The Diabetes Prevention Program (DPP) was a 3-year randomized clinical trial (RCT) with evaluation of lifestyle and metformin interventions compared with placebo for diabetes prevention in high-risk adults. Both interventions significantly reduced diabetes incidence, prompting the long-term Diabetes Prevention Program Outcomes Study (DPPOS) to assess the progression of diabetes and its complications over 22 years. During follow-up, departures from the original metformin or placebo assignment occurred primarily because of development of diabetes that, by protocol, was managed by clinicians outside the study, after participants developed diabetes with HbA1c ≥7.0%. Diabetes development led to changes in metformin treatment and addition of other glucose-lowering therapies. Using statistical methods designed to estimate intervention effects despite these deviations, we consistently found that metformin reduced diabetes incidence. However, using these methods to evaluate whether use of metformin for prediabetes confers continued benefits after diabetes diagnosis did not substantially change the conclusions from those of the simpler intention-to-treat analysis that did not account for treatment changes. All of the analytic methods used resulted in similar metformin effect estimates with 95% CIs for hazard ratios including 1.0 (no effect) for all outcomes except for diabetes incidence. Elucidating metformin's long-term role in mitigating diabetes-related complications beyond its effects on diabetes prevention is challenging.

BACKGROUND:In the US Diabetes Prevention Program (DPP), a 3-year randomised clinical trial in 3234 adults with prediabetes, type 2 diabetes incidence was reduced by 58% with intensive lifestyle intervention (ILS) and by 31% with metformin, compared with placebo. We sought to assess the long-term effects and potential heterogeneity of treatment effects over approximately 21 years of follow-up. METHODS:The DPP trial was continued with protocol modifications as the DPP Outcomes Study (DPPOS). In the DPPOS, placebo was discontinued, metformin (850 mg twice a day as tolerated) was continued after unmasking, and group-based booster intervention classes were offered to the ILS group twice a year; additionally, all participants were offered group-based lifestyle intervention four times a year. The prespecified primary outcome during DPP and DPPOS was diabetes incidence defined by American Diabetes Association criteria. The DPPOS protocol specified continued diabetes incidence as an outcome; Feb 23, 2020, was chosen as the closing date for the present analysis, as a date prior to the COVID-19 pandemic, which caused major disruptions in clinic visits and complicated longitudinal data analyses. We assessed long-term persistence of intervention effects on diabetes incidence, and heterogeneity of effects in subgroups defined by baseline diabetes risk factors. Follow-up is reported for the combined study from July 31, 1996, to Feb 23, 2020, and analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, NCT00004992 (DPP) and NCT00038727 (DPPOS); follow-up is ongoing but the trial is closed to enrolment except for previous DPP participants. FINDINGS:3195 participants originally enrolled in the DPP were included in the present analyses. This population comprised 2171 (67·9%) female participants and 1024 (32·1%) male participants, with a mean baseline age of 50·6 years (SD 10·7). Individual follow-up times ranged from 0·2 to 23·2 years (median 8·0 years [IQR 3·0 to 18·0]); remaining numbers at risk decreased sharply after 21 years because of administrative censoring and thus follow-up was considered to represent a 21-year period. During follow-up, compared with placebo, diabetes incidence rate was reduced in the original ILS group (hazard ratio [HR] 0·76 [95% CI 0·68 to 0·85], rate difference [RD] -1·59 cases [95% CI -2·25 to -0·93] per 100 person-years) and in the original metformin group (HR 0·83 [0·74 to 0·93], RD -1·17 [-1·85 to -0·49]), with corresponding increases in median diabetes-free survival of 3·5 years and 2·5 years, and mean diabetes-free survival of 2·0 years (95% CI 1·2 to 2·8) and 1·2 years (0·4 to 2·0), respectively. The diabetes cumulative incidence curves separated early, especially in the first 3 years, with lower incidence rates in the metformin and ILS groups than in the placebo group. The metformin and ILS curves progressively converged with longer follow-up. The overall treatment effects appeared to result from large early effects during the DPP. Absolute intervention effects, measured as RDs versus placebo, were greater with ILS in participants with higher values for baseline fasting glucose, HbA1c, and multivariable clinical and physiological risk indices, and with metformin in younger participants. INTERPRETATION:The large initial intervention effects seen in the DPP trial were followed by sustained reductions in cumulative diabetes incidence for 21 years. Intervention effects were heterogeneous according to some baseline variables. These findings could guide precision interventions to help address the current type 2 diabetes epidemic. FUNDING:US National Institute of Diabetes and Digestive and Kidney Diseases and other agencies. TRANSLATION:For the Spanish translation of the abstract see Supplementary Materials section.

Meta-analyses have reported a decrease in overall cancer incidence of approximately 10% to 40% with metformin use among individuals with diabetes. Lifestyle change could potentially reduce cancer incidence. The objective was to determine whether metformin or intensive lifestyle (ILS) intervention reduces the risk of cancer among adults at high risk of diabetes. The Diabetes Prevention Program (1996-2001) randomized 3,234 participants to ILS, metformin (850 mg twice daily), or blinded placebo. During follow-up through the Diabetes Prevention Program Outcomes Study, all participants were offered a modified lifestyle intervention, and metformin continued in an open-label metformin group. Participants reported cancer cases annually. Medical records were adjudicated for all reported events. The primary endpoint was total cancer incidence, comparing metformin versus placebo, with ILS versus placebo as a secondary objective. After a median follow-up of 21 years, 546 participants (173 metformin, 182 ILS, and 191 placebo) were diagnosed with a first incident cancer. Incidence rates of cancer were 9.8, 10.5, and 10.8 per 1,000 person-years in metformin, ILS, and placebo, respectively, with a HR of 0.90 (95% confidence interval, 0.73-1.10) for metformin compared with placebo and 0.96 (95% confidence interval, 0.79-1.18) for ILS compared with placebo. There were no differences between any treatment groups for obesity-related cancer or in sex-specific analyses. Neither assignment to metformin nor ILS reduced cancer incidence among adults at high risk of diabetes. These results may be impacted by increased nonstudy metformin usage over time due to the development of diabetes and reduced intensity of the ILS intervention over time. PREVENTION RELEVANCE:This study examines both metformin and ILS intervention as primary cancer prevention interventions in people at high risk for type 2 diabetes.

BACKGROUND:Modifying lifestyle factors may reduce the incidence of obesity, diabetes, and cancer. OBJECTIVES:We examined how alignment with the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations using the 2018 WCRF/AICR score was associated with incident lifestyle-related cancer in adults with prediabetes in the Diabetes Prevention Program (DPP, 1996-2001) and DPP Outcomes Study (DPPOS, 2002-2020), an observational follow-up of a randomized clinical trial. METHODS:Participants were randomly assigned to lifestyle, metformin, or placebo interventions (mean: 3 y) and followed for an additional 19 y. The 2018 WCRF/AICR score (0-7 points; higher score, better alignment) was calculated from body weight, physical activity, diet, and alcohol components at 0, 1, 5, 6, 9, and 15 y after randomization. Incident cancer was based on the 2018 WCRF/AICR 3rd Expert Report (18 cancers associated with lifestyle). Adjusted Cox proportional hazard models estimated associations between the score (baseline [0], change from 0 to 1 y, time dependent) and lifestyle-related cancer. RESULTS:Participants' (N = 3000) mean baseline WCRF/AICR score was 3.2 (SD: 1.1). There were 403 incident lifestyle-related cancer cases. Scores improved after 1 and 15 y (mean increase = 0.43 and 0.27 points, respectively, both P < 0.001). The baseline score was not associated with cancer risk. However, a 1-unit score improvement from 0 to 1 y and time-dependent scores were significantly associated with a 14% (hazard ratio [HR]: 0.86; 95% confidence interval [95% CI]: 0.76, 0.97) and 9% (HR: 0.91; 95% CI: 0.83, 0.997) lower risk, respectively, with no effect modification by intervention group or diabetes status. In exploratory by-component analyses, no single component was associated with risk. CONCLUSIONS:Alignment with WCRF/AICR recommendations may lower cancer risk in adults with prediabetes and type 2 diabetes, highlighting the importance of considering lifestyle factors for cancer prevention. TRIAL REGISTRATION NUMBER:Diabetes Prevention Program, NCT00004992; Diabetes Prevention Program Outcomes Study, NCT00038727.

OBJECTIVE:Type 2 diabetes (T2D) and its associated complications develop heterogeneously over decades, but few studies span the progression from prediabetes to clinical events. We investigated whether long-term metabolic trajectories beginning in prediabetes delineate subgroups with differential complication risk. RESEARCH DESIGN AND METHODS:Clinical data from 1,732 Diabetes Prevention Program/Outcomes Study participants (follow-up 19 years) were analyzed across 12 phenotypes. Tensor decomposition was used to capture longitudinal patterns, and Gaussian mixture modeling was used to define longitudinal clusters. Cluster-specific complications were quantified with Cox and logistic regression. RESULTS:Four clusters emerged. Clusters 1 and 2 (73% of participants) maintained stable glycemia, blood pressure, and lipids. Although 49% and 71%, respectively, developed T2D, cumulative micro- and macrovascular events remained low. Cluster 3 (12%) showed the steepest rise in insulin resistance and hyperglycemia, with 92% of the subgroup progressing to T2D and a markedly higher rate of retinopathy (odds ratio [OR] 8.8, 95% CI 3.9-20.1) and neuropathy (OR 3.4, 95% CI 2.1-5.5). Cluster 4 (15%) presented with baseline microalbuminuria often prior to the development of T2D (73%). It was distinguished by progressive estimated glomerular filtration rate decline and a doubling of cardiovascular events (hazard ratio 2.0, 95% CI 1.4-3.0), despite serum lipids comparable with other groups. CONCLUSIONS:Two-thirds of individuals with prediabetes follow metabolically resilient trajectories, whereas distinct insulin-resistant or renal-dysfunction trajectories precede micro- or macrovascular complications, respectively. The optimal window for macrovascular complication prevention in individuals with prediabetes microalbuminuria may precede progression to T2D.

Introduction and Objective: Effects of the COVID-19 pandemic on clinical trials and longitudinal cohorts were profound, but impacts on health-related and social factors of such cohorts have not been examined. We report the impact of COVID-19 on DPPOS participants. Methods: The study included 1877 adults who had high risk of T2D at enrollment in 1996-1999 were followed semi-annually. Study visits were conducted virtually from March until August 2020, with in-person visits resuming site-by-site thereafter. A COVID-19 pandemic impact survey was completed by phone or in-person from January 2021 to June 2022. Linear mixed models explored differences in health outcomes measured in the clinic both before and after pandemic closures. Results: Through June 2022, 322 DPPOS participants (17%) self-reported a COVID-19 illness, 60 (18.6% of 322) were hospitalized and 20 (6.2%) died from COVID-19; 1745 (94%) reported being vaccinated. Among 1859 participants who completed at least one survey, common burdens included: decreased physical activity (PA, 50%), increased food intake (27%), negative impact on relationships (19%), lost job/income (9%), new or increased caring for family member (7%), and difficulty getting food/medications (7%). Overall, greater burden was observed among women, younger participants, and American Indian participants. Women were more likely than men to report an increase in food intake (17% men, 31% women) and a decrease in PA (34% men, 56% women). Of 1329 participants with longitudinal in-person measurements both before March 2020 and between July 2020-June 2022, there were no significant changes in weight/BMI, blood pressure or HbA1c post-pandemic. Conclusion: Hospitalization and death from COVID-19 were significant, as was the overall burden of the pandemic, particularly among women. The pandemic was associated with personal burden but not T2D-specific health outcomes, underscoring the social impact of the pandemic on individuals from varying sociodemographic groups. A.H. Tjaden: None. K.A. Temple: None. S. Edelstein: None. W.C. Knowler: None. V. Shah: None. S. Kuo: None. P. Wander: None. M.G. Araneta: None. J.M. Noble: None. D. Dabelea: None. R.L. Dubin: None. J.P. Crandall: None. D. Research Group: None. National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (U01 DK048489, U01 DK048339, U01 DK048377, U01 DK048349, U01 DK048381, U01 DK048468, U01 DK048434, U01 DK048485, U01 DK048375, U01 DK048514, U01 DK048437, U01 DK048413, U01 DK048411, U01 DK048406, U01 DK048380, U01 DK048397, U01 DK048412, U01 DK048404, U01 DK048387, U01 DK048407, U01 DK048443, and U01 DK048400)

OBJECTIVE:The clinical presentation, symptoms, and signs of neuropathy vary substantially. We determined whether painful neuropathic symptoms and distal symmetrical polyneuropathy (DSPN) were associated with different risk factors in a longitudinal study of Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study (DPP/DPPOS) participants. RESEARCH DESIGN AND METHODS:We assessed neuropathy in 1,779 DPP/DPPOS participants ∼21 years after DPP randomization. Symptoms were assessed using the Michigan Neuropathy Screening Instrument (MNSI) questionnaire and signs using pinprick, vibration, and monofilament testing. We defined four mutually exclusive neuropathy phenotypes: 1) no symptoms or signs of DSPN, 2) neuropathic pain without signs, 3) other neurologic symptoms without pain or signs, and 4) DSPN (MNSI questionnaire score ≥4 or any signs). We used multinomial logistic regression models to compare nonglycemic and glycemic risk factors among participants to better understand risk factors associated with painful neuropathic symptoms and DSPN. RESULTS:Among the participants, 501 (28%) had no symptoms or signs, 144 (8%) had painful neuropathic symptoms without signs, and 473 (27%) had DSPN. Compared with participants with neither symptoms nor signs, those with painful neuropathic symptoms were more likely to be women, to have greater weight, and lower estimated glomerular filtration rate. Painful symptoms were not associated with glycemia. In contrast, DSPN, when compared with painful symptoms, was associated with older age, White race, and glycemic exposure. CONCLUSIONS:In this cohort, risk factors for painful neuropathic symptoms and DSPN differed. Improved recognition of painful neuropathic symptoms and better consensus on diagnostic criteria may facilitate research into their causes, prevention, and treatment.

Introduction and Objective: Overweight/obesity are determinants of cardiovascular risk. This post hoc analysis evaluated the effect of magnitude of early weight loss during the Diabetes Prevention Program (DPP) on major adverse cardiovascular events (MACE) in DPP and its Outcomes Study (DPPOS). Methods: The DPP randomized 3,234 adults at high risk for type 2 diabetes to intensive lifestyle intervention (ILS), metformin, or placebo (PBO), and subsequently followed the cohort in the DPPOS. Weight loss at DPP Year 1 was assessed categorically (defined as: weight gain/weight neutral (reference category); >0 to <5% weight loss; 5 to <10% weight loss; and ≥10% weight loss). This analysis includes 3,100 participants with Year 1 weight and who did not experience MACE or death prior to Year 1. Time to first occurrence of MACE (death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke) during 22 years of follow-up was assessed using log-rank tests. Risk of MACE was assessed with adjusted Cox proportional hazards models and 95% confidence intervals (aHR; 95% CI) in the overall cohort and in separate treatment groups. Results: Time to first MACE differed by weight loss category (p=0.004) in the overall cohort, with the ≥10% loss weight loss category experiencing significantly lower risk of MACE compared with the weight gain/weight neutral reference category (0.59; 0.37 - 0.94). Weight loss of 5 to <10% in PBO was associated with greater risk of MACE compared with weight gain/weight neutral reference category (2.12; 1.19 - 3.76). Conclusion: Overall, a high magnitude (≥10%) of weight loss over 1 year of intervention was associated with lower risk of MACE in a cohort at high risk for type 2 diabetes, but moderate weight loss in the placebo group was associated with greater risk of MACE. These findings may suggest benefits of intervention-related weight loss and increased risks associated with unintentional or unexpected weight loss. V.R. Aroda: Research Support; Applied Therapeutics. Consultant; Applied Therapeutics. Research Support; Boehringer-Ingelheim, Corcept Therapeutics. Consultant; Corcept Therapeutics, Pfizer Inc, AstraZeneca. Research Support; AstraZeneca. Consultant; Mediflix, Novo Nordisk. Research Support; Novo Nordisk. Consultant; Sanofi. Research Support; Rhythm Pharmaceuticals, Inc. Consultant; Fractyl Health, Inc. Research Support; Fractyl Health, Inc., Eli Lilly and Company. Other Relationship; Merck & Co., Inc, AditumBio. Research Support; Amgen Inc. N.P. Malkani: None. L. Doherty: None. M.J. O'Brien: None. D. Dabelea: None. U.N. Ibebuogu: None. W.C. Knowler: None. S. Kuo: None. N.N. Mathioudakis: None. S. Edelstein: None. D. Research Group: None. National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (U01 DK048489, U01 DK048339, U01 DK048377, U01 DK048349, U01 DK048381, U01 DK048468, U01 DK048434, U01 DK048485, U01 DK048375, U01 DK048514, U01 DK048437, U01 DK048413, U01 DK048411, U01 DK048406, U01 DK048380, U01 DK048397, U01 DK048412, U01 DK048404, U01 DK048387, U01 DK048407, U01 DK048443, and U01 DK048400)

Chemotherapy treatment-related side effects are common and increase the risk of suboptimal outcomes. Exercise interventions during cancer treatment improve self-reported physical functioning, fatigue, anxiety, and depression, but it is unclear whether these interventions improve important clinical outcomes, such as chemotherapy relative dose intensity. The National Cancer Institute funded the Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO) Consortium to address this knowledge gap. This article describes the mechanisms hypothesized to underpin intervention effects on clinically relevant treatment outcomes, briefly outlines each project's distinct research aims, summarizes the scope and organizational structure of ENICTO, and provides an overview of the integrated common data elements used to pursue research questions collectively. In addition, the article includes a description of consortium-wide activities and broader research community opportunities for collaborative research. Findings from the ENICTO Consortium have the potential to accelerate a paradigm shift in oncology care such that patients with cancer could receive exercise and nutrition programming as the standard of care in tandem with chemotherapy to improve relative dose intensity for a curative outcome.

ObjectivesType 2 diabetes (T2D) and prediabetes are associated with poor walking endurance, a marker of physical function. We aimed to examine the long-term effects of metformin or intensive lifestyle intervention in adults at high risk of T2D on their 6-min walk test (6MWT) performance.MethodsParticipants were randomized in the 3-year Diabetes Prevention Program (DPP) to one of the three groups: lifestyle intervention, metformin, or placebo, and were subsequently followed in the DPP Outcomes Study. A 6MWT was conducted 20 years after randomization. Associations between DPP interventions and 6MWT completion (achieving a distance ≥200 m) were assessed using logistic regression. Among the test completers, differences in distance walked (6MWD) were evaluated using multivariable linear regression. Additional variables of interest included concomitant measures of body mass index (BMI) and grip strength along with mean measures of HbA1c and self-reported physical activity (PA).ResultsData on 1830 participants were analyzed. The interventions were not associated with test completion or the 6MWD among test completers (362, 364, and 360 m in the lifestyle, metformin, and placebo groups, respectively, p = 0.8). Age, education, grip strength, and PA were each significantly associated with the 6MWT completion and the 6MWD after adjustment. Grip strength, PA, and education were positively associated with the 6MWD, while age, BMI, and HbA1c were negatively associated with the 6MWD.ConclusionWe confirmed that the 6MWT is related to other measures of physical ability such as PA and grip strength in persons at risk for and with T2D, suggesting potential long-term benefits of maintaining a healthy lifestyle. However, we did not observe a sustained effect of the original randomized interventions.Clinical trial registrationhttp://www.clinicaltrials.gov/ct/show/NCT00004992, identifier DPP NCT00004992; http://www.clinicaltrials.gov/ct/show/NCT00038727, identifier DPPOS NCT00038727

Introduction & Objective: Type 2 Diabetes (T2D) complications cause morbidity and mortality, but occur heterogeneously among those at risk. While some individuals maintain stable health over time, others decompensate. Using data from the DPPOS, this study aimed to identify unbiased, data driven subgroups of adults at risk for T2D with heterogeneous metabolic trajectories and clinical outcomes over time. Methods: Data from 1736 DPP participants over 39 semi-annual visits with repeated clinical parameters (glycemia, insulin, lipids, body mass index (BMI), waist circumference, blood pressure (BP), microalbuminuria (MA) and eGFR) were analyzed. A 3-dimensional tensor of individuals x clinical parameters x visits was constructed. Nonnegative tensor decomposition was performed and the resulting factors were clustered using K-means. Cohesion and separation were computed to select an optimal number of clusters. Cumulative incidence of T2D and kidney dysfunction (eGFR < 60 mL/min) were tabulated for each cluster. Results: Nine longitudinal clusters of varying sizes were identified. One cluster represented a healthy group with stable clinical parameters (n=556). Kidney dysfunction was found in two clusters with differing patterns and trajectories: 1) slowly declining eGFR without MA or T2D (n=198), 2) MA, elevated BP and delayed eGFR decline (n=138). Other clusters segregated by patterns of glycemia and insulin resistance (IR) ranging from stable IR, glycemia and elevated BMI (n=253), to rapidly accelerating IR, dysglycemia and T2D (n=34). Conclusion: Temporal trajectories of clinical parameters revealed marked heterogeneity in metabolic decompensation over time for DPPOS participants. A minority had accelerated metabolic and renal decompensation, important groups to target for early intervention. These groups also form the basis for novel biomarker discovery efforts to improve prediction of future complications. Disclosure E. Kobayashi: None. N. Linden: None. S. Edelstein: None. M. Temprosa: None. P. Rangamani: None. A.R. Majithia: None.

Introduction: Vaccine hesitancy presents a challenge to COVID-19 control efforts. To identify beliefs asso-ciated with delayed vaccine uptake, we developed and implemented a vaccine hesitancy survey for the COVID-19 Community Research Partnership.Methods: In June 2021, we assessed attitudes and beliefs associated with COVID-19 vaccination using an online survey. Self-reported vaccination data were requested daily through October 2021. We compared responses between vaccinated and unvaccinated respondents using absolute standardized mean differ-ences (ASMD). We assessed validity and reliability using exploratory factor analysis and identified latent factors associated with a subset of survey items. Cox proportional hazards models and mediation analy-ses assessed predictors of subsequent vaccination among those initially unvaccinated.Results: In June 2021, 29,522 vaccinated and 1,272 unvaccinated participants completed surveys. Among those unvaccinated in June 2021, 559 (43.9 %) became vaccinated by October 31, 2021. In June, unvacci-nated participants were less likely to feel "very concerned" about getting COVID-19 than vaccinated par-ticipants (10.6 % vs. 43.3 %, ASMD 0.792). Among those initially unvaccinated, greater intent to become vaccinated was associated with getting vaccinated and shorter time to vaccination. However, even among participants who reported no intention to become vaccinated, 28.5 % reported vaccination before study end. Two latent factors predicted subsequent vaccination-being 'more receptive' was derived from moti-vation to protect one's own or others' health and resume usual activities; being 'less receptive' was derived from concerns about COVID-19 vaccines. In a Cox model, both factors were partially mediated by vaccination intention.Conclusion: This study characterizes vaccine hesitant individuals and identifies predictors of eventual COVID-19 vaccination through October 31, 2021. Even individuals with no intention to be vaccinated can shift to vaccine uptake. Our data suggest factors of perceived severity of COVID-19 disease, vaccine safety, and trust in the vaccine development process are predictive of vaccination and may be important opportunities for ongoing interventions.(c) 2023 Elsevier Ltd. All rights reserved.

Background: Monitoring the effectiveness of COVID-19 vaccines against SARS-CoV-2 infections remains important to inform public health responses. Estimation of vaccine effectiveness (VE) against serological evidence of SARS-CoV-2 infection might provide an alternative measure of the benefit of vaccination against infection. Methods: We estimated mRNA COVID-19 vaccine effectiveness (VE) against development of SARS-CoV-2 anti-nucleocapsid antibodies in March-October 2021, during which the Delta variant became predomi-nant. Participants were enrolled from four participating healthcare systems in the United States, and completed electronic surveys that included vaccination history. Dried blood spot specimens collected on a monthly basis were analyzed for anti-spike antibodies, and, if positive, anti-nucleocapsid antibodies. We used detection of new anti-nucleocapsid antibodies to indicate SARS-CoV-2 infection, and estimated VE by comparing 154 case-participants with new detection of anti-nucleocapsid antibodies to 1,540 seronegative control-participants matched by calendar period. Using conditional logistic regression, we estimated VE >= 14 days after the 2nd dose of an mRNA vaccine compared with no receipt of a COVID-19 vaccine dose, adjusting for age group, healthcare worker occupation, urban/suburban/rural residence, healthcare system region, and reported contact with a person testing positive for SARS-CoV-2. Results: Among individuals who completed a primary series, estimated VE against seroconversion from SARS-CoV-2 infection was 88.8% (95% confidence interval [CI], 79.6%-93.9%) after any mRNA vaccine, 87.8% (95% CI, 75.9%-93.8%) after BioNTech vaccine and 91.7% (95% CI, 75.7%-97.2%) after Moderna vac-cine. VE was estimated to be lower >= 3 months after dose 2 compared with < 3 months after dose 2, and among participants who were older or had underlying health conditions, although confidence intervals overlapped between subgroups. Conclusions: VE estimates generated using infection-induced antibodies were consistent with published estimates from clinical trials and observational studies that used virologic tests to confirm infection dur-ing the same period. Our findings support recommendations for eligible adults to remain up to date with COVID-19 vaccination.Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).

Aims Previous work found poor reproducibility for measures of glycemia in individuals at risk for dysglycemia. Differences between youth and adults have not been assessed. Using youth and adults in the Restoring Insulin Secretion Study, we tested variability and classification concordance for hemoglobin A1C (HbA1c), fasting and 2-hour glucose from oral glucose tolerance tests (OGTTs). Methods HbA1c and glucose on repeated samples obtained ∼6 weeks apart were compared in 66 youth (mean age 14.2 years) and 354 adults (52.7 years). Changes, coefficient of variation (CV), and concordance of diagnostic categories between the 2 visits were compared. Results Mean difference between the 2 visits in HbA1c was higher in youth than adults (P < .001), while fasting glucose was similar and 2-hour glucose was lower in youth (P = .051). CV was smallest for HbA1c compared to fasting and 2-hour glucose. For HbA1c, youth had higher CV (P < .001); whereas CV for 2-hour glucose was lower for youth (P = .041). Classification concordance by HbA1c was lower in youth (P = .004). Using OGTT or HbA1c for classification, intervisit variability produced discordant classification in 20% of youth and 28% of adults. Using both fasting glucose and HbA1c, intervisit variability reduced discordant classification to 16% of adults while not improving classification in youth. Conclusions Poor reproducibility and lack of classification concordance highlight the limitations of one-time testing, with important implications for assessing eligibility in clinical trials. Consideration should be given to using more than a single parameter for screening and diagnosis, especially when classification category is important.

Face masks have been recommended to reduce SARS‐CoV‐2 transmission. However, evidence of the individual benefit of face masks remains limited, including by vaccination status.

Objective: To evaluate how DSPN differs across the randomized DPP treatment groups and is associated with diabetes (DM) status, DM duration, and cumulative glycemic exposure. Methods: In the DPP, adults ≥25 years of age at high risk for DM (n=3234) were randomized to determine the effects of intensive lifestyle modification (ILS) or metformin (MET) compared to placebo (PLA) on incident diabetes. After DPP ended, participants were invited to join the DPPOS during which metformin was continued in those randomized to receive it. DSPN was rigorously assessed in 1,792 participants at DPPOS year 17 based on both symptoms and signs (pinprick, vibration, and monofilament). Multivariable logistic regression models were used to determine whether DSPN was associated with randomized treatment group, DM status and duration, and cumulative glycemic exposure. Results: At 21 years following DPP randomization, 66% had developed DM with median duration of 15 years. The prevalence of DSPN did not differ by DPP treatment group (21.5%, 21.5% and 21.9% in ILS, MET and PLA, respectively), but was slightly lower for those at risk for DM (19.6%) vs. those with DM (22.7%). There was a significant effect modification by age of the association between DPP treatment group and DSPN (p<0.05): the odds ratio (OR) for DSPN with ILS vs PLA decreased by 3.7% (95% CI 0.6-6.7) with each 1 year increase in age. MET vs. PLA was not associated with DSPN and age did not influence the null association. In models adjusted for treatment group, demographics, cardiometabolic risks, and low vitamin B12 or B12 supplement use, DSPN was associated with DM status (OR 1.40, p<0.001 vs. no DM), greater DM duration (OR 1.04 per 1 year, p<0.001), and higher time-weighted HbA1c (OR 1.85 per 1% increase, p<0.001). Conclusions: The likelihood of DSPN was higher for those with DM, longer DM duration, and higher cumulative glycemic exposure. Although ILS did not prevent DSPN overall, there were ILS benefits with increasing age. Disclosure C.Lee: Employee; Pfizer Inc. N.White: None. W.H.Herman: Advisory Panel; National Committee for Quality Assurance, Consultant; Merck Sharp & Dohme Corp., Other Relationship; National Institutes of Health, American Diabetes Association. D.Research group: None. A.Ciarleglio: None. S.Edelstein: None. J.P.Crandall: Research Support; Abbott Diabetes. D.Dabelea: None. R.B.Goldberg: None. S.E.Kahn: Advisory Panel; Anji Pharmaceuticals, Bayer Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck & Co., Inc., Other Relationship; Novo Nordisk. W.C.Knowler: None. M.Ma: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (UDK048489, UDK048339, UDK048377, UDK048349, UDK048381, UDK048468, UDK048434, UDK048485, UDK048375, UDK048514, UDK048437, UDK048413, UDK048411, UDK048406, UDK048380, UDK048397, UDK048412, UDK048404, UDK048387, UDK048407, UDK048443, UDK048400)

We assessed the association between self-reported mask use during non-household interactions and COVID-19 infection during three pandemic periods. Odds of infection for those who did not always compared to those who always wore a mask was 66% higher during pre-Delta, 53% higher during Delta, declining to 16% higher during Omicron.