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In North Carolina, USA, the SARS-CoV-2 Omicron variant was associated with changing symptomology in daily surveys, including increasing rates of self-reported cough and sore throat and decreased rates of loss of taste and smell. Compared with the pre-Delta period, Delta and Omicron (pre-BA.4/BA.5) variant periods were associated with shorter symptom duration.

The largest and longest clinical trial of metformin for the prevention of diabetes is the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study (DPP/DPPOS). In this review, we summarise data from the DPP/DPPOS, focusing on metformin for diabetes prevention, as well as its long-term glycaemic and cardiometabolic effects and safety in people at high-risk of developing diabetes. The DPP (1996–2001) was a RCT of 3234 adults who, at baseline, were at high-risk of developing diabetes. Participants were assigned to masked placebo ( n  = 1082) or metformin ( n  = 1073) 850 mg twice daily, or intensive lifestyle intervention ( n  = 1079). The masked metformin/placebo intervention phase ended approximately 1 year ahead of schedule because of demonstrated efficacy. Primary outcome was reported at 2.8 years. At the end of the DPP, all participants were offered lifestyle education and 88% ( n  = 2776) of the surviving DPP cohort continued follow-up in the DPPOS. Participants originally assigned to metformin continued to receive metformin, unmasked. The DPP/DPPOS cohort has now been followed for over 15 years with prospective assessment of glycaemic, cardiometabolic, health economic and safety outcomes. After an average follow-up of 2.8 years, metformin reduced the incidence of diabetes by 31% compared with placebo, with a greater effect in those who were more obese, had a higher fasting glucose or a history of gestational diabetes. The DPPOS addressed the longer-term effects of metformin, showing a risk reduction of 18% over 10 and 15 years post-randomisation. Metformin treatment for diabetes prevention was estimated to be cost-saving. At 15 years, lack of progression to diabetes was associated with a 28% lower risk of microvascular complications across treatment arms, a reduction that was no different among treatment groups. Recent findings suggest metformin may reduce atherosclerosis development in men. Originally used for the treatment of type 2 diabetes, metformin, now proven to prevent or delay diabetes, may serve as an important tool in battling the growing diabetes epidemic. Long-term follow-up, currently underway in the DPP/DPPOS, is now evaluating metformin’s potential role, when started early in the spectrum of dysglycaemia, on later-stage comorbidities, including cardiovascular disease and cancer. Trial registration : ClinicalTrials.gov NCT00038727 and NCT00004992.

The global epidemic of type 2 diabetes has prompted numerous studies and public health efforts to reduce its development. A variety of interventions, including lifestyle modifications and pharmacological agents directed at ameliorating the major risk factors for type 2 diabetes, are of proven efficacy in reducing the development of type 2 diabetes in people with impaired glucose tolerance. While prevention of the hyperglycaemia characteristic of diabetes is arguably an important, clinically relevant outcome, a more compelling outcome with greater clinical significance is the prevention or reduction of the relatively diabetes-specific microvascular and less-specific cardiovascular disease (CVD) complications associated with diabetes. These complications cause the majority of morbidity and excess mortality associated with diabetes. Any reduction in diabetes should, logically, also reduce the occurrence of its long-term complications; however, most diabetes prevention trials have not been of sufficient duration to allow such an evaluation. The limited long-term data, largely from the Da Qing Diabetes Prevention Study (DQDPS) and the Diabetes Prevention Program (DPP) and their respective follow-up studies (DQDPOS and DPPOS), suggest a reduction in microvascular complications and amelioration of CVD risk factors. Only the DQDPOS and Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) studies have shown a reduction in CVD events and only DQDPOS has demonstrated a decrease in CVD and overall mortality. While these limited data are promising, whether diabetes prevention directly reduces complication-related morbidity and mortality remains unclear. Longer follow-up of prevention studies is needed to supplement the limited current clinical trial data, to help differentiate the effects of diabetes prevention itself from the means used to reduce diabetes development and to understand the balance among benefits, risks and costs of prevention.

Effect of Weight Loss With Lifestyle Intervention on Risk of Diabetes Richard F. Hamman , MD, DRPH 1 , Rena R. Wing , PHD 2 , Sharon L. Edelstein , SCM 3 , John M. Lachin , SCD 3 , George A. Bray , MD 4 , Linda Delahanty , MS, RD 5 , Mary Hoskin , MS, RD 6 , Andrea M. Kriska , PHD 7 , Elizabeth J. Mayer-Davis , PHD 8 , Xavier Pi-Sunyer , MD 9 , Judith Regensteiner , PHD 1 , Beth Venditti , PHD 7 , Judith Wylie-Rosett , EDD, RD 10 and for the Diabetes Prevention Program Research Group 1 University of Colorado at Denver and Health Sciences Center, Denver, Colorado 2 Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island 3 Biostatistics Center, George Washington University, Washington, DC 4 Pennington Biomedical Research Center, Baton Rouge, Louisiana 5 Diabetes Research Center, Massachusetts General Hospital, Boston, Massachussetts 6 Southwestern Indian Center, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona 7 Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania 8 University of South Carolina School of Public Health, Columbia, South Carolina 9 Roosevelt-St. Luke’s Hospital, New York, New York 10 Albert Einstein College of Medicine, Bronx, New York Address correspondence and reprint requests to Richard F. Hamman, MD, DrPH, Diabetes Prevention Program Coordinating Center, The Biostatistics Center, George Washington University, 6110 Executive Blvd., Suite 750, Rockville, MD 20852. E-mail: dppmail{at}biostat.bsc.gwu.edu Abstract OBJECTIVE —Diabetes Prevention Program (DPP) participants randomized to the intensive lifestyle intervention (ILS) had significantly reduced risk of diabetes compared with placebo participants. We explored the contribution of changes in weight, diet, and physical activity on the risk of developing diabetes among ILS participants. RESEARCH DESIGN AND METHODS —For this study, we analyzed one arm of a randomized trial using Cox proportional hazards regression over 3.2 years of follow-up. RESULTS —A total of 1,079 participants were aged 25–84 years (mean 50.6 years, BMI 33.9 kg/m 2 ). Weight loss was the dominant predictor of reduced diabetes incidence (hazard ratio per 5-kg weight loss 0.42 [95% CI 0.35–0.51]; P < 0.0001). For every kilogram of weight loss, there was a 16% reduction in risk, adjusted for changes in diet and activity. Lower percent of calories from fat and increased physical activity predicted weight loss. Increased physical activity was important to help sustain weight loss. Among 495 participants not meeting the weight loss goal at year 1, those who achieved the physical activity goal had 44% lower diabetes incidence. CONCLUSIONS —Interventions to reduce diabetes risk should primarily target weight reduction. DPP, Diabetes Prevention Program IGR, insulin-to-glucose ratio ILS, intensive lifestyle intervention Footnotes A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted June 5, 2006. Received March 14, 2006. DIABETES CARE

Abstract Purpose HbA1c levels are higher in blacks than non-Hispanic whites (NHWs). We investigated whether genetics could explain this difference in Diabetes Prevention Program (DPP) participants. Methods We tested (i) genetic variants causing hemoglobinopathies, (ii) a genetic risk score (GRS) based on 60 variants associated with HbA1c from genome-wide association meta-analysis, and (iii) principal component (PC) factors that capture continental ancestry derived from genetic markers distributed across the genome. Results Of 2658 eligible DPP participants, 537 (20%) self-identified as black and 1476 (56%) as NHW. Despite comparable fasting and 2-hour glucose levels, blacks had higher HbA1c (mean ± SD = 6.2 ± 0.6%) compared with NHWs (5.8 ± 0.4%; P < 0.001). In blacks, the genetic variant causing sickle cell trait was associated with higher HbA1c [β (SE) = +0.44 (0.08)%; P = 2.1 × 10−4]. The GRS was associated with HbA1c in both blacks and NHWs. Self-identified blacks were distributed along the first PC axis, as expected in mixed ancestry populations. The first PC explained 60% of the 0.4% difference in HbA1c between blacks and NHWs, whereas the sickle cell variant explained 16% and GRS explained 14%. Conclusions A large proportion of HbA1c difference between blacks and NHWs was associated with the first PC factor, suggesting that unidentified genetic markers influence HbA1c in blacks in addition to nongenetic factors. We studied genetic markers to explain HbA1c difference between AAs and whites. We found that the first principal component capturing genetic ancestry explained 60% of the 0.4 unit difference.

Abstract 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.

Vaccine hesitancy presents a challenge to COVID-19 control efforts. To identify beliefs associated with delayed vaccine uptake, we developed and implemented a vaccine hesitancy survey for the COVID-19 Community Research Partnership. 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 differences (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 analyses assessed predictors of subsequent vaccination among those initially unvaccinated. 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, unvaccinated participants were less likely to feel “very concerned” about getting COVID-19 than vaccinated participants (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 motivation 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. 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.

The COVID-19 Community Research Partnership is a population-based longitudinal syndromic and sero-surveillance study. The study includes over 17,000 participants from six healthcare systems in North Carolina who submitted over 49,000 serology results. The purpose of this study is to use these serology data to estimate the cumulative proportion of the North Carolina population that has either been infected with SARS-CoV-2 or developed a measurable humoral response to vaccination. Adult community residents were invited to participate in the study between April 2020 and February 2021. Demographic information was collected and daily symptom screen was completed using a secure, HIPAA-compliant, online portal. A portion of participants were mailed kits containing a lateral flow assay to be used in-home to test for presence of anti-SARS-CoV-2 IgM or IgG antibodies. The cumulative proportion of participants who tested positive at least once during the study was estimated. A standard Cox proportional hazards model was constructed to illustrate the probability of seroconversion over time up to December 20, 2020 (before vaccines available). A separate analysis was performed to describe the influence of vaccines through February 15, 2021. 17,688 participants contributed at least one serology result. 68.7% of the population were female, and 72.2% were between 18 and 59 years of age. The average number of serology results submitted per participant was 3.0 (±1.9). By December 20, 2020, the overall probability of seropositivity in the CCRP population was 32.6%. By February 15, 2021 the probability among healthcare workers and non-healthcare workers was 83% and 49%, respectively. An inflection upward in the probability of seropositivity was demonstrated around the end of December, suggesting an influence of vaccinations, especially for healthcare workers. Among healthcare workers, those in the oldest age category (60+ years) were 38% less likely to have seroconverted by February 15, 2021. Results of this study suggest more North Carolina residents may have been infected with SARS-CoV-2 than the number of documented cases as determined by positive RNA or antigen tests. The influence of vaccinations on seropositivity among North Carolina residents is also demonstrated. Additional research is needed to fully characterize the impact of seropositivity on immunity and the ultimate course of the pandemic.

Introduction: Observational studies of SARS-CoV-2 vaccine effectiveness depend on accurate ascertainment of vaccination receipt, date, and product type. Self-reported vaccine data may be more readily available to and less expensive for researchers than assessing medical records. Methods: We surveyed adult participants in the COVID-19 Community Research Partnership who had an authenticated Electronic Health Record (EHR) (N = 41,484) concerning receipt of SARS-CoV-2 vaccination using a daily survey beginning in December 2020 and a supplemental survey in September–October 2021. We compared self-reported information to that available in the EHR for the following data points: vaccine brand, date of first dose, and number of doses using rates of agreement and Bland–Altman plots for visual assessment. Self-reported data was available immediately following vaccination (in the daily survey) and at a delayed interval (in a secondary supplemental survey). Results: For the date of first vaccine dose, self-reported “immediate” recall was within ±7 days of the date reported in the “delayed” survey for 87.9% of participants. Among the 19.6% of participants with evidence of vaccination in their EHR, 95% self-reported vaccination in one of the two surveys. Self-reported dates were within ±7 days of documented EHR vaccination for 97.6% of the “immediate” surveys and 92.0% of the “delayed” surveys. Self-reported vaccine product details matched those in the EHR for over 98% of participants for both “immediate” and “delayed” surveys. Conclusions: Self-reported dates and product details for COVID-19 vaccination can be a good surrogate when medical records are unavailable in large observational studies. A secondary confirmation of dates for a subset of participants with EHR data will provide internal validity.

BACKGROUND: Individual barriers to weight loss and physical activity goals in the Diabetes Prevention Program, a randomized trial with 3.2 years average treatment duration, have not been previously reported. Evaluating barriers and the lifestyle coaching approaches used to improve adherence in a large, diverse participant cohort can inform dissemination efforts. METHODS: Lifestyle coaches documented barriers and approaches after each session (mean session attendance = 50.3 ± 21.8). Subjects were 1076 intensive lifestyle participants (mean age = 50.6 years; mean BMI = 33.9 kg/m²; 68% female, 48% non-Caucasian). Barriers and approaches used to improve adherence were ranked by the percentage of the cohort for whom they applied. Barrier groupings were also analyzed in relation to baseline demographic characteristics. RESULTS: Top weight loss barriers reported were problems with self-monitoring (58%); social cues (58%); holidays (54%); low activity (48%); and internal cues (thought/mood) (44%). Top activity barriers were holidays (51%); time management (50%); internal cues (30%); illness (29%), and motivation (26%). The percentage of the cohort having any type of barrier increased over the long-term intervention period. A majority of the weight loss barriers were significantly associated with younger age, greater obesity, and non-Caucasian race/ethnicity (p-values vary). Physical activity barriers, particularly thought and mood cues, social cues and time management, physical injury or illness and access/weather, were most significantly associated with being female and obese (p < 0.001 for all). Lifestyle coaches used problem-solving with most participants (≥75% short-term; > 90% long term) and regularly reviewed self-monitoring skills. More costly approaches were used infrequently during the first 16 sessions (≤10%) but increased over 3.2 years. CONCLUSION: Behavioral problem solving approaches have short and long term dissemination potential for many kinds of participant barriers. Given minimal resources, increased attention to training lifestyle coaches in the consistent use of these approaches appears warranted.