High Rates Of Type Research Articles

Major aorto-pulmonary arteries in transposition of the great arteries: Impact and management

Major aorto-pulmonary collateral arteries (MAPCA) are frequent in patients with simple transposition of the great arteries (TGA). However, only few studies describe postoperative management. We analyzed predictive factors of hemodynamically significant MAPCAs, their clinical impact and we reported treatment and outcome after embolisations of these collaterals. All neonates admitted with simple TGA between January 2014 and December 2019 in our center were retrospectively reviewed and divided in 2 groups according to the presence of significant MAPCAS. Demographic data at birth, surgical data, pre- and post-procedural data if catheterization was performed, and outcome were reported. In total, 129 patients were included. Twenty-five had significant MAPCAS diagnosed on TTE and confirmed on angiography. All of them were successfully embolized, with a mean of 1.9 ± 0.77 MAPCA closure. Mean delay between surgery and catheterization was 6.8 ± 8.1 days. There were no complication reported after embolization. Mean days between catheterization and extubation were 2.9 ± 3.3 days. When comparing the 2 groups, weight, gestational age and prenatal diagnosis rate were similar but there was a statistically significant higher need of Rashkind's manoeuver ( P = 0.04) and prostaglandin infusion ( P = 0.03) in the MAPCAS group. Mean age at surgery was 7.4 ± 4.4 in the group with MAPCAS and 6 ± 7.8 in the second group ( P = 0.48). Bypass time was similar in both groups: 138 ± 24 minutes in the MAPCAS group versus 137 ± 37 minutes in the second group. Coronary anatomy was different in the 2 groups with higher rate of type A anatomy in the group without MAPCAS (60% versus 11%, P = 0.01). When comparing the 2 groups in the postoperative period, the MAPCA group had a more complex course: ICU stay (12.8 versus 5.8 days, P = 0.037), inotropic support (9 versus 5.35 days, P = 0.024) and hospital stay (21.18 versus 13.9 days, P = 0.0019) were longer. Patients with simple TGA with hemodynamically significant MAPCAS were more cyanosed at birth with higher need of prostaglandins and Rashkind procedure. They had a more complex postoperative course with higher inotropic support and longer ICU and hospitalization time. These results suggest the importance of diagnosing MAPCAs and treating them as quickly as possible in order to ease postoperative course.

Racial disparity in uterine cancer treatment and survival: A matter of Black women’s lives.

6550 Background: Despite similar incidence rates of uterine cancer (UC) in Black and White women, the former have worse prognosis and survival. Absence of denominator correction for UC hysterectomy (prevalence varies within the United States [US] by race/region) may underestimate incidence. The objective of this study is to compare treatment and survival of patients with UC by race in a large, contemporary, population-based study with at least 5 years of follow-up. Methods: With the latest available data from the Surveillance, Epidemiology, and End Results database, comparisons between Black and White patients were made using chi-square and Mann-Whitney tests. Cox proportional hazards regression estimated the adjusted risk of mortality by including age at diagnosis, race, US region, tumor histology/stage/grade, and receipt of hysterectomy as covariates. Results: A total of 105,036 women (11,028 Black and 94,008 White) newly diagnosed with UC in 2000-2013 and followed through 2018 were identified. Median age at diagnosis was 62 years, and more patients in the South were Black (41% vs 17%, P<.0001). Higher rates of type 2 (15% vs 6%), late-stage (44% vs 28%), and high-grade (48% vs 25%) tumors at diagnosis were also found in Black women (all Ps<.0001; Table). Compared with White women, Black women had lower 5-year survival rate (18% vs 37%, P<.0001), shorter survival (median 49 vs 78 months, P<.0001), and higher adjusted mortality risk (hazard ratio [HR]: 1.3, 95% CI: [1.3, 1.4], P<.0001). Lack or unknown status of hysterectomy was also associated with higher death risk (HR: 3.6, 95% CI: [3.4, 3.9], P<.0001). Conclusions: Correcting for hysterectomy attenuates racial disparity in incidence; however, black women have inferior outcomes primarily due to increased aggressive histology, late-stage, and high-grade tumors as well as decreased use of hysterectomy. Underestimation of at-risk populations may be misdirecting cancer control efforts, highlighting the importance of accurate reporting to inform potential treatment adaptations. Next steps are to assess cancer-specific mortality with Fine-Gray competing risk models.[Table: see text]

Feasibility and Acceptability of a Language Concordant Health Coaching Intervention Delivered by Nurses for Latinx With Type 2 Diabetes.

Latinx immigrants have high rates of type 2 diabetes (T2D), exhibit out-of-range glycemic control, and have higher rates of diabetes-related complications than non-Latinx whites, with limited English proficiency (LEP) being a major barrier to care. We tested the feasibility and acceptability of a language concordant (provider that is proficient in the patient's preferred language) health coaching intervention delivered by nurse and nurse practitioner students in a pilot study of Latinx immigrants with T2D and LEP. A sample of 17 Latinx immigrants with T2D and LEP were split into intervention and control groups. The control group received basic diabetes care and written educational materials on diabetes self-management in Spanish. Individuals in the intervention group received the standard diabetes care offered by the clinic and six biweekly health coaching sessions (intervention) with a trained language concordant health coach. The language concordant health coaching intervention was both feasible (delivery) and acceptable (satisfactory) to Latinx immigrants with T2D and LEP and resulted in clinically meaningful differences in key diabetes-related outcomes. Our findings suggest that lack of language concordance between provider and patient has an important and meaningful impact on the ability of an LEP Latinx patient to receive, and perhaps act upon, adequate education for T2D management. Receiving biweekly coaching calls could have offered further emotional support for participants to discuss living with T2D, which may have helped to alleviate symptoms of depression and anxiety that individuals with T2D frequently endure.

Low Bottleneck Detection in Long-Lived Species Despite Lost Genetic Diversity: A Case Study of Tuatara and Eastern Massasauga Rattlesnakes.

Population bottlenecks can reduce genetic diversity and may lead to inbreeding depression. However, some studies have provided evidence that long lifespans buffer negative genetic effects of bottlenecks. Others have cautioned that longevity might merely mask the effects of genetic drift, which will still affect long-term population viability. We used microsatellite data from actual populations of tuatara (Sphenodon punctatus) and eastern massasaugas (Sistrurus catenatus) as a starting point for simulated population declines to evaluate the performance of bottleneck tests under a range of scenarios. We quantified losses in genetic diversity for each scenario and assessed the power of commonly used tests (i.e., M-ratio, heterozygosity excess, and mode-shift) to detect known bottlenecks in these moderate- to long-lived species. Declines in genetic diversity were greater in bottlenecks simulated for eastern massasaugas, the shorter-lived species, and mode-shift and heterozygosity excess tests were more sensitive to population declines in this species. Conversely, M-ratio tests were more sensitive to bottlenecks simulated in tuatara. Despite dramatic simulated population declines, heterozygosity excess and mode-shift tests often failed to detect bottlenecks in both species, even when large losses in genetic diversity had occurred (both allelic diversity and heterozygosity). While not eliminating type II error, M-ratio tests generally performed best and were most reliable when a critical value (Mc) of 0.68 was used. However, in tuatara simulations, M-ratio tests had high rates of type I error when Mc was calculated assuming θ = 10. Our results suggest that reliance on these tests could lead to misguided species management decisions.

HbA1c Performance in African Descent Populations in the United States With Normal Glucose Tolerance, Prediabetes, or Diabetes: A Scoping Review.

IntroductionAfrican descent populations in the United States have high rates of type 2 diabetes and are incorrectly represented as a single group. Current glycated hemoglobin A1c (HbA1c) cutoffs (5.7% to <6.5% for prediabetes; ≥6.5% for type 2 diabetes) may perform suboptimally in evaluating glycemic status among African descent groups. We conducted a scoping review of US-based evidence documenting HbA1c performance to assess glycemic status among African American, Afro-Caribbean, and African people.MethodsA PubMed, Scopus, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) search (January 2020) yielded 3,238 articles published from January 2000 through January 2020. After review of titles, abstracts, and full texts, 12 met our criteria. HbA1c results were compared with other ethnic groups or validated against the oral glucose tolerance test (OGTT), fasting plasma glucose (FPG), or previous diagnosis. We classified study results by the risk of false positives and risk of false negatives in assessing glycemic status.ResultsIn 5 studies of African American people, the HbA1c test increased risk of false positives compared with White populations, regardless of glycemic status. Three studies of African Americans found that HbA1c of 5.7% to less than 6.5% or HbA1c of 6.5% or higher generally increased risk of overdiagnosis compared with OGTT or previous diagnosis. In one study of Afro-Caribbean people, HbA1c of 6.5% or higher detected fewer type 2 diabetes cases because of a greater risk of false negatives. Compared with OGTT, HbA1c tests in 4 studies of Africans found that HbA1c of 5.7% to less than 6.5% or HbA1c of 6.5% or higher leads to underdiagnosis.ConclusionHbA1c criteria inadequately characterizes glycemic status among heterogeneous African descent populations. Research is needed to determine optimal HbA1c cutoffs or other test strategies that account for risk profiles unique to African American, Afro-Caribbean, and African people living in the United States.

Clinical and metabolomic predictors of regression to normoglycemia in a population at intermediate cardiometabolic risk

BackgroundImpaired fasting glucose (IFG) is a prevalent and potentially reversible intermediate stage leading to type 2 diabetes that increases risk for cardiometabolic complications. The identification of clinical and molecular factors associated with the reversal, or regression, from IFG to a normoglycemia state would enable more efficient cardiovascular risk reduction strategies. The aim of this study was to identify clinical and biological predictors of regression to normoglycemia in a non-European population characterized by high rates of type 2 diabetes.MethodsWe conducted a prospective, population-based study among 9637 Mexican individuals using clinical features and plasma metabolites. Among them, 491 subjects were classified as IFG, defined as fasting glucose between 100 and 125 mg/dL at baseline. Regression to normoglycemia was defined by fasting glucose less than 100 mg/dL in the follow-up visit. Plasma metabolites were profiled by Nuclear Magnetic Resonance. Multivariable cox regression models were used to examine the associations of clinical and metabolomic factors with regression to normoglycemia. We assessed the predictive capability of models that included clinical factors alone and models that included clinical factors and prioritized metabolites.ResultsDuring a median follow-up period of 2.5 years, 22.6% of participants (n = 111) regressed to normoglycemia, and 29.5% progressed to type 2 diabetes (n = 145). The multivariate adjusted relative risk of regression to normoglycemia was 1.10 (95% confidence interval [CI] 1.25 to 1.32) per 10 years of age increase, 0.94 (95% CI 0.91–0.98) per 1 SD increase in BMI, and 0.91 (95% CI 0.88–0.95) per 1 SD increase in fasting glucose. A model including information from age, fasting glucose, and BMI showed a good prediction of regression to normoglycemia (AUC = 0.73 (95% CI 0.66–0.78). The improvement after adding information from prioritized metabolites (TG in large HDL, albumin, and citrate) was non-significant (AUC = 0.74 (95% CI 0.68–0.80), p value = 0.485).ConclusionIn individuals with IFG, information from three clinical variables easily obtained in the clinical setting showed a good prediction of regression to normoglycemia beyond metabolomic features. Our findings can serve to inform and design future cardiovascular prevention strategies.

The Impact of Patient Age ≥80 Years on Postoperative Outcomes and Treatment Costs Following Pancreatic Surgery.

As life expectancy is increasing, elderly patients are evaluated more frequently for resection of benign or malignant pancreatic lesions. However, the impact of age on postoperative morbidity, mortality, and treatment costs in octogenarian patients (≥80 years) undergoing major pancreatic surgery needs further investigation. The clinicopathological data of patients who underwent pancreatic surgery between January 2015 and March 2019 in a major hepatopancreatobiliary center in Switzerland were assessed. Postoperative outcomes and hospital costs of octogenarians and younger patients were compared in univariate and multivariate regression analysis. During the study period, 346 patients underwent pancreatic resection. Pancreatoduodenectomy, distal pancreatectomy, total pancreatectomy, and other procedures were performed in 54%, 20%, 13%, and 13% of patients, respectively. The major postoperative morbidity rate and postoperative mortality rate were 25% and 3.5%, respectively. A total of 39 patients (11%) were ≥80 years old, and 307 patients were <80 years old. The majority of octogenarians suffered from ductal adenocarcinoma, whereas among younger patients, other indications for a pancreatic resection were predominant (ductal adenocarcinoma 64% vs. 41%, p = 0.006). Age ≥80 was associated with more frequent postoperative medical (pulmonary, cardiovascular) and surgical (high-grade pancreatic fistula, postoperative hemorrhage) complications. Postoperative mortality was significantly higher in octogenarians (15.4% vs. 2%, p < 0.0001). This finding may be explained by the higher rate of type C pancreatic fistula (13% vs. 5%), resulting more frequently in postoperative hemorrhage (18% vs. 5%, p = 0.002) among patients ≥80 years old. In the multivariate logistic regression analysis, patient age ≥80 years predicted postoperative mortality independently of the tumor entity and surgical technique (p = 0.013, OR 6.71, 95% CI [1.5–30.3]). Increased major postoperative morbidity was responsible for lower cost recovery in octogenarians (94% vs. 102%, p = 0.046). In conclusion, patient age ≥80 years is associated with increased postoperative medical and surgical morbidity after major pancreatic surgery leading to lower cost recovery and a lower chance for successful resuscitation in patients requiring revisional surgery for postoperative hemorrhage and/or pancreatic fistula. In octogenarian patients suffering from pancreatic tumors, careful selection, and thorough prehabilitation is crucial to achieve the best postoperative and long-term oncologic outcomes.

The existence of butterfly effect and its impact on the dentinal microhardness and crack formation after root canal instrumentation.

To compare the microhardness and crack formation in root dentine presented with butterfly effect in lower premolars. Sixty mature lower premolars were selected and divided into the control and experimental groups. Teeth in the experimental group were instrumented up to size 30/.04. The roots were cut horizontally into twelve parts of 1-mm-thick cross-section and were numbered accordingly. They were divided into coronal, middle, and apical root sections. Sections were then viewed under a microscope to determine the presence of butterfly effect and subsequently scored. 8 teeth from both control and experimental groups with the highest and lowest score were selected. Crack formation was inspected and classified into four different types of cracks. Microhardness test was performed using a Vickers hardness test. Higher frequency of butterfly effect was found in the apical root section and root dentine with butterfly effect were harder mesiodistally. The middle and apical root sections with butterfly effect were harder than the coronal section. No significant difference of dentine hardness between the control and experimental groups. Cracks only occurred in the experimental group and presented in buccolingual direction with a higher rate of Type 1 and Type 2 cracks. Prevalence of butterfly effect in lower premolars increased from coronal to apical with increased hardness mesiodistally. More buccolingual cracks were found in radicular dentine with butterfly effect and most of them exhibited Type 1 and Type 2 cracks. Roots of lower premolar with butterfly effect may be susceptible to a higher rate of vertical root fracture in buccolingual direction, especially after root canal treatment. Thus, special attention should be given not to overload instruments during root canal preparation.

Family model diabetes self-management education and support in faith-based organizations in the republic of the Marshall Islands study protocol

BackgroundMarshallese living in the Republic of the Marshall Islands (RMI) experience significant health disparities, with high rates of type 2 diabetes mellitus. In addition to health disparities, the RMI experienced nuclear testing that exposed inhabitants to nuclear fallout, unethical research practices, and contaminated natural food sources. ObjectivesThis research uses a community-based participatory research (CBPR) approach to effectively engage community partners and honor their contributions in all stages of the research. A CBPR approach will leverage culturally situated knowledge and practices of the Marshallese community in the RMI to ensure the success of the research. MethodsThis manuscript describes the methods used to test the feasibility of delivering a culturally adapted family model of diabetes self-management education and support in faith-based organizations in the RMI. ConclusionsThis manuscript describes the protocol for creating working with community partners and implementing a feasibility study in the RMI.

An Investigation of the Genetic Variability of Metabolic Syndrome and Hemoglobin A1c among African Americans: Rethinking Current Standards of Type 2 Diabetes Diagnosis

Biological markers for Metabolic Syndrome, such as serum lipids and Hemoglobin A1c may have genetic variability among African Americans versus their Caucasian American counterparts. Although cases of Type 2 diabetes and its sequela significantly outweigh Caucasian Americans in the US, paradoxically research has found a lower prevalence of Metabolic Syndrome among blacks versus whites despite there being higher rates of Type 2 diabetes among the former population. Research has shown Metabolic Syndrome lipid parameters among African Americans are more favorable despite outstanding Type 2 diabetes incidence. With the emergence of the Human Genome Project and Genome Wide Association Studies, genetic differences in these parameters have been uncovered and genetic variability may play a role in such paradoxical mismatch. It may be reasonable to consider modifying Metabolic Syndrome parameters as given this new biological evidence. Hemoglobin A1c, also a biological marker used to monitor glucose levels over time, shows variability in its measurements with respect to African Americans. Genetic factors may play a role in the discrepancies among African Americans populations when using this parameter to monitor blood glucose. Precision medicine is now at the forefront of a biomedical new age, to find therapies that cater to specific populations based on genetic research. African Americans may not benefit from such a revolutionary paradigm shift in medicine due to evidence of lack of inclusivity in such studies like the Human Genome Project. Consideration should be made to the future of molecular medicine to include more minority populations such as African Americans in order to cater to specific differences rather than generalized standards of care.

Association of Long-Term Air Pollution with Prevalence and Incidence of Distal Sensorimotor Polyneuropathy: KORA F4/FF4 Study.

Background:Air pollution contributes to type 2 diabetes and cardiovascular diseases, but its relevance for other complications of diabetes, in particular distal sensorimotor polyneuropathy (DSPN), is unclear. Recent studies have indicated that DSPN is also increasingly prevalent in obesity.Objectives:We aimed to assess associations of air pollutants with prevalent and incident DSPN in a population-based study of older individuals with high rates of type 2 diabetes and obesity.Methods:Cross-sectional analyses on prevalent DSPN were based on 1,075 individuals 62–81 years of age from the German Cooperative Health Research in the Region of Augsburg (KORA) F4 survey (2006–2008). Analyses on incident DSPN included 424 individuals without DSPN at baseline (KORA F4), of whom 188 had developed DSPN by the KORA FF4 survey (2013–2014). Associations of annual average air pollutant concentrations at participants’ residences with prevalent and incident DSPN were estimated using Poisson regression models with a robust error variance adjusting for multiple confounders.Results:Higher particle number concentrations (PNCs) were associated with higher prevalence [risk ratio (RR) per interquartile range (IQR) (95% CI: 1.01, 1.20)] and incidence [1.11 (95% CI: 0.99, 1.24)] of DSPN. In subgroup analyses, particulate (PNC, , , , and ) and gaseous (, ) pollutants were positively associated with prevalent DSPN in obese participants, whereas corresponding estimates for nonobese participants were close to the null [e.g., for an IQR increase in PNC, (95% CI: 1.05, 1.31) vs. 1.06 (95% CI: 0.95, 1.19); ]. With the exception of , corresponding associations with incident DSPN were positive in obese participants but null or inverse for nonobese participants, with [e.g., for PNC, (95% CI: 1.08, 1.51) vs. 1.03 (95% CI: 0.90, 1.18); ].Discussion:Both particulate and gaseous air pollutants were positively associated with prevalent and incident DSPN in obese individuals. Obesity and air pollution may have synergistic effects on the development of DSPN. https://doi.org/10.1289/EHP7311

1252-P: Effects of a Pilot Sugar-Reduction Intervention on Diet and Continuous Blood Glucose in Teenagers on the Remote Pacific Island of Kiritimati

Introduction: Kiritimati is a remote Pacific Island with a high rate of type 2 diabetes (∼30%), potentially related to high sugar consumption starting early in life. This pilot study aimed to determine the effects of a short-term sugar-reduction intervention in Kiritimati teenagers. Methods: The two high schools on the island were randomly assigned to a 7-day sugar-reduction intervention group (n=46) or control group (n=32). The intervention consisted of installation of a water filter at the school, distribution of individual water bottles, and a sugar-reduction presentation by a registered dietitian. 24-hour diet recalls were conducted at baseline and follow-up. Continuous blood glucose monitors (CGMs; FreeStyle Libre Pro) were used to assess 94 interstitial glucose measures over 14 days. A difference-in-differences analysis was used to address baseline differences between the schools. Data are presented as mean ± SD. Results: At baseline, overweight/obesity prevalence was 50% (control group) vs. 43% (intervention group); age 17.2 ± 1.6 vs. 16.8 ± 1.8 years; mean blood glucose 88.3 ± 7.8 vs. 89.3 ± 31.5 mg/dL; added sugar consumption 122 ± 87 vs. 139 ± 77g/day; and %kcal from added sugars 18.3 ± 10.4 vs. 20.1 ± 9.5%. After the intervention, added sugar consumption decreased to 39 ± 47g (7.3 ± 8.3%kcal) in the intervention group without changing (133 ± 116g/19.2 ± 9.7%kcal) in the control group (time x group interaction p=0.003). However, there were no significant effects on any of the CGM measures. Conclusion: Despite high rates of type 2 diabetes on the island as a whole, blood glucose was normal in high-school teenagers, and was unaffected by the intervention. However, added sugar consumption was high (∼20 %kcal), which was greatly improved after the intervention (∼7 %kcal). This study suggests that a simple sugar-reduction intervention could improve diet quality in teenagers on Pacific Islands with high rates of type 2 diabetes such as Kiritimati. Disclosure J. Plows: None. C. Rios: None. P. Berger: None. R.B. Jones: None. T.L. Alderete: None. S. Steinberg: None. T. Bangao: None. E. Beale: None. M.I. Goran: Advisory Panel; Self; Yumi. Other Relationship; Self; Penguin Random House.

1651-P: Low Leg Fat and Ethnicity Are Predictors for Genetic Insulin Resistance in a Multiethnic Sample of Early Pubertal Children

In the United States, Hispanic- and African-Americans (HA and AA, respectively) have been shown to have a higher prevalence of type 2 diabetes than their European-American (EA) counterparts. A recent genome-wide association study revealed that genetic variants linked to insulin resistance (IR) phenotypes were associated with lower levels of leg fat mass. We investigated whether leg fat deposition and genetic risk for IR differed by ethnicity in a cross-sectional study of 82 AA, 75 HA, and 83 EA children aged 7-12 years. Participants were genotyped with the Metabochip array for 46 single nucleotide polymorphisms (SNPs) associated with IR, and a genetic risk score (GRS) was developed using the weighted sum of the risk alleles. An intravenous glucose tolerance test and minimal modeling were used to derive the insulin sensitivity index (SI), while body composition was measured by DXA. Multiple linear regression was used to compare differences among ethnicity after adjustment for sex, age, Tanner stage, and socioeconomic status. Leg fat models were also adjusted for total body fat and BMI percentile, while SI models were adjusted for adiposity. Mean leg fat deposition relative to total body fat was significantly lower in HA compared to EA and AA (P &amp;lt; 0.001 for both comparisons). Additionally, GRS independently predicted both leg fat (β = -0.34 (0.13), P = 0.012) and SI (β = -1.33 (0.59), P = 0.027) in HA. In contrast, GRS was not an independent predictor of either outcome in AA or EA. These results suggest that HA may have a genetically impaired ability to store lipid in peripheral adipose tissue depots, consequently leading to deposition in ectopic regions and IR. Our findings highlight a potential mechanism contributing to the higher rate of type 2 diabetes observed in Hispanic-American populations. Disclosure L.A. Fowler: None. J.R. Fernandez: None. B. Gower: None. Funding National Institutes of Health (R01DK067426); National Center for Research Resources (M01RR000032); University of Alabama at Birmingham Nutrition Obesity Research Center (P30DK056336, T32DK062710); University of Alabama at Birmingham Diabetes Research Center (P60DK079626)

Gut Microbiota Metabolites and Cardiometabolic Risk Among Older Puerto Ricans: Findings from the Boston Puerto Rican Health Study

Abstract Objectives Puerto Ricans are the second-largest Hispanic sub-group and have high rates of type 2 diabetes (T2D). Yet, there is limited understanding of the molecular pathways that contribute to cardiometabolic risk in this high-risk group. We hypothesized that circulating gut microbiota metabolites, which have been linked to T2D risk in non-Hispanic whites, are associated with a higher T2D likelihood and cardiometabolic risk markers among older Puerto Ricans. Methods We developed a case-control study within the Boston Puerto Rican Health Study (BPRHS) with 275 prevalent T2D cases and 275 age and sex matched controls (mean age = 58.1 y, 71% female). We used LC/MS to measure baseline plasma gut microbiota metabolites (L-carnitine, betaine, choline, trimethylamine oxide [TMAO], and betaine: choline). We used conditional logistic regression to model the likelihood of prevalent T2D for each standard deviation (SD) increase in metabolites. Among controls free of T2D, we examined cross-sectional and prospective (2-year) linear associations (β [SD]) between metabolites and glycemia and dyslipidemia measures. Results After multivariable adjustment, significant differences in T2D likelihood [OR (95% CI)] were observed for each SD increase in L-carnitine [0.78 (0.62–0.99)], choline [1.33 (1.05–1.68)], betaine: choline [0.69 (0.54–0.88)], and TMAO [1.32 (1.04–1.67)]. We replicated findings for L-carnitine and betaine: choline in the WHI metabolomics study. Among BPRHS controls, cross-sectionally, higher betaine was associated with lower HOMA-IR (−9.97 [3.02]), insulin (−9.78 [2.83]), triglycerides (−11.4 [2.54]), and higher HDL-C (2.05 [0.65]). Prospectively, higher betaine and betaine: choline were associated with lower HOMA-IR (betaine −11.5 [3.63], betaine: choline −9.57 [3.68]), insulin (betaine −9.21 [3.27], betaine: choline −8.01 [3.31]), and glucose (betaine −2.17 [0.74], betaine: choline −1.58 [0.76]) concentrations, while higher choline was prospectively associated with higher triglycerides (5.17 [2.09]). No associations were seen between L-carnitine, TMAO, and cardiometabolic markers among controls. Conclusions Plasma betaine, choline, and betaine: choline may be markers of cardiometabolic risk in this high-risk population. Future research should examine dietary and lifestyle correlates of betaine and choline. Funding Sources NIH.

Obesity After Kidney Transplantation-Results of a KTx360°Substudy.

ObjectiveThere is solid evidence that kidney transplant (KTx) patients are susceptible to weight gain after transplantation. Post-transplantation obesity [body mass index (BMI) ≥ 30 kg/m2] seems to be associated with higher risks of hypertension, dyslipidemia, diabetes mellitus, and cardiovascular events, while there are contradicting findings regarding the association between obesity and mortality, graft failure after transplantation as well as other variables. We aimed to evaluate the course of weight after KTx and to assess the prevalence of post-transplant obesity in a large sample of German KTx patients. Further, we focused on potential associations between weight gain, obesity, and BMI after transplantation with sociodemographic, medical, psychological [levels of anxiety and depression measured with the Hospital Anxiety and Depression Scale (HADS)], and donation-specific variables.MethodsIn a structured post-transplant care program 433 KTx patients were evaluated at Hannover Medical School. Information on the pre-transplant body weight/dry weight of dialysis patients was taken from the electronic patient charts. At post-transplant assessment body weight was measured in the transplant center. For statistical analyses, descriptive statistics, analyses of variance, tests for correlations, and regression analyses were used.ResultsMean age was 51.3 years, 59% were male and 26.3% had ≥12 years of school attendance. Regarding somatic conditions 6.0% were suffering from type 2 diabetes mellitus, 6.9% were affected by new-onset diabetes after transplantation (NODAT), and the mean estimated glomerular filtration rate (eGFR) was 47.7 ml/min/1.73m2. The prevalence rates of obesity before and after kidney transplantation were 14.8 and 19.9%, respectively. This represents an increase of 34%. Obesity after transplantation was associated with higher rates of type 2 diabetes mellitus and of NODAT. Additionally, there was an association between increasing pre-transplant as well as post-transplant BMI and decreasing eGFR. Higher age and female sex were associated with higher rates of post-transplant obesity.ConclusionsOur results suggest that obesity represents a serious problem in KTx patients, especially regarding the association between increasing BMI and decreasing graft functioning (eGFR). However, this aspect is often overlooked and information on effective treatment options for these patients are scarce making further research on this topic necessary.

Pancreatic Fat Infiltration Is Associated with a Higher Risk of Pancreatic Ductal Adenocarcinoma

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor survival rate, partly due to delayed diagnosis. Identifying high-risk individuals could lead to early detection and improve survival. A number of risk factors such as alcohol consumption and metabolic syndrome are associated with fatty infiltration of the pancreas. Experimental models show that a fatty pancreas promotes tissue inflammation and fibrosis, which could promote PDAC. Methods: We conducted a case-control study in a single-university tertiary hospital. Sixty-eight PDAC cases with recent non-contrast computed tomography (CT) and 235 controls were studied. The controls had no history of malignancy and underwent CT colonography for cancer screening in the same period. Pancreatic fat was estimated by calculating pancreatic (P) attenuation, corrected to splenic (S) attenuation, measured in three 1.0-cm² regions of the pancreas. The P.S100 value calculated was used to estimate fatty infiltration of the pancreas (FIP), with a lower P.S100 representing a higher FIP. Results: The PDAC patients had a lower BMI and a higher rate of type 2 diabetes mellitus. The P.S100 was lower in cases than in controls (86.452 vs. 92.414, p = 4.016e-06), suggesting that FIP is higher with PDAC. The risk of developing PDAC steadily increased significantly for the quartiles with a higher FIP compared to the low FIP quartile. No correlation between BMI and FIP (r = –0.1031179; 95% confidence interval [CI] –0.22267106 to 0.01949092) was found. Adjusting for confounders (age, sex, BMI, and DM), the risk of developing PDAC according to the FIP was estimated to be 3.75 (95% CI 1.9234408–7.993337; p = 0.000171). FIP was stable before and after the diagnosis of PDAC in 9 cases with prior CT scans when no pancreatic tumor was identifiable. Conclusion: Fatty pancreas is associated with an increased risk of pancreatic cancer. Once confirmed in larger-scale studies, these findings could help to identify at-risk individuals, particularly in high-risk groups such as chronic alcohol consumers

Genetics of type 2 diabetes and coronary artery disease and their associations with twelve cardiometabolic traits in the United Arab Emirates population.

The United Arab Emirates (UAE) population has a high rate of type 2 diabetes mellitus (T2DM) and other metabolic risk factors for coronary artery disease (CAD). Previous studies have indicated strong genetic associations between T2DM and CAD. The objective of this study was to replicate previously reported significant genetic associations for T2DM and CAD which were in a genome-wide significance level in a cohort from the Arab population of the UAE, and to investigate the associations of these loci with twelve cardiometabolic traits that may influence the development of T2DM and CAD. A total of nine hundreds and fourteen Emiratis were recruited to this study to investigate associations of 101 loci for T2DM (422 patients and 455 controls), and 53 loci for CAD (160 patients and 245 controls), using logistic regression models which incorporating possible confounding factors. Results are presented using odds ratios with their corresponding 95% confidence intervals and p-values. Linear regression models, which included possible covariates were applied to determine any associations between the T2DM and CAD reported loci with the twelve cardiometabolic traits and results were presented as effect sizes (beta), standard errors, and p-values. Furthermore, the overall risks for all the loci found to be associated with T2DM and CAD were determined using the cumulative effects of the risk alleles. For those found to be associated with the twelve cardiometabolic traits, risks were determined using calculations of their polygenic risk scores. The mean age of the T2DM group was 61.5±11.3 and of the CAD group was 66.2±9.3years. The prevalence of most of the cardiovascular disease risk factors in this cohort were high: mean body mass index (BMI)=29.4, T2DM (51.9%), hypertension (60.9%), dyslipidemia (68.8%), and smoking (47.9%). All individuals who were tested for CAD (n=405) also had a diagnosis of T2DM. The highest association variant for T2DM was in SNP rs1977833 in HHEX (p=0.0016, OR=0.56 for allele A), which is a multi-ethnic locus for T2DM. The strongest association with CAD was detected with SNP rs264 in LPL, which encodes lipoprotein lipase (p=0.009, OR=1.96 for allele A). For the cardiometabolic traits analyses, most notable associations were those of FTO with BMI and waist circumference; ABO with height; KCNK16 with diastolic blood pressure; PROX1-AS1, GCKR, and MIR129-LEP with fasting blood glucose; random blood glucose with ZEB2 and THADA; HbA1c levels with TLE1 and FAM99B loci; HDL-cholesterol levels with BRAF; and triglyceride levels with ZEB2. Furthermore, accumulation of risk alleles and polygenic scores of the associated loci was clearly associated with increased risks for all tested diseases and traits in this cohort. The present study highlighted many known genetic loci, which are linked to T2DM and CAD and their associations with major cardiometabolic traits in Arab descendants. We confirmed that some loci are associated with T2DM, CAD, and metabolic traits independently of the ethnic background, with a novel association also detected between height and ABO.

A province wide review of transition practices for young adult patients with type 1 diabetes.

Many studies on the transition from paediatric to adult care focus on practices within a single institution or program. We examine the transition for young adults with type 1 diabetes across an entire Canadian province with a small, mostly rural population and high rates of type 1 diabetes: Newfoundland and Labrador (NL). Our aim is to determine how transition is occurring across the jurisdiction and identify methods for improving clinical services for paediatric patients with a chronic condition during their move into adult care. A provincial diabetes database and hospital admission data were reviewed for a cohort of young adults with type 1 diabetes who transitioned into adult care. Semi-structured interviews were conducted with paediatric and adult diabetes providers. Between 2008 and 2013, 93 patients with type 1 diabetes transitioned into adult care. Rates of diabetes-related hospitalizations increased from 15.6/100 person-years in the 3 years before their 18th birthday to 16.7/100 person-years in the three-year period after. Between 2017 and 2019, 15 interviews were conducted across the province's four regional health authorities. Various models of transition care are being employed, reflecting staff and resource availability in different centres. While no formal transition program was identified in either region, some providers, particularly in rural areas, reported being comfortable with their current transition practices. Suggested improvements included more structured processes, shared educational resources, expanding the role played by primary care physicians, and a dedicated transfer clinic. We found different approaches for transitioning patients with diabetes into adult care across NL. Yet this variation may not negatively impact patient outcomes, particularly in rural areas. The approach we employed of combining reviews of administration data with a detailed analysis of current processes could be employed in other jurisdictions to identify appropriate quality improvement initiatives.

Gender differences in immediate outcomes of patients with acute non-ST-elevation myocardial infarction undergoing off-pump coronary artery bypass grafting

Aim.To determine gender differences in immediate outcomes of patients with acute non-ST-elevation myocardial infarction undergoing off-pump coronary artery bypass grafting (CABG).Methods.CABG was indicated to patients with persistent myocardial ischemia (postinfarction angina) who did not meet criteria for percutaneous coronary intervention. Hybrid procedures and CABG aimed at repairing mechanical complications of AMI were not considered. Men (n = 66, 65.3%) were assigned to Group 1, whereas women (n = 35, 34.7%) were assigned to Group 2. Women were older and obese (grades 2-3), had higher GRACE scores, levels of cardiospecific troponin and higher rate of type 2 diabetes (p&lt;0.05). Men and women commonly had three-vessel CAD (3.0; 4.0). The mean SYNTAX score for men and women was 29.0 (24.0; 33.0) and 27.0 (24.0; 28.0), p&gt;0.05.Results.The median preoperative period was 4.0 days (3.8; 5.0) in male patients and 5.0 (4.0; 6.0) days in female patients (p&gt;0.05). The groups did not have any significant differences in technical aspects of CABG (p&gt;0.05). Mortality was 3.0% in men and 2.9% in women (p&gt;0.05). No deaths were recorded from the onset of AMI till the first 72 hours after CABG. Three patients who under CABG died after 72 hours from the onset of MI (p&gt;0.05). The total number of complications was 13 (19.7%) in men and 5 (14.3%) in women (p&gt;0.05). There were no cases of conversion to cardiopulmonary bypass.Conclusion.The immediate outcomes of delayed of-pump CABG in both, men and women with acute non-ST-segment myocardial infarction, were comparable in mortality and complications (p&gt;0.05). The immediate outcomes of CABG performed within 72 hours in both, men and women, were comparable in mortality as compared to surgeries performed after 72 hours from the MI onset. Obtained data demonstrated safety of early open-heart surgeries for acute non-ST-elevation myocardial infarction.

Abstract 22: Novel Plasma Lipids Predict Risk of Diabetes: A Longitudinal Lipidomics Study in American Indians

Background: American Indians (AIs) suffer disproportionately high rate of type 2 diabetes (T2D). Traditional biomarkers have limited value in predicting and tracking early onset and progression of T2D. There is an urgent need for early biomarkers in this high-risk but understudied minority population. Objective: To identify novel lipids predictive of T2D onset among American Indians, independent of standard risk factors. Methods: We studied 2,000 American Indians attending two clinical exams (2001-2003, 2006-2009, average 5-yr apart) in the Strong Heart Family Study (SHFS). Fasting plasma lipids were repeatedly measured by untargeted lipidomics using LC-MS/MS. All participants were free of overt CVD at baseline (2001-2003) and followed through 2017 (average 16-yr follow-up). Cox regression with frailty model was used to identify lipids predictive of T2D onset, adjusting for traditional risk factors including age, sex, smoking, BMI, triglyceride, HDL, insulin resistance, eGFR and dietary intake of protein. Longitudinal analysis was conducted by regressing changes in lipids on changes in T2D-related traits (e.g., fasting glucose, HbA1c, or insulin resistance) between baseline and 5-yr follow-up, adjusting for changes in BMI, triglyceride, HDL, and eGFR. Incremental prognostic value of lipids in diabetes risk prediction above traditional risk factors was estimated using area under the curve (AUC). Network analysis was conducted to examine the dynamic changes in lipid networks between baseline and 5-yr follow-up. Multiple testing was controlled by FDR. Results: Of 1,628 non-diabetic participants at baseline (mean age 39.8, 62% women), 189 and 359 individuals developed incident T2D after 5-yr and 16-yr follow-up, respectively. Our high-resolution lipidomics detected 1,826 lipids, of which 1,119 lipids (460 known, 659 unknown) passed stringent quality control. Seven lipids with known structures significantly predict over 30% increased (FA(18:1), FA(20:2), FA(22:2), SM(d34:0) ) or 19% decreased (PC(37:4), PC(37:5), PC(38:4)) risk of T2D onset at both follow-ups. Nine unknown lipids also predicted T2D onset. Longitudinal changes in CE(20:2), CE(22:6), PC(32:0) and two unknowns explain about 6.4% changes in fasting plasma glucose. These newly identified lipids significantly improve the performance of risk prediction over traditional risk factors (AUC increased from 0.787 to 0.803, P=0.002). Network topology analysis revealed that the network connectivity among lipids was much stronger in participants who developed new T2D compared to those who didn’t (degree of network connectivity, 4.2 vs 2.5, P&lt;0.001). Conclusion: We identified several novel plasma lipids significantly predictive of incident T2D, independent of traditional risk factors. These findings highlight the importance of identifying novel lipid markers in early diabetes risk prediction.