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Background: There is growing interest in identifying factors associated with healthy aging. This cross‐sectional study evaluated associations of psychological resilience with factors associated with aging in older adults with type 2 diabetes mellitus (T2DM). Methods: Participants were 3199 adults (72.2 ± 6.2 years of age, 61% female, 61% White, body mass index [BMI] = 34.2 ± 8.2 kg/m2) with T2DM enrolled in Look AHEAD (a multi‐site randomized clinical trial comparing an intensive lifestyle intervention for weight loss to diabetes education and support). Participants were followed observationally after the 10‐year intervention was discontinued. The following items were assessed approximately 14.4 years post‐randomization in a cross‐sectional analysis: Brief Resilience Scale; overnight hospitalizations in past year; physical functioning measured objectively (gait speed, grip strength) and via self‐report (Pepper Assessment Tool for Disability; physical quality of life [QOL; SF‐36]); a measure of phenotypic frailty based on having ≥3 of unintentional weight loss, low energy, slow gait, reduced grip strength, and physical inactivity. Depressive symptoms (PHQ‐9) and mental QOL (SF‐36) were also measured. Logistic/linear/multinomial regression was used to evaluate the association of variables with resilience adjusted for age, race/ethnicity, and gender. Results: Greater psychological resilience was associated with lower BMI, fewer hospitalizations, better physical functioning (i.e., lower self‐reported disability, better physical QOL, faster gait speed, greater grip strength, lower likelihood of frailty), fewer depressive symptoms, and greater mental QOL (all p < 0.05). Psychological resilience moderated the relationship of number of hospitalizations in the past year with self‐reported disability and grip strength. Conclusions: Psychological resilience is associated with better physical function and QOL among older adults. Results should be interpreted cautiously given cross‐sectional nature of analyses. Exploring the clinical benefits of resilience is consistent with efforts to shift the narrative on aging beyond "loss and decline" to highlight opportunities to facilitate healthy aging. [ABSTRACT FROM AUTHOR]

The study aims to evaluate the efficacy of estrogen plus progestin on the incidence of breast cancer and mortality in postmenopausal women. The results indicate that such a form of treatment resulted in an increased risk of breast cancer and mortality.

Background. Cognitive function and physical performance are associated, but the common sequence of cognitive and physical decline remains unclear. Methods. In the Women's Health Initiative Memory Study (WHIMS) clinical trial, we examined associations at baseline and over a 6-year follow-up period between the Modified Mini-Mental State (3MS) Examination and three physical performance measures (PPMs): gait speed (meters/second), chair stands (number of stands in 15 seconds), and grip strength (kilograms). Using mixed models, we examined the baseline 3MS as predictor of change in PPM, change in the 3MS as predictor of change in PPM, and baseline PPM as predictors of 3MS change. Results. Among 1,793 women (mean age = 70.3 years, 89% white, and mean 3MS score = 95.1), PPM were weakly correlated with 3MS--gait speed: r = .06, p = .02; chair stands: r = .09, p < .001 ; and grip strength: r =. 10, p < .001. Baseline 3MS score was associated with subsequent PPM decline after adjustment for demographics, comorbid conditions, medications, and lifestyle factors. For every SD (4.2 points) higher 3MS score, 0.04 SD (0.04 m/s) less gait speed and 0.05 SD (0.29 kg) less grip strength decline is expected over 6 years (p [less than or equal to] .01 both). Changes in 3MS and PPM were associated, particularly with chair stands and grip strength (p < .003 both). Baseline PPMs were not associated with subsequent 3MS change. Conclusions. Baseline global cognitive function and change in global cognitive function were associated with physical performance change, but baseline physical performance was not associated with cognitive change in this cohort. These analyses support the hypothesis that cognitive decline on average precedes or co-occurs with physical performance decline. Key Words: Cognitive function--Physical performance--Cognition--Physical function. doi: 10.1093/gerona/glp149

Purpose of Review: Weight loss is recommended for improving glycemic control and reducing cardiovascular risk factors in persons with diabetes. However, both diabetes and weight loss have been associated with detrimental skeletal health. This review aims to summarize recent study findings on the effects of lifestyle interventions for weight loss on skeletal health among persons with type 2 diabetes (T2D). Recent Findings: A few large-scale observational studies have demonstrated an increased fragility fracture risk associated with weight loss among persons with T2D. Randomized control trials in persons with T2D also have shown that intentional lifestyle interventions for weight loss are associated with a greater decrease in bone mineral density (BMD) and an increase in the risk of fracture. The biological mechanisms underlying the compromised bone health during lifestyle interventions for weight loss are complex and not yet conclusive. However, there is evidence to suggest that bone loss and increased fracture risk during intentional weight loss may be mitigated by some intervention approaches, such as high protein intake, calcium supplementation, and resistance and balance training. Summary: There is still a lack of studies investigating the effects of different interventions for weight loss on skeletal health among persons with T2D. However, certain types of diet and physical activity intervention combined with bone monitoring and fracture risk prediction may help achieve weight loss goals and maintain skeletal health among persons with T2D during intentional weight loss. [ABSTRACT FROM AUTHOR]

Objective: The 10-year intensive lifestyle intervention (ILI) of the Look AHEAD study left a legacy of relative deficits in cognitive function among participants who entered the clinical trial with obesity or a history of cardiovascular disease. We hypothesized that altered levels of two weight-sensitive proangiogenic cytokines, leptin and vascular endothelial growth factor (VEGF), accounted for this concerning finding.Methods: Serum leptin and VEGF concentrations were determined in 1,279 Look AHEAD participants at baseline, proximal to cessation of the interventions (Epoch 1), and an average of 4 years later (Epoch 2). Up to four standardized assessments of attention, executive function, and memory were collected during follow-up. Mixed effects models were used to assess relative differences in leptin and VEGF concentrations between intervention groups and whether these accounted for changes in cognitive composite scores.Results: ILI and diabetes support and education differences in VEGF, but not leptin, concentrations varied depending on baseline history of cardiovascular disease and obesity, but neither leptin nor VEGF concentrations accounted for the relative decrements in cognitive function in participants assigned to ILI.Conclusions: Alterations in two weight-sensitive proangiogenic cytokines did not account for the long-term adverse effects of ILI on cognitive function among adults with diabetes and either obesity or cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background Recommended systolic blood pressure targets often do not consider the relationship of low diastolic blood pressure (DBP) levels with cardiovascular disease (CVD) and all-cause mortality risk, which is especially relevant for older people with concurrent comorbidities. We examined the relationship of DBP levels to CVD and all-cause mortality in older women in the Women's Health Initiative Long Life Study (WHI-LLS). Methods The study sample included 7,875 women (mean age: 79 years) who underwent a blood pressure measurement at an in-person home visit conducted in 2012–2013. CVD and all-cause mortality were centrally adjudicated. Hazard ratios (HRs) were obtained from adjusted Cox proportional hazards models. Results After 5 years follow-up, all-cause mortality occurred in 18.4% of women. Compared with a DBP of 80 mm Hg, the fully adjusted HR for mortality was 1.33 (95% confidence interval [CI]: 1.04–1.71) for a DBP of 50 mm Hg and 1.67 (95% CI: 1.29–2.16) for a DBP of 100 mm Hg. The HRs for CVD were 1.14 (95% CI: 0.78–1.67) for a DBP of 50 mm Hg and HR 1.50 (95% CI: 1.03–2.17) for a DBP of 100 mm Hg. The nadir DBP associated with lowest mortality risk was 72 mm Hg overall. Conclusions In older women, consideration should be given to the potential adverse effects of low and high DBP. Low DBP may serve as a risk marker. DBP target levels between 68 and 75 mm Hg may avoid higher mortality risk. [ABSTRACT FROM AUTHOR]

Background/objectives: Routine use of vitamin D supplements has increased substantially in the United States. However, the safety and tolerability of long-term use of high-dose vitamin D are not known. We assessed the safety and tolerability of high-dose, daily vitamin D3 in the vitamin D and type 2 diabetes (D2d) study.Subjects/methods: In total, 2423 overweight/obese persons with prediabetes were randomized in a double-blind manner to either 4000 IU of vitamin D3 (the tolerable upper intake level for adults by the National Academy of Medicine) taken daily or matching placebo. All participants were included in this analysis. Incident adverse events (AE) were ascertained 4 times a year at in-person visits (twice a year) and interim remote encounters (twice a year) and were defined as untoward or unfavorable medical occurrences. Serious adverse events (SAE) included death, life-threatening events, and hospitalizations.Results: A total of 8304 AEs occurred during 3 years of follow-up and were less frequent in the vitamin D group compared to placebo (Incidence Rate Ratio [IRR] = 0.94; 95% Confidence Interval (CI) 0.90, 0.98). The overall frequency of protocol-specified AEs of interest, which included nephrolithiasis, hypercalcemia, hypercalciuria, or low estimated glomerular filtration rate, was low and did not differ by group. There were no significant between-group differences in total SAEs (IRR = 0.96 (0.81, 1.14)).Conclusion: Vitamin D3 supplementation at 4000 IU per day was safe and well tolerated among overweight/obese participants at high risk for diabetes who were appropriately monitored for safety. In this population, this dose of vitamin D3 did not increase risk of AEs or SAEs, including those previously associated with vitamin D such as hypercalcemia, hypercalciuria, or nephrolithiasis.Clinical Trial Registration: ClinicalTrials.gov NCT01942694, prospectively registered September 16, 2013. [ABSTRACT FROM AUTHOR]

Background: Indices of multimorbidity and deficit accumulation (ie, frailty indices) have been proposed as markers of biological aging. If true, changes in these indices over time should predict downstream changes in cognition and physical function, and mortality.Methods: We examined associations that 8-year changes in (i) a multimorbidity index comprised of 9 chronic diseases and (ii) a frailty index (FI) based on deficit accumulation in functional, behavioral, and clinical characteristics had with subsequent measures of cognitive and physical function over 10 years. We drew data from 3 842 participants in the Action for Health in Diabetes clinical trial. They were aged 45-76 years at baseline and at risk for accelerated biological aging due to overweight/obesity and type 2 diabetes mellitus.Results: A total of 1 501 (39%) of the cohort had 8-year increases of 1 among the 9 diseases tracked in the multimorbidity index and 868 (23%) had increases of ≥2. Those with greatest increases in multimorbidity tended to be older individuals, males, and non-Hispanic Whites. Greater FI increases tended to occur among individuals who were older, non-Hispanic White, heavier, and who had more baseline morbidities. Changes in multimorbidity and FI were moderately correlated (r = 0.26; p < .001). Increases in both multimorbidity and FI were associated with subsequently poorer composite cognitive function and 400-m walk speed and increased risk for death (all p < .001).Conclusions: Accelerated biological aging, as captured by multimorbidity and frailty indices, predicts subsequent reduced function and mortality. Whether intensive lifestyle interventions generally targeting multimorbidity and FI reduce risks for downstream outcomes remains to be seen. Clinical Trials Registration Number: NCT00017953. [ABSTRACT FROM AUTHOR]

The study evaluates the association between serum fetuin-A levels and incident diabetes mellitus in older persons. Evidence suggests serum fetuin-A is associated with incident diabetes in well-functioning older persons, independent of other insulin resistance markers.

Background. This study examines the association between socioeconomic status (SES) and inflammatory markers in well-functioning older adults and seeks to determine whether any association remains after adjusting for biomedical and behavioral factors typically related to elevated serum levels of inflammatory markers. Methods. Data were obtained from 3044 men and women, aged 70-79 from Pittsburgh, Pennsylvania and Memphis, Tennessee participating in the Health, Aging and Body Composition study. Three indicators of SES were used: education, income, and ownership of financial assets. Serum levels of interleukin-6, C-reactive protein, and tumor necrosis factor-[alpha] were measured. Results. Low SES was associated with significantly elevated levels of interleukin-6, C-reactive protein, and tumor necrosis factor-[alpha] compared to high SES. Behavioral factors (including smoking, drinking, obesity) explained a substantial part of the inverse association between SES and inflammatory markers. Adjustment for prevalent diseases (including heart diseases, lung disease, and diabetes) associated with inflammation explained less of the association. Conclusions. This study suggests that interventions to improve health behaviors, even in old age and especially in low SES groups, may be useful in reducing risks associated with inflammation.