Intergenerational effects of maternal lifetime stressor exposure on offspring telomere length in Black and White women.

BACKGROUND: Although maternal stressor exposure has been associated with shorter telomere length (TL) in offspring, this literature is based largely on White samples. Furthermore, timing of maternal stressors has rarely been examined. Here, we examined how maternal stressors occurring during adolescence, pregnancy, and across the lifespan related to child TL in Black and White mothers. METHOD: Mothers (112 Black; 110 White; Mage = 39) and their youngest offspring (n = 222; Mage = 8) were part of a larger prospective cohort study, wherein mothers reported their stressors during adolescence (assessed twice during adolescence for the past year), pregnancy (assessed in midlife for most recent pregnancy), and across their lifespan (assessed in midlife). Mother and child provided saliva for TL measurement. Multiple linear regression models examined the interaction of maternal stressor exposure and race in relation to child TL, controlling for maternal TL and child gender and age. Race-stratified analyses were also conducted. RESULTS: Neither maternal adolescence nor lifespan stressors interacted with race in relation to child TL. In contrast, greater maternal pregnancy stressors were associated with shorter child TL, but this effect was present for children of White but not Black mothers. Moreover, this effect was significant for financial but not social pregnancy stressors. Race-stratified models revealed that greater financial pregnancy stressors predicted shorter telomeres in offspring of White, but not Black mothers. CONCLUSIONS: Race and maternal stressors interact and are related to biological aging across generations, but these effects are specific to certain races, stressors, and exposure time periods.

Association of abdominal muscle area and density with glucose regulation: The multi-ethnic study of atherosclerosis (MESA).

AIMS: Previous characterisation of body composition as a type 2 diabetes mellitus (T2DM) risk factor has largely focused on adiposity, but less is known about the independent role of skeletal muscle. We examined associations between abdominal muscle and measures of glucose regulation. MATERIALS AND METHODS: Cross-sectional analysis of 1,891 adults enrolled in the Multi-Ethnic Study of Atherosclerosis. Multivariable regression assessed associations between abdominal muscle area and density (measured by computed tomography) with fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR), and prevalent T2DM (fasting glucose ≥126 mg/dL or medication use). RESULTS: In minimally adjusted models (age, sex, race/ethnicity, income), a 1-SD increment in abdominal muscle area was associated with higher HOMA-IR (ß = 0.20 ± SE 0.03; 95%CI: 0.15, 0.25; P < 0.01) and odds of T2DM (OR = 1.47; 95%CI: 1.18, 1.84; P < 0.01), while higher density was associated with lower fasting glucose (-4.49 ± 0.90; -6.26, -2.72; P < 0.01), HOMA-IR (-0.16 ± 0.02; -0.20, -0.12; P < 0.01), and odds of T2DM (0.64; 0.52, 0.77; P < 0.01). All associations persisted after adjustment for comorbidities and health behaviours. However, after controlling for height, BMI, and visceral adiposity, increasing muscle area became negatively associated with fasting glucose (-2.23 ± 1.01; -4.22, -0.24; P = 0.03), while density became positively associated with HOMA-IR (0.09 ± 0.02; 0.05, 0.13; P < 0.01). CONCLUSIONS: Increasing muscle density was associated with salutary markers of glucose regulation, but associations inverted with further adjustment for body size and visceral adiposity. Conversely, after full adjustment, increasing muscle area was associated with lower fasting glucose, suggesting some patients may benefit from muscle-building interventions.

Low plasma adropin concentrations increase risks of weight gain and metabolic dysregulation in response to a high-sugar diet in male nonhuman primates.

Mouse studies linking adropin, a peptide hormone encoded by the energy homeostasis-associated (ENHO) gene, to biological clocks and to glucose and lipid metabolism suggest a potential therapeutic target for managing diseases of metabolism. However, adropin's roles in human metabolism are unclear. In silico expression profiling in a nonhuman primate diurnal transcriptome atlas (GSE98965) revealed a dynamic and diurnal pattern of ENHO expression. ENHO expression is abundant in brain, including ventromedial and lateral hypothalamic nuclei regulating appetite and autonomic function. Lower ENHO expression is present in liver, lung, kidney, ileum, and some endocrine glands. Hepatic ENHO expression associates with genes involved in glucose and lipid metabolism. Unsupervised hierarchical clustering identified 426 genes co-regulated with ENHO in liver, ileum, kidney medulla, and lung. Gene Ontology analysis of this cluster revealed enrichment for epigenetic silencing by histone H3K27 trimethylation and biological processes related to neural function. Dietary intervention experiments with 59 adult male rhesus macaques indicated low plasma adropin concentrations were positively correlated with fasting glucose, plasma leptin, and apolipoprotein C3 (APOC3) concentrations. During consumption of a high-sugar (fructose) diet, which induced 10% weight gain, animals with low adropin had larger increases of plasma leptin and more severe hyperglycemia. Declining adropin concentrations were correlated with increases of plasma APOC3 and triglycerides. In summary, peripheral ENHO expression associates with pathways related to epigenetic and neural functions, and carbohydrate and lipid metabolism, suggesting co-regulation in nonhuman primates. Low circulating adropin predicts increased weight gain and metabolic dysregulation during consumption of a high-sugar diet.

A generic arboviral model framework for exploring trade-offs between vector control and environmental concerns.

Effective public health measures must balance potentially conflicting demands from populations they serve. In the case of infectious disease risks from mosquito-borne infections, such as Zika virus, public concern about the pathogen may be counterbalanced by public concern about environmental contamination from chemical agents used for vector control. Here we introduce a generic framework for modeling how the spread of an infectious pathogen might lead to varying public perceptions, and therefore tolerance, of both disease risk and pesticide use. We consider how these dynamics might impact the spread of a vector-borne disease. We tailor and parameterize our model for direct application to Zika virus as spread by Aedes aegypti mosquitoes, though the framework itself has broad applicability to any arboviral infection. We demonstrate how public risk perception of both disease and pesticides may drastically impact the spread of a mosquito-borne disease in a susceptible population. We conclude that models hoping to inform public health decision making about how best to mitigate arboviral disease risks should explicitly consider the potential public demand for, or rejection of, chemical control of mosquito populations.

Fructose-induced hypertriglyceridemia in rhesus macaques is attenuated with fish oil or ApoC3 RNA interference.

Dyslipidemia and insulin resistance are significant adverse outcomes of consuming high-sugar diets. Conversely, dietary fish oil (FO) reduces plasma lipids. Diet-induced dyslipidemia in a rhesus model better approximates the pathophysiology of human metabolic syndrome (MetS) than rodent models. Here, we investigated relationships between metabolic parameters and hypertriglyceridemia in rhesus macaques consuming a high-fructose diet (n = 59) and determined the effects of FO supplementation or RNA interference (RNAi) on plasma ApoC3 and triglyceride (TG) concentrations. Fructose supplementation increased body weight, fasting insulin, leptin, TGs, and large VLDL particles and reduced adiponectin concentrations (all P < 0.001). In multiple regression analyses, increased plasma ApoC3 was the most consistent and significant variable related to diet-induced hypertriglyceridemia. FO supplementation, which attenuated increases of plasma TG and ApoC3 concentrations, reversed fructose-induced shifts of lipoprotein particle size toward IDL and VLDL, a likely mechanism contributing to beneficial metabolic effects, and reduced hepatic expression of genes regulated by the SREBP pathway, particularly acetyl-CoA carboxylase. Furthermore, RNAi-mediated ApoC3 inhibition lowered plasma TG concentrations in animals with diet-induced hypertriglyceridemia. In summary, ApoC3 is an important independent correlate of TG-rich lipoprotein concentrations in rhesus macaques consuming a high-fructose diet. ApoC3 is a promising therapeutic target for hypertriglyceridemia in patients with MetS and diabetes.

Metabolic markers, regional adiposity, and adipose cell size: relationship to insulin resistance in African-American as compared with Caucasian women.

BACKGROUND/OBJECTIVES: African-American women have the greatest prevalence of obesity in the United States, and higher rates of type 2 diabetes than Caucasian women, yet paradoxically lower plasma triglycerides (TG), visceral fat and intrahepatic fat, and higher high-density lipoprotein (HDL)-cholesterol. Visceral fat has not been evaluated against insulin resistance in African-American women, and TG/HDL-cholesterol has been criticized as a poor biomarker for insulin resistance in mixed-sex African-American populations. Adipocyte hypertrophy, reflecting adipocyte dysfunction, predicts insulin resistance in Caucasians, but has not been studied in African-Americans. Our goal was to assess whether traditional correlates of insulin resistance, measures of adiposity and adipocyte characteristics similarly predict peripheral insulin resistance in African-American and Caucasian women. SUBJECTS/METHODS: Thirty-four healthy African-American (n = 17) and Caucasian (n = 17) women, matched for age (mean = 53.0 yrs) and body mass index (BMI) (mean = 30 kg/m2), underwent a steady-state plasma glucose test to measure insulin sensitivity; computed tomography (fat distribution); and a periumbilical scalpel biopsy (adipocyte characterization). By-race analyzes utilized analysis of covariance; linear regressions evaluated relationships between metabolic/adipose variables. All analyses adjusted for BMI and menopausal status. RESULTS: Insulin sensitivity did not differ between groups (p = 0.65). Neither BMI, nor %body fat or thigh fat predicted insulin resistance in African-American women. Fasting TG (p = 0.046), HDL-cholesterol (p = 0.0006) and TG/HDL-cholesterol ratio (p = 0.009) strongly predicted insulin resistance in African-American women. Despite being lower in African-American women, hepatic fat and visceral adipose tissue (VAT) correlated with insulin resistance in both groups, as did fasting glucose, VAT/SAT (subcutaneous adipose tissue) ratio, and %SAT (inverse). CONCLUSIONS: Total adiposity measures and adipocyte hypertrophy did not predict insulin resistance in African-American women, but did in Caucasian women. Plasma TG and HDL-cholesterol were significant predictors of insulin resistance in African-American women. Our findings demonstrate the need to identify race and sex-specific biomarkers for metabolic risk profiling.

Plasma fatty acid ethanolamides are associated with postprandial triglycerides, ApoCIII, and ApoE in humans consuming a high-fructose corn syrup-sweetened beverage.

Epidemiological and clinical research studies have provided ample evidence demonstrating that consumption of sugar-sweetened beverages increases risk factors involved in the development of obesity, Type 2 diabetes, and cardiovascular disease (CVD). Our previous study demonstrated that when compared with aspartame (Asp), 2 wk of high-fructose corn syrup (HFCS)-sweetened beverages provided at 25% of daily energy requirement was associated with increased body weight, postprandial (pp) triglycerides (TG), and fasting and pp CVD risk factors in young adults. The fatty acid ethanolamide, anandamide (AEA), and the monoacylglycerol, 2-arachidonoyl- sn-glycerol (2-AG), are two primary endocannabinoids (ECs) that play a role in regulating food intake, increasing adipose storage, and regulating lipid metabolism. Therefore, we measured plasma concentrations of ECs and their analogs, oleoylethanolamide (OEA), docosahexaenoyl ethanolamide (DHEA), and docosahexaenoyl glycerol (DHG), in participants from our previous study who consumed HFCS- or Asp-sweetened beverages to determine associations with weight gain and CVD risk factors. Two-week exposure to either HFCS- or Asp-sweetened beverages resulted in significant differences in the changes in fasting levels of OEA and DHEA between groups after the testing period. Subjects who consumed Asp, but not HFCS, displayed a reduction in AEA, OEA, and DHEA after the testing period. In contrast, there were significant positive relationships between AEA, OEA, and DHEA vs. ppTG, ppApoCIII, and ppApoE in those consuming HFCS, but not in those consuming Asp. Our findings reveal previously unknown associations between circulating ECs and EC-related molecules with markers of lipid metabolism and CVD risk after HFCS consumption.

Efficacy and pharmacokinetics of subcutaneous exendin (9-39) in patients with post-bariatric hypoglycaemia.

AIM: To evaluate the efficacy, pharmacokinetic (PK) profile and tolerability of subcutaneous (s.c.). exendin 9-39 (Ex-9) injection in patients with post-bariatric hypoglycaemia (PBH). METHODS: Nine women who had recurrent symptomatic hypoglycaemia after undergoing Roux-en-Y gastric bypass were enrolled in this 2-part, single-blind, single-ascending-dose study. In Part 1, a single participant underwent equimolar low-dose intravenous (i.v.) vs s.c. Ex-9 administration; in Part 2, 8 participants were administered single ascending doses of s.c. Ex-9 during an oral glucose tolerance test (OGTT). Glycaemic, hormonal, PK and symptomatic responses were compared with those obtained during the baseline OGTT. RESULTS: Although an exposure-response relationship was observed, all doses effectively prevented hyperinsulinaemic hypoglycaemia and improved associated symptoms. On average, the postprandial glucose nadir was increased by 66%, peak insulin was reduced by 57%, and neuroglycopenic symptoms were reduced by 80%. All doses were well tolerated with no treatment-emergent adverse events observed. CONCLUSIONS: Injection s.c. of Ex-9 appears to represent a safe, effective and targeted therapeutic approach for treatment of PBH. Further investigation involving multiple doses with chronic dosing is warranted.

Understanding the Impact of Added Sugar Consumption on Risk for Type 2 Diabetes.

The association between dietary sugar and type 2 diabetes (T2D) is likely mediated by the unregulated hepatic metabolism of fructose, which promotes hepatic and whole-body insulin resistance. Experimental evidence from clinical studies that utilize sensitive methods to test the effects of added sugar on insulin sensitivity is required. Establishing a causal link between added sugar and insulin resistance will help to stimulate health policies that target the reduction of added sugar consumption and T2D prevention.

Associations between muscle quality and N-terminal pro-B-type natriuretic peptide (NT-proBNP): The multi-ethnic study of atherosclerosis.

INTRODUCTION: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is widely used in clinical settings to identify cardiac stress, diagnose, and manage heart failure (HF). We explored the associations between NT-proBNP and both muscle area and density. METHODS: A cross-sectional analysis including 1,489 participants from the MESA. Plasma NT-proBNP concentrations and inflammatory biomarkers and health history questionnaires were analyzed. Computed tomography quantified abdominal body composition. Separate multivariable linear regression models were used to assess the associations between both muscle (MA) area and density (MD) and NT-proBNP. RESULTS: In models adjusted for sociodemographic characteristics, risk factors for cardiovascular disease, anthropometric variables, and subcutaneous and visceral adiposity, NT-proBNP was inversely associated with total abdominal and psoas MAs. Adjustment for inflammatory markers and MD attenuated these associations to the null. Stabilization MA and NT-proBNP were not significantly associated. Analyses per quartiles of MA confirmed lack of a consistent association between stabilization and total abdominal MAs and NT-proBNP. While the third and fourth quartiles of psoas MA were inversely associated with NT-proBNP, adding inflammation biomarkers and MD to the model attenuated the association to the null. Conversely, after full adjustment, NT-proBNP was inversely and significantly associated with total abdominal, stabilization and psoas MDs. For psoas MD, but not the other muscle density variables, the addition of MA to the model attenuated the association to the null. The quartiles of MD were consistently inversely associated with NT-proBNP, where higher MDs showed larger estimates of the association compared to the lowest quartiles, for all muscle groups investigated. CONCLUSION: Muscle density is inversely associated with NT-proBNP, while muscle area is not after adjustment for inflammation and muscle density.

Physical Activity Type and Intensity Are Associated With Abdominal Muscle Area and Density: The Multiethnic Study of Atherosclerosis.

BACKGROUND: Using data from a multiethnic cohort, the authors tested associations of multiple types and intensities of physical activity (PA) with abdominal muscle area and density. METHODS: 1895 Multiethnic Study of Atherosclerosis participants (mean age 64.6 [9.6] y) completed health history and PA questionnaires and computed tomography to quantify body composition and measurements of cardiovascular and inflammatory biomarkers. Analyses included multivariable regression. RESULTS: Compared with those not meeting PA guidelines for Americans, those meeting the guidelines had higher total abdominal muscle area (odds ratio, 95% confidence interval 1.60, 1.20 to 2.15), stability muscle area (1.68, 1.28 to 2.20), and stability muscle density (1.35, 1.03 to 1.76). After adjustment for relevant covariates, each SD increase in total moderate to vigorous PA was associated with a higher total abdominal (ß, 95% confidence interval = 0.068, 0.036 to 0.173), stability (0.063, 0.027 to 0.099), and locomotor (0.069, 0.039 to 0.099) muscle area and higher locomotor muscle density (0.065, 0.022 to 0.108, P < .01). Only intentional and conditioning exercise were associated with total abdominal and stability muscle density (P < .05). Light PA and walking were not associated with muscle area or density. CONCLUSIONS: Most types of PA are positively associated with abdominal muscle area and density across functional categories, independent of relevant covariates. These results provide additional evidence for promoting PA for healthy muscle aging.

Differences in gut microbiome by insulin sensitivity status in Black and White women of the National Growth and Health Study (NGHS): A pilot study.

The prevalence of overweight and obesity is greatest amongst Black women in the U.S., contributing to disproportionately higher type 2 diabetes prevalence compared to White women. Insulin resistance, independent of body mass index, tends to be greater in Black compared to White women, yet the mechanisms to explain these differences are not completely understood. The gut microbiome is implicated in the pathophysiology of obesity, insulin resistance and cardiometabolic disease. Only two studies have examined race differences in Black and White women, however none characterizing the gut microbiome based on insulin sensitivity by race and sex. Our objective was to determine if gut microbiome profiles differ between Black and White women and if so, determine if these race differences persisted when accounting for insulin sensitivity status. In a pilot cross-sectional analysis, we measured the relative abundance of bacteria in fecal samples collected from a subset of 168 Black (n = 94) and White (n = 74) women of the National Growth and Health Study (NGHS). We conducted analyses by self-identified race and by race plus insulin sensitivity status (e.g. insulin sensitive versus insulin resistant as determined by HOMA-IR). A greater proportion of Black women were classified as IR (50%) compared to White women (30%). Alpha diversity did not differ by race nor by race and insulin sensitivity status. Beta diversity at the family level was significantly different by race (p = 0.033) and by the combination of race plus insulin sensitivity (p = 0.038). Black women, regardless of insulin sensitivity, had a greater relative abundance of the phylum Actinobacteria (p = 0.003), compared to White women. There was an interaction between race and insulin sensitivity for Verrucomicrobia (p = 0.008), where among those with insulin resistance, Black women had four fold higher abundance than White women. At the family level, we observed significant interactions between race and insulin sensitivity for Lachnospiraceae (p = 0.007) and Clostridiales Family XIII (p = 0.01). Our findings suggest that the gut microbiome, particularly lower beta diversity and greater Actinobacteria, one of the most abundant species, may play an important role in driving cardiometabolic health disparities of Black women, indicating an influence of social and environmental factors on the gut microbiome.

A Landscape of Subjective and Objective Stress in African-American Dementia Family Caregivers.

Stress is a significant part of daily life, and systemic social inequities, such as racism and discrimination, are well-established contributors of chronic stress for African Americans. Added exposure to the stress of caregiving may exacerbate adverse health outcomes. This secondary analysis describes subjective and objective stress in African American family caregivers, and relationships of subjective and objective stress to health outcomes. Baseline data from 142 African American dementia family caregivers from the "Great Village" study were described using means and frequencies; regression models and Pearson's correlation were used to examine associations between demographics, social determinants of health, and health outcomes. Mixed models were used to examine change and change variation in cortisol. Most caregivers had moderate degrees of stress. Stress was associated with sleep disruption and depressive symptoms, and discrimination appeared to be an independent contributor to depressive symptoms. This work provides a foundation for interpreting subjective and objective indicators of stress to tailor existing multicomponent interventions.

The Dose-Response Effects of Consuming High Fructose Corn Syrup-Sweetened Beverages on Hepatic Lipid Content and Insulin Sensitivity in Young Adults.

Increased hepatic lipid content and decreased insulin sensitivity have critical roles in the development of cardiometabolic diseases. Therefore, our objective was to investigate the dose-response effects of consuming high fructose corn syrup (HFCS)-sweetened beverages for two weeks on hepatic lipid content and insulin sensitivity in young (18-40 years) adults (BMI 18-35 kg/m2). In a parallel, double-blinded study, participants consumed three beverages/day providing 0% (aspartame: n = 23), 10% (n = 18), 17.5% (n = 16), or 25% (n = 28) daily energy requirements from HFCS. Magnetic resonance imaging for hepatic lipid content and oral glucose tolerance tests (OGTT) were conducted during 3.5-day inpatient visits at baseline and again at the end of a 15-day intervention. During the 12 intervening outpatient days participants consumed their usual diets with their assigned beverages. Significant linear dose-response effects were observed for increases of hepatic lipid content (p = 0.015) and glucose and insulin AUCs during OGTT (both p = 0.0004), and for decreases in the Matsuda (p = 0.0087) and Predicted M (p = 0.0027) indices of insulin sensitivity. These dose-response effects strengthen the mechanistic evidence implicating consumption of HFCS-sweetened beverages as a contributor to the metabolic dysregulation that increases risk for nonalcoholic fatty liver disease and type 2 diabetes.

A Pilot Study Comparing the Effects of Consuming 100% Orange Juice or Sucrose-Sweetened Beverage on Risk Factors for Cardiometabolic Disease in Women.

Overconsumption of sugar-sweetened beverages increases risk factors associated with cardiometabolic disease, in part due to hepatic fructose overload. However, it is not clear whether consumption of beverages containing fructose as naturally occurring sugar produces equivalent metabolic dysregulation as beverages containing added sugars. We compared the effects of consuming naturally-sweetened orange juice (OJ) or sucrose-sweetened beverages (sucrose-SB) for two weeks on risk factors for cardiometabolic disease. Healthy, overweight women (n = 20) were assigned to consume either 3 servings of 100% orange juice or sucrose-SB/day. We conducted 16-hour serial blood collections and 3-h oral glucose tolerance tests during a 30-h inpatient visit at baseline and after the 2-week diet intervention. The 16-h area under the curve (AUC) for uric acid increased in subjects consuming sucrose-SB compared with subjects consuming OJ. Unlike sucrose-SB, OJ did not significantly increase fasting or postprandial lipoproteins. Consumption of both beverages resulted in reductions in the Matsuda insulin sensitivity index (OJ: -0.40 ± 0.18, p = 0.04 within group; sucrose-SB: -1.0 ± 0.38, p = 0.006 within group; p = 0.53 between groups). Findings from this pilot study suggest that consumption of OJ at levels above the current dietary guidelines for sugar intake does not increase plasma uric acid concentrations compared with sucrose-SB, but appears to lead to comparable decreases of insulin sensitivity.

Consuming Sucrose- or HFCS-sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults.

CONTEXT: Studies in rodents and humans suggest that high-fructose corn syrup (HFCS)-sweetened diets promote greater metabolic dysfunction than sucrose-sweetened diets. OBJECTIVE: To compare the effects of consuming sucrose-sweetened beverage (SB), HFCS-SB, or a control beverage sweetened with aspartame on metabolic outcomes in humans. METHODS: A parallel, double-blinded, NIH-funded study. Experimental procedures were conducted during 3.5 days of inpatient residence with controlled feeding at a research clinic before (baseline) and after a 12-day outpatient intervention period. Seventy-five adults (18-40 years) were assigned to beverage groups matched for sex, body mass index (18-35 kg/m2), and fasting triglyceride, lipoprotein and insulin concentrations. The intervention was 3 servings/day of sucrose- or HFCS-SB providing 25% of energy requirement or aspartame-SB, consumed for 16 days. Main outcome measures were %hepatic lipid, Matsuda insulin sensitivity index (ISI), and Predicted M ISI. RESULTS: Sucrose-SB increased %hepatic lipid (absolute change: 0.6 ±â€…0.2%) compared with aspartame-SB (-0.2 ±â€…0.2%, P < 0.05) and compared with baseline (P < 0.001). HFCS-SB increased %hepatic lipid compared with baseline (0.4 ±â€…0.2%, P < 0.05). Compared with aspartame-SB, Matsuda ISI decreased after consumption of HFCS- (P < 0.01) and sucrose-SB (P < 0.01), and Predicted M ISI decreased after consumption of HFCS-SB (P < 0.05). Sucrose- and HFCS-SB increased plasma concentrations of lipids, lipoproteins, and uric acid compared with aspartame-SB. No outcomes were differentially affected by sucrose- compared with HFCS-SB. Beverage group effects remained significant when analyses were adjusted for changes in body weight. CONCLUSION: Consumption of both sucrose- and HFCS-SB induced detrimental changes in hepatic lipid, insulin sensitivity, and circulating lipids, lipoproteins and uric acid in 2 weeks.