High Risk Of Type Research Articles

Discovery and validation of plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance and diabetes progression or regression among Puerto Rican adults.

Many studies have examined the relationship between plasma metabolites and type 2 diabetes progression, but few have explored saliva and multi-fluid metabolites. We used LC/MS to measure plasma (n=1051) and saliva (n=635) metabolites among Puerto Rican adults from the San Juan Overweight Adults Longitudinal Study. We used elastic net regression to identify plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting baseline HOMA-IR in a training set (n=509) and validated these scores in a testing set (n=340). We used multivariable Cox proportional hazards models to estimate HRs for the association of baseline metabolomic scores predicting insulin resistance with incident type 2 diabetes (n=54) and prediabetes (characterised by impaired glucose tolerance, impaired fasting glucose and/or high HbA1c) (n=130) at 3 years, along with regression from prediabetes to normoglycaemia (n=122), adjusting for traditional diabetes-related risk factors. Plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance included highly weighted metabolites from fructose, tyrosine, lipid and amino acid metabolism. Each SD increase in the plasma (HR 1.99 [95% CI 1.18, 3.38]; p=0.01) and multi-fluid (1.80 [1.06, 3.07]; p=0.03) metabolomic scores was associated with higher risk of type 2 diabetes. The saliva metabolomic score was associated with incident prediabetes (1.48 [1.17, 1.86]; p=0.001). All three metabolomic scores were significantly associated with lower likelihood of regressing from prediabetes to normoglycaemia in models adjusting for adiposity (HRs 0.72 for plasma, 0.78 for saliva and 0.72 for multi-fluid), but associations were attenuated when adjusting for lipid and glycaemic measures. The plasma metabolomic score predicting insulin resistance was more strongly associated with incident type 2 diabetes than the saliva metabolomic score. Only the saliva metabolomic score was associated with incident prediabetes.

Low Concentration of Lipoprotein(a) is an Independent Predictor of Incident Type 2 Diabetes.

The aim of the study was to assess the association between lipoprotein(a) [Lp(a)] concentration and incident type 2 diabetes. A meta-analysis of qualified studies on the relationship of low levels of Lp(a) concentration with incident type 2 diabetes was conducted. PubMed and Cochrane libraries were searched for randomized controlled trials containing data on events. Seven randomized trials with 227178 subjects were included in this analysis. We found an inverse association of the levels of Lp(a) concentration with risk of type 2 diabetes with approximately 37% lower relative risk in the group with the highest concentration compared with group with the lowest concentration. The current available evidence from prospective studies suggests that there is an inverse association between the levels of Lp(a) concentration and risk of type 2 diabetes, with a higher risk of type 2 diabetes at low levels of Lp(a) concentration. Therefore, we believe that the low levels of Lp(a) concentration is an independent predictor of incident type 2 diabetes.

Using continuous electronic urine output monitoring for the management of acute cardio-renal syndrome in patients with acute decompensated heart failure

Abstract Funding Acknowledgements None. Background Patients admitted for acute decompensated heart failure (ADHF) are at high risk for type I cardio-renal syndrome (CRS) related to venous congestion and diuretic resistance. Positive fluid balance has been associated with adverse outcomes including acute kidney injury (AKI) and mortality. In critically ill patients urine output (UO) is used both to assess deterioration of renal function as well as for management of fluid balance .We investigated the possible effect of real-time UO monitoring, fluid balance, renal outcomes and 30-day mortality of patients admitted to the cardiac intensive care unit (ICU) with ADHF. Methods We performed a case series of 50 patients admitted to the cardiac ICU from July 2021 and June 2023 with ADHF. Their standard foley catheter was connected to an electronic monitoring system that continuously monitors UO in real-time. Its technology is described elsewhere (1). The UO monitoring system displays UO trends on the consoles that are updated in real-time. UO trends were utilized to guide an individualized approach for the pharmacologic management of each patient, based on blood pressure, hourly UO and total fluid balance. Daily and accumulated fluid balance was registered at up to 72 hours following admission. Patient outcomes included change in fluid balance, incidence of AKI and 30-day mortality. The case series group was than compared to a historical group of 50 matched controlled patients admitted between 2019-2020. Patients were matched according to cause of admission, age and glomerular filtration rate. Results In the study cohort the median age was 71±12 years, and 36 (72%) were men. In the historical cohort the median age was 71±13 years, and 36 (72%) were men. Patients in the electronic urinary monitoring cohort demonstrated significantly more negative daily and cumulative fluid balance as compared to the historical cohort, (P<0.001 for all, Figure 1). Incidence of AKI and the combined endpoint of AKI and 30-day mortality was significantly lower in the electronic UO monitoring cohort (24% vs. 46%, p=0.0197 and 40% vs 78%, P<0.0001 respectively). These changes were more prominent in the subgroup of patients with chronic kidney disease (Figure 2). Conclusion We demonstrated that real time monitoring of UO was associated with better prevention of fluid overload and the management of type I CRS in patients with ADHF. Further studies on larger populations are required to validate the potential utility of UO trending in the management of critically ill patients with ADHF.Fluid balance renal senseAKI and 30-day mortality

Abstract PO5-08-12: Ethnic Admixture Affects Breast Cancer Incidence in Native Hawaiians: The Multiethnic Cohort

Abstract Background Native Hawaiians (NH) have the highest breast cancer incidence and the poorest survival of any ethnic group in Hawaii [1]. Since it has been shown that different ethnic groups have disparate risk of breast cancer in Hawaii and NHs are commonly of mixed ancestry, it is possible that the specific ethnic admixture may present an altered risk profile. For example, NH with Asian admixture was associated with higher risk for type 2 diabetes independent of known risk factors [2] compared to those without. The objective of this study was to calculate crude and age-adjusted breast cancer incidences by ethnic admixture group among participants of the Multiethnic Cohort (MEC). Methods: Based on self-reports, 106,525 eligible women were categorized by broad ethnic categories: Native Hawaiian, White, Black, Latino, and Japanese. In total there were 9257 breast cancer cases in the MEC cohort (1996-2019) at time of analysis. The Native Hawaiian population was further categorized into the following subgroups: Native Hawaiian only, Native Hawaiian & White, Native Hawaiian & Chinese, Native Hawaiian & White & Chinese. Crude and age-adjusted incidence rates (per 1000 person-years) were calculated for the various groups. The direct method of age adjustment using the US 2000 Standard population was used. Results: The ethnicity with the highest crude incidence were White=88.46, followed by Black=85.20, Latino=84.27, Japanese=84.90, and Native Hawaiian=81.28. However, after age-adjustment the highest were Japanese=159.1, White=153.8, Latino=148.3, Black=147.4, and Native Hawaiian=139.1. Crude incidence rates for Native Hawaiian ethnic admixture was found to be highest for Native Hawaiian & White=83.5, Native Hawaiian only=82.5, Native Hawaiian & Chinese=80.8, and Native Hawaiian & White & Chinese=80.4. After age adjustment, the highest was Native Hawaiian & Chinese=173.9, followed by Native Hawaiian & White=154.3, Native Hawaiian only=148.7, and finally Native Hawaiian & White & Chinese=120.8. Conclusion: These findings indicate that ethnic admixture in Native Hawaiians may be at elevated age-adjusted breast cancer incidence when compared to Native Hawaiian alone. When a woman was Native Hawaiian and Chinese the incidence was notably higher than any other group at 173.9 when compared to all Native Hawaiian=139.1. Furthermore, the group that had the lowest age-adjusted incidence was the mixed group of Native Hawaiian & White & Chinese=120.8 which seems to account for why the overall Native Hawaiian group=139.1 had one of the lowest incidence rates of the 5 major ethnic groups. 1. Loo, L.W., M. Williams, and B.Y. Hernandez, The high and heterogeneous burden of breast cancer in Hawaii: A unique multiethnic US Population. Cancer epidemiology, 2019. 58: p. 71-76. 2. Maskarinec, G., et al., Ethnic admixture affects diabetes risk in native Hawaiians: the Multiethnic Cohort. Eur J Clin Nutr, 2016. 70(9): p. 1022-7. Citation Format: Dustin Valdez, Arianna Bunnell, David Bogumil, Gertraud Maskarinec, John Shepherd. Ethnic Admixture Affects Breast Cancer Incidence in Native Hawaiians: The Multiethnic Cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-08-12.

Clustering of health behaviors and their associations with cardiometabolic risk factors among adults at high risk for type 2 diabetes in India: A latent class analysis.

We aimed to identify clusters of health behaviors and study their associations with cardiometabolic risk factors in adults at high risk for type 2 diabetes in India. Baseline data from the Kerala Diabetes Prevention Program (n = 1000; age 30-60 years) were used for this study. Information on physical activity (PA), sedentary behavior, fruit and vegetable intake, sleep, and alcohol and tobacco use was collected using questionnaires. Blood pressure, waist circumference, 2-h plasma glucose, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides were measured using standardized protocols. Latent class analysis was used to identify clusters of health behaviors, and multilevel mixed-effects linear regression was employed to examine their associations with cardiometabolic risk factors. Two classes were identified, with 87.4% of participants in class 1 and 12.6% in class 2. Participants in both classes had a high probability of not engaging in leisure-time PA (0.80 for class 1; 0.73 for class 2) and consuming <5 servings of fruit and vegetables per day (0.70 for class 1; 0.63 for class 2). However, participants in class 1 had a lower probability of sitting for >=3 h per day (0.26 vs 0.42), tobacco use (0.10 vs 0.75), and alcohol use (0.08 vs 1.00) compared to those in class 2. Class 1 had a significantly lower mean systolic blood pressure (β = -3.70 mm Hg, 95% confidence interval [CI] -7.05, -0.36), diastolic blood pressure (β = -2.45 mm Hg, 95% CI -4.74, -0.16), and triglycerides (β = -0.81 mg/dL, 95% CI -0.75, -0.89). Implementing intervention strategies, tailored to cluster-specific health behaviors, is requiredfor the effective prevention of cardiometabolic disorders among high-risk adults for type 2 diabetes.

The association of insulin responses and insulin sensitivity with cognition in adults with pre-diabetes: The Diabetes Prevention Program Outcomes Study

ObjectiveDysglycemia is a significant risk factor for cognitive impairment. However, which pathophysiologic determinant(s) of dysglycemia, impaired insulin sensitivity (ISens) or the islet β-cell's response (IResp), contribute to poorer cognitive function, independent of dysglycemia is not established. Among 1052 adults with pre-diabetes from the Diabetes Prevention Program Outcomes Study (DPPOS), we investigated the relationship between IResp, ISens and cognitive function. Research design and methodsIResp was estimated by the insulinogenic index (IGI; pmol/mmol) and ISens as 1/fasting insulin from repeated annual oral glucose tolerance tests. The mean IResp and mean ISens were calculated over approximately 12 years of follow-up. Verbal learning (Spanish-English Verbal Learning Test [SEVLT]) and executive function (Digital Symbol Substitution Test [DSST]) were assessed at the end of the follow-up period. Linear regression models were run for each cognitive outcome and were adjusted for dysglycemia and other factors. ResultsHigher IResp was associated with poorer performance on the DSST (−0.69 points per 100 unit increase in IGI, 95 % CI: −1.37, −0.01). ISens was not associated with DSST, nor were IResp or ISens associated with performance on the SEVLT. ConclusionsThese results suggest that a greater β-cell response in people at high risk for type 2 diabetes is associated with poorer executive function, independent of dysglycemia and ISens.

Longitudinal leisure-time physical activity profiles throughout adulthood and related characteristics: a 36-year follow-up study of the older Finnish Twin Cohort

BackgroundPersonalized interventions aiming to increase physical activity in individuals are effective. However, from a public health perspective, it would be important to stimulate physical activity in larger groups of people who share the vulnerability to be physically inactive throughout adulthood. To find these high-risk groups, we identified 36-year leisure-time physical activity profiles from young adulthood to late midlife in females and males. Moreover, we uncovered which anthropometric-, demographic-, lifestyle-, and health-related characteristics were associated with these physical activity profiles.MethodsWe included 2,778 females and 1,938 males from the population-based older Finnish Twin Cohort Study, who responded to health and behavior surveys at the mean ages of 24, 30, 40 and 60. Latent profile analysis was used to identify longitudinal leisure-time physical activity profiles.ResultsWe found five longitudinal leisure-time physical activity profiles for both females and males. Females’ profiles were: 1) Low increasing moderate (29%), 2) Moderate stable (23%), 3) Very low increasing low (20%), 4) Low stable (20%) and 5) High increasing high (9%). Males’ profiles were: 1) Low increasing moderate (29%), 2) Low stable very low (26%), 3) Moderate decreasing low (21%), 4) High fluctuating high (17%) and 5) Very low stable (8%). In both females and males, lower leisure-time physical activity profiles were associated with lower education, higher body mass index, smoking, poorer perceived health, higher sedentary time, high blood pressure, and a higher risk for type 2 diabetes. Furthermore, lower leisure-time physical activity was linked to a higher risk of depression in females.ConclusionsWe found several longitudinal leisure-time physical activity profiles with unique changes in both sexes. Fewer profiles in females than in males remained or became low physically active during the 36-year follow-up. We observed that lower education, higher body mass index, and more smoking already in young adulthood were associated with low leisure-time physical activity profiles. However, the fact that several longitudinal profiles demonstrated a change in their physical activity behavior over time implies the potential for public health interventions to improve leisure-time physical activity levels.

The causal relationship between sarcoidosis and autoimmune diseases: a bidirectional Mendelian randomization study in FinnGen.

Sarcoidosis has been considered to be associated with many autoimmune diseases (ADs), but the cause-and-effect relationship between these two diseases has not been fully explored. Therefore, the objective of this study is to explore the possible genetic association between sarcoidosis and ADs. We conducted a bidirectional Mendelian randomization (MR) study using genetic variants associated with ADs and sarcoidosis (4,041 cases and 371,255 controls) from the FinnGen study. The ADs dataset comprised 96,150 cases and 281,127 controls, encompassing 44 distinct types of autoimmune-related diseases. Subsequently, we identified seven diseases within the ADs dataset with a case size exceeding 3,500 and performed subgroup analyses on these specific diseases. The MR evidence supported the causal association of genetic predictors of ADs with an increased risk of sarcoidosis (OR = 1.79, 95% CI = 1.59 to 2.02, PIVW-FE = 1.01 × 10-21), and no reverse causation (OR = 1.05, 95% CI 0.99 to 1.12, P IVW-MRE = 9.88 × 10-2). Furthermore, subgroup analyses indicated that genetic predictors of type 1 diabetes mellitus (T1DM), celiac disease, and inflammatory bowel disease (IBD) were causally linked to an elevated risk of sarcoidosis (All P < 6.25 × 10-3). Conversely, genetic predictors of sarcoidosis showed causal associations with a higher risk of type 1 diabetes mellitus (P < 6.25 × 10-3). The present study established a positive causal relationship between genetic predictors of ADs (e.g. T1DM, celiac disease, and IBD) and the risk of sarcoidosis, with no evidence of reverse causation.

Reframing prediabetes: A call for better risk stratification and intervention.

Prediabetes is an intermediate state of glucose homeostasis whereby plasma glucose concentrations are above normal but below the threshold of diagnosis for diabetes. Over the last several decades, criteria for prediabetes have changed as the cut points for normal glucose concentration and diagnosis of diabetes have shifted. Global consensus does not exist for prediabetes criteria; as a result, the clinical course and risk for type 2 diabetes vary. At present, we can identify individuals with prediabetes based on three glycemic tests (hemoglobin A1c, fasting plasma glucose, and 2-h plasma glucose during an oral glucose tolerance test). The majority of individuals diagnosed with prediabetes meet only one of these criteria. Meeting one, two, or all glycemic criteria changesrisk for type 2 diabetes, but this information is not widely known and does not currently guide intervention strategies for individuals with prediabetes. This review summarizes current epidemiology, prognosis, and intervention strategies for individuals diagnosed with prediabetes and suggests a call for more precise risk stratification of individuals with prediabetes as elevated (one prediabetes criterion), high risk (two prediabetes criteria), and very high risk (three prediabetes criteria). In addition, the roles of oral glucose tolerance testing and continuous glucose monitoring in the diagnostic criteria for prediabetes need reassessment. Finally, we must reframe our goals for prediabetes and prioritize intensive interventions for those at high and very high risk for type 2 diabetes.

The impact of intermittent hypoxemia on type 1 retinopathy of prematurity in preterm infants.

Intermittent hypoxemia (IH) may influence retinopathy of prematurity (ROP) development in preterm infants, however, previous studies had mixed results. This study tests the hypothesis that increased IH is associated with Type 1 ROP; a stage beyond which treatment is indicated. IH was quantified by continuously monitoring oxygen saturation (SpO2) using high-resolution pulse oximeters during the first 10 weeks of life. Statistical analyses assessed the relationship and predictive ability of weekly and cumulative IH for Type 1 ROP development. Most analyses showed no association between IH and Type 1 ROP adjusting for gestational age (GA) and birth weight (BW). However, cumulative IH of longer duration during weeks 5-10, 6-10, and 7-10 were significantly associated with Type 1 ROP adjusting for GA and BW, e.g., the adjusted odds ratio of Type 1 ROP was 2.01 (p = 0.03) for every 3.8 seconds increase in IH duration from week 6-10. IH did not provide statistically significant added predictive ability above GA and BW. For most analyses there was no significant association between IH and Type 1 ROP adjusting for GA and BW. However, infants with longer IH duration during the second month of life had higher risk for Type 1 ROP. The relationship and predictive ability of intermittent hypoxemia (IH) on retinopathy of prematurity (ROP) is controversial. This study shows no significant association between IH events and Type 1 ROP after adjusting for gestational age (GA) and birth weight (BW), except for cumulative IH of longer duration in the second month of life. In this cohort, IH does not provide a statistically significant improvement in ROP prediction over GA and BW. This study is the first to assess the cumulative impact of IH measures on Type 1 ROP. Interventions for reducing IH duration during critical postnatal periods may improve ROP outcomes.

Longitudinal study of the impact of the COVID-19 pandemic on diet and physical activity among Latinos of Mexican ancestry

BackgroundThe COVID-19 pandemic caused societal disruption in the United States and most of the world, affecting many aspects of life, including healthcare and health-related behaviors such as diet, food security, and physical activity. Communities with economic and health disparities may have been particularly affected. This study was undertaken to determine how conditions in the early pandemic (January, 2021–February, 2022) affected Latino patients of Mexican Ancestry at high risk of type 2 diabetes mellitus who participated in El Banco por Salud biobank project in Tucson, Arizona.MethodsBaseline, prepandemic measurements were available in 17, 21, and 60 patients with normal hemoglobin A1c (HbA1c), prediabetes, and type 2 diabetes, respectively.ResultsPeople with healthy HbA1c were significantly younger, less obese, and had higher HDL cholesterol. HbA1c was unaffected by the pandemic in any group. Triglycerides, total and HDL cholesterol levels fell in all groups during the pandemic. Physical activity levels in all groups were remarkably low, with most reporting no engagement in any voluntary physical activity. Engagement in physical activity or its enjoyment was lower in patients with diabetes and prediabetes than in younger, less obese patients. Major diet differences were between men and women and were present before the pandemic. Women consumed significantly more vegetables, fruit, and salad than men. The only pandemic-related change in diet was a drop in egg consumption, possibly explaining the fall in total cholesterol.ConclusionSocietal disruption during the COVID-19 pandemic had minimal effects on adverse health-related behaviors, cardiometabolic risk, or changes in glycemic control in a Latino community with diabetes and healthcare disparities in the Southwest US.

Development and validation of a lifetime prediction model for incident type 2 diabetes in patients with established cardiovascular disease: the CVD2DM model.

Identifying patients with established cardiovascular disease (CVD) who are at high risk of type 2 diabetes (T2D) may allow for early interventions, reducing the development of T2D and associated morbidity. The aim of this study was to develop and externally validate the CVD2DM model to estimate the 10-year and lifetime risks of T2D in patients with established CVD. Sex-specific, competing risk-adjusted Cox proportional hazard models were derived in 19 281 participants with established CVD and without diabetes at baseline from the UK Biobank. The core model's pre-specified predictors were age, current smoking, family history of diabetes mellitus, body mass index, systolic blood pressure, fasting plasma glucose, and HDL cholesterol. The extended model also included HbA1c. The model was externally validated in 3481 patients from the UCC-SMART study. During a median follow-up of 12.2 years (interquartile interval 11.3-13.1), 1628 participants with established CVD were diagnosed with T2D in the UK Biobank. External validation c-statistics were 0.79 [95% confidence interval (CI) 0.76-0.82] for the core model and 0.81 (95% CI 0.78-0.84) for the extended model. Calibration plots showed agreement between predicted and observed 10-year risk of T2D. The 10-year and lifetime risks of T2D can be estimated with the CVD2DM model in patients with established CVD, using readily available clinical predictors. The model would benefit from further validation across diverse ethnic groups to enhance its applicability. Informing patients about their T2D risk could motivate them further to adhere to a healthy lifestyle.

Effects of 3 months of 10-h per-day time-restricted eating and 3 months of follow-up on bodyweight and cardiometabolic health in Danish individuals at high risk of type 2 diabetes: the RESET single-centre, parallel, superiority, open-label, randomised controlled trial

Time-restricted eating (TRE) has been suggested to be a simple, feasible, and effective dietary strategy for individuals with overweight or obesity. We aimed to investigate the effects of 3 months of 10-h per-day TRE and 3 months of follow-up on bodyweight and cardiometabolic risk factors in individuals at high risk of type 2 diabetes. This was a single-centre, parallel, superiority, open-label randomised controlled clinical trial conducted at Steno Diabetes Center Copenhagen (Denmark). The inclusion criteria were age 30-70 years with either overweight (ie, BMI ≥25 kg/m2) and concomitant prediabetes (ie, glycated haemoglobin [HbA1c] 39-47 mmol/mol) or obesity (ie, BMI ≥30 kg/m2) with or without prediabetes and a habitual self-reported eating window (eating and drinking [except for water]) of 12 h per day or more every day and of 14 h per day or more at least 1 day per week. Individuals were randomly assigned 1:1 to 3 months of habitual living (hereafter referred to as the control group) or TRE, which was a self-selected 10-h per-day eating window placed between 0600 h and 2000 h. Randomisation was done in blocks varying in size and was open for participants and research staff, but outcome assessors were masked during statistical analyses. The randomisation list was generated by an external statistician. The primary outcome was change in bodyweight, assessed after 3 months (12 weeks) of the intervention and after 3 months (13 weeks) of follow-up. Adverse events were reported and registered at study visits or if participants contacted study staff to report events between visits. This trial is registered on ClinicalTrials.gov (NCT03854656). Between March 12, 2019, and March 2, 2022, 100 participants (66 [66%] were female and 34 [34%] were male; median age 59 years [IQR 52-65]) were enrolled and randomly assigned (50 to each group). Of those 100, 46 (92%) in the TRE group and 46 (92%) in the control group completed the intervention period. After 3 months of the intervention, there was no difference in bodyweight between the TRE group and the control group (-0·8 kg, 95% CI -1·7 to 0·2; p=0·099). Being in the TRE group was not associated with a lower bodyweight compared with the control group after subsequent 3-month follow-up (-0·2 kg, -1·6 to 1·2). In the per-protocol analysis, participants who completed the intervention in the TRE group lost 1·0 kg (-1·9 to -0·0; p=0·040) bodyweight compared with the control group after 3 months of intervention, which was not maintained after the 3-month follow-up period (-0·4 kg, -1·8 to 1·0). During the trial and follow-up period, one participant in the TRE group reported a severe adverse event: development of a subcutaneous nodule and pain when the arm was in use. This side-effect was evaluated to be related to the trial procedures. 3 months of 10-h per-day TRE did not lead to clinically relevant effects on bodyweight in middle-aged to older individuals at high risk of type 2 diabetes. Novo Nordisk Foundation, Aalborg University, Helsefonden, and Innovation Fund Denmark.

Unravelling genetic architecture of circulatory amino acid levels, and their effect on risk of complex disorders.

Variations in serum amino acid levels are linked to a multitude of complex disorders. We report the largest genome-wide association study (GWAS) on nine serum amino acids in theUK Biobank participants (117944, European descent). We identified 34 genomic loci for circulatory levels of alanine, 48 loci for glutamine, 44 loci for glycine, 16 loci for histidine, 11 loci for isoleucine, 19 loci for leucine, 9 loci for phenylalanine, 32 loci for tyrosine and 20 loci for valine. Our gene-based analysis mapped 46-293 genes associated with serum amino acids, including MIP,GLS2, SLCgene family, GCKR, LMO1, CPS1and COBLL1.The gene-property analysis across 30 tissues highlighted enriched expression of the identified genes in liver tissues for all studied amino acids, except for isoleucine and valine, in muscle tissues for serum alanine and glycine, in adrenal gland tissues for serum isoleucine and leucine, and in pancreatic tissues for serum phenylalanine. Mendelian randomization (MR) phenome-wide association studyanalysis and subsequent two-sample MR analysis provided evidence that every standard deviation increase in valine is associated with 35% higher risk of type 2 diabetes and elevated levels of serum alanine and branched-chain amino acidswith higher levels of total cholesterol, triglyceride andlow-density lipoprotein, and lower levels ofhigh-density lipoprotein. In contrast to reports by observational studies, MR analysis did not support a causal association between studied amino acids and coronary artery disease, Alzheimer's disease, breast canceror prostate cancer. In conclusion, we explored the genetic architecture of serum amino acids and provided evidence supporting a causal role of amino acids in cardiometabolic health.

Abstract P132: Paso a Paso, Designing a Culturally Relevant Diabetes Prevention Intervention for Hispanic/Latino (H/L) People That Adheres to Evidence Based, Diabetes Prevention Program (DPP) Intervention Principles in the Hispanic/Latino (H/L) Community of Salt Lake County

One of five Salt Lake County residents identify as Hispanic/Latino(H/L) and are at higher risk for type 2 diabetes(T2D) compared to non-Hispanic whites. Evidence-based interventions to reduce T2D have not been as effective for H/Ls as for non-H/L whites. This study uses a shared-leadership, community-engaged approach to develop a model for H/L T2D prevention based on DPP with members of the H/L community, community-based organization partners (Utah Mexican Consulate; University Neighborhood Partners), and an interdisciplinary University of Utah team. Two groups of 10-15 people each (one for community members (CM) eligible to participate in a diabetes prevention program; one for community organization members(CBO) potential DPP-like program implementers). As part of a comprehensive participatory planning and evaluation(CPPE) process, each group met to (1)review existing Spanish DPP program components, learning objectives, and materials, (2)identify barriers to successful T2D prevention, and (3)suggest facilitators and areas for adaptation specific to H/L audiences. Participants in each group rated the DPP program structure and content related to healthy eating, increasing physical activity (PA), self-monitoring and meal planning using validated measures of acceptability, appropriateness, and feasibility. In addition, qualitative data was gathered and reduced to provide directions for potential adaptations. Quantitative data (Figure 1) indicates CM and CBO agree on importance of DPP program structure and content, however CBO members rated the acceptability, appropriateness, and feasibility more neutrally than CM participants. Qualitative data indicated a stronger focus on collective support, culturally aligned healthful eating options, and PA promotion that addressed safe activities for laborers. Conclusions CM and CBO participants found DPP to be an important resource for the H/L community, but also identified adaptations that could improve program reach, retention, and effectiveness.

Telomere length as biomarker of nutritional therapy for prevention of type 2 diabetes mellitus development in patients with coronary heart disease: CORDIOPREV randomised controlled trial

BackgroundTelomere Length (TL), a marker of cellular aging, holds promise as a biomarker to elucidate the molecular mechanism of diabetes. This study aimed to investigate whether shorter telomeres are associated with a higher risk of type 2 diabetes mellitus (T2DM) incidence in patients with coronary heart disease; and to determine whether the most suitable dietary patterns, particularly a Mediterranean diet or a low-fat diet, can mitigate the development of diabetes in these patients after a follow-up period of five years.MethodsThe CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study) was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20–75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive two healthy diets. Clinical investigators were masked to treatment assignment; participants were not. Quantitative-PCR was used to assess TL measurements.Findings1002 patients (59.5 ± 8.7 years and 82.5% men) were enrolled into Mediterranean diet (n = 502) or a low-fat diet (n = 500) groups. In this analysis, we included all 462 patients who did not have T2DM at baseline. Among them, 107 patients developed T2DM after a median of 60 months. Cox regression analyses showed that patients at risk of short telomeres (TL < percentile 20th) are more likely to experience T2DM than those at no risk of short telomeres (HR 1.65, p-value 0.023). In terms of diet, patients at high risk of short telomeres had a higher risk of T2DM incidence after consuming a low-fat diet compared to patients at no risk of short telomeres (HR 2.43, 95CI% 1.26 to 4.69, p-value 0.008), while no differences were observed in the Mediterranean diet group.ConclusionPatients with shorter TL presented a higher risk of developing T2DM. This association could be mitigated with a specific dietary pattern, in our case a Mediterranean diet, to prevent T2DM in patients with coronary heart disease.Trial RegistrationClinicaltrials.gov number NCT00924937.

Efficacy of 1-hour postload plasma glucose as a suitable measurement in predicting type 2 diabetes and diabetes-related complications: A post hoc analysis of the 30-year follow-up of the Da Qing IGT and Diabetes Study.

To evaluate whether 1-hour plasma glucose (1hPG) can be a comparable measurement to 2-hour plasma glucose (2hPG) in identifying individuals at high risk of developing diabetes. A total of 1026 non-diabetic subjects in the Da Qing IGT and Diabetes Study were included and classified according to baseline postload 1hPG. The participants were followed up and assessed at 6-, 20- and 30year follow-up for outcomes including diabetes, all-cause and cardiovascular mortality, cardiovascular disease (CVD) events, and microvascular disease. We then conducted a proportional hazards analysis in this post hoc study to determine the risks of developing type 2 diabetes and its complications in a '1hPG-normal' group (1hPG <8.6 mmol/L) and a '1hPG-high' group (≥8.6 mmol/L). The predictive values of 1hPG and 2hPG were evaluated using a time-dependent receiver-operating characteristic (ROC) curve. Compared with the 1hPG-normal group, the 1hPG-high group had increased risk of diabetes (hazard ratio [HR] 4.45, 95% CI 3.43-5.79), all-cause mortality (HR 1.46, 95% CI 1.07-2.01), CVD mortality (HR 1.84, 95% CI 1.16-2.95), CVD events (HR 1.39, 95% CI 1.03-1.86) and microvascular disease (HR 1.70, 95% CI: 1.03-2.79) after adjusting for confounders. 1hPG exhibited a higher area under the ROC curve (AUC) for predicting diabetes than 2hPG during the long-term follow-up (AUC [1hPG vs. 2hPG]: 10 years: 0.86 vs. 0.84, p = 0.08; 20 years: 0.88 vs. 0.87, p = 0.04; 30 years: 0.85 vs. 0.82, p = 0.009). Elevated 1hPG level (≥8.6 mmol/L) was associated with increased risk of developing type 2 diabetes and its long-term complications, and could be considered as a suitable measurement for identifying individuals at high risk of type 2 diabetes.

SGLT2 inhibitors: from glucose-lowering to cardiovascular benefits.

An increasing number of individuals are at high risk of type 2 diabetes (T2D) and its cardiovascular complications, including heart failure (HF), chronic kidney disease (CKD), and eventually premature death. The sodium-glucose co-transporter-2 (SGLT2) protein sits in the proximal tubule of human nephrons to regulate glucose reabsorption and its inhibition by gliflozins represents the cornerstone of contemporary T2D and HF management. Herein, we aim to provide an updated overview of the pleiotropy of gliflozins, provide mechanistic insights and delineate related cardiovascular (CV) benefits. By discussing contemporary evidence obtained in preclinical models and landmark randomized controlled trials, we move from bench to bedside across the broad spectrum of cardio- and cerebrovascular diseases. With landmark randomized controlled trials confirming a reduction in major adverse CV events (MACE; composite endpoint of CV death, non-fatal myocardial infarction, and non-fatal stroke), SGLT2 inhibitors strongly mitigate the risk for heart failure hospitalization in diabetics and non-diabetics alike while conferring renoprotection in specific patient populations. Along four major pathophysiological axes (i.e. at systemic, vascular, cardiac, and renal levels), we provide insights into the key mechanisms that may underlie their beneficial effects, including gliflozins' role in the modulation of inflammation, oxidative stress, cellular energy metabolism, and housekeeping mechanisms. We also discuss how this drug class controls hyperglycaemia, ketogenesis, natriuresis, and hyperuricaemia, collectively contributing to their pleiotropic effects. Finally, evolving data in the setting of cerebrovascular diseases and arrhythmias are presented and potential implications for future research and clinical practice are comprehensively reviewed.

Tailoring of Health-Promotion Video Messaging for Reproductive-Aged Women at Risk for Developing Cardiometabolic Disease: Qualitative Focus-Groups Study.

Targeting reproductive-aged women at high risk for type 2 diabetes (T2D) provides an opportunity for prevention earlier in the life course. A woman's experiences during her reproductive years may have a large impact on her future risk of T2D. Her risk is 7 to 10 times higher if she has had gestational diabetes (GDM). Despite these risks, T2D is preventable. Evidence-based programs, such as the National Diabetes Prevention Program (DPP), can reduce the risk of developing T2D by nearly 60%. However, only 0.4% of adults with prediabetes have participated in the DPP to date and reproductive-aged women are 50% less likely to participate than older women. In prior work, our team developed a mobile 360° video to address diabetes risk awareness and promote DPP enrollment among at-risk adults; this video was not designed, however, for reproductive-aged women. This study aims to obtain feedback from reproductive-aged women with cardiometabolic disease risk about a 360° video designed to promote enrollment in the DPP, and to gather suggestions about tailoring video messages to reproductive-aged women. Focus groups and a qualitative descriptive approach were used. Women with at least 1 previous pregnancy, aged 18 to 40 years, participated in one of three focus groups stratified by the following health risks: (1) a history of GDM or a hypertensive disorder of pregnancy, (2) a diagnosis of prediabetes, or (3) a BMI classified as obese. Focus-group questions addressed several topics; this report shared findings regarding video feedback. The 3 focus-group discussions were conducted via Zoom and were recorded and transcribed for analysis. Deductive codes were used to identify concepts related to the research question and inductive codes were created for novel insights shared by participants. The codes were then organized into categories and themes. The main themes identified were positive feedback, negative feedback, centering motherhood, and the importance of storytelling. While some participants said the video produced a sense of urgency for health-behavior change, all participants agreed that design changes could improve the video's motivating effect on health-behavior change in reproductive-aged women. Participants felt a tailored video should recognize the complexities of being a mother and how these dynamics contribute to women's difficulty engaging in healthy behaviors without stirring feelings of guilt. Women desired a video with a positive, problem-solving perspective, and recommended live links as clickable resources for practical solutions promoting health behavior change. Women suggested using storytelling, both to describe how complications experienced during pregnancy impact long-term health and to motivate health behavior change. Reproductive-aged women require tailored lifestyle-change messaging that addresses barriers commonly encountered by this population (eg, parenting or work responsibilities). Moreover, messaging should prioritize a positive tone that harnesses storytelling and human connection while offering realistic solutions.

Associations of a proinflammatory diet, habitual salt intake, and the onset of type 2 diabetes: A prospective cohort study from the UK Biobank.

To explore the relationship between proinflammatory diet, habitual salt intake and the onset of type 2 diabetes. This prospective study was conducted among 171 094 UK Biobank participants who completed at least one 24-h dietary questionnaire and were free of diabetes at baseline. Participants were followed up until 1 March 2023 for type 2 diabetes incidence, with diagnosis information obtained from linked medical records. An Energy-adjusted Diet Inflammatory Index (E-DII) was calculated based on 28 food parameters. Habitual salt intake was determined through the self-reported frequency of adding salt to foods. The associations between E-DII, habitual salt intake and type 2 diabetes incidence were tested by the Cox proportional hazard regression model. Over a median follow-up period of 13.5 years, 6216 cases of type 2 diabetes were documented. Compared with participants with a low E-DII (indicative of an anti-inflammatory diet), participants with a high E-DII (indicative of a proinflammatory diet) had an 18% heightened risk of developing type 2 diabetes. The association between E-DII and type 2 diabetes tends to be linear after adjustment for major confounders. Participants with a proinflammatory diet and always adding salt to foods had the highest risk of type 2 diabetes incidence (hazard ratio 1.60, 95% confidence interval 1.32-1.94). Our findings indicate that a proinflammatory diet and higher habitual salt intake were associated with an increased risk of type 2 diabetes. These results support the public health promotion of an anti-inflammatory diet and reducing salt intake to prevent the onset of type 2 diabetes.