More rapid bone mineral density loss in older men with diabetes: The Osteoporotic Fractures in Men (MrOS) Study.

CONTEXT: Type 2 diabetes mellitus (T2D) is associated with more rapid bone loss in women, but less evidence is available for men or those with prediabetes. OBJECTIVE: To determine whether bone loss rate is affected by diabetes status in older men, we analyzed data from the Osteoporotic Fractures in Men (MrOS) study. METHODS: The multisite MrOS study enrolled 5,994 men aged ≥65 years. Diabetes status was defined by self-report, diabetes medication use, or elevated fasting serum glucose at baseline. Hip bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DXA) at baseline and a follow-up visit after 4.6 ± 0.4 years. This analysis included 4095 men, excluding those without a follow-up DXA or with unknown diabetes status. Changes in hip BMD in participants with normoglycemia (NG), prediabetes, or T2D, excluding thiazolidinedione (TZD) users, were evaluated using generalized linear models (GLM). Diabetes medication use and BMD loss among those with T2D were also evaluated with GLM. RESULTS: In adjusted models, loss in hip BMD was greater in men with T2D (- 2.23%: 95% CI: -2.54 to -1.91; p<0.001) but not in men with prediabetes (-1.45%; 95% CI -1.63 to -1.26; p=0.33) compared to NG (-1.57%: 95% CI -1.73 to -1.41). Among men with T2D, TZD, insulin and sulfonylurea use were associated with greater hip BMD loss. CONCLUSIONS: Men with T2D, but not prediabetes, experienced an accelerated bone loss compared to participants with normoglycemia. More rapid bone loss predicts increased risk of fractures and mortality in broader populations.

The Association of Skeletal Muscle Energetics With Recurrent Falls in Older Adults Within the Study of Muscle, Mobility and Aging.

BACKGROUND: Falls in the older population are a major public health concern. While many physiological and environmental factors have been associated with fall risk, muscle mitochondrial energetics has not yet been investigated. METHODS: In this analysis, 835 Study of Muscle, Mobility and Aging (SOMMA) participants aged 70-94 were surveyed for number of falls (total), recurrent falls (2+), and fall-related injuries over the past 12 months at baseline and again after 1 year. Skeletal muscle energetics were assessed at baseline in vivo using 31P Magnetic Resonance Spectroscopy for the maximal rate of adenosine triphosphate recovery (ATPmax) after an acute bout of exercise, and ex vivo by High-Resolution Respirometry for the maximal rate of complex I and II supported oxygen consumption (MaxOXPHOS) in permeabilized muscle fibers from the vastus lateralis. RESULTS: At least 1 fall was reported in 28.7% of SOMMA participants in the first year of the study, with 12% of older adults reporting recurrent falls (2+). Individuals who experienced recurrent falls had a slower 400-m walk gait speed (1.0 ± 0.2 vs 1.1 ± 0.2, p < .001), reported fewer alcoholic drinks per week in the past year (2.4 ± 4.3 vs 2.8 ± 4.4, p = .054), and took a significantly greater number of medication in the 30 days before their baseline visit (5.6 ± 4.4 vs 4.2 ± 3.4, p < .05). A history of falls was reported in 63% of individuals who experienced recurrent falls in the first year of the study compared to 22.8% who experienced 1 or fewer falls. MaxOXPHOS was significantly lower in those who reported recurrent falls (p = .008) compared to those with 1 or fewer falls, but there was no significant difference in ATPmax (p = .369). Neither muscle energetics measure was significantly associated with total number of falls or injurious falls, but recurrent falls were significantly higher with lower MaxOXPHOS (risk ratio = 1.33, 95% confidence interval = 1.02-1.73, p = .033). However, covariates accounted for the increased risk. CONCLUSIONS: Mitochondrial energetics were largely unrelated to fall risk in older adults when accounting for variables, suggesting that the complex etiology of falls may not be related to a single "hallmark of aging" biological pathway.

The association of skeletal muscle energetics with recurrent falls in older adults within the Study of Muscle, Mobility and Aging (SOMMA).

Background: Falls in the older population are a major public health concern. While many physiological and environmental factors have been associated with fall risk, muscle mitochondrial energetics has not yet been investigated. Methods: In this analysis, 835 Study of Muscle, Mobility and Aging (SOMMA) participants aged 70-94 were surveyed for recurrent falls (2+) after one year. Skeletal muscle energetics were assessed at baseline in vivo using 31 P Magnetic Resonance Spectroscopy (MRS) (ATPmax) and ex vivo by High Resolution Respirometry (HRR) of permeabilized muscle fibers from the vastus lateralis (MaxOXPHOS). Results: SOMMA participants who reported recurrent falls (12%) had a slower 400m walk gait speed compared to those with 0-1 falls (1.0 +/-0.2 vs. 1.1 +/-0.2, p<.001) and took a greater number of medication in the 30 days before their baseline visit (5.6 +/-4.4 vs. 4.2 +/-3.4, p<0.05). MaxOXPHOS was significantly lower in those who reported recurrent falls (p=0.008) compared to those with one or fewer falls, but there was no significant difference in ATPmax (p=0.369). Neither muscle energetics measure was significantly associated with total number of falls or injurious falls, but recurrent falls were significantly higher with lower MaxOXPHOS (RR=1.33, 95% CI= 1.02-1.73, p=0.033). However, covariates accounted for the increased risk. Conclusions: Ex vivo maximal muscle mitochondrial energetics were lower in older adults who experienced recurrent falls, but covariates accounted for its association with recurrent fall risk, suggesting this "hallmark of aging" may not be directly implicated in the complex etiology of falls.

Validation of the Pittsburgh Performance Fatigability Index in the Study of Muscle, Mobility and Aging.

BACKGROUND: The Pittsburgh Performance Fatigability Index (PPFI) quantifies the percent decline in cadence using accelerometry during standardized walking tasks. Although PPFI has shown strong correlations with physical performance, the developmental sample was relatively homogenous and small, necessitating further validation. METHODS: Participants from the Study of Muscle, Mobility and Aging (N = 805, age = 76.4 ±â€…5.0 years, 58% women, 85% White) wore an ActiGraph GT9X on the nondominant wrist during usual-paced 400 m walk. Tri-axial accelerations were analyzed to compute PPFI (higher score = greater fatigability). To evaluate construct and discriminant validity, Spearman correlations (rs) between PPFI and gait speed, Short Physical Performance Battery (SPPB), chair stand speed, leg peak power, VO2peak, perceived fatigability, and mood were examined. Sex-specific PPFI cut-points that optimally discriminated gait speed using classification and regression tree were then generated. Their discriminate power in relation to aforementioned physical performance were further evaluated. RESULTS: Median PPFI score was 1.4% (25th-75th percentile range: 0%-21.7%), higher among women than men (p < .001). PPFI score was moderate-to-strongly correlated with gait speed (rs = -0.75), SPPB score (rs = -0.38), chair stand speed (rs = -0.36), leg peak power (rs = -0.34) and VO2peak (rs = -0.40), and less strongly with perceived fatigability (rs = 0.28-0.29), all p < .001. PPFI score was not correlated with mood (|rs| < 0.08). Sex-specific PPFI cut-points (no performance fatigability: PPFI = 0%; mild performance fatigability: 0% < PPFI < 3.5% [women], 0% < PPFI < 5.4% [men]; moderate-to-severe performance fatigability: PPFI ≥ 3.5% [women], PPFI ≥ 5.4% [men]) discriminated physical performance (all p < .001), adjusted for demographics and smoking status. CONCLUSION: Our work underscores the utility of PPFI as a valid measure to quantify performance fatigability in future longitudinal epidemiologic studies and clinical/pharmaceutical trials.

Role of Perceived Physical and Mental Fatigability Severity on Prospective, Recurrent, and Injurious Fall Risk in Older Men.

BACKGROUND: Falls occur annually in 25% of adults aged ≥65 years. Fall-related injuries are increasing, highlighting the need to identify modifiable risk factors. METHODS: Role of fatigability on prospective, recurrent, and injurious fall risk was examined in 1 740 men aged 77-101 years in the Osteoporotic Fractures in Men Study. The 10-item Pittsburgh Fatigability Scale measured perceived physical and mental fatigability (0-50/subscale) at Year 14 (2014-16); established cut-points identified men with more severe perceived physical (≥15, 55.7%), more severe mental (≥13, 23.7%) fatigability, or having both (22.8%). Prospective, recurrent (≥2), and injurious falls were captured by triannual questionnaires ≥1 year after fatigability assessment; risk of any fall was estimated with Poisson generalized estimating equations, and likelihood of recurrent/injurious falls with logistic regression. Models adjusted for age, health conditions, and other confounders. RESULTS: Men with more severe physical fatigability had a 20% (p = .03) increased fall risk compared with men with less physical fatigability, with increased odds of recurrent and injurious falls, 37% (p = .04) and 35% (p = .035), respectively. Men with both more severe physical and mental fatigability had a 24% increased risk of a prospective fall (p = .026), and 44% (p = .045) increased odds of recurrent falling compared with men with less severe physical and mental fatigability. Mental fatigability alone was not associated with fall risk. Additional adjustment for previous fall history attenuated associations. CONCLUSIONS: More severe fatigability may be an early indicator to identify men at high risk for falls. Our findings warrant replication in women, as they have higher rates of fatigability and prospective falls.

The Study of Muscle, Mobility and Aging (SOMMA): A Unique Cohort Study About the Cellular Biology of Aging and Age-related Loss of Mobility.

BACKGROUND: The Study of Muscle, Mobility and Aging (SOMMA) aims to understand the biological basis of many facets of human aging, with a focus on mobility decline, by creating a unique platform of data, tissues, and images. METHODS: The multidisciplinary SOMMA team includes 2 clinical centers (University of Pittsburgh and Wake Forest University), a biorepository (Translational Research Institute at Advent Health), and the San Francisco Coordinating Center (California Pacific Medical Center Research Institute). Enrollees were age ≥70 years, able to walk ≥0.6 m/s (4 m); able to complete 400 m walk, free of life-threatening disease, and had no contraindications to magnetic resonance or tissue collection. Participants are followed with 6-month phone contacts and annual in-person exams. At baseline, SOMMA collected biospecimens (muscle and adipose tissue, blood, urine, fecal samples); a variety of questionnaires; physical and cognitive assessments; whole-body imaging (magnetic resonance and computed tomography); accelerometry; and cardiopulmonary exercise testing. Primary outcomes include change in walking speed, change in fitness, and objective mobility disability (able to walk 400 m in 15 minutes and change in 400 m speed). Incident events, including hospitalizations, cancer diagnoses, fractures, and mortality are collected and centrally adjudicated by study physicians. RESULTS: SOMMA exceeded its goals by enrolling 879 participants, despite being slowed by the COVID-19 pandemic: 59.2% women; mean age 76.3 ± 5.0 years (range 70-94); mean walking speed 1.04 ± 0.20 m/s; 15.8% identify as other than Non-Hispanic White. Over 97% had data for key measurements. CONCLUSIONS: SOMMA will provide the foundation for discoveries in the biology of human aging and mobility.

The Association of Metabolic Syndrome and Obesity With Clinical Hip Osteoarthritis in the Study of Osteoporotic Fractures and the Osteoporotic Fractures in Men Study Cohorts.

OBJECTIVE: Metabolic dysregulation frequently co-occurs with obesity, which has been shown to be a risk factor for lower extremity osteoarthritis (OA). We evaluated the association between metabolic syndrome (MetS), alone and in combination with obesity, and hip OA. METHODS: In two parallel cross-sectional analyses, we studied 403 women from the Study of Osteoporotic Fractures (SOF) and 2354 men from the Osteoporotic Fractures in Men (MrOS) study. We used multivariable logistic regression to evaluate associations of obesity (body mass index ≥30 kg/m2 ) and/or MetS (three of five National Cholesterol Education Program Adult Treatment Panel III criteria) with clinical hip OA, defined as a modified Croft score of 2 or more or total hip replacement, and pain or limited range of motion. Our analysis adjusted for demographics. RESULTS: Approximately 3.5% of SOF women and 5.4% of MrOS men had clinical hip OA. Among women, obesity was not associated with hip OA, yet those with MetS had a 365% higher odds of hip OA (95% CI: 1.37-15.83). Among men, those who had obesity had a 115% higher odds of hip OA (95% CI: 1.39-3.32), yet MetS was not associated with hip OA. There was no interaction between MetS, obesity, and hip OA in either women or men. CONCLUSION: In women, but not in men, MetS was associated with hip OA. In men, but not in women, obesity was associated with hip OA. These findings suggest that mechanical effects of obesity may predominate in the pathogenesis of hip OA in men, whereas metabolic effects predominate in women.

Pre- and Early Peri-menopausal Physical Function and Risk of Cardiovascular Events: The Study of Women's Health Across the Nation.

OBJECTIVES: To determine whether physical function (PF) before menopause is related to cardiovascular disease (CVD) risk. METHODS: Participants were N = 2950 pre-/early peri-menopausal women (median age 46, (25th-75th percentile: 43-48 years). Physical function was assessed at baseline using the Physical Function subscale of the SF-36 and scores were trichotomized (no, some, or substantial limitations). Clinical CVD events were ascertained at annual/biennial clinical assessments through the 15th follow-up visit. Risk of CVD was determined with Cox proportional hazards models. Results: Women were followed for a median of 19.1 years, during which 220 women had a CVD event. In fully adjusted models, women with substantial limitations at baseline had higher CVD risk compared to women with no limitations (hazards ratio [HR] = 1.55, 95% confidence interval [CI]: 1.12-2.33). Discussion: Substantial PF limitations in pre- and early peri-menopausal women are associated with higher risk of clinical CVD events, consistent with literature in older adults.

Lower Leg Power and Grip Strength Are Associated With Increased Fall Injury Risk in Older Men: The Osteoporotic Fractures in Men Study.

BACKGROUND: Past research has not investigated both lower-extremity power and upper-extremity strength in the same fall injury study, particularly nonfracture fall injuries. METHODS: In the Osteoporotic Fractures in Men Study (baseline: N = 5 994; age 73.7 ± 5.9 years; 10.2% non-White), fall injuries (yes/no) were assessed prospectively with questionnaires approximately every 3 years over 9 years. Maximum leg power (Watts) from Nottingham single leg press and maximum grip strength (kg) from handheld dynamometry were assessed at baseline and standardized to kg body weight. Physical performance included gait speed (6-m usual; narrow walk) and chair stands speed. RESULTS: Of men with ≥1/4 follow-ups (N = 5 178; age 73.4 ± 5.7 years), 40.4% (N = 2 090) had ≥1 fall injury. In fully adjusted repeated-measures logistic regressions, lower power/kg and grip strength/kg had higher fall injury risk (trend across quartiles: both p < .0001), with lower quartiles at significantly increased risk versus highest Q4 except for grip strength Q3 versus Q4. Fall injury risk was 19% higher per 1 standard deviation (SD) lower power/kg (95% confidence interval [CI]: 1.12-1.26) and 16% higher per SD lower grip strength/kg (95% CI: 1.10-1.23). In models including both leg power/kg and grip strength/kg, odds ratios (ORs) were similar and independent of each other and physical performance (leg power/kg OR per SD = 1.13, 95% CI: 1.06-1.20; grip strength/kg OR per SD = 1.11, 95% CI: 1.05-1.17). CONCLUSIONS: Lower leg power/kg and grip strength/kg predicted future fall injury risk in older men independent of physical performance. Leg power potentially identifies fall injury risk better than grip strength at higher muscle function, though grip strength may be more suitable in clinical/practice settings.

The Association Between Severity of Radiographic Knee OA and Recurrent Falls in Middle and Older Aged Adults: The Osteoarthritis Initiative.

BACKGROUND: Knee osteoarthritis (KOA) is the most prevalent type of OA and a leading cause of disability in the United States. Falls are a major public health concern in older adults. Our aim was to examine how the severity of radiographic KOA affects recurrent falls in a cohort of middle-aged and older individuals enrolled in the Osteoarthritis Initiative. METHODS: About 3 972 participants, mean age of 63 years, 58% female were included. Participants were divided into 5 mutually exclusive groups based on their worst Kellgren-Lawrence grade of radiographic KOA from annual x-rays from baseline to 36 months. Generalized estimating equations for repeated logistic regression were used to model the association between KOA severity and the likelihood of recurrent falls (≥2 falls/year) over 5 years of follow-up (>36 to 96 months). RESULTS: Older adults (≥age 65) with KOA were at higher odds of recurrent falls in comparison to individuals without KOA in multivariate models (possible OA odds ratio [OR] = 2.22, 95% CI = 1.09-4.52; mild OA OR = 2.48, 95% CI = 1.34-4.62; unilateral moderate-severe OA OR = 2.84, 95% CI = 1.47-5.50; bilateral moderate-severe OA OR = 2.52, 95% CI = 1.13-5.62). Middle-aged adults (aged 45-64) with KOA did not have increased odds of recurrent falls in comparison to those without KOA except for possible KOA (OR = 1.86, 95% CI = 1.01-2.78; KOA severity × Age interaction = 0.025). CONCLUSION: Older adults with radiographic evidence of KOA have an increased likelihood of experiencing recurrent falls in comparison to those without KOA independent of established risk factors. Our results suggest that fall prevention efforts should include older adults with all stages of KOA.

Associations of Lower Extremity Peripheral Nerve Impairment and Risk of Dementia in Black and White Older Adults.

BACKGROUND AND OBJECTIVES: Peripheral nerve impairments and dementia are common among older adults and share risk factors. However, few studies have examined whether peripheral nerve function and dementia are associated. We evaluated whether lower extremity peripheral nerve impairments were associated with higher incidence of dementia and whether associations differed by comorbidity subgroups (diabetes, low vitamin B12, and APOE ε4 allele carriers). METHODS: We studied Black and White Health, Aging, and Body Composition Study participants 70 to 79 years of age and without dementia at enrollment. Lower extremity sensory and motor peripheral nerve function was measured at year 4 (the analytic baseline of this study). Sensory nerve impairments were measured with monofilament (1.4 g, 10 g) and vibration threshold of the toe. Monofilament insensitivity was defined as unable to detect monofilament (3 of 4 touches), and vibration detection impairment was defined as >130 µm. Fibular motor impairments were defined as <1 mV compound motor action potential (CMAP) amplitude and slow nerve conduction velocity <40 m/s. Incident dementia over the following 11 years was determined from medical records, cognitive scores, and medications. Cox proportional hazard models adjusted for demographics and health conditions assessed associations of nerve impairments with incident dementia. RESULTS: Among 2,174 participants (52% women, 35% Black), 45% could not detect monofilament 1.4 g, 9% could not detect monofilament 10 g, 6% could not feel vibration, 10% had low CMAP amplitude, and 24% had slow conduction velocity. Monofilament 10 g (hazard ratio [HR] 1.35, 95% CI 0.99-1.84) and vibration detection insensitivity (HR 1.73, 95% CI 1.24-2.40) were associated/borderline associated with a higher risk of dementia after covariate adjustment. Estimates were elevated but not significant for monofilament 1.4 g, CMAP amplitude, and conduction velocity (p > 0.05). Increasing number of peripheral nerve impairments was associated with higher risk of dementia in a graded fashion; for ≥3 impairments, the HR was 2.37 (95% CI 1.29-4.38). In subgroup analyses, effect estimates were generally higher among those with diabetes, low vitamin B12, and APOE ε4 allele except for vibration detection. DISCUSSION: Peripheral nerve impairments, especially sensory, were associated with a higher risk of dementia even after adjustment for age and other health factors. These associations may represent a shared susceptibility to nervous system degeneration.

No Evidence of Association Between Undercarboxylated Osteocalcin and Incident Type 2 Diabetes.

Mouse models suggest that undercarboxylated osteocalcin (ucOC), produced by the skeleton, protects against type 2 diabetes development, whereas human studies have been inconclusive. We aimed to determine if ucOC or total OC is associated with incident type 2 diabetes or changes in fasting glucose, insulin resistance (HOMA-IR), or beta-cell function (HOMA-Beta). A subcohort (n = 338; 50% women; 36% black) was identified from participants without diabetes at baseline in the Health, Aging, and Body Composition Study. Cases of incident type 2 diabetes (n = 137) were defined as self-report at an annual follow-up visit, use of diabetes medication, or elevated fasting glucose during 8 years of follow-up. ucOC and total OC were measured in baseline serum. Using a case-cohort design, the association between biomarkers and incident type 2 diabetes was assessed using robust weighted Cox regression. In the subcohort, linear regression models analyzed the associations between biomarkers and changes in fasting glucose, HOMA-IR, and HOMA-Beta over 9 years. Higher levels of ucOC were not statistically associated with increased risk of incident type 2 diabetes (adjusted hazard ratio = 1.06 [95% confidence interval, 0.84-1.34] per 1 standard deviation [SD] increase in ucOC). Results for %ucOC and total OC were similar. Adjusted associations of ucOC, %ucOC, and total OC with changes in fasting glucose, HOMA-IR, and HOMA-Beta were modest and not statistically significant. We did not find evidence of an association of baseline undercarboxylated or total osteocalcin with risk of incident type 2 diabetes or with changes in glucose metabolism in older adults. © 2022 American Society for Bone and Mineral Research (ASBMR).

Factors Associated With 10-Year Declines in Physical Health and Function Among Women During Midlife.

Importance: Women in midlife often develop chronic conditions and experience declines in physical health and function. Identifying factors associated with declines in physical health and function among these women may allow for targeted interventions. Objective: To examine the factors associated with clinically important 10-year declines in the physical component summary score (PCS) of the Short Form 36 (SF-36), a widely used patient-reported outcome measure, in women in midlife. Design, Setting, and Participants: This longitudinal cohort study collected data from geographically dispersed sites in the US. Participants were part of the Study of Women's Health Across the Nation (SWAN), a racially and ethnically diverse cohort of women enrolled at or immediately before the menopause transition. Women have been followed for up to 21 years, between 1996 and 2016, with annual visits. Data were analyzed from October 2020 to March 2021. Exposures: Demographic indicators, health status measures, and laboratory and imaging assessments. Main Outcomes and Measures: The main outcome was a clinically important decline (≥8 points) on the PCS, based on the 10-year difference in scores between ages 55 and 65 years. Results: From the SWAN cohort of 3302 women, 1091 women (median [IQR] age, 54.8 [54.3-55.4] years; 264 [24.2%] Black women; 126 [11.6%] Chinese women; 135 [12.4%] Japanese women; 566 [51.9%] White women) were eligible for analyses based on duration of follow-up and availability of SF-36 data. At age 55, women had a median (IQR) body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 27.0 (23.2-32.6), a median (IQR) baseline PCS of 53.1 (46.8-56.7), 108 women (9.9%) were current smokers, and 938 women (86.3%) had at least 1 comorbidity. Between ages 55 and 65 years, the median (IQR) change in PCS was -1.02 (-6.11 to 2.53) points with 206 women (18.9%) experiencing declines of 8 points or more. In multivariable models, factors associated with clinically important decline included higher baseline PCS (odds ratio [OR], 1.08; 95% CI, 1.06-1.11), greater BMI (OR, 1.06; 95% CI, 1.03-1.09), less educational attainment (OR, 1.87; 95% CI, 1.32-2.65), current smoking (OR, 1.93; 95% CI, 1.14-3.26), osteoarthritis (OR, 1.46; 95% CI, 1.01-2.09), clinically significant depressive symptoms (OR, 2.03; 95% CI, 1.34-3.09), and cardiovascular disease (OR, 2.06; 95% CI, 1.26-3.36). Conclusions and Relevance: In this cohort study, clinically important declines in women's physical health and function were relatively common between ages 55 and 65 years. Several variables associated with these declines were identified as potentially useful components in a clinical score identifying women at increased risk of physical health and functional declines.

Metabolic Syndrome Trajectories and Objective Physical Performance in Mid-to-Early Late Life: The Study of Women's Health Across the Nation (SWAN).

BACKGROUND: Little is known about how adverse, midlife metabolic profiles affect future physical functioning. We hypothesized that a higher number of midlife metabolic syndrome (MetS) components are associated with poorer physical performance in early old age for multiethnic women. METHODS: MetS status from 1996 to 2011 (8 visits) and objective physical performance in 2015/2016 (Short Physical Performance Battery [SPPB; 0-12], 40-foot walk [meter/second], 4-meter gait speed [meter/second], chair stands [seconds], stair climb [seconds]) were assessed in the Study of Women's Health Across the Nation (SWAN; n = 1722; age 65.4 ± 2.7 years; 26.9% African American, 10.1% Chinese, 9.8% Japanese, 5.5% Hispanic). Poisson latent class growth modeling identified MetS component trajectory groups: none (23.9%), 1 = low-MetS (28.7%), 2 = mid-MetS (30.9%), and ≥3 = high-MetS (16.5%). Adjusted linear regression related MetS groups to physical performance outcomes. RESULTS: High-MetS versus none had higher body mass index, pain, financial strain, and lower physical activity and self-reported health (p < .0001). Compared with White, African American and Hispanic women were more likely to be in the high-MetS groups and had worse physical functioning along with Chinese women (SPPB, chair stand, stair climb, and gait speed-not Hispanic). After adjustments, high-MetS versus none demonstrated significantly worse 40-ft walk (ß: -0.08; 95% CI: -0.13, -0.03), gait speed (ß: -0.09; 95% CI: -0.15, -0.02), SPPB (ß: -0.79; 95% CI: -1.15, -0.44), and chair stands (ß: 0.69; 95% CI: 0.09, 1.28), but no difference in stair climb. CONCLUSIONS: Midlife MetS groups were related to poor physical performance in early old age multiethnic women. Midlife management of metabolic function may improve physical performance later in life.

Persistent polypharmacy and fall injury risk: the Health, Aging and Body Composition Study.

BACKGROUND: Older adults receive treatment for fall injuries in both inpatient and outpatient settings. The effect of persistent polypharmacy (i.e. using multiple medications over a long period) on fall injuries is understudied, particularly for outpatient injuries. We examined the association between persistent polypharmacy and treated fall injury risk from inpatient and outpatient settings in community-dwelling older adults. METHODS: The Health, Aging and Body Composition Study included 1764 community-dwelling adults (age 73.6 ± 2.9 years; 52% women; 38% black) with Medicare Fee-For-Service (FFS) claims at or within 6 months after 1998/99 clinic visit. Incident fall injuries (N = 545 in 4.6 ± 2.9 years) were defined as the initial claim with an ICD-9 fall E-code and non-fracture injury, or fracture code with/without a fall code from 1998/99 clinic visit to 12/31/08. Those without fall injury (N = 1219) were followed for 8.1 ± 2.6 years. Stepwise Cox models of fall injury risk with a time-varying variable for persistent polypharmacy (defined as ≥6 prescription medications at the two most recent consecutive clinic visits) were adjusted for demographics, lifestyle characteristics, chronic conditions, and functional ability. Sensitivity analyses explored if persistent polypharmacy both with and without fall risk increasing drugs (FRID) use were similarly associated with fall injury risk. RESULTS: Among 1764 participants, 636 (36%) had persistent polypharmacy over the follow-up period, and 1128 (64%) did not. Fall injury incidence was 38 per 1000 person-years. Persistent polypharmacy increased fall injury risk (hazard ratio [HR]: 1.31 [1.06, 1.63]) after adjusting for covariates. Persistent polypharmacy with FRID use was associated with a 48% increase in fall injury risk (95%CI: 1.10, 2.00) vs. those who had non-persistent polypharmacy without FRID use. Risks for persistent polypharmacy without FRID use (HR: 1.22 [0.93, 1.60]) and non-persistent polypharmacy with FRID use (HR: 1.08 [0.77, 1.51]) did not significantly increase compared to non-persistent polypharmacy without FRID use. CONCLUSIONS: Persistent polypharmacy, particularly combined with FRID use, was associated with increased risk for treated fall injuries from inpatient and outpatient settings. Clinicians may need to consider medication management for FRID and other fall prevention strategies in community-dwelling older adults with persistent polypharmacy to reduce fall injury risk.

Urine creatinine concentration and clinical outcomes in older adults: The Cardiovascular Health Study.

PURPOSE: Loss of muscle mass and strength are associated with long-term adverse health outcomes in older adults. Urine creatinine concentrations (Ucr; mg/dl) are a measure of muscle tissue mass and turnover. This study assessed the associations of a spot Ucr level with muscle mass and with risk of hospitalization, mortality, and diabetes mellitus in older adults. METHODS: We examined 3424 participants from the Cardiovascular Health Study who provided spot urine samples in 1996-1997 and who were followed through June 2015. All participants underwent baseline measurement of grip strength. In a sub-cohort, 1331 participants underwent dual energy X-ray absorptiometry (DEXA) scans, from which lean muscle mass was derived. Participants were followed for a median of 10 years for hospitalizations and mortality, and 9 years for diabetes mellitus. RESULTS: In linear regression analysis, a one standard deviation higher Ucr concentration (64.6 mg/dl) was associated with greater grip strength (kg force) ß = 0.44 [0.16, 0.72]; p = 0.002) and higher lean muscle mass (kg) (ß = 0.43 [0.08, 0.78]; p = 0.02). In Cox regression analyses, each standard deviation greater Ucr concentration was associated with lower rates of hospitalizations (0.94 [95% confidence interval, 0.90, 0.98]; p < 0.001) and lower mortality risk (0.92 [0.88, 0.97]; p < 0.001), while a one standard deviation increase in muscle mass derived from DEXA had no such significant association. Ucr levels were not associated with incident diabetes mellitus risk (0.97 [0.85, 1.11]; p = 0.65). CONCLUSION: A higher spot Ucr concentration was favorably associated with muscle mass and strength and with health outcomes in older community-living adults. The ease of obtaining a spot Ucr makes it an attractive analyte to use for gauging the health of older adults.

Associations of Body Mass Index and Waist Circumference in Young Adulthood with Later Life Incident Diabetes.

CONTEXT: The independent contribution of young adult exposure to overweight and obesity to later-life incident diabetes is not well studied. OBJECTIVE: To assess the associations of exposures to elevated body mass index (BMI) and waist circumference (WC) in young adulthood (ages 18-39 years) with incident diabetes later in life (≥40 years). DESIGN: Pooled data from 6 US prospective cohorts (Atherosclerosis Risk in Communities Study, Cardiovascular Risk Development in Young Adults Study, Cardiovascular Health Study, (4) Framingham Heart Study Offspring Cohort, (5) Health, Aging and Body Composition Study, and (6) Multi-Ethnic Study of Atherosclerosis. SETTING: Population-based cohort studies. PARTICIPANTS: 30 780 participants (56.1% female, 69.8% non-Hispanic white) without a diagnosis of diabetes by age 40. INTERVENTIONS: We imputed BMI and WC trajectories from age 18 for every participant and estimated time-weighted average exposures to BMI or WC during young adulthood and later life. MAIN OUTCOME MEASURE(S): Incident diabetes defined as fasting glucose ≥126 mg/dL, nonfasting glucose ≥200 mg/dL, or use of diabetes medications. RESULTS: During a 9-year median follow-up, 4323 participants developed incident diabetes. Young adult BMI and WC were associated with later-life incident diabetes after controlling for later-life exposures [hazard ratios (HR) 1.99 for BMI ≥ 30 kg/m2 and 2.13 for WC > 88cm (women)/>102cm (men) compared to normal ranges]. Young adult homeostatic model of insulin resistance mediated 49% and 44% of the association between BMI and WC with later-life incident diabetes. High-density lipoproteins and triglycerides mediated a smaller proportion of these associations. CONCLUSIONS: Elevated BMI and WC during young adulthood were independently associated with later-life incident diabetes. Insulin resistance may be a key mediator.

Impact of Maintenance Session Attendance and Early Weight Loss Goal Achievement on Weight Loss Success in a Community-Based Diabetes Prevention Program Intervention.

PURPOSE: The purpose of this study was to examine how maintenance session attendance and 6-month weight loss (WL) goal achievement impacted 12-month 5% WL success in older adults participating in a community-based Diabetes Prevention Program (DPP) lifestyle intervention. METHODS: Data were combined from 2 community trials that delivered the 12-month DPP-based Group Lifestyle Balance (GLB) to overweight/obese adults (mean age = 62 years, 76% women) with prediabetes and/or metabolic syndrome. Included participants (n = 238) attended ≥4 core sessions (months 0-6) and had complete data on maintenance attendance (≥4 of 6 sessions during months 7-12) and 6- and 12-month WL (5% WL goal, yes/no). Multivariate logistic regression was used to estimate the odds of 12-month 5% WL associated with maintenance attendance and 6-month WL. Associations between age (Medicare-eligible ≥65 vs <65 years) and WL and attendance were examined. RESULTS: Both attending ≥4 maintenance sessions and meeting the 6-month 5% WL goal increased the odds of meeting the 12-month 5% WL goal. For those not meeting the 6-month WL goal, maintenance session attendance did not improve odds of 12-month WL success. Medicare-eligible adults ≥65 years were more likely to meet the 12-month WL goal (odds ratio = 3.03, 95% CI, 1.58-5.81) versus <65 years. CONCLUSIONS: The results of this study provide important information regarding participant attendance and WL for providers offering DPP-based lifestyle intervention programs across the country who are seeking Medicare reimbursement. Understanding Medicare reimbursement-defined success will allow these providers to focus on and develop strategies to enhance program effectiveness and sustainability.