Case-control study of environmental toxins and risk of amyotrophic lateral sclerosis involving the national ALS registry.

Objective: Neurotoxic chemicals are suggested in the etiology of amyotrophic lateral sclerosis (ALS). We examined the association of environmental and occupational risk factors including persistent organochlorine pesticides (OCPs) and ALS risk among cases from the Centers for Disease Control and Prevention National ALS Registry and age, sex, and county-matched controls. Methods: Participants completed a risk factor survey and provided a blood sample for OCP measurement. ALS cases were confirmed through the Registry. Conditional logistic regression assessed associations between ALS and risk factors including OCP levels. Results: 243 matched case-control pairs (61.7% male, mean [SD] age = 62.9 [10.1]) were included. Fifteen of the 29 OCPs examined had sufficient detectable levels for analysis. Modest correlations of self-reported years of exposure to residential pesticide mixtures and OCP serum levels were found (p<.001). Moreover, occupational exposure to lead including soldering and welding with lead/metal dust and use of lead paint/gasoline were significantly related to ALS risk (OR = 1.77, 95% CI: 1.11-2.83). Avocational gardening was a significant risk factor for ALS (OR = 1.57, 95% CI: 1.04-2.37). ALS risk increased for each 10 ng/g of α-Endosulfan (OR = 1.42, 95% CI: 1.14-1.77) and oxychlordane (OR = 1.24, 95% CI: 1.01-1.53). Heptachlor (detectable vs. nondetectable) was also associated with ALS risk (OR = 3.57, 95% CI: 1.50-8.52). Conclusion: This national case-control study revealed both survey and serum levels of OCPs as risk factors for ALS. Despite the United States banning many OCPs in the 1970s and 1980s, their use abroad and long half-lives continue to exert possible neurotoxic health effects.

Exposure to ambient air toxicants and the risk of amyotrophic lateral sclerosis (ALS): A matched case control study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with few risk factors identified and no known cure. Gene-environment interaction is hypothesized especially for sporadic ALS cases (90-95%) which are of unknown etiology. We aimed to investigate risk factors for ALS including exposure to ambient air toxics. METHODS: This population-based case-control study included 267 ALS cases (from the United States [U.S.] Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry National ALS Registry and Biorepository) and 267 age, sex, and county-matched controls identified via a commercial database. Exposure assessment for 34 ambient air toxicants was performed by assigning census tract-level U.S. Environmental Protection Agency (EPA) 2011 National Air Toxics Assessment (NATA) data to participants' residential ZIP codes. Conditional logistic regression was used to compute adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for individual compounds, chemical classes, and overall exposure. Sensitivity analyses using both conditional logistic regression and Bayesian grouped weighted quartile sum (GWQS) models were performed to assess the integrity of findings. RESULTS: Using the 2011 NATA, the highest exposure quartile (Q4) compared to the lowest (Q1) of vinyl chloride (aOR = 6.00, 95% CI: 1.87-19.25), 2,4-dinitrotoluene (aOR = 5.45, 95% CI: 1.53-19.36), cyanide (aOR = 4.34, 95% CI: 1.52-12.43), cadmium (aOR = 3.30, 95% CI: 1.11-9.77), and carbon disulfide (aOR = 2.98, 95% CI: 1.00-8.91) was associated with increased odds of ALS. Residential air selenium showed an inverse association with ALS (second quartile [Q2] vs. Q1: aOR = 0.38, 95% CI: 0.18-0.79). Additionally, residential exposure to organic/chlorinated solvents (Q4 vs Q1: aOR = 2.62, 95% CI: 1.003-6.85) was associated with ALS. CONCLUSIONS: Our findings using the 2011 NATA linked by census tract to residential area provide evidence of increased ALS risk in cases compared to controls for 2,4-dinitrotoluene, vinyl chloride, cyanide, and the organic/chlorinated solvents class. This underscores the importance of ongoing surveillance of potential exposures for at-risk populations.

Translating the Diabetes Prevention Program Lifestyle Intervention to the Military Setting.

INTRODUCTION: Diabetes and obesity pose a significant burden for the U.S. military beneficiary population, creating a great need to provide evidence-based diabetes and obesity prevention services for military personnel, retirees, and their dependents. Despite increasing dissemination of the Diabetes Prevention Program (DPP) lifestyle intervention nationwide, formal evaluation of implementation of this highly successful program is limited in the military setting. The purpose of this study is to prospectively evaluate delivery of a direct adaptation of a 1-year DPP lifestyle intervention at a U.S. Air Force medical facility, Wright-Patterson Medical Center (WPMC), to determine the feasibility of delivery of the program in a group of at-risk active duty military, retirees, and family members, as well as assess effectiveness in improving weight and other risk factors for type 2 diabetes. MATERIALS AND METHODS: A pre/post study design was utilized to evaluate feasibility and effectiveness of the DPP Group Lifestyle Balance (GLB), an up-to-date, 22-session direct adaptation of the DPP curriculum, at WPMC. Participants chose to complete the 1-year program either in coach-led face-to-face groups or via DVD with weekly telephonic coach contact. The study was approved by the University of Pittsburgh and WPMC Institutional Review Boards. RESULTS: A total of 99 individuals enrolled in the study, with 83 (84%) and 77 (78%) completing 6- and 12-month follow-up assessments, respectively. The mean age of participants at baseline was 57 (range 20-85 years), with 63% being female. The group was comprised of individuals who were non-Hispanic White (73.7%), non-Hispanic Black (18.2%), and other race or Hispanic ethnicity (8.1%). Within this group, there were 10 active duty military, 37 retirees, and 52 family members. The DPP-GLB program was shown to be feasible to implement in this military healthcare setting as demonstrated by the high engagement over the course of the year-long program. Significant improvements were shown in the two main behavioral goals: mean weight (-12.8 lbs, -6.3%, P < .001) and mean physical activity (PA) (+18.9 Met-hrs/wk, P < .001). In addition, significant improvements in other diabetes and cardiovascular risk factors including low-density lipoprotein cholesterol, fasting insulin, diastolic blood pressure, and waist circumference were noted, as well as improvement in health-related quality of life. CONCLUSIONS: These results demonstrate that the DPP-GLB program delivered via face-to-face groups or DVD was feasible and effective in improving weight, PA levels, and diabetes and cardiovascular risk factors in this group of active and retired military personnel and their family members. The program was well received by the program participants as well as the WPMC team. These findings offer a model for provision of the DPP-GLB program throughout the Military Health System.

Long-term air pollution and risk of amyotrophic lateral sclerosis mortality in the Women's Health Initiative cohort.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no cure. Although the etiology of sporadic ALS is largely unknown, environmental exposures may affect ALS risk. OBJECTIVE: We investigated relationships between exposure to long-term ambient particulate matter (PM) and gaseous air pollution (AP) and ALS mortality. METHODS: Within the Women's Health Initiative (WHI) cohort of 161,808 postmenopausal women aged 50-79 years at baseline (1993-1998), we performed a nested case-control study of 256 ALS deaths and 2486 matched controls with emphasis on PM constituents (PM2.5, PM10, and coarse PM [PM10-2.5]) and gaseous pollutants (NOx, NO2, SO2, and ozone). Time-varying AP exposures estimates were averaged 5, 7.5, and 10 years prior to ALS death using both a GIS-based spatiotemporal generalized additive mixed model and ordinary kriging (empirical and multiple imputation, MI). Conditional logistic regression was used to estimate the relative risk of ALS death. RESULTS: In general, PM2.5 and PM10-related risks were not significantly elevated using either method. However, for PM10-2.5, odds ratios (ORs) were >1.0 for both methods at all time periods using MI and empirical data for PM10-2.5 (coarse) except for 5 and 7.5 years using the kriging method with covariate adjustment. CONCLUSION: This investigation adds to the body of information on long-term ambient AP exposure and ALS mortality. Specifically, the 2019 US Environmental Protection Agency (EPA) Integrated Science Assessment summarized the neurotoxic effects of PM2.5, PM10, and PM10-2.5. The conclusion was that evidence of an effect of coarse PM is suggestive but the data is presently not sufficient to infer a causal relationship. Further research on AP and ALS is warranted. As time from symptom onset to death in ALS is ∼2-4 years, earlier AP measures may also be of interest to ALS development. This is the first study of ALS and AP in postmenopausal women controlling for individual-level confounders.

Serum α-KL, a potential early marker of diabetes complications in youth with T1D, is regulated by miRNA 192.

Despite the wealth of information on biomarkers of diabetes complications in adults with type 1 diabetes, data in the pediatric population is limited. Diabetic nephropathy (DN), the leading cause of mortality in type 1 diabetes T1D), could be potentially missed in youth, as albuminuria, the current "gold" standard, may be transient and may not reflect permanent renal impairment. Soluble alpha KL has emerged as a potential marker of early diabetic nephropathy. Seventy-nine pediatric patients with type 1 diabetes meeting ISPAD criteria for nephropathy screening were consecutively recruited (90% Caucasian, 51% male, mean age 16.1 ± 3.1 years, duration of T1D 7.2 ± 3.9 years, 2-year average HbA1c 8.0 ± 1.3%, and serum and urine samples were collected for analysis. Serum Klotho (KL) and circulating miRNA levels of select miRNA involved in the pathogenesis of DN were estimated. KL had a strong inverse correlation with diabetes duration and HbA1c, two important risk factors in the development of diabetes complications. Serum miR-192 were negatively associated with KL among children with prolonged duration of diabetes (≥12 years) after adjustment for age and sex. In cell culture, overexpression of miR-192 significantly downregulated KL mRNA and protein levels, and reduced KL levels in the media. miR-192 mimic reduced luciferase activity in a reporter containing the KL 3' UTR (60% compared to controls, p<0.01), and the inhibitor rescued it. Deletion of a potential binding site for miR-192 in the KL 3'UTR completely abolished the effect of miR-192 in the reporter assay, suggesting that KL is a direct target gene of miR-192. Overexpression of miR-192 significantly increased oxidative stress (MDA) and expression of inflammatory and senescence markers IL-6 and p16. Inhibition of miR-192 significantly reduced levels of MDA, IL-6 and p16. In summary, we demonstrate an increase in miR-192 and a decrease in KL levels in children with prolonged duration of T1D. We demonstrate a novel role for miR-192 in directly regulating KL levels, and through that, senescence and oxidative stress, key pathological processes in the development of DN. miR-192 and/or KL levels are altered with severity and duration of diabetes and could serve as early biomarkers for DN.

The Likely Underestimated Impact of Lifestyle Intervention: Diabetes Prevention Program Translation Examples.

INTRODUCTION: Lifestyle interventions promoting weight loss and physical activity are important elements of prevention efforts with the evaluation of program impact typically limited to weight loss. Unfortunately, diabetes/cardiovascular disease risk factors and activity are infrequently reported and inconsistent in findings when examined. This inconsistency may partially be due to a lack of consideration for ceiling effects because of broad risk profile inclusion criteria in community translation efforts. To demonstrate this, change in each individual cardiometabolic risk factor limited to those who, at baseline, had a clinically defined abnormal value for that risk factor was examined in 2 cohorts using identical community translations of the Diabetes Prevention Program lifestyle intervention. METHODS: For both studies (2010-2014, 2014-2019), adults with prediabetes and/or metabolic syndrome were recruited through community centers. Outcome measures collected at baseline and 6 months included BMI, activity, blood pressure, lipids, and fasting glucose. Data analyses examined pre-post change in each variable after 6 months of intervention and change within randomized groups at 6 months. RESULTS: Change results were examined for the entire cohort and separately for participants with baseline values outside the recommended range for that risk factor. Whether assessing the pre-post intervention change or change within the randomized groups at 6 months, often the risk factor-specific approach demonstrated a greater effect size for that variable and sometimes newly reached statistical significance. CONCLUSIONS: When examining the effectiveness of community translation efforts, consideration of the individual's baseline profile with risk factor-specific analysis is suggested to understand the full extent of the impact of the intervention.

The role of Sociodemographic factors on goal achievement in a community-based diabetes prevention program behavioral lifestyle intervention.

BACKGROUND: The Diabetes Prevention Program (DPP) behavioral lifestyle intervention was effective among a diverse sample of adults with prediabetes. Demonstrated effectiveness in translated versions of the DPP lifestyle intervention (such as Group Lifestyle Balance, DPP-GLB) led to widescale usage with national program oversight and reimbursement. However, little is known about the success of these DPP-translation programs across subgroups of sociodemographic factors. This current effort investigated potential disparities in DPP-translation program primary goal achievement (physical activity and weight) by key sociodemographic factors. METHODS: Data were combined from two 12-month community-based DPP-GLB trials among overweight/obese individuals with prediabetes and/or metabolic syndrome. We evaluated change in weight (kilograms and percent) and activity (MET-hrs/week) and goal achievement (yes/no; ≥5% weight loss and 150 min per week activity) after 6 and 12 months of intervention within and across subgroups of race/ethnicity (non-Hispanic white, non-Hispanic black), employment status, education, income, and gender. RESULTS: Among 240 participants (85%) with complete data, most sociodemographic subgroups demonstrated significant weight loss. However, non-Hispanic white lost more weight at both 6 and 12 months compared to non-Hispanic black participants [median weight loss (IQR), 6 months: 5.7% (2.7-9.0) vs. 1.5% (1.2-7.5) p = .01 and 12 months: 4.8% (1.1-9.6) vs. 1.1% (- 2.0-3.7) p = .01, respectively]. In addition, a larger percentage of non-Hispanic white demonstrated a 5% weight loss at 6 and 12 months. Employment was significantly related to 12-month weight loss, with retired participants being the most successful. Men, participants with graduate degrees, and those with higher income were most likely to meet the activity goal at baseline and 12 months. Differences in physical activity goal achievement across gender, education, and income groups were significant at baseline, attenuated after 6 months, then re-emerged at 12 months. CONCLUSIONS: The DPP-GLB was effective in promoting weight loss and helped to alleviate disparities in physical activity levels after 6 months. Despite overall program success, differences in weight loss achievement by race/ethnicity were found and disparities in activity re-emerged after 12 months of intervention. These results support the need for intervention modification providing more tailored approaches to marginalized groups to maximize the achievement and maintenance of DPP-GLB behavioral goals. TRIAL REGISTRATION: NCT01050205 , NCT02467881 .

The Impact of a Yearlong Diabetes Prevention Program-Based Lifestyle Intervention on Cardiovascular Health Metrics.

INTRODUCTION: The American Heart Association created "Life's Simple Seven" metrics to estimate progress toward improving US cardiovascular health in a standardized manner. Given the widespread use of federally funded Diabetes Prevention Program (DPP)-based lifestyle interventions such as the Group Lifestyle Balance (DPP-GLB), evaluation of change in health metrics within such a program is of national interest. This study examined change in cardiovascular health metric scores during the course of a yearlong DPP-GLB intervention. METHODS: Data were combined from 2 similar randomized trials offering a community based DPP-GLB lifestyle intervention to overweight/obese individuals with prediabetes and/or metabolic syndrome. Pre/post lifestyle intervention participation changes in 5 of the 7 cardiovascular health metrics were examined at 6 and 12 months (BMI, blood pressure, total cholesterol, fasting plasma glucose, physical activity). Smoking was rare and diet was not measured. RESULTS: Among 305 participants with complete data (81.8% of 373 eligible adults), significant improvements were demonstrated in all 5 risk factors measured continuously at 6 and 12 months. There were significant positive shifts in the "ideal" and "total" metric scores at both time points. Also noted were beneficial shifts in the proportion of participants across categories for BMI, activity, and blood pressure. CONCLUSION: AHA-metrics could have clinical utility in estimating an individual's cardiovascular health status and in capturing improvement in cardiometabolic/behavioral risk factors resulting from participation in a community-based translation of the DPP lifestyle intervention.

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.

Effect of a Primary Care-Based Diabetes Education Model on Provider Referrals and Patient Participation.

PURPOSE: The purpose of this study was to evaluate the impact of a primary care (PC)-based delivery model on diabetes self-management education and support (DSMES) referrals and participation. Despite evidence that DSMES is a critical component of diabetes care, referrals and participation remain low. METHODS: PC practices were assigned to the intervention (n = 6) or usual care (n = 6). Intervention practices had direct access to a diabetes educator (DE) and applied patient-centered medical home elements to DSMES delivery. Usual care practices referred patients to traditional hospital-based outpatient DSMES programs. DSMES referrals and participation were examined for patients with diabetes, 18 to 75 years old, presenting to PC over 18 months (n = 4,894) and compared between groups. RESULTS: Compared to the usual care group, a higher percentage of patients in the intervention practices were referred to DSMES (18.4% vs 13.4%; P < .0001), and of those referred, a higher percentage of patients in the intervention practices participated in DSMES (34.9% vs 26.1%; P = .02). Patient-level factors predicting referrals were obesity (odds ratio [OR] = 1.6), higher A1C (OR = 1.4), female (OR = 1.3), and younger age (OR = 0.98). The only patient-level factor that predicted DSMES participation was lower A1C (OR = 0.9). CONCLUSIONS: This study demonstrates the positive influence of a PC-based intervention on DSMES referral and participation. However, modest improvements in DSMES rates, even with targeted efforts to address reported barriers, raise questions as to what is truly needed to drive meaningful change.

Leisure Sedentary Behavior Levels and Meeting Program Goals in a Community Lifestyle Intervention for Diabetes Prevention.

BACKGROUND: The importance of leisure sedentary behavior (LSB) change in diabetes prevention efforts is not well known. This study examines the relationships between changes in self-reported LSB and the primary intervention goals (weight and moderate-intensity to vigorous-intensity physical activity [MVPA]) during a community-based translation of the Diabetes Prevention Program (the Group Lifestyle Balance Program). METHODS: A total of 322 adults at risk for type 2 diabetes were recruited from 3 community centers, a worksite, and military site. Community and worksite participants were randomized to immediate or delayed-delivery (control) intervention. All military site participants (n = 99) received immediate intervention. Logistic and linear generalized estimating equations were used to determine associations between LSB changes and weight-related outcomes and MVPA. RESULTS: Results were obtained for 259 (80.4%) participants. The LSB decreased after 6 and 12 months (mean [95% confidence interval]: -25.7 [-38.6 to -12.8] and -16.1 [-28.2 to -3.9] min/d; both P < .05). Each 20-minute reduction in LSB was associated with a 5% increase in odds of meeting the weight-loss goal (6 mo: odds ratio = 1.05 [1.002 to 1.102]; P = .042; adjusted model including MVPA), but LSB was not related to changes in reported MVPA minutes or MVPA goal achievement. CONCLUSION: Within the context of existing lifestyle intervention programs, reducing sedentary behavior has the potential to contribute to weight loss separately from reported MVPA improvement.

Participant food and activity costs in a translational Diabetes Prevention Program.

The Diabetes Prevention Program (DPP) and its translational adaptations have been shown to be effective. However, individual-level economic impacts, such as the out-of-pocket costs borne by participants due to involvement in these programs have not been consistently and thoroughly evaluated. As cost is an important consideration that will impact the willingness of individuals to participate in such programs, this study examined direct monetary costs to participants in the Group Lifestyle Balance (GLB) DPP. Older adults (n = 134, mean age 62.8 years) with body mass index (BMI) ≥24 kg/m2 and prediabetes and/or metabolic syndrome participated in this GLB intervention, with two-thirds randomized to begin the intervention immediately and one-third functioning as a control for 6 months before receiving the entire intervention. Food and activity time and costs borne by participants were measured by self-report at baseline and after 6 months. Significant improvements in clinical metabolic measures, weight, and physical activity levels were achieved after 6 months in the intervention group compared both with baseline and the controls. Food costs did not increase among intervention participants. Costs related to physical activity did not change consistently over the course of the intervention. This DPP-GLB lifestyle intervention was effective in reducing risk factors for Type 2 diabetes mellitus among a diverse group of older participants without significantly increasing their out-of-pocket costs for food or physical activity over the course of the intervention. These results should help reduce concerns of individuals who are hesitant to participate in similar programs due to costs. The clinical trial registration number of this study is NCT01050205.

Group Lifestyle Phone Maintenance for Weight, Health, and Physical Function in Adults Aged 65-80 Years: A Randomized Clinical Trial.

BACKGROUND: Group lifestyle sessions with phone maintenance could improve weight, health, and function in vulnerable older adults. METHODS: Community-dwelling adults (N = 322) with body mass index (BMI, kg/m2) ≥27 and additional risk factors received 12 one-hour in-person behavioral weight management group sessions then were randomized to 8 half-hour telephone sessions (n = 162) or newsletter control (n = 160) from 4 to 12 months with no treatment contact thereafter. Primary outcome was 0- to 12-month weight change. Cardiometabolic, short physical performance battery (SPPB), and self-reported activity changes were assessed at 12 and 24 months. RESULTS: At baseline, the mean (SD) age was 71.2 (4.3) and BMI was 33.8 (5.1). Participants were 77% women, 13% Black, 85% retired, averaging 4 medical conditions, and taking blood pressure (67.4%) and lipid-lowering (51.6%) medications. At 12 months, a greater proportion of the phone group (66.0%) achieved ≥5% weight loss compared with newsletter control (53.2%; p = .02). Mean (95% CI) weight loss was greater for phone (-6.6 kg [-7.5, -5.8]) than newsletter (-5.1 kg [-7.2, -3.0]); p = .01. Modest lipid, glucose, and blood pressure improvements were found, but did not differ significantly between groups. Small SPPB and activity improvements were maintained at 12 and 24 months in both groups. CONCLUSIONS: Brief phone contacts compared to newsletters enhanced weight loss maintenance among older high-risk adults at 1 year, but not cardiometabolic outcomes. Modest functional improvements were observed in both. Lower-intensity maintenance contacts (phone or newsletter) for weight, health, and physical function in older adults warrant further study. CLINICAL TRIALS REGISTRATION NUMBER: NCT03192475.

A Coordinated Population Health Approach to Diabetes Education in Primary Care.

PURPOSE: The purpose of this feasibility study was to determine the effectiveness of an insurer-based diabetes educator (DE)-driven intervention that relies on systematic restructuring of primary care (PC) linking DE services through population health, practice redesign, and coordinated care for patients with diabetes mellitus (DM) identified as high risk. METHODS: Two DEs were introduced as members of PC teams and worked with practice-based care managers (PBCMs) to identify and refer DM patients considered at high risk, A1C >9%, DM-related emergency room visit or hospitalization, or reported barriers to care. Elements shown to ensure quality, including population management, diabetes self-management education and support (DSMES), and coordinated patient-centered team-based PC, were central to intervention. A1C, low-density lipoprotein (LDL), and body mass index (BMI) were collected at baseline and outcomes were followed at 3, 6, 9, and 12 months after intervention. RESULTS: For patients who received intervention, A1C decreased on average 1.2% (95% confidence interval [CI], 0.8-1.5) from 9.6% (81 mmol/mol) to 8.4% (68 mmol/mol) over 6 months and by 1.1% (95% CI, 0.7-1.5) from 9.2% (77 mmol/mol) to 8.1% (65 mmol/mol) over 12 months, indicating durable improvement in glycemic control. There was no significant change in BMI, and LDL improvement observed at 9 months was lost by 12-month follow-up. CONCLUSION: Findings support the feasibility of a DE-driven intervention for patients with DM at high risk through a coordinated PC approach that improves glycemic control. The feasibility and clinical outcome of this model warrant consideration of a fresh role for DEs in the complex environment of value-based care.

Celiac Autoimmunity Is Associated With Lower Blood Pressure and Renal Risk in Type 1 Diabetes.

Context: Though the long-term consequences of celiac disease (CD) in type 1 diabetes are unclear, CD has been associated with increased prevalence of end-stage renal disease (ESRD) independent of type 1 diabetes. Objective: We evaluated whether celiac autoimmunity is related to the cumulative incidence of microalbuminuria [albumin excretion rate (AER) 20 to 200 µg/min], macroalbuminuria (AER >200 µg/min), and ESRD. Design, Patients, and Methods: In the prospective follow-up of the Pittsburgh Epidemiology of Diabetes Complications study of childhood-onset type 1 diabetes, 618 participants were screened for tissue transglutaminase (tTG) antibodies with a clinical assay. Nephropathy outcomes were determined at 25 years of diabetes duration. Results: Overall, the 33 subjects (5.3%) with strongly positive tTG levels (≥3 times the upper limit of normal) or a reported clinical history of CD had lower baseline blood pressure and lipid values. At 25 years of diabetes duration, a lower cumulative incidence of macroalbuminuria in strongly positive subjects compared with those with negative serology (3.6% vs 30.0%; P = 0.003) remained significant after adjustment for age, HbA1c, lipid measures, and blood pressure (adjusted P = 0.004). No considerable differences between these subjects and tTG-negative groups were found for microalbuminuria (40.0% vs 57.1%) or ESRD (0 vs 4.1%). Conclusions: These findings show that strongly positive celiac autoimmunity status in individuals with childhood-onset type 1 diabetes is associated with lower baseline blood pressure and cholesterol measurements as well as lower macroalbuminuria risk after 25 years of type 1 diabetes duration with no increase in the risk of microalbuminuria or ESRD.

Evaluation of a Diabetes Prevention Program Lifestyle Intervention in Older Adults: A Randomized Controlled Study in Three Senior/Community Centers of Varying Socioeconomic Status.

Purpose The purpose of this study is to evaluate the feasibility and effectiveness of an adapted Diabetes Prevention Program (DPP) lifestyle program, DPP Group Lifestyle Balance (GLB), delivered in 3 economically diverse senior/community centers. Methods The DPP-GLB was implemented in 3 senior/community centers in Allegheny County, PA. A 6-month delayed control intervention design was used. Participants were randomized to begin the DPP-GLB immediately (immediate) or after a 6-month delay (delayed). Adults (n = 134; mean age = 62.8 years) with BMI ≥24 kg/m2 and prediabetes and/or the metabolic syndrome took part. Weight, physical activity (PA), and diabetes and cardiovascular disease (CVD) risk factors were assessed at 6, 12, and 18 months from baseline. Results At 6 months, the immediate group demonstrated greater mean weight loss than the delayed control group as well as significantly greater improvements in PA, A1C, fasting insulin, and waist circumference. In pre-post analyses, both randomized groups showed similar success that was maintained at 18 months. Conclusions The DPP-GLB delivered in economically diverse community centers was effective in this group of older adults. These findings support provision of coverage for prevention programs in older adults at risk for diabetes/CVD, which is important considering the large number of individuals who will be Medicare eligible in the near future.

Characteristics of slow progression to diabetes in multiple islet autoantibody-positive individuals from five longitudinal cohorts: the SNAIL study.

AIMS/HYPOTHESIS: Multiple islet autoimmunity increases risk of diabetes, but not all individuals positive for two or more islet autoantibodies progress to disease within a decade. Major islet autoantibodies recognise insulin (IAA), GAD (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A). Here we describe the baseline characteristics of a unique cohort of 'slow progressors' (n = 132) who were positive for multiple islet autoantibodies (IAA, GADA, IA-2A or ZnT8A) but did not progress to diabetes within 10 years. METHODS: Individuals were identified from five studies (BABYDIAB, Germany; Diabetes Autoimmunity Study in the Young [DAISY], USA; All Babies in Southeast Sweden [ABIS], Sweden; Bart's Oxford Family Study [BOX], UK and the Pittsburgh Family Study, USA). Multiple islet autoantibody characteristics were determined using harmonised assays where possible. HLA class II risk was compared between slow progressors and rapid progressors (n = 348 diagnosed <5 years old from BOX) using the χ2 test. RESULTS: In the first available samples with detectable multiple antibodies, the most frequent autoantibodies were GADA (92%), followed by ZnT8A (62%), IAA (59%) and IA-2A (41%). High risk HLA class II genotypes were less frequent in slow (28%) than rapid progressors (42%, p = 0.011), but only two slow progressors carried the protective HLA DQ6 allele. CONCLUSION: No distinguishing characteristics of slow progressors at first detection of multiple antibodies have yet been identified. Continued investigation of these individuals may provide insights into slow progression that will inform future efforts to slow or prevent progression to clinical diabetes.

Factors related to lifestyle goal achievement in a diabetes prevention program dissemination study.

The U.S. Diabetes Prevention Program (DPP) showed that lifestyle participants who achieved ≥7% weight loss and ≥150 min/week physical activity experienced the greatest reduction in type 2 diabetes incidence. Demographic, clinical, and program factors that are related to achieving both these lifestyle goals have seldom been explored in community-delivered DPP programs. The purpose of this investigation is to examine factors associated with concurrent achievement of weight loss and physical activity goals in a 12-month community DPP lifestyle intervention. Adults [n = 223; age = 58.4 (SD = 11.5); BMI = 33.8 (SD = 6.0)] with glucose or HbA1c values in the pre-diabetes range and/or metabolic syndrome risk factors enrolled from one worksite and three community centers in the Pittsburgh, PA metropolitan area between January 2011 and January 2014. Logistic regression analyses determined the demographic, clinical and program adherence factors related to goal achievement at 6, 12, and 18 months. Participants achieving both intervention goals at 6 months (n = 57) were more likely to attend sessions [Adjusted Odds Ratio (AOR) =1.48], self-weigh (AOR = 1.19), and self-monitor behaviors (AOR = 1.18) than those meeting neither goal (n = 35; all p < 0.05). Baseline BMI (AOR = 0.87, p < 0.01), elevated glycemic status (AOR = 0.49, p < 0.05), and female sex (AOR = 0.52, p < 0.05) were inversely related to goal achievement at 6 months. Meeting either lifestyle goal at 6 months had the strongest association with meeting both goals at 12 and 18 months. Our study supports the importance of early engagement, regular attendance, self-monitoring, and self-weighing for goal achievement. Dissemination efforts should consider alternative approaches for those not meeting goals by 6 months to enhance long-term success.

Physical Activity Levels in a Community Lifestyle Intervention: A Randomized Trial.

BACKGROUND: A behavioral lifestyle intervention program with goals of increasing physical activity (PA) and losing weight was shown to be efficacious for preventing type 2 diabetes and decreasing risk for cardiovascular disease in the U.S. Diabetes Prevention Program (DPP). Modified versions of the DPP lifestyle intervention are being translated into diverse community settings and have been successful in decreasing weight and improving metabolic markers. However, comprehensive evaluations of PA levels within these community translation intervention efforts are rare. PURPOSE: To evaluate the effectiveness of a DPP-based community lifestyle intervention for improving PA levels. METHODS: 223 overweight adults at-risk for type 2 diabetes and/or cardiovascular disease were randomized (immediate or 6-month delayed-start) to a 12-month DPP-based lifestyle intervention. Past-month PA level was assessed at baseline and post-intervention with the Modifiable Activity Questionnaire. Simple and mixed-effects regression models were used to determine changes in PA level between and within groups over time. RESULTS: The between-group mean difference for change in PA levels from baseline to 6 months indicated significantly greater improvement in the intervention compared to the delayed-start group [+6.72 (SE=3.01) MET-hrs/week; p=0.03]. Examining combined within-group change from baseline to post-intervention, mean PA levels significantly increased by +14.69 (SE=1.43) and +9.50 (SE= 1.40) MET-hrs/week at 6 and 12 months post-intervention, respectively. This PA change offset to approximately +10 MET-hrs/week at both 6 and 12 months after adjusting for baseline PA level and season (all; p<0.01). Other than season, sex impacted on change in PA level. CONCLUSIONS: This community-based lifestyle intervention significantly increased PA levels among overweight adults at risk for type 2 diabetes and cardiovascular disease, even after adjusting for key variables. CLINICALTRIALSGOV IDENTIFIER: NCT01050205.

Impact of a community-based lifestyle intervention program on health-related quality of life.

BACKGROUND: The presence of risk factors for type 2 diabetes and cardiovascular disease, or the conditions themselves, contributes to lower health-related quality of life (HRQoL) among adults. Although community-based lifestyle intervention programs have been shown to be effective for improving risk factors for these diseases, the impact of these interventions on HRQoL has rarely been described. PURPOSE: To examine changes in HRQoL following participation in the Group Lifestyle Balance program, a community translation of the Diabetes Prevention Program lifestyle intervention for adults with prediabetes and/or the metabolic syndrome. METHODS: Participants enrolled in the 12-month, 22-session intervention program (N = 223) completed the EuroQol Health Questionnaire (EQ-5D-3L) at baseline, 6, and 12 months. Linear mixed-effects regression models determined change in EQ-5D-visual analog scale (VAS) and Index scores post-intervention. RESULTS: Mean EQ-5D-VAS was improved by +7.38 (SE = 1.03) at 6 months and by +6.73 (SE = 1.06) at 12 months post-intervention (both; p < 0.0001). Mean changes in EQ-5D index values were +0.00 (SE = 0.01; NS) and +0.01 (SE = 0.01; p < 0.05), respectively. Adjusted for age, baseline score, and achieving intervention goals, mean change in EQ-5D-VAS was +11.83 (SE = 1.61) at 6 months and +11.23 (SE = 1.54) at 12 months (both; p < 0.0001). Adjusted mean change in EQ-5D index value was +0.04 (SE = 0.01) at 6 months and +0.05 (SE = 0.01) at 12 months (both; p < 0.01). CONCLUSION: Participation in a community lifestyle intervention program resulted in improved HRQoL among adults with prediabetes and/or the metabolic syndrome. These benefits to HRQoL, together with improved clinical and behavioral outcomes, should increase the appeal of such programs for improving health.