Diabetes Prevention Program Trial Research Articles

391 Value estimation of the Diabetes Prevention Program: How well does clinical trial-based cost-effectiveness apply to the real world?

OBJECTIVES/GOALS: Many economic evaluations rely on clinical trial data that may not represent real world populations and intervention effectiveness. We compare risk and cost-effectiveness for the Diabetes Prevention Program (DPP) clinical trial cohort and a real world population eligible for the national DPP to assess the impact of using real world data. METHODS/STUDY POPULATION: To produce real world (US population) representative results, we identified National Health and Nutrition Examination Survey (NHANES) subjects eligible for the national DPP and adjusted projections using survey weights. We used clinical predictive models to estimate individual diabetes risk, and microsimulation to estimate lifetime costs, benefits, and net monetary benefits (NMB) for lifestyle intervention and metformin. We compared results across the DPP clinical trial and NHANES populations. RESULTS/ANTICIPATED RESULTS: Three-year risk of diabetes onset for the DPP trial population (mean of 19.7%, median of 10.3%) exceeded corresponding risk for the NHANES population (mean of 14.6%, median of 4.8%). The proportion of individuals with a three-year diabetes risk < 10% for the DPP trial population (49%) was less than the corresponding proportion for NHANES (67%). Mean NMB for metformin for the DPP trial population ($9,749) exceeded the corresponding value for NHANES ($5,391). The proportion of subjects with negative NMB was 49% for the DPP trial population and 67% for NHANES. Lifestyle intervention had a mean NMB of $34,889 for the DPP trial population and $28,652 for NHANES. Only 20% of the NHANES population eligible for national DPP met inclusion/exclusion criteria for the DPP trial. DISCUSSION/SIGNIFICANCE: Real world populations eligible for the national DPP include a greater proportion of low-risk individuals, and for these people, prevention programs may confer smaller benefits. Technology assessments based on clinical trial data should be revised using real world population and treatment effect data.

The cost-effectiveness of metformin in the US diabetes prevention program trial: Simple interpretations need not apply

Based on previously published US Diabetes Prevention Program (DPP) cost-effectiveness analyses (CEAs) metformin continues to be promoted as “cost-effective.” We review the DPP within-trial CEA to assess this claim. Treatment alternatives included placebo (plus standard lifestyle advice), branded metformin and individual lifestyle modification. We added generic metformin as an alternative. Original published CEA data were taken as given and re-analyzed according to accepted principles for calculating incremental cost-effectiveness ratios (ICERs) in the economic evaluation field. With more than two treatments as in the DPP, these require attention to the rankings of interventions according to cost or effect prior to stipulating appropriate ICERs to calculate. With proper ICERs neither branded nor generic metformin was cost-effective, regardless of the value assumed for the willingness to pay for the quality-adjusted life year outcome assessed. Metformin alternatives were technically inefficient compared to placebo or the lifestyle modification alternative. Net loss calculations indicated substantial costs/health losses to using metformin instead of the optimal lifestyle alternative in response to metformin having been inaccurately labelled “cost-effective” in the original CEA. That CEA and subsequent analyses and citations of such analyses continue to claim that both metformin and lifestyle modification are cost-effective in diabetes prevention based on DPP data. Using metformin implies substantial costs and health losses compared to the cost-effective lifestyle modification. It may be that metformin has a role in cost-effective diabetes prevention, but this has yet to be shown based on DPP data.

1269-P: Trajectories of MicroRNAs Are Associated with Trajectories of Weight but Not Fasting Blood Glucose in the Diabetes Prevention Program Trial

Introduction: Circulating microRNAs (miRs) are emerging as promising biomarkers of risk for type 2 diabetes (T2D) and responses to risk-reduction interventions, but no prior study has examined longitudinal associations between miRs and fasting blood glucose (FBG) or weight in adults at high risk for T2D. Prior studies have been cross-sectional or only measured longitudinal outcomes. We determined the association between longitudinal trajectories of miRs, FBG, and weight in a subset of participants from the Diabetes Prevention Program (DPP). Methods: This study was a secondary analysis of a subset of participants (N=150) from DPP. A custom Fireplex assay was used to quantify 58 miRs from banked plasma samples collected at baseline, 1-year, and 2-years. Generalized linear mixed models were used to analyze associations between the miRs, FBG (mg/dL), and weight (kg) over time, adjusting for covariates (i.e., age, body mass index, race or ethnicity, gender, trial arm, and high density lipoprotein cholesterol). The Benjamini-Hochberg false discovery rate method was used to adjust for multiple comparisons. Results: The sample was 73% female, 19% Black, 14% Hispanic, and mean age was 51 ± 11 years. At baseline, the participants were normotensive, obese, and had dyslipidemia and prediabetes. After adjusting for multiple comparisons, 39 miRs were significantly associated with weight, of which 12 miRs (let-7c-5p, miR-1066-5p, miR-1287-5p, miR-133b, miR-15a-5p, miR-15b-5p, miR-181c-3p, miR-197-5p, miR-23b-5p, miR-296-5p, miR-877-5p, miR-98-5p) remained significant after adjusting for covariates. In the FBG model, none of the miRs were significant. Conclusions: Twelve miRs were associated with longitudinal weight but no miRs were associated with FBG trajectories in a subset of participants from the DPP trial. These miRs may provide mechanistic, diagnostic, or therapeutic insights about T2D prevention. Disclosure K.A.Lewis: None. J.C.Florez: Consultant; AstraZeneca, Novo Nordisk, Other Relationship; AstraZeneca, Merck & Co., Inc. B.Aouizerat: None. A.M.Kanaya: None. E.Flowers: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK124228, X01DK115999)

MicroRNAs Associated with Incident Diabetes in the Diabetes Prevention Program.

MicroRNAs (miRs) are short (i.e., 18-26 nucleotide) regulatory elements of messenger RNA translation to amino acids. The purpose of this study was to assess whether miRs are predictive of incident T2D in the Diabetes Prevention Program (DPP) trial. This was a secondary analysis (n = 1,000) of a subset of the DPP cohort that leveraged banked biospecimens to measure miRs. We used random survival forest and Lasso to identify the optimal miR predictors and cox proportional hazards to model time to T2D overall and within intervention arms. We identified five miRs (miR-144, miR-186, miR-203a, miR-205, miR-206) that constituted the optimal predictors of incident T2D after adjustment for covariates (hazards ratio 2.81 (95% confidence interval (CI) 2.05, 3.87); p < 0.001). Predictive risk scores following cross-validation showed the HR for the highest quartile risk group compared to the lowest quartile risk group was 5.91 (95% CI (2.02, 17.3); p < 0.001). There was significant interaction between the intensive lifestyle (HR 3.60, 95% CI (2.50, 5.18); p < 0.001) and the metformin (HR 2.72; 95% CI (1.47, 5.00); p = 0.001) groups compared to placebo. Of the five miRs identified, one targets a gene with prior known associations with risk for T2D. We identified five miRs that are optimal predictors of incident T2D in the DPP cohort. Future directions include validation of this finding in an independent sample in order to determine whether this risk score may have potential clinical utility for risk stratification of individuals with prediabetes, and functional analysis of the potential genes and pathways targeted by the miRs that were included in the risk score.

Looking back and forward from the Diabetes Prevention Program (DPP): A commentary on the importance of research aimed at intervention optimization.

This article discusses the Diabetes Prevention Program (DPP). DPP was an extremely successful clinical trial that demonstrated the efficacy of lifestyle intervention in the prevention of type 2 diabetes in those at increased risk. Many have asked how this study came to be. The author presents a historical perspective on the DPP trial, stressing both the many years of research that preceded and permitted this successful study and its impact on both clinical approaches and subsequent research directions. The author discusses the tension that seems to exist between two important types of research-conducting systematic research aimed at optimizing an intervention to ensure that it will successfully change the targeted behavior versus moving more rapidly to clinical trials testing the health benefits derived from changing the targeted behavior. Today studies that propose to conduct programmatic research related to intervention optimization are criticized for not also testing if these interventions produce clinically important health outcomes. It is not cost-effective to seek answers to questions about health outcomes before developing and demonstrating the efficacy of the intervention on changing the behavioral targets. There are many examples of large clinical trials examining the effect of changing a behavior on an important health outcome that have failed to achieve significant differences in health outcomes because the intervention was not successful in changing the behavior relative to the control condition. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Perceived Heart Attack Likelihood in Adults with a High Diabetes Risk

BackgroundHeart disease is the leading cause of death for women and men in the United States. Yet, little is known about the motivation for care-seeking behavior for heart attack and the perception of self-risk of a heart attack in individuals, especially those at high risk for developing type 2 diabetes. ObjectivesThis study aimed to describe knowledge and awareness of heart attacks and perceived risk for future heart attacks and evaluate factors associated with a low perceived risk of a heart attack in adults with a high risk for type 2 diabetes. MethodsIn this secondary data, cross-sectional study, the screening/baseline data of 80 adults participating in the mobile phone-based diabetes prevention program trial were analyzed. Validated measures assessed knowledge, self-efficacy, and heart attack risk perception were used. Logistic regressions were performed. ResultsThe mean (standard deviation) age of participants was 55.4 (9.0) years. 32.5% of the sample failed to identify any heart attack symptoms. Half of the sample did not perceive their risk of having a heart attack in their lifetime. Older age, lower body mass index, not having a family history of heart attack, and current smokers were significantly associated with a lower perceived risk of heart attack (P < .05). ConclusionsHealthcare providers need to assess the discrepancies between the individual's risk perception and the presence of actual risk factors of a heart attack in adults with a high risk for type 2 diabetes.

1097-P: Comparative Effectiveness of Diabetes Prevention Program Implementation Strategies

Background: In the US Diabetes Prevention Program (DPP) trial, a lifestyle intervention program focused on changes in diet and physical activity led to a 58% reduction in risk of developing type 2 diabetes. A variety of modifications to the DPP have been tested in clinical trials. We sought to compare the effects of different strategies for implementation of the US DPP on weight and other cardiometabolic outcomes. Methods: We conducted systematic searches of MEDLINE and Embase from January 2002 to August 2020. We included randomized controlled trials of adults that tested the effect of an intervention based on the US DPP on change in weight. Studies of at least 6 months duration were included. Two investigators independently extracted data. DPP implementation strategies were classified into eight different categories. Results: A total of 30 comparisons from 28 articles with 8,284 participants were included. Different strategies for implementing the DPP led to significant decreases in change in weight in the DPP compared with control arms during follow-up (Table). These strategies included intervention delivery through group sessions or combination of group and individual sessions. Additionally, interventions delivered by telehealth or by a combination of in-person and telehealth were effective. Conclusion: A number of different strategies for implementing the DPP lead to clinically meaningful decreases in weight. Disclosure K. S. Dorans: None. K. T. Mills: None. Y. Feng: None. A. A. Sethi: None. X. Li: None. J. He: None. Funding National Institute of General Medical Sciences (1P20GM109036-01A1)

Examining the Relationship Between Physical Activity and Self-Efficacy for Exercise Among Overweight and Obese Marshallese Adults.

This study examined associations between physical activity frequency and self-efficacy for exercise (SEE) among Marshallese adults in the United States. Data were collected from overweight and obese Marshallese participants (N = 378) enrolled in a Diabetes Prevention Program trial. Logistic and ordinal logistic regressions were employed to examine associations between physical activity and SEE, adjusting for covariates. SEE was significantly associated with engaging in sufficient total physical activity [odds ratio (OR) = 1.70], moderate physical activity (OR = 2.23), and vigorous physical activity (OR = 2.13). Unemployment was associated with less frequent moderate physical activity (OR = 0.59). Younger age (OR = 0.98), being male (OR = 2.67), and reporting excellent health (OR = 3.14) or good health (OR = 2.06) were associated with more frequent vigorous physical activity. Physical activity is a modifiable lifestyle behavior associated with many chronic disease disparities faced by the Marshallese community, and the study results will be useful for practitioners and researchers working to address these disparities.

Per- and polyfluoroalkyl substances and calcifications of the coronary and aortic arteries in adults with prediabetes: Results from the diabetes prevention program outcomes study

BackgroundPer- and polyfluoroalkyl substances (PFAS) are endocrine disrupting chemicals that have been associated with cardiovascular risk factors including elevated body weight and hypercholesterolemia. Therefore, PFAS may contribute to the development of atherosclerosis and cardiovascular disease (CVD). However, no previous study has evaluated associations between PFAS exposure and arterial calcification. Methods and resultsThis study used data from 666 prediabetic adults enrolled in the Diabetes Prevention Program trial who had six PFAS quantified in plasma at baseline and two years after randomization, as well as measurements of coronary artery calcium (CAC) and ascending (AsAC) and descending (DAC) thoracic aortic calcification 13–14 years after baseline. We performed multinomial regression to test associations between PFAS and CAC categorized according to Agatston score [low (<10), moderate (11–400) and severe (>400)]. We used logistic regression to assess associations between PFAS and presence of AsAC and DAC. We adjusted models for baseline sex, age, BMI, race/ethnicity, cigarette smoking, education, treatment assignment (placebo or lifestyle intervention), and statin use. PFAS concentrations were similar to national means; 53.9% of participants had CAC > 11, 7.7% had AsAC, and 42.6% had DAC. Each doubling of the mean sum of plasma concentrations of linear and branched isomers of perfluorooctane sulfonic acid (PFOS) was associated with 1.49-fold greater odds (95% CI: 1.01, 2.21) of severe versus low CAC. This association was driven mainly by the linear (n-PFOS) isomer [1.54 (95% CI: 1.05, 2.25) greater odds of severe versus low CAC]. Each doubling of mean plasma N-ethyl-perfluorooctane sulfonamido acetic acid concentration was associated with greater odds of CAC in a dose-dependent manner [OR = 1.26 (95% CI:1.08, 1.47) for moderate CAC and OR = 1.37 (95% CI:1.07, 1.74) for severe CAC, compared to low CAC)]. Mean plasma PFOS and n-PFOS were also associated with greater odds of AsAC [OR = 1.67 (95% CI:1.10, 2.54) and OR = 1.70 (95% CI:1.13, 2.56), respectively], but not DAC. Other PFAS were not associated with outcomes. ConclusionsPrediabetic adults with higher plasma concentrations of select PFAS had higher risk of coronary and thoracic aorta calcification. PFAS exposure may be a risk factor for adverse cardiovascular health among high-risk populations.

Targeting of the diabetes prevention program leads to substantial benefits when capacity is constrained.

Approximately 84 million people in the USA have pre-diabetes, but only a fraction of them receive proven effective therapies to prevent type 2 diabetes. We estimated the value of prioritizing individuals at highest risk of progression to diabetes for treatment, compared to non-targeted treatment of individuals meeting inclusion criteria for the Diabetes Prevention Program (DPP). Using microsimulation to project outcomes in the DPP trial population, we compared two interventions to usual care: (1) lifestyle modification and (2) metformin administration. For each intervention, we compared targeted and non-targeted strategies, assuming either limited or unlimited program capacity. We modeled the individualized risk of developing diabetes and projected diabetic outcomes to yield lifetime costs and quality-adjusted life expectancy, from which we estimated net monetary benefits (NMB) for both lifestyle and metformin versus usual care. Compared to usual care, lifestyle modification conferred positive benefits and reduced lifetime costs for all eligible individuals. Metformin's NMB was negative for the lowest population risk quintile. By avoiding use when costs outweighed benefits, targeted administration of metformin conferred a benefit of $500 per person. If only 20% of the population could receive treatment, when prioritizing individuals based on diabetes risk, rather than treating a 20% random sample, the difference in NMB ranged from $14,000 to $20,000 per person. Targeting active diabetes prevention to patients at highest risk could improve health outcomes and reduce costs compared to providing the same intervention to a similar number of patients with pre-diabetes without targeted selection.

Per- and polyfluoroalkyl substances and kidney function: Follow-up results from the Diabetes Prevention Program trial

Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to determine longitudinal associations of plasma PFAS concentrations with estimated glomerular filtration rate (eGFR) and evaluate whether a lifestyle intervention modify the associations. We studied 875 participants initially randomized to the lifestyle or placebo arms in the Diabetes Prevention Program (DPP, 1996–2002) trial and Outcomes Study (DPPOS, 2002–2014). We ran generalized linear mixed models accounting a priori covariates to evaluate the associations between baseline PFAS concentrations and repeated measures of eGFR, separately, for six PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA); then used quantile-based g-computation to evaluate the effects of the six PFAS chemicals as a mixture. The cohort was 64.9% female; 73.4% 40–64 years-old; 29.4% with hypertension; 50.5% randomized to lifestyle intervention and 49.5% to placebo and had similar plasma PFAS concentrations as the general U.S. population in 1999–2000. Most participants had normal kidney function (eGFR > 90 mL/min/1.73 m2) over the approximately 14 years of follow-up. We found that plasma PFAS concentrations during DPP were inversely associated with eGFR during DPPOS follow-up. Each quartile increase in baseline plasma concentration of the 6 PFAS as a mixture was associated with 2.26 mL/min/1.73 m2 lower eGFR (95% CI: −4.12, −0.39) at DPPOS Year 5, approximately 9 years since DPP randomization and PFAS measurements. The lifestyle intervention did not modify associations, but inverse associations were stronger among participants with hypertension at baseline. Among prediabetic adults, we found inverse associations between baseline plasma PFAS concentrations and measures of eGFR throughout 14 years of follow-up. The lifestyle intervention of diet, exercise and behavioral changes did not modify the associations, but persons with hypertension may have heightened susceptibility.

Per- and polyfluoroalkyl substance plasma concentrations and metabolomic markers of type 2 diabetes in the Diabetes Prevention Program trial.

Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals, some of which have been linked to type 2 diabetes. We tested whether PFAS concentrations were cross-sectionally associated with metabolites previously shown to predict incident type 2 diabetes using the Diabetes Prevention Program (DPP), a trial of individuals at high risk of type 2 diabetes. We evaluated 691 participants enrolled in the DPP with baseline measures of 10 PFAS (including total perfluorooctanesulfonic acid (PFOS), total perfluorooctanoic acid (PFOA), and Sb-PFOA [branched isomers of PFOA]) and 77 metabolites. We used log2-transformed PFAS concentrations as exposures and standardized metabolite concentrations as outcomes in linear regression models adjusted for age, sex, race/ethnicity, use of anti-hyperlipidemic or triglyceride-lowering medication, income, years of education, marital status, smoking, and family history of diabetes, with Benjamini-Hochberg linear step-up false discovery rate correction. Sb-PFOA was associated with the largest number of tested metabolites (29 of 77). Each doubling in Sb-PFOA was associated with higher leucine (β=0.07 [95%CI: 0.02, 0.11] SD) and lower glycine (-0.08 [95%CI: 0.03, -0.13] SD). Each doubling of either total PFOA or n-PFOA was associated with -0.13 [95%CI: 0.04, -0.22] SD lower glycine. PFOA and Sb-PFOA were positively associated with multiple triacylglycerols and diacylglycerols, and total PFOS, total PFOA, and Sb-PFOA were positively associated with phosphatidylethanolamines. PFAS concentrations are associated with metabolites linked to type 2 diabetes (particularly amino acid, glycerolipid and glycerophospholipid pathways). Further prospective research is needed to test whether these metabolites mediate associations of PFAS and type 2 diabetes.

Dietary characteristics associated with plasma concentrations of per- and polyfluoroalkyl substances among adults with pre-diabetes: Cross-sectional results from the Diabetes Prevention Program Trial

Diet is assumed to be the main source of exposure to per- and polyfluoroalkyl substances (PFAS) in non-occupationally exposed populations, but studies on the diet-PFAS relationship in the United States are scarce. We extracted multiple dietary variables, including daily intakes of food group, diet scores, and dietary patterns, from self-reported dietary data collected at baseline (1996–1999) from adults with pre-diabetes enrolled in the Diabetes Prevention Program, and used linear regression models to evaluate relationships of each dietary variable with plasma concentrations of six PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid (EtFOSAA), 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA), perfluorononanoic acid (PFNA) adjusting for covariates. Participants (N = 941, 65% female, 58% Caucasian, 68% married, 75% with higher education, 95% nonsmoker) had similar PFAS concentrations compared to the general U.S. population during 1999–2000. Using a single food group approach, fried fish, other fish/shellfish, meat and poultry had positive associations with most PFAS plasma concentrations. The strongest effect estimate detected was between fried fish and PFNA [13.6% (95% CI: 7.7, 19.9) increase in median concentration per SD increase]. Low-carbohydrate and high protein diet score had positive association with plasma PFHxS. Some food groups, mostly vegetables and fruits, and the Dietary Approaches to Stop Hypertension diet score had inverse associations with PFOS and MeFOSAA. A vegetable diet pattern was associated with lower plasma concentrations of MeFOSAA, while high-fat meat and low-fiber and high-fat grains diet patterns were associated with higher plasma concentrations of PFOS, PFHxS, MeFOSAA and PFNA. We summarized four major dietary characteristics associated with variations in PFAS plasma concentrations in this population. Specifically, consuming more meat/fish/shellfish (especially fried fish, and excluding Omega3-rich fish), low-fiber and high-fat bread/cereal/rice/pasta, and coffee/tea was associated with higher plasma concentrations while dietary patterns of vegetables, fruits and Omega-3 rich fish were associated with lower plasma concentrations of some PFAS.

Translating Knowledge into Action to Prevent Type 2 Diabetes: Medicare Expansion of the National Diabetes Prevention Program Lifestyle Intervention

Many evidence-based health interventions never achieve national implementation. This article analyzes factors that supported the translation and national implementation of a lifestyle change intervention to prevent or delay type 2 diabetes in individuals with prediabetes. We used the Knowledge to Action framework, which was developed to map how science is translated into effective health programs, to examine how the evidence-based intervention from the 2002 Diabetes Prevention Program trial was translated into the Centers for Disease Control and Prevention's large-scale National Diabetes Prevention Program, eventually resulting in payment for the lifestyle intervention as a Medicare-covered service. Key findings of our analysis include the importance of a collaboration among researchers, policymakers, and payers to encourage early adopters; development of evidence-based, national standards to support widespread adoption of the intervention; and use of public input from community organizations to scale the intervention to a national level. This analysis offers timely lessons for other high-value, scalable interventions attempting to move beyond the evidence-gathering phase and into translation and institutionalization.

32 - Core Outcome Set for Diabetes After Pregnancy Prevention Studies

In women averaging 10 years following gestational diabetes (GDM), the American Diabetes Prevention Program trial demonstrated reduced diabetes after pregnancy (DAP) with health behaviour change. Recent trials for women within 5 years of GDM are neither large enough nor long enough to measure incident diabetes. Such shorter-term trials are needed before investing in large trials. We conducted an online 2-round Delphi survey as a step to develop an international core outcome set (COS) for shorter-term DAP prevention studies.

Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Incident Diabetes and Microvascular Disease.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are suspected endocrine disruptors widely detected across populations. We examine the extent to which PFASs are associated with diabetes incidence and microvascular disease. Secondarily, we tested whether a lifestyle intervention modifies associations and decreases concentrations. We analyzed data from a prospective cohort of 957 participants from the Diabetes Prevention Program (DPP) trial and Diabetes Prevention Program Outcomes Study (DPPOS). At baseline, participants were randomized to an intensive lifestyle intervention of diet, physical activity, and behavior modification or a placebo medication. We quantified plasma concentrations of six PFASs at baseline and 2 years after randomization. Participants were monitored for ∼15 years, repeatedly tested for diabetes, and evaluated for microvascular disease at the end of the follow-up. A doubling in baseline branched perfluorooctanoic acid concentration was associated with a 14% increase in diabetes risk for the placebo (hazard ratio [HR] 1.14, 95% CI 1.04, 1.25) but not in the lifestyle intervention group (HR 1.01, 95% CI 0.92, 1.11, P interaction = 0.11). Mean change in plasma baseline branched perfluorooctanoic acid concentration was greater for the placebo (0.96 ng/mL; 95% CI 0.71, 1.22) compared with the lifestyle intervention group (0.31 ng/mL; 95% CI 0.14, 0.48) 2 years after randomization. Each doubling in N-ethyl-perfluorooctane sulfonamido acetic acid was associated with 17% greater odds of prevalent microvascular disease (OR 1.17, 95% CI 1.05, 1.31), and a similar association was observed for perfluorodimethylhexane sulfonic acid (OR 1.18, 95% CI 1.04, 1.35), regardless of treatment. Some plasma PFASs were associated with diabetes and microvascular disease. Our results suggest that exercise and diet may attenuate the diabetogenic association of PFASs.

830-P: Influence of Social Circumstances on Maintenance of Body Weight and Incident Type 2 Diabetes: Analyses from the Diabetes Prevention Program

The impact of social and environmental circumstances on success in an intensive behavioral intervention to lose weight and reduce risk of type 2 diabetes is unknown. We examined the association of social and environmental circumstances such as provisions of social relations and support, home and work environment, and adverse life events on weight loss and diabetes incidence in the Diabetes Prevention Program (DPP) randomized controlled trial. We included data on 650 female and 319 male adults from the DPP lifestyle intervention group with information on social circumstances and body weight at baseline and follow-up after 6 months (24 weeks of lifestyle intervention), 1, and 2 years. We applied Cox proportional hazards model to obtain hazard ratios (HRs), with social circumstances as the exposures and body weight gain (&amp;gt;7%) or development of diabetes as outcome, adjusting for baseline age, sex, marital status, and number of individuals in the home of the participant. Life style intervention participants who experienced events or changes at work during the DPP trial had a 44% higher risk of developing diabetes [HRR=1.44, 95% CI:1.02;2.04] as compared to lifestyle intervention participants who did not have such experiences at work. Adjustment of body weight gain after the intervention period explained a small component of this risk: 1.38 [95% CI:0.94;2.03]. Negative changes in the home environment [HRR=1.09, 95% CI:0.76;1.56], low provision of social relations [HRR=1.15, 95% CI:0.81;1.65] or adverse life events [HRR=1.14, 95% CI:0.81;1.62] did not increase the HR of developing diabetes. Social circumstances were not associated with &amp;gt;7% body weight increase between the end of the intervention period and 1 or year 2. Thus, our results suggest that work changes and stresses may worsen the possibility of lowering diabetes risk through intensive lifestyle interventions. Disclosure J. NIelsen: None. M.K. Ali: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases; General Clinical Research Center; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Aging; Office of Research on Women's Health; Office of Research on Minority Health; Centers for Disease Control and Prevention

5-LB: Improving Diabetes Prevention with Benefit-Based Tailored Treatment: Disseminating Individualized Risk Estimates

Objective: Implement in an electronic health record (EHR) a predictive model for people with prediabetes that provides individualized benefit estimates for taking metformin or participating in the Diabetes Prevention Program (DPP). This model stratifies people with prediabetes by the potential to reduce their risk of progression to diabetes based on regression models developed directly on the DPP trial and recalibrated to Optum data. With 1/3 of adults having prediabetes, health systems need a way to prioritize. Study Design: Pre/post implementation study including provider and patient surveys and data on use of the predictive model. The model estimates risk of progression to diabetes with usual care, the DPP, or metformin, based on 11 demographic, biometric and diagnosis variables available in the EHR. Population Studied: Patients with prediabetes at 10 pilot primary care clinics, where providers access the model via an EHR click and the data elements are automatically populated from the EHR. Principal Findings: The predictive model was used on 68% (n=2,304) of patients with prediabetes between 5/1/18 and 1/31/19. A total of 43% of patients were classified as high-risk, 54% as moderate-risk, and 4% as low-risk. Treatment - either referrals to the DPP or prescriptions for metformin - was provided for 63% of high-risk, 15% of moderate-risk, and 4% of low-risk patients. DPP referrals and metformin prescriptions for these high-risk patients increased substantially after implementation of the calculator (DPP: 0% to 44%; Metformin: 2% to 19%). Conclusions: A predictive model, embedded in the EHR, that predicts individual patient risk for developing diabetes at the point of care improved treatment for patients with prediabetes. Use of individualized risk estimates resulted in the prioritization of treatment for patients at greatest risk of developing type 2 diabetes. Disclosure E.L. Ciemins: None. J.E. Powelson: None. J.P. Nelson: None. F.R. Colangelo: None. J.K. Cuddeback: None. D.M. Kent: None. Funding Patient-Centered Outcomes Research Institute

Association of Perfluoroalkyl and Polyfluoroalkyl Substances With Adiposity

ImportancePerfluoroalkyl and polyfluoroalkyl substances (PFASs) are ubiquitous synthetic chemicals that are suspected endocrine disruptors.ObjectivesTo determine the extent to which PFASs are associated with increases in weight and body size and evaluate whether a lifestyle intervention modifies this association.Design, Setting, and ParticipantsThis prospective cohort study included 957 individuals who participated in the Diabetes Prevention Program trial, conducted from July 1996 to May 2001, and the Diabetes Prevention Program Outcomes Study, conducted from September 2002 to January 2014. Statistical analysis was conducted from September 1, 2017, to May 25, 2018.Interventions and ExposuresThe initial lifestyle intervention consisted of training in diet, physical activity, and behavior modification, with the major goals of achieving 7% weight loss with subsequent maintenance and a minimum of 150 minutes per week of physical activity. Participants randomized to placebo received standard information about diet and exercise. A total of 6 plasma PFASs were quantified at baseline and 2 years after randomization, means were calculated from baseline and year 2 concentrations, and means were summed to assess total PFAS burden.Main Outcomes and MeasuresWeight, waist circumference, and hip girth were measured at baseline and at scheduled visits.ResultsOf the 957 participants, 625 (65.3%) were women and 731 participants (76.4%) were between 40 and 64 years of age; 481 participants were randomized to the lifestyle intervention and 476 participants were randomized to the placebo arm. The PFAS concentrations were not different by treatment arm and were similar to concentrations reported for the US population in 1999-2000. The association of PFAS and weight change differed by treatment. Each doubling in total PFAS concentration was associated with an increase of 1.80 kg (95% CI, 0.43-3.17 kg; P = .01) from baseline to 9 years after randomization for the placebo group but not the lifestyle intervention group (−0.59 kg; 95% CI, –1.80 to 0.62 kg; P = .34). Similarly, each doubling in PFAS was associated with a 1.03-cm increase in hip girth in the Diabetes Prevention Program trial for the placebo group (95% CI, 0.18-1.88 cm; P = .02) but not the lifestyle intervention group (−0.09 cm; 95% CI, −0.82 to 0.63 cm; P = .80). No associations were observed for changes in mean waist circumference.Conclusions and RelevanceAmong adults at high risk for diabetes, higher plasma PFAS concentration was associated with increases in weight and hip girth over time, but a lifestyle intervention attenuated these associations. Diet and exercise may mitigate the obesogenic effects of environmental chemicals.Trial RegistrationClinicalTrials.gov Identifier: NCT00004992 and NCT00038727

Plasma Concentrations of Per- and Polyfluoroalkyl Substances at Baseline and Associations with Glycemic Indicators and Diabetes Incidence among High-Risk Adults in the Diabetes Prevention Program Trial.

Background:Several per- and polyfluoroalkyl substances (PFAS) are ubiquitous anthropogenic pollutants almost universally detected in humans. Experimental evidence indicates that PFAS alter glucose metabolism and insulin secretion. However, epidemiological studies have yielded inconsistent results.Objective:We sought to examine associations between plasma PFAS concentrations, glycemic indicators, and diabetes incidence among high-risk adults.Methods:Within the Diabetes Prevention Program (DPP), a trial for the prevention of type 2 diabetes among high-risk individuals, we quantified baseline plasma concentrations of nine PFAS among 957 participants randomized to a lifestyle intervention or placebo. We evaluated adjusted associations for plasma PFAS concentrations with diabetes incidence and key glycemic indicators measured at baseline and annually over up to 4.6 y.Results:Plasma PFAS concentrations were similar to those reported in the U.S. population in 1999–2000. At baseline, in cross-sectional analysis, a doubling in plasma perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) concentrations was associated with higher homeostatic model assessment of insulin resistance (HOMA-IR) [; 95% confidence interval (CI): 0.13, 0.66; ; 95% CI: 0.34, 0.94], function () (; 95% CI: 1.55, 17.70; ; 95% CI: 6.78, 25.08), fasting proinsulin (; 95% CI: 0.50, 2.25; ; 95% CI: 0.72, 2.71), and glycated hemoglobin () (; 95% CI: 0.002, 0.07; ; 95% CI: 0.001, 0.07). There was no strong evidence of associations between plasma PFAS concentrations and diabetes incidence or prospective changes in glycemic indicators during the follow-up period.Conclusions:At baseline, several PFAS were cross-sectionally associated with small differences in markers of insulin secretion and function. However, there was limited evidence suggesting that PFAS concentrations are associated with diabetes incidence or changes in glycemic indicators during the follow-up period. https://doi.org/10.1289/EHP1612