Effects of Longitudinal Glucose Exposure on Cognitive and Physical Function: Results from the Action for Health in Diabetes Movement and Memory Study.

OBJECTIVES: To test whether average long-term glucose exposure is associated with cognitive and physical function in middle-aged and younger-old adults with type 2 diabetes mellitus. DESIGN: Prospective cohort study. SETTING: Data obtained as part of the Action for Health in Diabetes (Look AHEAD) trial (NCT00017953) and Look AHEAD Movement and Memory ancillary study (NCT01410097). PARTICIPANTS: Overweight and obese individuals with type 2 diabetes mellitus aged 45 to 76 at baseline (N = 879). MEASUREMENTS: Glycosylated hemoglobin (HbA1c) was measured at regular intervals over 7 years, and objective measures of cognitive function (Trail-Making Test, Modified Stroop Color-Word Test, Digit Symbol-Coding, Rey Auditory Verbal Learning Test, Modified Mini-Mental State Examination) and physical function (Short Physical Performance Battery, expanded Physical Performance Battery, 400-m and 20-m gait speed) and strength (grip and knee extensor strength) were assessed at the Year 8 or 9 follow-up examination. RESULTS: Average HbA1c exposure was 7.0 ± 1.1% (53 ± 11.6 mmol/mol), with 57% of participants classified as having HbA1c levels of less than 7% (<53 mmol/mol), 27% having levels of 7% to 8% (53-64 mmol/mol), and 16% having levels of greater than 8% (>64 mmol/mol). After adjustment for age, sex, race, education, smoking status, alcohol intake, knee pain, physical fitness, body mass index, diabetes mellitus medication and statin use, ancillary year visit, and study arm and site, higher HbA1c was associated with worse physical but not cognitive function. Further adjustment for prevalent diabetes mellitus-related comorbidities made all associations nonsignificant. Results did not differ when stratified according to participant baseline age (<60 vs ≥ 60). CONCLUSION: Results presented here suggest that, in the absence of diabetes mellitus-related complications, longitudinal glucose exposure is not associated with future cognitive and physical function. Optimal management of diabetes mellitus-related comorbidities may prevent or reduce the burden of disability associated with type 2 diabetes mellitus.

Risk of early mortality after placement of a temporary-permanent pacemaker.

BACKGROUND: Temporary-permanent pacemakers [TPPM] are externally placed permanent generators attached to active fixation transvenous leads. TPPM can be used as an alternative to standard temporary pacing leads when placement of a permanent pacemaker is contraindicated. We sought to determine the incidence and risk factors for early (within 6months) mortality after placement of a TPPM. METHODS: Electronic medical records were used to extract baseline characteristics for 152 patients from Wake Forest Baptist Medical Center who had a TPPM placed between the years 2007 and 2012. Multivariable adjusted Cox proportional hazard models were used to estimate hazard ratios [HR] and 95% confidence intervals [C]) for baseline characteristics [age, sex, race, hypertension, diabetes, heart failure, coronary artery disease, smoking, dyslipidemia, chronic kidney disease [CKD], and indication for pacemaker] on early mortality. RESULTS: Of the 152 patients [mean age 68.9years; 57.2% female; 86.8% white], 45 [29.6%] died within the first 6months after TPPM placement. No deaths occurred as a direct result of TPPM placement, and only 1 patient experienced documented non-fatal complications. Maximum time to PPM from the date of insertion of TPPM was 336days. Using a backward multivariable adjusted hazard regression model, independent risk factors for early mortality were pre-existing CKD [HR (95% CI): 2.240 (1.002-5.010) for eGFR 30-59 and 7.645 (3.594-16.263) for eGFR <30 compared to eGFR >60] and history of smoking [HR (95% CI): 2.015 (1.099-3.696)]. Surprisingly, dyslipidemia was protective of early mortality [HR (95%CI): 0.470 (0.240-0.924)]. CONCLUSION: TPPM placement is a safe procedure with rare direct complications. CKD and smoking are predictive of increased risk for early mortality in patients undergoing TPPM placement.

Impact of intensive lifestyle intervention on preference-based quality of life in type 2 diabetes: Results from the Look AHEAD trial.

OBJECTIVE: To assess the effect of an intensive lifestyle intervention (ILI) compared with standard diabetes support and education (DSE) on preference-based health-related quality of life (HRQOL) in persons with overweight or obesity and type 2 diabetes. METHODS: Look AHEAD was a multisite, randomized trial of 5,145 participants assigned to ILI or DSE. Four instruments were administered during the trial: Feeling Thermometer (FT), Health Utilities Index Mark 2 (HUI2), Health Utilities Index Mark 3 (HUI3), and Short Form 6D (SF-6D). Linear mixed effect models were used to estimate the mean difference in preference scores by treatment group for 9 years. RESULTS: The ILI had higher mean FT (0.019, 95% CI, 0.015-0.024, P < 0.001) and SF-6D (0.011, 95% CI, 0.006-0.014, P < 0.001) scores than the DSE. No significant group differences were observed for the HUI2 (0.004, 95% CI, -0.003 to 0.010, P = 0.23) and HUI3 (0.004, -0.004 to 0.012, P = 0.36). In year 1, the ILI had higher mean preference scores for all instruments. Thereafter, the increases remained significant only for FT and SF-6D, and the effects also become smaller. CONCLUSIONS: ILI aimed at reducing body weight among persons with overweight or obesity and type 2 diabetes improves preference-based HRQOL in the short term, but its long-term effect is unclear.

Analysis and Interpretation of Accelerometry Data in Older Adults: The LIFE Study.

BACKGROUND: Accelerometry has become the gold standard for evaluating physical activity in the health sciences. An important feature of using this technology is the cutpoint for determining moderate to vigorous physical activity (MVPA) because this is a key component of exercise prescription. This article focused on evaluating what cutpoint is appropriate for use with older adults 70-89 years who are physically compromised. METHODS: The analyses are based on data collected from the Lifestyle Interventions and Independence for Elders (LIFE) study. Accelerometry data were collected during a 40-minute, overground, walking exercise session in a subset of participants at four sites; we also used 1-week baseline and 6-month accelerometry data collected in the main trial. RESULTS: There was extreme variability in median counts per minute (CPM) achieved during a controlled bout of exercise (n = 140; median = 1,220 CPM (25th, 75th percentile = 715, 1,930 CPM). An equation combining age, age(2), and 400 m gait speed explained 61% of the variance in CPM achieved during this session. When applied to the LIFE accelerometry data (n = 1,448), the use of an individually tailored cutpoint based on this equation resulted in markedly different patterns of MVPA as compared with using standard fixed cutpoints. CONCLUSIONS: The findings of this study have important implications for the use and interpretations of accelerometry data and in the design/delivery of physical activity interventions with older adults.

Correction: Light intensity physical activity and sedentary behavior in relation to body mass index and grip strength in older adults: cross-sectional findings from the Lifestyle Interventions and Independence for Elders (LIFE) study.

[This corrects the article DOI: 10.1371/journal.pone.0116058.].

Light Intensity physical activity and sedentary behavior in relation to body mass index and grip strength in older adults: cross-sectional findings from the Lifestyle Interventions and Independence for Elders (LIFE) study.

BACKGROUND: Identifying modifiable determinants of fat mass and muscle strength in older adults is important given their impact on physical functioning and health. Light intensity physical activity and sedentary behavior are potential determinants, but their relations to these outcomes are poorly understood. We evaluated associations of light intensity physical activity and sedentary time-assessed both objectively and by self-report-with body mass index (BMI) and grip strength in a large sample of older adults. METHODS: We used cross-sectional baseline data from 1130 participants of the Lifestyle Interventions and Independence for Elders (LIFE) study, a community-dwelling sample of relatively sedentary older adults (70-89 years) at heightened risk of mobility disability. Time spent sedentary and in light intensity activity were assessed using an accelerometer worn for 3-7 days (Actigraph GT3X) and by self-report. Associations between these exposures and measured BMI and grip strength were evaluated using linear regression. RESULTS: Greater time spent in light intensity activity and lower sedentary times were both associated with lower BMI. This was evident using objective measures of lower-light intensity, and both objective and self-reported measures of higher-light intensity activity. Time spent watching television was positively associated with BMI, while reading and computer use were not. Greater time spent in higher but not lower intensities of light activity (assessed objectively) was associated with greater grip strength in men but not women, while neither objectively assessed nor self-reported sedentary time was associated with grip strength. CONCLUSIONS: In this cross-sectional study, greater time spent in light intensity activity and lower sedentary times were associated with lower BMI. These results are consistent with the hypothesis that replacing sedentary activities with light intensity activities could lead to lower BMI levels and obesity prevalence among the population of older adults. However, longitudinal and experimental studies are needed to strengthen causal inferences.

Association of objectively measured physical activity with cardiovascular risk in mobility-limited older adults.

BACKGROUND: Data are sparse regarding the impacts of habitual physical activity (PA) and sedentary behavior on cardiovascular (CV) risk in older adults with mobility limitations. METHODS AND RESULTS: This study examined the baseline, cross-sectional association between CV risk and objectively measured PA among participants in the Lifestyle Interventions and Independence for Elders (LIFE) study. The relationship between accelerometry measures and predicted 10-year Hard Coronary Heart Disease (HCHD) risk was modeled by using linear regression, stratified according to CVD history. Participants (n=1170, 79±5 years) spent 642±111 min/day in sedentary behavior (ie, <100 accelerometry counts/min). They also spent 138±43 min/day engaging in PA registering 100 to 499 accelerometry counts/min and 54±37 min/day engaging in PA ≥500 counts/min. Each minute per day spent being sedentary was associated with increased HCHD risk among both those with (0.04%, 95% CI 0.02% to 0.05%) and those without (0.03%, 95% CI 0.02% to 0.03%) CVD. The time spent engaging in activities 100 to 499 as well as ≥500 counts/min was associated with decreased risk among both those with and without CVD (P<0.05). The mean number of counts per minute of daily PA was not significantly associated with HCHD risk in any model (P>0.05). However, a significant interaction was observed between sex and count frequency (P=0.036) for those without CVD, as counts per minute was related to HCHD risk in women (ß=-0.94, -1.48 to -0.41; P<0.001) but not in men (ß=-0.14, -0.59 to 0.88; P=0.704). CONCLUSIONS: Daily time spent being sedentary is positively associated with predicted 10-year HCHD risk among mobility-limited older adults. Duration, but not intensity (ie, mean counts/min), of daily PA is inversely associated with HCHD risk score in this population-although the association for intensity may be sex specific among persons without CVD. CLINICAL TRIAL REGISTRATION URL: www.clinicaltrials.gov Unique identifier: NCT01072500.

Increased cardiovascular stiffness and impaired age-related functional status.

Our objective was to determine if increased cardiovascular (CV) stiffness is associated with disability in middle-aged and older adults at risk for congestive heart failure. CV stiffness (brachial pulse pressure/left ventricular stroke volume indexed to body surface area) and total disability (the summed assessment of activities of daily living, mobility, and instrumental activities of daily living) were measured in 445 individuals. A subset of 109 randomly selected individuals also underwent physical function testing. Total disability was associated with CV stiffness (p = .01), driven by an association with mobility (p = .005), but not activities of daily living (p = .13) or instrumental activities of daily living (p = .61). After accounting for age, these correlations remained significant for men (p = .04), but not for women. CV stiffness was also associated with increased 400-m walk time (p = .02). In middle-aged and elderly men at risk for congestive heart failure, CV stiffness is associated with decreased mobility and physical function, and increased overall disability.

Impact of an intensive lifestyle intervention on use and cost of medical services among overweight and obese adults with type 2 diabetes: the action for health in diabetes.

OBJECTIVE: To assess the relative impact of an intensive lifestyle intervention (ILI) on use and costs of health care within the Look AHEAD trial. RESEARCH DESIGN AND METHODS: A total of 5,121 overweight or obese adults with type 2 diabetes were randomly assigned to an ILI that promoted weight loss or to a comparison condition of diabetes support and education (DSE). Use and costs of health-care services were recorded across an average of 10 years. RESULTS: ILI led to reductions in annual hospitalizations (11%, P = 0.004), hospital days (15%, P = 0.01), and number of medications (6%, P < 0.001), resulting in cost savings for hospitalization (10%, P = 0.04) and medication (7%, P < 0.001). ILI produced a mean relative per-person 10-year cost savings of $5,280 (95% CI 3,385-7,175); however, these were not evident among individuals with a history of cardiovascular disease. CONCLUSIONS: Compared with DSE over 10 years, ILI participants had fewer hospitalizations, fewer medications, and lower health-care costs.

Effect of intensive versus standard blood pressure control on depression and health-related quality of life in type 2 diabetes: the ACCORD trial.

OBJECTIVE: We tested the hypothesis that intensive (systolic blood pressure [SBP] <120 mmHg) rather than standard (SBP 130-139 mmHg) blood pressure (BP) control improves health-related quality of life (HRQL) in those with type 2 diabetes. RESEARCH DESIGN AND METHODS: Subjects were 1,028 ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP trial HRQL substudy participants who completed baseline and one or more 12-, 36-, or 48-month HRQL evaluations. Multivariable linear regression assessed impact of BP treatment assignment on change in HRQL. RESULTS: Over 4.0 years of follow-up, no significant differences occurred in five of six HRQL measures. Those assigned to intensive (vs. standard) BP control had statistically significant worsening of the Medical Outcomes Study 36-item short-form health survey (SF36) physical component scores (-0.8 vs. -0.2; P = 0.02), but magnitude of change was not clinically significant. Findings persisted across all prespecified subgroups. CONCLUSIONS: Intensive BP control in the ACCORD trial did not have a clinically significant impact, either positive or negative, on depression or patient-reported HRQL.

Depression predicts all-cause mortality: epidemiological evaluation from the ACCORD HRQL substudy.

OBJECTIVE: Depression affects up to 20-25% of adults with type 2 diabetes and may increase all-cause mortality, but few well-designed studies have examined the effects of depression on the full range of cardiovascular disease outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 2,053 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) Health-Related Quality of Life substudy completed the Patient Health Questionnaire (PHQ)-9 measure of depression symptoms at baseline and 12, 36, and 48 months. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) (95% CI) for the time-varying impact of depression on protocol-defined clinical outcomes with and without adjustment for demographic, trial-related, clinical, and behavioral variables. RESULTS: In fully adjusted models, depression was not significantly related to the ACCORD primary composite outcome (cardiovascular death, nonfatal heart attack, or stroke) (HR 1.53 [95% CI 0.85-2.73]) or to the ACCORD microvascular composite outcome (0.93 [0.53-1.62]), but all-cause mortality was significantly increased both in those with PHQ-assessed probable major depression (2.24 [1.24-4.06]) and PHQ score of ≥ 10 (1.84 [1.17-2.89]). The effect of depression on all-cause mortality was not related to previous cardiovascular events or to assignment to intensive or standard glycemia control. Probable major depression (by PHQ-9) had a borderline impact on the ACCORD macrovascular end point (1.42 [0.99-2.04]). CONCLUSIONS: Depression increases the risk of all-cause mortality and may increase the risk of macrovascular events among adults with type 2 diabetes at high risk for cardiovascular events.

Baseline comparison of three health utility measures and the feeling thermometer among participants in the Action to Control Cardiovascular Risk in Diabetes trial.

BACKGROUND: Health utility (HU) measures are used as overall measures of quality of life and to determine quality adjusted life years (QALYs) in economic analyses. We compared baseline values of three HUs including Short Form 6 Dimensions (SF-6D), and Health Utilities Index, Mark II and Mark III (HUI2 and HUI3) and the feeling thermometer (FT) among type 2 diabetes participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. We assessed relationships between HU and FT values and patient demographics and clinical variables. METHODS: ACCORD was a randomized clinical trial to test if intensive controls of glucose, blood pressure and lipids can reduce the risk of major cardiovascular disease (CVD) events in type 2 diabetes patients with high risk of CVD. The health-related quality of life (HRQOL) sub-study includes 2,053 randomly selected participants. Interclass correlations (ICCs) and agreement between measures by quartile were used to evaluate relationships between HU's and the FT. Multivariable regression models specified relationships between patient variables and each HU and the FT. RESULTS: The ICCs were 0.245 for FT/SF-6D, 0.313 for HUI3/SF-6D, 0.437 for HUI2/SF-6D, 0.338 for FT/HUI2, 0.337 for FT/HUI3 and 0.751 for HUI2/HUI3 (P < 0.001 for all). Common classification by quartile was found for the majority (62%) of values between HUI2 and HUI3, which was significantly (P < 0.001) higher than between other HUs and the FT: SF-6D/HUI3 = 40.8%, SF-6D/HUI2 = 40.9%, FT/HUI3 = 35.0%, FT/HUI2 = 34.9%, and FT/SF-6D = 31.9%. Common classification was higher between SF-6D/HUI2 and SF-6D/HUI3 (P < 0.001) than between FT/SF-6D, FT/HUI2, and FT/HUI3. The mean difference in HU values per patient ranged from -0.024 ± 0.225 for SF-6D/ HUI3 to -0.124 ± 0.133 for SF-6D/HUI2. Regression models were significant; clinical and demographic variables explained 6.1% (SF-6D) to 7.7% (HUI3) of the variance in HUs. CONCLUSIONS: The agreements between the different HUs were poor except for the two HUI measures; therefore HU values derived different measures may not be comparable. The FT had low agreement with HUs. The relationships between HUs and demographic and clinical measures demonstrate how severity of diabetes and other clinical and demographic factors are associated with HUs and FT measures. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00000620.