Pretreatment, Psychological, and Behavioral Predictors of Weight Outcomes Among Lifestyle Intervention Participants in the Diabetes Prevention Program (DPP)

OBJECTIVE To identify the most important pretreatment characteristics and changes in psychological and behavioral factors that predict weight outcomes in the Diabetes Prevention Program (DPP). RESEARCH DESIGN AND METHODS Approximately 25% of DPP lifestyle intervention participants (n = 274) completed questionnaires to assess weight history and psychological and behavioral factors at baseline and 6 months after completion of the 16-session core curriculum. The change in variables from baseline to 6 months was assessed with t tests. Multivariate models using hierarchical logistic regression assessed the association of weight outcomes at end of study with each demographic, weight loss history, psychological, and behavioral factor. RESULTS At end of study, 40.5% had achieved the DPP 7% weight loss goal. Several baseline measures (older age, race, older age when first overweight, fewer self-implemented weight loss attempts, greater exercise self-efficacy, greater dietary restraint, fewer fat-related dietary behaviors, more sedentary activity level) were independent predictors of successful end-of-study weight loss with the DPP lifestyle program. The DPP core curriculum resulted in significant improvements in many psychological and behavioral targets. Changes in low-fat diet self-efficacy and dietary restraint skills predicted better long-term weight loss, and the association of low-fat diet self-efficacy with weight outcomes was explained by dietary behaviors. CONCLUSIONS Health care providers who translate the DPP lifestyle intervention should be aware of pretreatment characteristics that may hamper or enhance weight loss, consider prioritizing strategies to improve low-fat diet self-efficacy and dietary restraint skills, and examine whether taking these actions improves weight loss outcomes

Sex Differences in the Management and Outcomes of Heart Failure with Preserved Ejection Fraction in Patients Presenting to the Emergency Department with Acute Heart Failure

Background Heart failure (HF) with preserved ejection fraction (HFpEF) is more common in women than in men; data characterizing sex differences in the management and outcomes of HFpEF patients presenting to the emergency department (ED) are limited. Methods and Results Using Acute Decompensated Heart Failure National Registry Emergency Module data linked to Medicare claims, we conducted a retrospective analysis of acute HF patients in the ED, identifying HFpEF (ejection fraction [EF] ≥40%) patients and stratifying by sex to compare baseline characteristics, ED therapies, hospital length of stay (LOS), in-hospital mortality, and post-discharge outcomes. Of 4161 HFpEF patients, 2808 (67%) were women, who were more likely to be older and hypertensive, but less likely to be diabetic or smokers (all P 140 mm Hg (62.5% vs 56.4%; P = .0001) and higher EF. There were no sex differences in ED therapies, adjusted 30- and 180-day all-cause mortality, in-hospital mortality, or 30- and 180-day readmissions. After adjustment, women had longer LOS (0.40 days, 95% confidence interval [CI] 0.10–0.70; P = .008). Conclusions Women with HFpEF presenting to the ED were more likely to have elevated systolic blood pressure, but overall ED management strategies were similar to those in men. We observed adjusted differences in hospital LOS, but no differences in 30- and 180-day outcomes

The olfactory landscape concept : a key source of past, present, and future information driving animal movement and decision-making

Odor is everywhere, emitted across the landscape from predators, prey, decaying carcasses, conspecifics, vegetation, surface water, and smoke. Many animals exploit odor to find food, avoid threats, and attract or judge potential mates. Here, we focus on odor in terrestrial ecosystems to introduce the concept of an olfactory landscape: real-time dynamic olfactory contours reflecting the patchy distribution of resources and risks, providing a key source of information used by many animals in their movement and decision-making. Incorporating the olfactory landscape into current frameworks of movement ecology and animal behavior will provide a mechanistic link to help answer significant questions about where, why, and when many animals move, and how they do so efficiently in both space and time. By understanding how animals use the olfactory landscape to make crucial decisions affecting their fitness, we can then manipulate the landscape to modify ecological interactions and, ultimately, ecosystem consequences of these interactions.An Australian Research Council ARC Discovery Grant.https://academic.oup.com/biosciencehj2023Mammal Research Institut

Trends in the Association of Parental History of Obesity over 60 Years

Objective: The association of familial as compared to genetic factors in the current obesogenic environment, compared to earlier, leaner time periods, is uncertain. Design and Methods Participants from the Framingham Heart Study were classified according to parental obesity status in the Original, Offspring, and Third Generation cohorts; mean BMI levels were estimated and we compared the association of parental history across generations. Finally, a genetic risk score comprised of 32 well-replicated single nucleotide polymorphisms for BMI was examined in association with BMI levels in 1948, 1971, and 2002. Results: BMI was 1.49 kg/m2 higher per each affected parent among the Offspring, and increased to 2.09 kg/m2 higher among the Third Generation participants (p-value for the cohort comparison=0.007). Parental history of obesity was associated with increased weight gain (p<0.0001) and incident obesity (p=0.009). Despite a stronger association of parental obesity with offspring BMI in more contemporary time periods, we observed no change in the effect size of a BMI genetic risk score from 1948 to 2002 (p=0.11 for test of trend across the time periods). Conclusions: The association of parental obesity has become stronger in more contemporary time period, whereas the association of a BMI genetic risk score has not changed

Genetic Risk Reclassification for Type 2 Diabetes by Age Below or Above 50 Years Using 40 Type 2 Diabetes Risk Single Nucleotide Polymorphisms

OBJECTIVE: To test if knowledge of type 2 diabetes genetic variants improves disease prediction. RESEARCH DESIGN AND METHODS: We tested 40 single nucleotide polymorphisms (SNPs) associated with diabetes in 3,471 Framingham Offspring Study subjects followed over 34 years using pooled logistic regression models stratified by age (<50 years, diabetes cases = 144; or ≥50 years, diabetes cases = 302). Models included clinical risk factors and a 40-SNP weighted genetic risk score. RESULTS: In people <50 years of age, the clinical risk factors model C-statistic was 0.908; the 40-SNP score increased it to 0.911 (P = 0.3; net reclassification improvement (NRI): 10.2%, P = 0.001). In people ≥50 years of age, the C-statistics without and with the score were 0.883 and 0.884 (P = 0.2; NRI: 0.4%). The risk per risk allele was higher in people <50 than ≥50 years of age (24 vs. 11%; P value for age interaction = 0.02). CONCLUSIONS: Knowledge of common genetic variation appropriately reclassifies younger people for type 2 diabetes risk beyond clinical risk factors but not older people

A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma

AZD6244 is a MEK1/2 inhibitor with significant preclinical activity in multiple myeloma (MM) cells. This phase 2 study used a two-stage Simon design to determine the AZD6244 response rate in patients with relapsed or refractory MM

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Survival Data and Predictors of Functional Outcome an Average of 15 Years after the Fontan Procedure: The Pediatric Heart Network Fontan Cohort

ObjectiveMulticenter longitudinal outcome data for Fontan patients surviving into adulthood are lacking. The aim of this study was to better understand contemporary outcomes in Fontan survivors by collecting follow‐up data in a previously well‐characterized cohort.DesignBaseline data from the Fontan Cross‐Sectional Study (Fontan 1) were previously obtained in 546 Fontan survivors aged 11.9 ± 3.4 years. We assessed current transplant‐free survival status in all subjects 6.8 ± 0.4 years after the Fontan 1 study. Anatomic, clinical, and surgical data were collected along with socioeconomic status and access to health care.ResultsThirty subjects (5%) died or underwent transplantation since Fontan 1. Subjects with both an elevated (>21 pg/mL) brain natriuretic peptide and a low Child Health Questionnaire physical summary score (<44) measured at Fontan 1 were significantly more likely to die or undergo transplant than the remainder, with a hazard ratio of 6.2 (2.9–13.5). Among 516 Fontan survivors, 427 (83%) enrolled in this follow‐up study (Fontan 2) at 18.4 ± 3.4 years of age. Although mean scores on functional health status questionnaires were lower than the general population, individual scores were within the normal range in 78% and 88% of subjects for the Child Health Questionnaire physical and psychosocial summary score, and 97% and 91% for the SF‐36 physical and mental aggregate score, respectively. Since Fontan surgery, 119 (28%) had additional cardiac surgery; 55% of these (n = 66) in the interim between Fontan 1 and Fontan 2. A catheter intervention occurred in 242 (57%); 32% of these (n = 78) after Fontan 1. Arrhythmia requiring treatment developed in 118 (28%) after Fontan surgery; 58% of these (n = 68) since Fontan 1.ConclusionsWe found 95% interim transplant‐free survival for Fontan survivors over an average of 7 years of follow‐up. Continued longitudinal investigation into adulthood is necessary to better understand the determinants of long‐term outcomes and to improve functional health status.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110738/1/chd12193.pd

Consistent Directions of Effect for Established Type 2 Diabetes Risk Variants Across Populations: The Population Architecture using Genomics and Epidemiology (PAGE) Consortium

Common genetic risk variants for type 2 diabetes (T2D) have primarily been identified in populations of European and Asian ancestry. We tested whether the direction of association with 20 T2D risk variants generalizes across six major racial/ethnic groups in the U.S. as part of the Population Architecture using Genomics and Epidemiology Consortium (16,235 diabetes case and 46,122 control subjects of European American, African American, Hispanic, East Asian, American Indian, and Native Hawaiian ancestry). The percentage of positive (odds ratio [OR] >1 for putative risk allele) associations ranged from 69% in American Indians to 100% in European Americans. Of the nine variants where we observed significant heterogeneity of effect by racial/ethnic group (Pheterogeneity 1) in at least five groups. The marked directional consistency of association observed for most genetic variants across populations implies a shared functional common variant in each region. Fine-mapping of all loci will be required to reveal markers of risk that are important within and across populations