, and health outcome characteristics of the sample, stratified by baseline VMS. We then calculated the unadjusted incidence rate of diabetes by VMS characteristics. The time to event was defined as days from enrollment to self-reported diabetes, and censoring time for non-events was defined as days from enrollment to the date of last follow-up contact.
The model exploring associations with VMS type included the two dichotomous any hot flashes and any night sweats variables, as well as their interaction, which allowed assessment of whether associations with diabetes differed if women reported both versus a single symptom.
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We examined associations with VMS timing by including the two dichotomous early and late symptom variables and their interaction, which facilitated examination of whether associations with diabetes differed for women reporting both early and late symptoms compared to symptoms in a single timeframe. To examine type and severity simultaneously, the three-level severity variables for each of hot flashes and night sweats were included in the model as ordinal variables, along with their interaction. The reference group for each of these Cox proportional hazards models was women reporting no VMS.
Lastly, we examined the association between VMS duration and diabetes, with duration modeled linearly in 5-year increments. Analyses were performed in Stata Recognizing that baseline HT use or a history of hysterectomy or oophorectomy may influence both VMS and diabetes risk, 23 — 26 we repeated all analyses 1 excluding women on HT at baseline, 2 among women on HT at baseline, and 3 excluding women with hysterectomy or oophorectomy Figure 1.
A prior study found evidence of racial differences in the association between VMS and glucose levels 11 ; therefore, we also examined interactions between each of the VMS characteristics and race white vs.
Models included 3-way interactions for VMS type, timing, combined type and severity. We modeled VMS severity ordinally in these models to facilitate interpretation. Because sleep disturbance may be related to both VMS and diabetes, 2728 in post hoc analyses we examined the unadjusted prevalence of insomnia, sleep disordered breathing, and short sleep duration by VMS characteristics.
In post hoc analyses we also examined associations of diabetes with VMS timing adjusted for VMS duration, as women with both early and late symptoms would inherently have a longer duration of VMS than those with only early symptoms, which may confound the association with diabetes. Baseline characteristics of women with and without vasomotor symptoms VMS; hot flashes and night sweats at baseline.
Vasomotor symptom characteristics: are they risk factors for incident diabetes?
There were 18, incident cases of diabetes and average follow-up time among participants was The overall incidence of diabetes was 9. Among women without baseline VMS, diabetes incidence was 8. Adjusted association between incident diabetes and vasomotor symptom presence, severity, type, and timing a. Diabetes risk increased with severity of symptoms.
Severity of reported night sweats was associated with increased diabetes risk, regardless of hot flash severity Figure 2. For hot flashes, there was limited evidence of an association between severity and diabetes risk. Associations of hot flash and night sweat severity with incident diabetes. Panel A shows the relationship between hot flash severity and diabetes across severity of night sweats. Panel B displays the relationship between night sweat severity and diabetes across severity of hot flashes.
Across all hot flash severities, increasing severity of night sweats was positively associated with diabetes risk. Associations among women not on HT at baseline were slightly attenuated compared to the full sample, and associations with hot flashes were no longer ificant for VMS type and combined type and severity analyses.
Among women on HT at baseline, associations were more pronounced, and there were ificant positive associations between hot flash severity and diabetes in the combined type and severity analyses. Comparable to when excluding women on HT, excluding women with hysterectomy or oophorectomy resulted in associations between reported hot flashes and diabetes that were no longer statistically ificant and in once case were reversed for combined type and timing analyses.
When restricting to women from the OS, conclusions remained essentially unchanged and associations were generally more pronounced see Tables, Supplemental Digital Content 4 and 5which display of sensitivity analyses in OS participants. There were no statistically ificant interactions between race and VMS presence, type, timing, combined type and severity, or duration.
As expected, given that night sweats occur at night, women who reported any night sweats with or without hot flashes had a higher prevalence of sleep disturbance than women reporting only hot flashes, which increased with symptom severity Figure 3.
Lastly, women reporting any late symptoms had a higher prevalence of disturbance than women reporting only early symptoms. Unadjusted prevalence of sleep disturbance by vasomotor symptom VMS characteristics.
Women with any VMS had a greater prevalence of each sleep disturbance than women without VMS, and prevalence increased with symptom severity. Insomnia and sleep disordered breathing were more common among women with any night sweats than among those with only hot flashes. Compared to women with only early pre- or perimenopausal VMS, women with any late postmenopausal symptoms had a greater prevalence of sleep disturbance.
We examined associations between VMS and incident diabetes, finding evidence of a positive relationship that varied by reported symptom type and timing of onset. The heightened risk associated with VMS was predominately observed among women reporting night sweats, irrespective of concurrent reporting of hot flashes, and women who had late postmenopausal symptoms. Few investigations of VMS and diabetes or its precursors have been undertaken.
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Among three studies examining associations between VMS and insulin resistance, one reported a positive association and two no association. In the only study of diagnosed diabetes, Herber-Gast et al. Differences in study populations and de may partially for discrepancies in menopausal stage findings.
WHI enrolled women ages 50—79 years with natural or surgical menopause, whereas Herber-Gast et al. Furthermore, Herber-Gast et al. Similarly contrasting findings regarding the role of VMS timing have also been found in studies with CVD-related endpoints, the reasons for which remain unclear. Our also suggest that night sweats or their effects may be largely responsible for the association between VMS overall and diabetes.
Examinations of the influence of reported hot flashes and night sweats separately on the risk of cardiovascular and metabolic outcomes are scarce. Similar positive relationships were reported with insulin resistance for both hot flashes and night sweats.
There are several potential explanations for our pattern of findings. The most plausible and consistent explanation may be through associations with sleep disturbance.