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The impact of global diabetes prevention efforts has been modest despite the promise of landmark diabetes prevention trials nearly twenty years ago. While national and regional initiatives show potential, challenges remain to adapt large-scale strategies in the real-world that fits individuals and their communities. Additionally, the sedentary lifestyle changes during the COVID-19 pandemic and guidelines that now call for earlier screening (e.g., US Preventative Task Force) will increase the pool of eligible adults worldwide. Thus, a more adaptable, person-centered approach that expands the current toolkit is urgently needed to innovate and revitalize our approach to diabetes prevention. This review identifies key priorities to optimize the population-level delivery of diabetes prevention based on a consensus-based evaluation of the current evidence among experts in global translational programs; key priorities identified include (1) participant eligibility, (2) intervention intensity, (3) delivery components, (4) behavioral economics, (5) technology, and (6) the role of pharmacotherapy. We offer a conceptual framework for a broader, person-centered approach to better address an individual’s risk, readiness, barriers, and digital competency.

Background It is critical to assess implementation fidelity of evidence-based interventions and factors moderating fidelity, to understand the reasons for their success or failure. However, fidelity and fidelity moderators are seldom systematically reported. The study objective was to conduct a concurrent implementation fidelity evaluation and examine fidelity moderators of CHORD (Community Health Outreach to Reduce Diabetes), a pragmatic, cluster-randomized, controlled trial to test the impact of a Community Health Workers (CHW)-led health coaching intervention to prevent incident type 2 Diabetes Mellitus in New York (NY). Methods We applied the Conceptual Framework for Implementation Fidelity to assess implementation fidelity and factors moderating it across the four core intervention components: patient goal setting, education topic coaching, primary care (PC) visits, and referrals to address social determinants of health (SDH), using descriptive statistics and regression models. PC patients with prediabetes receiving care from safety-net patient-centered medical homes (PCMHs) at either, VA NY Harbor or at Bellevue Hospital (BH) were eligible to be randomized into the CHW-led CHORD intervention or usual care. Among 559 patients randomized and enrolled in the intervention group, 79.4% completed the intake survey and were included in the analytic sample for fidelity assessment. Fidelity was measured as coverage, content adherence and frequency of each core component, and the moderators assessed were implementation site and patient activation measure. Results Content adherence was high for three components with nearly 80.0% of patients setting ≥ 1 goal, having ≥ 1 PC visit and receiving ≥ 1 education session. Only 45.0% patients received ≥ 1 SDH referral. After adjusting for patient gender, language, race, ethnicity, and age, the implementation site moderated adherence to goal setting (77.4% BH vs. 87.7% VA), educational coaching (78.9% BH vs. 88.3% VA), number of successful CHW-patient encounters (6 BH vs 4 VA) and percent of patients receiving all four components (41.1% BH vs. 25.7% VA). Conclusions The fidelity to the four CHORD intervention components differed between the two implementation sites, demonstrating the challenges in implementing complex evidence-based interventions in different settings. Our findings underscore the importance of measuring implementation fidelity in contextualizing the outcomes of randomized trials of complex multi-site behavioral interventions. Trial registration The trial was registered with ClinicalTrials.gov on 30/12/2016 and the registration number is NCT03006666.

ImportanceInterindividual variability in postprandial glycemic response (PPGR) to the same foods may explain why low glycemic index or load and low-carbohydrate diet interventions have mixed weight loss outcomes. A precision nutrition approach that estimates personalized PPGR to specific foods may be more efficacious for weight loss.ObjectiveTo compare a standardized low-fat vs a personalized diet regarding percentage of weight loss in adults with abnormal glucose metabolism and obesity.Design, Setting, and ParticipantsThe Personal Diet Study was a single-center, population-based, 6-month randomized clinical trial with measurements at baseline (0 months) and 3 and 6 months conducted from February 12, 2018, to October 28, 2021. A total of 269 adults aged 18 to 80 years with a body mass index (calculated as weight in kilograms divided by height in meters squared) ranging from 27 to 50 and a hemoglobin A1c level ranging from 5.7% to 8.0% were recruited. Individuals were excluded if receiving medications other than metformin or with evidence of kidney disease, assessed as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration equation, to avoid recruiting patients with advanced type 2 diabetes.InterventionsParticipants were randomized to either a low-fat diet (Main Outcomes and MeasuresThe primary outcome was the percentage of weight loss from baseline to 6 months. Secondary outcomes included changes in body composition (fat mass, fat-free mass, and percentage of body weight), resting energy expenditure, and adaptive thermogenesis. Data were collected at baseline and 3 and 6 months. Analysis was based on intention to treat using linear mixed modeling.ResultsOf a total of 204 adults randomized, 199 (102 in the personalized group vs 97 in the standardized group) contributed data (mean [SD] age, 58 [11] years; 133 women [66.8%]; mean [SD] body mass index, 33.9 [4.8]). Weight change at 6 months was −4.31% (95% CI, −5.37% to −3.24%) for the standardized group and −3.26% (95% CI, −4.25% to −2.26%) for the personalized group, which was not significantly different (difference between groups, 1.05% [95% CI, −0.40% to 2.50%]; P = .16). There were no between-group differences in body composition and adaptive thermogenesis; however, the change in resting energy expenditure was significantly greater in the standardized group from 0 to 6 months (difference between groups, 92.3 [95% CI, 0.9-183.8] kcal/d; P = .05).Conclusions and RelevanceA personalized diet targeting a reduction in PPGR did not result in greater weight loss compared with a low-fat diet at 6 months. Future studies should assess methods of increasing dietary self-monitoring adherence and intervention exposure.Trial RegistrationClinicalTrials.gov Identifier: NCT03336411

Ensuring the public has a fundamental understanding of human–microbe interactions, immune responses, and vaccines is a critical challenge in the midst of a pandemic. These topics are commonly taught in undergraduate- and graduate-level microbiology and immunology courses; however, creating engaging methods of teaching these complex concepts to students of all ages is necessary to keep younger students interested when science seems hard. Building on the Tactile Teaching Tools with Guided Inquiry Learning (TTT-GIL) method we used to create an interactive lac operon molecular puzzle, we report here two TTT-GIL activities designed to engage diverse learners from middle schoolers to masters students in exploring molecular interactions within the immune system. By pairing physical models with structured activities built on the constructivist framework of Process-Oriented Guided Inquiry Learning (POGIL), TTT-GIL activities guide learners through their interaction with the model, using the Learning Cycle to facilitate construction of new concepts. Moreover, TTT-GIL activities are designed utilizing Universal Design for Learning (UDL) principles to include all learners through multiple means of engagement, representation, and action. The TTT-GIL activities reported here include a web-enhanced activity designed to teach concepts related to antibody–epitope binding and specificity to deaf and hard-of-hearing middle and high school students in a remote setting and a team-based activity that simulates the evolution of the Major Histocompatibility Complex (MHC) haplotype of a population exposed to pathogens. These activities incorporate TTT-GIL to engage learners in the exploration of fundamental immunology concepts and can be adapted for use with learners of different levels and educational backgrounds.

Pleural biopsy findings offer greater diagnostic sensitivity in malignant pleural effusions compared with pleural fluid. The adequacy of pleural biopsy techniques in achieving molecular marker status has not been studied, and such information (termed "actionable" histology) is critical in providing a rational, efficient, and evidence-based approach to diagnostic investigation.What is the adequacy of various pleural biopsy techniques at providing adequate molecular diagnostic information to guide treatment in malignant pleural effusions?This study analyzed anonymized data on 183 patients from four sites across three countries in whom pleural biopsy results had confirmed a malignant diagnosis and molecular profiling was relevant for the diagnosed cancer type. The primary outcome measure was adequacy of pleural biopsy for achieving molecular marker status. Secondary outcomes included clinical factors predictive of achieving a molecular diagnosis.The median age of patients was 71 years (interquartile range, 63-78 years), with 92 of 183 (50%) male. Of the 183 procedures, 105 (57%) were local anesthetic thoracoscopies (LAT), 12 (7%) were CT scan guided, and 66 (36%) were ultrasound guided. Successful molecular marker analysis was associated with mode of biopsy, with LAT having the highst yield and ultrasound-guided biopsy the lowest (LAT vs CT scan guided vs ultrasound guided: LAT yield, 95%; CT scan guided, 86%; and ultrasound guided, 77% [P = .004]). Biopsy technique and size of biopsy sample were independently associated with successful molecular marker analysis. LAT had an adjusted OR for successful diagnosis of 30.16 (95% CI, 3.15-288.56; P = .003) and biopsy sample size an OR of 1.18 (95% CI, 1.02-1.37) per millimeter increase in tissue sample size (P .03).Although previous studies have shown comparable overall diagnostic yields, in the modern era of targeted therapies, this study found that LAT offers far superior results to image-guided techniques at achieving molecular profiling and remains the optimal diagnostic tool.

Background: One of the current methods to diagnose prediabetes and predict diabetes incidence is based on 2-h plasma glucose (2-hPG) value following 75-g oral glucose tolerance test. Evidence demonstrates that 1-hour post-load plasma glucose (1-hPG) ≥ 155 mg/dl (8.6 mmol/L) in those with normal glucose tolerance at 2-hPG is highly predictive for T2D incidence. We conducted a health economic analysis to estimate long-term cost-effectiveness of using 1-hPG as compared to 2-hPG to screen and assess diabetes risk. Methods: The main outcome of the study was cost per quality-adjusted life-year (QALY) gained. We used a Monte Carlo-based Markov simulation model to simulate long-term effects of the two screening strategies on clinical and cost-effectiveness outcomes. The base case model included 20.000 simulated patients over 35-years. Transition probabilities were retrieved from landmark studies. Direct medical costs were sourced from the literature and inflated to 20Euros. Results: In the lifetime analysis, 1-hPG was projected to increase the number of years free from disease (2yr/patient) ; to delay the onset of T2D (1yr/patient) ; to reduce the incidence of T2D complications (0.6 Relative Risk/patient) and to increase the QALY gained (0.58/patient) . Though testing the 1-hPG resulted in higher initial costs owing to a larger number of preventive treatments, long-term diabetes and complications costs were reduced leading to -31,225,719.82€ saving over a lifetime as compared to 2-hPG. The incremental cost-effectiveness ratio was -8,214.7€ per each QALY gained for the overall population. Conclusions: Screening prediabetes by using 1h-PG is feasible and cost-effective resulting in QALYs gained and reduced costs. Notwithstanding the higher initial costs of 1-hPG compared to 2-hPG, due to the incremental number of preventive treatments, long-term diabetes and complications costs were reduced expecting an overall cost saving of -8,214.7€ per each QALY gained. Disclosure M.Andellini: None. M.Manco: None. M.Esposito: None. A.Tozzi: None. M.Bergman: None. M.Ritrovato: None.

Purpose: Although commonly used, HbA1c is insensitive for diagnosing prediabetes and diabetes. Glycemic variability (GV) or a 1-hour plasma glucose level (1-h PG) ≥ 155 mg/dL (8.6 mmol/L) during a 75-gram oral glucose tolerance test (OGTT) better identifies individuals with dysglycemia. The objectives were to (1) compare continuous glucose monitoring (CGM) with the OGTT for detecting dysglycemia in high-risk subjects with HbA1c < 5.7% (39 mmol/mol), and (2) correlate the 1-h PG with CGM-derived GV indices. Research Design and Methods: Subjects (n=15) with a HbA1c < 5.7% (39 mmol/mol) and at least one other risk factor for type 2 diabetes such as overweight, obesity, hypertension, or hyperlipidemia were recruited. A 2-h OGTT was performed within 3-7 days of CGM insertion, which was worn up to 14 days. Results: The average age was 50 ± 14 years, with the majority of participants being men (80%) and Caucasian (67%). The mean HbA1c was 5.3±0.2% (34 mmol/mol). The 1-h PG was highly correlated with 1-h CGM glucose levels (ρ=0.881, pConclusion: 1-h interstitial CGM glucose and 1-h PG can detect dysglycemia in high-risk subjects with HbA1c < 5.7% (39 mmol/mol). CGM may be an alternative screening tool for glucose disorders.

Resume Le prediabete est une anomalie metabolique frequemment rencontree. Son depistage est primordial, sachant qu’il est associe a un risque d’evolution vers le diabete « vrai » et/ou d’autres complications, en particulier cardiovasculaires. Le diagnostic de prediabete repose aujourd’hui sur des mesures glycemiques (glycemie a jeun et/ou a la 120e minute d’une surcharge orale en glucose) et/ou sur le dosage de l’hemoglobine glyquee (HbA1c). Plusieurs travaux suggerent que ce mode de diagnostic identifie le prediabete deja (trop) tard dans l’histoire naturelle de la dysglycemie. Une glycemie superieure a 155 mg/dL (8,6 mmol/L) a la 60e minute de l’epreuve d’hyperglycemie orale permet un diagnostic plus precoce, avec des dividendes en termes de prediction du risque de diabete, de maladies cardiovasculaires, et de mortalite. Cette approche pourrait donc etre une alternative rationnelle a la mesure de la glycemie a la 120e minute, en particulier en cas de discordance clinique et/ou biologique des tests de « premiere ligne » (glycemie a jeun ; HbA1c). Elle devrait aussi permettre une intervention therapeutique plus rapide avant le stade de prediabete patent, tel qu’il est defini a ce jour par les societes savantes.

For over 100 years, the oral glucose tolerance test (OGTT) has been the cornerstone for detecting prediabetes and type 2 diabetes (T2DM). In recent decades, controversies have arisen identifying internationally acceptable cut points using fasting plasma glucose (FPG), 2-h post-load glucose (2-h PG), and/or HbA1c for defining intermediate hyperglycemia (prediabetes). Despite this, there has been a steadfast global consensus of the 2-h PG for defining dysglycemic states during the OGTT. This article reviews the history of the OGTT and recent advances in its application, including the glucose challenge test and mathematical modeling for determining the shape of the glucose curve. Pitfalls of the FPG, 2-h PG during the OGTT, and HbA1c are considered as well. Finally, the associations between the 30-minute and 1-hour plasma glucose (1-h PG) levels derived from the OGTT and incidence of diabetes and its complications will be reviewed. The considerable evidence base supports modifying current screening and diagnostic recommendations with the use of the 1-h PG. Measurement of the 1-h PG level could increase the likelihood of identifying high-risk individuals when the pancreatic s-cell function is substantially more intact with the added practical advantage of potentially replacing the conventional 2-h OGTT making it more acceptable in the clinical setting.

Procyclicality of fiscal policy is a common feature in emerging markets, by contrast with high‐income economies, and leads to greater business‐cycle amplitudes. We investigate potential causes of fiscal procyclicality, including a host of economic and institutional variables of especial import in emerging markets. We employ dynamic panel methods in a large sample of countries to investigate what factors are associated with fiscal cyclicality. We find that fiscal procyclicality is mainly due to procyclical fluctuations in government investment expenditure. In addition, we find that procyclical fiscal policy is positively associated with government debt levels, terms‐of‐trade volatility, and costs of foreign borrowing, while negatively associated with better government efficiency. Only a weak association is found between International Monetary Fund program participation and fiscal procyclicality. Finally, we find that certain fiscal rules are associated with lower fiscal procyclicality and, in particular, balanced‐budget rules may help mitigate the adverse cyclicality effects of high terms‐of‐trade volatility and government debt burdens in emerging markets.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians, Inc., and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes the establishment of a Diabetes Prevention Clinic for veterans with prediabetes.

Introduction: There is limited research examining dietary changes in adults with prediabetes who are following a diet personalized to predict postprandial glycemic response (PPGR). Objective: We compared dietary changes in subjects randomized to a low-fat, one-size-fits-all diet ( Standardized ) or to a diet personalized to minimize PPGR ( Personalized ). Methods: Dietary data collected to-date were analyzed from the Personal Diet study, a clinical trial to compare two behavioral weight loss interventions in adults with prediabetes or early-stage type 2 diabetes. All subjects had resting energy expenditure (REE) measured at baseline using indirect calorimetry. Both arms were instructed to restrict energy intake (-500 kcal/day, based on REE and a physical activity factor of 1.4), log daily dietary intake with a smartphone app, and attend scheduled behavioral counseling sessions. The Standardized arm received app feedback about energy and fat intake, while the Personalized arm received app feedback about energy intake and meal specific predicted PPGR determined from a gut microbiome-based machine learning algorithm. At baseline, 3 months, and 6 months, subjects completed one 24-hour dietary recall using the Automated Self-Administered 24-hour Dietary Assessment Tool. Total energy, total carbohydrate, total sugars, fiber, total fat, saturated fat, monounsaturated fat, polyunsaturated fat, and protein were measured using the USDA Food and Nutrient Database for Dietary Studies 2011-2012. Macronutrient intakes were analyzed as percentage of energy (%E). Linear mixed modelling, with random intercepts and slopes and an unstructured covariance pattern, was used to analyze dietary changes within- and between-arms from baseline to 3 and 6 months. Fixed effects were included for study arm, time period, and interaction of study arm and time period. A random effect was included for subjects. Models were adjusted for age and sex. Results: Dietary assessments were completed at baseline (n=66 Personalized ; n=65 Standardized ), 3 months (n=50 Personalized ; n=36 Standardized ), and 6 months (n=47 Personalized ; n=39 Standardized ). The Personalized arm had a greater reduction than the Standardized arm in energy (β: -342 kcal; 95% CI: -672, -12) and %E from carbohydrate (β: -6.2; 95% CI: -11.7, -0.6) and sugars (β: -4.9; 95% CI: -8.8, -1.0) from baseline to 3 months, but there were no between-arm differences in dietary measures at 6 months. Within-arm, Personalized had decreases in energy (β: -327 kcal; 95% CI: -546, -108) and %E from carbohydrate (β: -4.6; 95% CI: -8.2, -0.9) from baseline to 3 months. In the Standardized arm, %E from sugars increased from baseline to 3 months (β: 3.0; 95% CI: 0.02, 5.9). Conclusions: Personalized had greater reductions than Standardized in energy and %E from carbohydrate and sugars over the first 3 months of the intervention, but dietary changes were similar by 6 months.

Individuals with high 1-hour post-load glucose (1-h PG 155 mg/dl; 8.6 mmol/l) during an oral glucose tolerance test are at increased risk of type 2 diabetes (T2D) and cardiovascular complications, hepatic steatosis, and mortality. However,the clinical relevance of 1-h PG for the severity of hepatic fibrosis risk remains undefined.Cross-sectional data of the CATAMERI study (n = 2335) were analyzed. Participants underwent anthropometric measurements, liver enzyme determinations, cardiometabolic profiling, and a75-gram oral glucose tolerance test, including fasting, 1-h and 2-h PG determinations and measurement of FIB-4 score to assess degree of hepatic fibrosis. Multivariable logistic regression analysis was performed to evaluate risk of advanced hepatic fibrosis with worsening glycemic status.We stratifiedthe study group into 6 categories based on glycemic status: normal glucose tolerance (NGT) 1h-PG Low, NGT 1h-PG High, iIFG 1h-PG Low, iIFG 1h-PG High, IGT, and newly detected T2D. Anthropometric and cardiometabolic profiles worsened gradually with glycemic status. Moreover, compared to NGT-1h-PG Low group, worsening glycemic status was significantly associated with the severity of fibrosis, independent of other significant clinical risk factors.1-PG is a valuable tool for stratifying subjects with NGT or IFG at heightened risk of hepatic fibrosis requiring further evaluation with elastography.

Introduction: Individuals with obesity and diabetes have increased risk for atherosclerosis; contributed by chronic systemic inflammation and elevated glycemic variability (GV). Bariatric surgery reduces circulating inflammatory markers. We aimed to determine the differences in GV and the expression of inflammatory genes from circulating white blood cells (WBC) after sleeve gastrectomy (SG) in those with and without non-insulin dependent diabetes. Methods: We conducted a prospective cohort study in subjects with obesity and type 2 diabetes (n=10) and subjects with obesity and no diabetes (n=11). Research visits occurred before SG and 6 months postoperatively. Elevated GV was defined by oral glucose tolerance test derived 1-h plasma glucose ≥155 mg/dL and elevated continuous glucose monitor derived GV index-MAGE (reference range 0-2.8 mmol/l). Bulk RNA-sequencing was performed on total WBCs, isolated neutrophils, monocytes, and lymphocytes to analyze genetic expression changes in chronic 6-month weight loss from baseline. Results: At 6 months, SG caused equivalent weight loss from baseline in both groups (22%). However, HbA1c, 1-h plasma glucose, and MAGE levels were different after SG between both groups. HbA1c decreased by 3.0±1.3% in the diabetes group (p94% of total genes) were different between both groups. Furthermore, our gene set analysis showed downregulated expression of WBC genes enriched in inflammatory pathways primarily in subjects without diabetes. Conclusion: Diabetes dampens the weight-loss induced changes to transcriptomes from WBC subsets that contribute to cardiovascular disease. Elevated GV after SG may contribute to these attenuated changes.

BackgroundIt is critical to assess implementation fidelity for complex interventions to understand the reasons for their success or failure. However, few interventions systematically report implementation evaluation. Therefore, we conducted a concurrent process evaluation of CHORD (Community Health Outreach to Reduce Diabetes), a pragmatic, cluster-randomized, controlled trial to test the impact of a Community Health Workers (CHW) led, health coaching intervention on preventing incident type 2 Diabetes Mellitus (DM). MethodsThe study population included primary care (PC) patients with prediabetes at 2 safety-net hospitals - VA NY Harbor and Bellevue (BH). PC teams were randomized to receive the one-year intervention or usual care. Of the 559 patients in the intervention group to date, 79.4% completed an intake survey, constituting the analytic sample for fidelity assessment. The Conceptual Framework for Implementation Fidelity (CFIF) was applied to measure implementation fidelity and factors moderating fidelity of four core intervention components: patient goal setting, education topic coaching, PC visits, and referrals to address social determinants of health, using descriptive statistics and regression models.ResultsBH contributed 60.0% of the sample and VA contributed 40.0%. Content adherence was high for three components with nearly 80.0% of patients setting >1 goal, having >1 PC visit and receiving coaching on >1 education topic. Only 45.0% patients received >1 referral. After adjusting for patient gender, language, race, ethnicity, and age, the study site moderated adherence to goal setting (77.4% BH vs. 87.7% VA), educational coaching (78.9% BH vs. 88.3% VA), number of successful CHW-patient encounters (6 BH vs 4 VA) and percent of patients receiving all four components (41.1% BH vs. 25.7% VA). ConclusionsThe CFIF enabled analysis of implementation fidelity of a complex, behavioral intervention. The fidelity of CHORD implementation varied across its four components and was moderated by site. Despite implementation in a research setting, interventions may not completely adhere to their core components, which can influence outcomes. Our study emphasizes the importance of examining implementation fidelity of interventions and of assessing moderating factors. Our study also empirically tested the CFIF using quantitative concurrent intervention fidelity evaluation.Trial registration: The trial was registered with ClinicalTrials.gov on 12/30/2016 and the registration number is NCT03006666. The link to trial registration is: https://clinicaltrials.gov/ct2/show/NCT03006666

Objectives To describe challenges and lessons learned in conducting a remote behavioral weight loss trial. Methods The Personal Diet Study is an ongoing randomized clinical trial which aims to compare two mobile health (mHealth) weight loss approaches, standardized diet vs. personalized feedback, on glycemic response. Over a six-month period, participants attended dietitian-led group meetings via remote videoconferencing and were encouraged to self-monitor dietary intake using a smartphone app. Descriptive statistics were used to report adherence to counseling sessions and self-monitoring. Challenges were tracked during weekly project meetings. Results Challenges in connecting to and engaging in the videoconferencing sessions were noted. To address these issues, we provided a step-by-step user manual and video tutorials regarding use of WebEx, encouraged alternative means to join sessions, and sent reminder emails/texts about the WebEx sessions and asking participants to join sessions early. Self-monitoring app-related issue included inability to find specific foods in the app database. To overcome this, the study team incorporated commonly consumed foods as “favorites” in the app database, provided a manual and video tutorials regarding use of the app and checked the self-monitoring app dashboard weekly to identify nonadherent participants and intervened as appropriate. Among 135 participants included in the analysis, the median attendance rate for the 14 remote sessions was 85.7% (IQR: 64.3%–92.9%). Conclusions Experience and lessons shared in this report may provide critical and timely guidance to other behavioral researchers and interventionists seeking to adapt behavioral counseling programs for remote delivery in the age of COVID-19.

Prediabetes affects at least 1 in 3 adults in the U.S. and 1 in 5 in Europe. Although guidelines advocate aggressive management of lipid parameters in diabetes, most guidelines do not address treatment of dyslipidemia in prediabetes despite the increased atherosclerotic cardiovascular disease (ASCVD) risk. Several criteria are used to diagnose prediabetes: impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and HbA1c of 5.7-6.4%. Individuals with prediabetes have a greater risk of diabetes, a higher prevalence of dyslipidemia with a more atherogenic lipid profile and an increased risk of ASCVD. In addition to calculating ASCVD risk using traditional methods, an OGTT may further stratify risk. Those with 1-hour plasma glucose ≥8.6 mmol/L (155 mg/dL) and/or 2-hour ≥7.8 mmol/L (140 mg/dL) (IGT) have a greater risk of ASCVD. Diet and lifestyle modification are fundamental in prediabetes. Statins, ezetimibe and PCSK9 inhibitors are recommended in people requiring pharmacotherapy. Although high-intensity statins may increase risk of diabetes, this is acceptable because of the greater reduction of ASCVD. The LDL-C goal in prediabetes should be individualized. In those with IGT and/or elevated 1-hour plasma glucose, the same intensive approach to dyslipidemia as recommended for diabetes should be considered, particularly if other ASCVD risk factors are present.

Accruing evidence indicates that accumulation of advanced glycation end products (AGEs) and activation of the receptor for AGEs (RAGE) play a significant role in obesity and type 2 diabetes. The concentrations of circulating RAGE isoforms, such as soluble RAGE (sRAGE), cleaved RAGE (cRAGE), and endogenous secretory RAGE (esRAGE), collectively sRAGE isoforms, may be implicit in weight loss and energy compensation resulting from caloric restriction.We aimed to evaluate whether baseline concentrations of sRAGE isoforms predicted changes (∆) in body composition [fat mass (FM), fat-free mass (FFM)], resting energy expenditure (REE), and adaptive thermogenesis (AT) during weight loss.Data were collected during a behavioral weight loss intervention in adults with obesity. At baseline and 3 mo, participants were assessed for body composition (bioelectrical impedance analysis) and REE (indirect calorimetry), and plasma was assayed for concentrations of sRAGE isoforms (sRAGE, esRAGE, cRAGE). AT was calculated using various mathematical models that included measured and predicted REE. A linear regression model that adjusted for age, sex, glycated hemoglobin (HbA1c), and randomization arm was used to test the associations between sRAGE isoforms and metabolic outcomes.Participants (This study demonstrates a novel link between RAGE and energy expenditure in human participants undergoing weight loss.This trial was registered at clinicaltrials.gov as NCT03336411.

For over 100 years, the oral glucose tolerance test (OGTT) has been the cornerstone for detecting prediabetes and type 2 diabetes (T2DM). In recent decades, controversies have arisen identifying internationally acceptable cut points using fasting plasma glucose (FPG), 2-h post-load glucose (2-h PG), and/or HbA1c for defining intermediate hyperglycemia (prediabetes). Despite this, there has been a steadfast global consensus of the 2-h PG for defining dysglycemic states during the OGTT. This article reviews the history of the OGTT and recent advances in its application, including the glucose challenge test and mathematical modeling for determining the shape of the glucose curve. Pitfalls of the FPG, 2-h PG during the OGTT, and HbA1c are considered as well. Finally, the associations between the 30-minute and 1-hour plasma glucose (1-h PG) levels derived from the OGTT and incidence of diabetes and its complications will be reviewed. The considerable evidence base supports modifying current screening and diagnostic recommendations with the use of the 1‐h PG. Measurement of the 1‐h PG level could increase the likelihood of identifying high-risk individuals when the pancreatic ß-cell function is substantially more intact with the added practical advantage of potentially replacing the conventional 2‐h OGTT making it more acceptable in the clinical setting.

Many health care providers screen high-risk individuals exclusively with an HbA1c despite its insensitivity for detecting dysglycemia. The 2 cases presented describe the inherent caveats of interpreting HbA1c without performing an oral glucose tolerance test (OGTT). The first case reflects the risk of overdiagnosing type 2 diabetes (T2D) in an older African American male in whom HbA1c levels, although variable, were primarily in the mid-prediabetes range (5.7-6.4% [39-46 mmol/mol]) for many years although the initial OGTT demonstrated borderline impaired fasting glucose with a fasting plasma glucose of 102 mg/dL [5.7 mmol/L]) without evidence for impaired glucose tolerance (2-hour glucose ≥140-199 mg/dl ([7.8-11.1 mmol/L]). Because subsequent HbA1c levels were diagnostic of T2D (6.5%-6.6% [48-49 mmol/mol]), a second OGTT performed was normal. The second case illustrates the risk of underdiagnosing T2D in a male with HIV having normal HbA1c levels over many years who underwent an OGTT when mild prediabetes (HbA1c = 5.7% [39 mmol/mol]) developed that was diagnostic of T2D. To avoid inadvertent mistreatment, it is therefore essential to perform an OGTT, despite its limitations, in high-risk individuals, particularly when glucose or fructosamine and HbA1c values are discordant. Innate differences in the relationship between fructosamine or fasting glucose to HbA1c are demonstrated by the glycation gap or hemoglobin glycation index.

Objective: Glycemic variability (GV) and 1 hour plasma glucose (1-h PG) ≥ 8.6 mmol/L during a 75-gram oral glucose tolerance test (OGTT) are associated with increased risk for type 2 diabetes (T2D). GV may be overlooked in high-risk individuals. The objectives of this study are: (1) to determine if continuous glucose monitoring (CGM) using the Abbott Freestyle Libre Pro can replace the OGTT in high-risk subjects with HbA1c < 5.7%; and (2) to determine if GV indices correlate with the OGTT-derived 1-h PG ≥ 8.6 mmol/L. Methods: Subjects were recruited with a HbA1c < 5.7% and at least one other risk factor including: overweight or obesity, PCOS, fatty liver, hypertension, family history of T2D, or history of gestational diabetes. The CGM, placed days prior to the OGTT, was worn up to 14 days. Anthropometric and vital signs were measured. HbA1c, fasting, 1-h and 2-h PG levels during an OGTT were obtained. Results: The 1-h PG correlated significantly with CGM glucose levels (r=0.883, p Conclusions: The 1-h CGM glucose and elevated GV indices significantly correlate with 1-h PG (> 8.6 mmol/L) in high-risk subjects with HbA1c < 5.7%. CGM could potentially replace the OGTT for detecting early dysglycemia in those with HbA1c < 5.7%. Disclosure B. Dorcely: None. E. Sifonte: None. A. Divakaran: None. K. Katz: None. R. Jagannathan: None. I.J. Goldberg: None. M. Bergman: None. Funding Abbott Diabetes Care; New York University Clinical and Translational Science Award (UL1 TR001445)

IntroductionRisk of insulin resistance, dyslipidemia, diabetes and cardiac death is increased in Asians and Europeans with normal glucose tolerance (NGT) and 1-hour glucose ≥8.6 mmol/L. As African descent populations often have insulin resistance but a normal lipid profile, the implications for Africans with NGT and glucose ≥8.6 mmol/L (NGT-1-hour-high) are unknown.ObjectiveWe performed oral glucose tolerance tests (OGTTs) in 434 African born-blacks living in Washington, DC (male: 66%, age 38±10 years (mean±SD)) and determined in the NGT group if either glucometabolic or lipid profiles varied according to a 1-hour-glucose threshold of 8.6 mmol/L.MethodsGlucose tolerance category was defined by OGTT criteria. NGT was subdivided into NGT-1-hour-high (glucose ≥8.6 mmol/L) and NGT-1-hour-normal (glucose ResultsOne-hour-glucose ≥8.6 mmol/L occurred in 17% (47/272) with NGT, 72% (97/134) with pre-diabetes and in 96% (27/28) with diabetes. Both insulin resistance and beta-cell function were worse in NGT-1-hour-high than in NGT-1-hour-normal. Dyslipidemia occurred in both the diabetes and pre-diabetes groups but not in either NGT group. One-hour glucose concentration ≥8.6 mmol/L showed substantial agreement for the two OGTTs (к=0.628).ConclusionsAlthough dyslipidemia did not occur in either NGT group, insulin resistance and beta-cell compromise were worse in NGT-1 hour-high. Subdividing the NGT group at a 1-hour glucose threshold of 8.6 mmol/L may stratify risk for diabetes in Africans.

Background. Patients with diabetes mellitus are prone to develop osteoporosis, osteomyelitis, or rheumatoid arthritis (RA). Furthermore, the presence of these complications in those with diabetes may lead to higher mortality. The aim of our study was to assess characteristics and mortality of osteoporosis, osteomyelitis, or rheumatoid arthritis in individuals with diabetes. Methods. We analyzed osteoporosis, osteomyelitis, and RA deaths associated with diabetes from 1999–2017 using the CDC WONDER system (CDC WONDER; https://wonder.cdc.gov). We used ICD-10 codes to categorize the underlying and contributing causes of death. Crude mortality rates (CMR) and age-adjusted mortality rates (AAMR) per 1,000,000 person-years were calculated. Results. The AAMR for osteoporosis in the population with diabetes was significantly higher in females (AAMR: 4.17, 95% CI: 4.10–4.24) than in males (AAMR: 1.12, 95% CI: 1.07–1.16). Deaths due to osteoporosis increased gradually from 1999, peaked in 2003 (AAMR: 3.78, 95% CI: 3.55–4.00), and reached a nadir in 2016 (AAMR: 2.32, 95% CI: 2.15–2.48). The AAMR for RA associated with diabetes was slightly higher in females (AAMR: 4.04, 95% CI: 3.98–4.11) than in males (AAMR: 2.45, 95% CI: 2.39–2.51). The mortality rate due to RA increased slightly from 1999 (AAMR: 3.18, 95% CI: 2.97–3.39) to 2017 (AAMR: 3.20, 95% CI: 3.02–3.38). The AAMR for osteomyelitis associated with diabetes was higher in males (AAMR: 4.36, 95% CI: 4.28–4.44) than in females (AAMR: 2.31, 95% CI: 2.26–2.36). From 1999 to 2017, the AAMR from osteomyelitis in this population was 2.63 (95% CI: 2.44–2.82) per 1,000,000 person-years in 1999 and 4.25 (95% CI: 4.05–4.46) per 1,000,000 person-years in 2017. Conclusions. We found an increase in the age-adjusted mortality rates of RA and osteomyelitis and a decrease of osteoporosis associated with diabetes from 1999 to 2017. We suggest that increased attention should therefore be given to these diseases in the population with diabetes, especially in efforts to develop preventative and treatment strategies.

We show that estimates of the half-life of deviations from LOOP are biased when not taking into account the precision when aggregating over types of goods. Using a comprehensive dataset with monthly price data for 124 homogeneous products across regions in Denmark over the period 1997–2010 we find a large positive aggregation bias. On average, we find that the half-life is 8.4 months when taking the bias into account compared to 28.7 months when applying the standard method. The heterogeneity in estimated half-life can be explained by price stickiness, distance between regions and whether the good is traded or non-traded. This article is protected by copyright. All rights reserved.

The paper presents a general method for estimating a country’s level of fundamental house prices and its interaction with actual house prices. We set up a unified empirical model which can be used to analyze the time-series behavior of the fundamental house price and to test various hypotheses regarding its relation to the actual house price. Conditional forecasts from the model allow us to simulate policy experiments. To illustrate how the methods work, we apply it to data for Sweden. We find a tendency for actual house prices to converge on fundamental prices, albeit rather slowly. To achieve a significant fall in actual house prices it is necessary to increase the user cost substantially.

One-hour glucose (1h-PG) during an oral glucose tolerance test (OGTT) is an emerging biomarker for diagnosis and prediction of prediabetes (preDM) and type 2 diabetes (T2D). Our objectives were to: (1) use a longitudinal mathematical model to predict the pattern of glucose rise in 1h-PG and 2h-PG concentration with time and (2) test our predictions in a longitudinal cohort of 52 Pima Indians (baseline age, 26.5±5.8 years; BMI, 36.6±5.8 kg/m2) who were followed for 7.2±3.5 years. Model simulations suggested that the 1h-PG would pass the threshold of 155 mg/dl before the 2h-PG passed the threshold of 140 mg/dl for most individuals, and that the time difference could be as much as several years, depending on the balance of impairments in insulin resistance and early-phase insulin secretion. Using the longitudinal data set, we estimated the times of crossing the 1h-PG and 2h-PG thresholds by fitting a linear mixed effect model to trajectories of individual participants. Participants had a median of 6 (range 3-11) separate OGTTs, 1.7±0.8 years apart. For most participants (48/52), 1h-PG of 155 mg/dl was observed before 2h-PG reached 140 mg/dl (time difference, 1.9±2.0 years). Using the linear fits we also estimated that the average 1h-PG value would be 217 mg/dl (12.0 mmol/L) when 2h-PG reached 200 mg/dl (11.1 mmol/L). Overall, the times of crossing the 1h-PG threshold of 155 mg/dl and the 2h-PG threshold of 140 mg/dl were correlated, but 1h-PG crossed earlier, thus providing an earlier indication of future hyperglycemia. Additionally, since 1h-PG and 2h-PG rise together during the progression from preDM to T2DM, a 1h-PG of 217 mg/dl could be an alternative marker to the 2h-PG of 200 mg/dl for the diagnosis of T2D. Disclosure J. Ha: None. S.T. Chung: None. A.E. Sumner: None. M. Bergman: None. C. Bogardus: None. A. Sherman: None.

We investigate how European policy initiatives influenced market assessments of sovereign default risk and banking sector fragility during the sovereign debt crisis in four adversely affected countries — Portugal, Ireland, Spain and Italy. We focus on three broad groups of policies: (a) ECB policy actions (monetary and financial support), (b) EU programs (financial and fiscal rules as well as financial support in crisis countries), and (c) domestic austerity programs. We measure immediate market impact effects: what policies changed risk perceptions, using CDS spreads on sovereign bonds and banks in this assessment. We employ dynamic panel and event study methodologies in the empirical work. We find that a number of programs initially stabilized sovereign and bank bond markets (e.g. Outright Monetary Transactions program), although announcement and implementation impacts on markets differed in some cases (e.g. second Covered Market Bond Program). Actions designed to shore up sovereign markets often lowered risk assessments in bank bond markets and policies designed to ensure safety and soundness of the European banking system in some cases significantly impacted sovereign debt markets. Finally, a number of policies designed to stabilize markets had surprisingly little immediate impact on either sovereign or bank bond market risk assessments.

This paper studies tax shifting of excise taxes on alcoholic and nonalcoholic beveragesin Denmark. We use a unique data set collected by Statistics Denmark focusing on sixepisodes of tax changes: three tax cuts and three tax hikes. We find that excise taxeson beer and soda are overshifted but those on liquor are undershifted. We also findthat the pass-through is inversely related to the size of the tax change and that there areasymmetric effects of tax changes on soda. Finally, the tax pass-through on beer and sodais an increasing function of the distance to the German border, This paper studies tax shifting of excise taxes on alcoholic and nonalcoholic beverages in Denmark. We use a unique data set collected by Statistics Denmark focusing on six episodes of tax changes: three tax cuts and three tax hikes. We find that excise taxes on beer and soda are overshifted but those on liquor are undershifted. We also find that the pass-through is inversely related to the size of the tax change and that there are asymmetric effects of tax changes on soda. Finally, the tax pass-through on beer and soda is an increasing function of the distance to the German border.

The above-referenced article contained an error in the far-right column heading in Table 2. The heading should read as follows: PPV % (TP/TP + …

New indices of fiscal rule strength are constructed and, using a dynamic panel econometric model for 27 EU countries over the period 1990–2012, we assess whether national fiscal rules alone help to promote sustainable public finances in the EU or whether they must be supported by good governance in order to be effective. We find that fiscal rules are effective in reducing structural primary deficits at all levels of government efficiency. However, the effect is smaller as government efficiency increases, indicating that fiscal rules and government efficiency are institutional substitutes in terms of promoting fiscal sustainability. We also find that balanced budget rules are the most effective form of fiscal rules. Multiple fiscal rules are found to enhance fiscal solvency. Other institutional features that enhance the effectiveness of fiscal rules are transparency of policies and commitment to implementation of fiscal programs. Supranational rules, however, do not affect the effectiveness of national fiscal rules in reducing the deficit bias. Our results are robust to alternative estimation methods and endogeneity assumptions.

Whether an OGTT reproducibly detects either type 2 diabetes (T2D) or prediabetes in Africans in unknown. Therefore, 131 Africans had two OGTT. Diagnostic reproducibility for T2D was excellent (κ = 0.84), but only moderate for prediabetes (κ = 0.51). A single OGTT positive for T2D may be sufficient to guide clinical care and inform epidemiologic study design. ClinicalTrials.gov Identifier: NCT00001853.

Prediabetes (intermediate hyperglycemia) consists of two abnormalities, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) detected by a standardized 75-gram oral glucose tolerance test (OGTT). Individuals with isolated IGT or combined IFG and IGT have increased risk for developing type 2 diabetes (T2D) and cardiovascular disease (CVD). Diagnosing prediabetes early and accurately is critical in order to refer high-risk individuals for intensive lifestyle modification. However, there is currently no international consensus for diagnosing prediabetes with HbA1c or glucose measurements based upon American Diabetes Association (ADA) and the World Health Organization (WHO) criteria that identify different populations at risk for progressing to diabetes. Various caveats affecting the accuracy of interpreting the HbA1c including genetics complicate this further. This review describes established methods for detecting glucose disorders based upon glucose and HbA1c parameters as well as novel approaches including the 1-hour plasma glucose (1-h PG), glucose challenge test (GCT), shape of the glucose curve, genetics, continuous glucose monitoring (CGM), measures of insulin secretion and sensitivity, metabolomics, and ancillary tools such as fructosamine, glycated albumin (GA), 1,5- anhydroglucitol (1,5-AG). Of the approaches considered, the 1-h PG has considerable potential as a biomarker for detecting glucose disorders if confirmed by additional data including health economic analysis. Whether the 1-h OGTT is superior to genetics and omics in providing greater precision for individualized treatment requires further investigation. These methods will need to demonstrate substantially superiority to simpler tools for detecting glucose disorders to justify their cost and complexity.

Many individuals with prediabetes, as presently defined, will progress to diabetes (T2D) despite the considerable benefit of lifestyle modification. Therefore, it is paramount to screen individuals at increased risk with a more sensitive method capable of identifying prediabetes at an even earlier time point in the lengthy trajectory to T2D. This petition reviews findings demonstrating that the 1-hour (1-h) postload plasma glucose (PG) ≥ 155 mg/dl (8.6 mmol/L) in those with normal glucose tolerance (NGT) during an oral glucose tolerance test (OGTT) is highly predictive for detecting progression to T2D, micro- and macrovascular complications and mortality in individuals at increased risk. Furthermore, the STOP DIABETES Study documented effective interventions that reduce the future risk of T2D in those with NGT and a 1-h PG ≥ 155 mg/dl (8·6 mmol/L). The 1-h OGTT represents a valuable opportunity to extend the proven benefit of diabetes prevention to the sizeable and growing population of individuals at increased risk of progression to T2D. The substantial evidence provided in this petition strongly supports redefining current diagnostic criteria for prediabetes with the elevated 1-h PG level. The authors therefore advocate a 1-h OGTT to detect prediabetes and hence, thwart the global diabetes epidemic.