Chronic Insufficient Sleep in Women Impairs Insulin Sensitivity Independent of Adiposity Changes: Results of a Randomized Trial.

OBJECTIVE: Insufficient sleep is associated with type 2 diabetes, yet the causal impact of chronic insufficient sleep on glucose metabolism in women is unknown. We investigated whether prolonged mild sleep restriction (SR), resembling real-world short sleep, impairs glucose metabolism in women. RESEARCH DESIGN AND METHODS: Women (aged 20-75 years) without cardiometabolic diseases and with actigraphy-confirmed habitual total sleep time (TST) of 7-9 h/night were recruited to participate in this randomized, crossover study with two 6-week phases: maintenance of adequate sleep (AS) and 1.5 h/night SR. Outcomes included plasma glucose and insulin levels, HOMA of insulin resistance (HOMA-IR) values based on fasting blood samples, as well as total area under the curve for glucose and insulin, the Matsuda index, and the disposition index from an oral glucose tolerance test. RESULTS: Our sample included 38 women (n = 11 postmenopausal women). Values are reported with ±SEM. Linear models adjusted for baseline outcome values demonstrated that TST was reduced by 1.34 ± 0.04 h/night with SR versus AS (P < 0.0001). Fasting insulin (ß = 6.8 ± 2.8 pmol/L; P = 0.016) and HOMA-IR (ß = 0.30 ± 0.12; P = 0.016) values were increased with SR versus AS, with effects on HOMA-IR more pronounced in postmenopausal women compared with premenopausal women (ß = 0.45 ± 0.25 vs. ß = 0.27 ± 0.13, respectively; P for interaction = 0.042). Change in adiposity did not mediate the effects of SR on glucose metabolism or change results in the full sample when included as a covariate. CONCLUSIONS: Curtailing sleep duration to 6.2 h/night, reflecting the median sleep duration of U.S. adults with short sleep, for 6 weeks impairs insulin sensitivity, independent of adiposity. Findings highlight insufficient sleep as a modifiable risk factor for insulin resistance in women to be targeted in diabetes prevention efforts.

Paradoxical Effects of Prolonged Insufficient Sleep on Lipid Profile: A Pooled Analysis of 2 Randomized Trials.

Background Insufficient sleep is associated with increased cardiovascular disease risk, but causality is unclear. We investigated the impact of prolonged mild sleep restriction (SR) on lipid and inflammatory profiles. Methods and Results Seventy-eight participants (56 women [12 postmenopausal]; age, 34.3±12.5 years; body mass index, 25.8±3.5 kg/m2) with habitual sleep duration 7 to 9 h/night (adequate sleep [AS]) underwent two 6-week conditions in a randomized crossover design: AS versus SR (AS-1.5 h/night). Total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, and inflammatory markers (CRP [C-reactive protein], interleukin 6, and tumor necrosis factor-α) were assessed. Linear models tested effects of SR on outcomes in the full sample and by sex+menopausal status (premenopausal versus postmenopausal women+men). In the full sample, SR increased high-density lipoprotein cholesterol compared with AS (ß=1.2±0.5 mg/dL; P=0.03). Sex+menopausal status influenced the effects of SR on change in total cholesterol (P-interaction=0.04), LDL-C (P-interaction=0.03), and interleukin 6 (P-interaction=0.07). Total cholesterol and LDL-C decreased in SR versus AS in premenopausal women (total cholesterol: ß=-4.2±1.9 mg/dL; P=0.03; LDL-C: ß=-6.3±2.0 mg/dL; P=0.002). Given paradoxical effects of SR on cholesterol concentrations, we explored associations between changes in inflammation and end point lipids under each condition. Increases in interleukin 6 and tumor necrosis factor-α during SR tended to relate to lower LDL-C in premenopausal women (interleukin 6: ß=-5.3±2.6 mg/dL; P=0.051; tumor necrosis factor-α: ß=-32.8±14.2 mg/dL; P=0.027). Conclusions Among healthy adults, prolonged insufficient sleep does not increase atherogenic lipids. However, increased inflammation in SR tends to predict lower LDL-C in premenopausal women, resembling the "lipid paradox" in which low cholesterol associates with increased cardiovascular disease risk in proinflammatory conditions. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02835261, NCT02960776.

Adverse Changes in Body Composition During the Menopausal Transition and Relation to Cardiovascular Risk: A Contemporary Review.

The menopausal transition period in aging women is strongly associated with weight gain. Evidence shows that weight changes during menopause increases the risk of developing cardiovascular disease (CVD) in postmenopausal women. However, the potential mechanisms that cause weight gain and adverse changes to body composition specifically during the menopausal transition period remain to be elucidated. In this contemporary review, we examined recent evidence for adverse changes in body composition at midlife during the menopausal transition and the link to increased CVD risk and described factors that may contribute to these changes, including normal chronological aging, hormonal factors (decreased estrogen, etc.), behavioral factors (changes in diet, physical activity), or other emerging factors (e.g., sleep). This review focused on identifying factors that make the menopausal transition period a critical window for prevention of CVD. Future study is needed to decipher the extent to which hormonal changes, age-related factors, and behavioral factors interact with and contribute to increased CVD risk in women undergoing menopause. Understanding the causes of weight gain during the menopausal transition may help to inform strategies to mitigate adverse CVD outcomes for women transitioning through menopause.

Actigraphy-Derived Sleep Is Associated with Eating Behavior Characteristics.

Poor sleep is a determinant of obesity, with overconsumption of energy contributing to this relationship. Eating behavior characteristics are predictive of energy intake and weight change and may underlie observed associations of sleep with weight status and obesity risk factors. However, relationships between sleep and dimensions of eating behavior, as well as possible individual differences in these relations, are not well characterized. Therefore, the aim of this study was to evaluate whether sleep behaviors, including duration, timing, quality, and regularity relate to dietary restraint, disinhibition, and tendency towards hunger and to explore whether these associations differ by sex. This cross-sectional study included 179 adults aged 20-73 years (68.7% women, 64.8% with BMI ≥ 25 kg/m2). Sleep was evaluated by accelerometry over 2 weeks. Eating behavior dimensions were measured with the Three-Factor Eating Questionnaire. Prolonged wake after sleep onset (WASO) (0.029 ± 0.011, p = 0.007), greater sleep fragmentation index (0.074 ± 0.036, p = 0.041), and lower sleep efficiency (-0.133 ± 0.051, p = 0.010) were associated with higher dietary restraint. However, higher restraint attenuated associations of higher WASO and sleep fragmentation with higher BMI (p-interactions < 0.10). In terms of individual differences, sex influenced associations of sleep quality measures with tendency towards hunger (p-interactions < 0.10). Stratified analyses showed that, in men only, higher sleep fragmentation index, longer sleep onset latency, and lower sleep efficiency were associated with greater tendency towards hunger (ß = 0.115 ± 0.037, p = 0.003, ß = 0.169 ± 0.072, p = 0.023, ß = -0.150 ± 0.055, p = 0.009, respectively). Results of this analysis suggest that the association of poor sleep on food intake could be exacerbated in those with eating behavior traits that predispose to overeating, and this sleep-eating behavior relation may be sex-dependent. Strategies to counter overconsumption in the context of poor quality sleep should be evaluated in light of eating behavior traits.

Synchronous, but separate, bladder and vaginal rhabdomyosarcoma: a novel genetic case report.

Embryonal rhabdomyosarcoma is a rare cancer that often requires multimodality therapy to treat; however, these therapies can cause changes in the biology of the tumor. Several reports have documented pathologic changes but only recently have genetic changes been mapped. We present case of two separate synchronous primary rhabdomyosarcomas in a 17-month-old patient and discuss the pathophysiology and genetic changes that occur with treatment. We hypothesize that a genetic field defect arising in development of the urogenital sinus caused the tumors, but that treatment modalities may have caused genetic alterations changing clinical behavior of the tumors and responses to treatment.