Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with ...insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supplemented BCAA (HF/BCAA), or standard chow (SC) diets. Despite having reduced food intake and a low rate of weight gain equivalent to the SC group, HF/BCAA rats were as insulin resistant as HF rats. Pair-feeding of HF diet to match the HF/BCAA animals or BCAA addition to SC diet did not cause insulin resistance. Insulin resistance induced by HF/BCAA feeding was accompanied by chronic phosphorylation of mTOR, JNK, and IRS1
Ser307 and by accumulation of multiple acylcarnitines in muscle, and it was reversed by the mTOR inhibitor, rapamycin. Our findings show that in the context of a dietary pattern that includes high fat consumption, BCAA contributes to development of obesity-associated insulin resistance.
Obesity treatment focuses primarily on reducing overall caloric intake with limited focus on improving diet quality. The Dietary Approaches to Stop Hypertension (DASH) dietary pattern is effective in ...managing hypertension and other chronic conditions, yet it is not clear whether behavioral weight control interventions improve DASH adherence. We conducted a post hoc analysis of a behavioral weight loss intervention that did not emphasize diet quality and examined whether the intervention impacted DASH adherence in medically vulnerable community health center patients.
Participants (n=306) were enrolled in Track, a randomized controlled weight loss intervention for patients with elevated cardiovascular risk. The trial compared usual care to an intervention with weekly self-monitoring, tailored feedback on diet and exercise goals, and dietitian and provider counseling in community health centers. Dietary intake was measured using the Block Food Frequency Questionnaires collected at baseline and 12 months. DASH adherence was determined using previously validated scoring indices that assessed adherence based on recommended nutrient or food group targets. Total scores for both indices ranged from 0 to 9, with higher scores indicating greater DASH adherence.
The mean (and standard deviation SD) age of participants was 51.1 (SD=8.8) years and the mean body mass index was 35.9 (SD=3.9). Most were female (69%) and black (51%); 13% were Hispanic. Half (51%) had an annual income <$25,000 and 33% had both diabetes and hypertension. At baseline, the mean DASH nutrient score was 1.81 (SD=1.42) with 6% achieving at least a score of 4.5. Similar scores were seen for the DASH foods index. The intervention group saw significantly greater, albeit small, improvements in mean DASH nutrient score (intervention: 1.28 SD=1.5 vs control: 0.20 SD=1.3; P<0.001), and there was no difference in DASH food score between study arms. There were no significant predictors of change in DASH score and no association between DASH adherence and changes in blood pressure. Within the intervention arm, improvements in DASH nutrient score were associated with greater weight loss (r=-0.28; P=0.003).
Although the intervention was not designed to increase adoption of DASH, the Track intervention produced significant weight loss and small improvements in DASH adherence. Despite these small improvements, overall adoption of DASH was poor among the medically vulnerable patients enrolled in Track. To further reduce chronic disease burden, weight loss interventions should include a focus on both caloric restriction and increasing diet quality.
The main 6-month results from the PREMIER trial showed that comprehensive behavioral intervention programs improve lifestyle behaviors and lower blood pressure.
To compare the 18-month effects of 2 ...multicomponent behavioral interventions versus advice only on hypertension status, lifestyle changes, and blood pressure.
Multicenter, 3-arm, randomized trial conducted from January 2000 through November 2002.
4 clinical centers and a coordinating center.
810 adult volunteers with prehypertension or stage 1 hypertension (systolic blood pressure, 120 to 159 mm Hg; diastolic blood pressure, 80 to 95 mm Hg).
A multicomponent behavioral intervention that implemented long-established recommendations ("established"); a multicomponent behavioral intervention that implemented the established recommendations plus the Dietary Approaches to Stop Hypertension (DASH) diet ("established plus DASH"); and advice only.
Lifestyle variables and blood pressure status. Follow-up for blood pressure measurement at 18 months was 94%.
Compared with advice only, both behavioral interventions statistically significantly reduced weight, fat intake, and sodium intake. The established plus DASH intervention also statistically significantly increased fruit, vegetable, dairy, fiber, and mineral intakes. Relative to the advice only group, the odds ratios for hypertension at 18 months were 0.83 (95% CI, 0.67 to 1.04) for the established group and 0.77 (CI, 0.62 to 0.97) for the established plus DASH group. Although reductions in absolute blood pressure at 18 months were greater for participants in the established and the established plus DASH groups than for the advice only group, the differences were not statistically significant.
The exclusion criteria and the volunteer nature of this cohort may limit generalizability. Although blood pressure is a well-accepted risk factor for cardiovascular disease, the authors were not able to assess intervention effects on clinical cardiovascular events in this limited time and with this sample size.
Over 18 months, persons with prehypertension and stage 1 hypertension can sustain multiple lifestyle modifications that improve control of blood pressure and could reduce the risk for chronic disease.
The National Institutes of Health (NIH) has prioritized efforts to increase diversity in the biomedical research workforce. NIH-funded institutional career development awards may serve as one ...mechanism to facilitate these efforts. In 2013, the Duke University KL2 program, an internal career development program funded by the National Center for Advancing Translational Sciences, set a goal to increase the number of investigators from underrepresented racial and ethnic groups (UREGs) to ≥ 50% of KL2 awardees. From 2013 to 2019, 133 KL2 applications were received, 38% from UREG investigators. Of the 21 scholars selected, 10 (47.6%) were UREG investigators; all were Black/African American. This represents a threefold increase in the proportion of UREG applications and a sixfold increase in the proportion of UREG KL2 scholars compared with Duke's previous KL2 cycles (2003-2012), during which only 13% of applicants and 8.3% of funded scholars were UREGs. Of the 12 KL2 scholars (7 UREG) who completed the program, 5 have received NIH funding as principal investigators of an external K award or R01, and 4 of them are UREG investigators; this constitutes a post-KL2 NIH funding success rate of 57% (4/7) for UREG scholars. Achieving this programmatic priority was facilitated by institutional support, clear communication of goals to increase the proportion of UREG KL2 awardees, and intentional strategies to identify and support applicants. Strategies included targeted outreach to UREG investigators, partnerships with other institutional entities, structured assistance for investigators with preparing their applications, and a KL2 program structure addressing common barriers to success for UREG investigators, such as lack of consistent mentorship, protected research time, and peer support. The authors' experience suggests that KL2 and other internal career development programs may represent a scalable, national strategy to increase diversity in the biomedical research workforce.
Background To improve methods for long-term weight management, the Weight Loss Maintenance (WLM) trial, a four-center randomized trial, was conducted to compare alternative strategies for maintaining ...weight loss over a 30-month period. This paper describes methods and results for the initial 6-month weight-loss program (Phase I). Methods Eligible adults were aged ≥25, overweight or obese (BMI=25–45 kg/m2 ), and on medications for hypertension and/or dyslipidemia. Anthropomorphic, demographic, and psychosocial measures were collected at baseline and 6 months. Participants ( n =1685) attended 20 weekly group sessions to encourage calorie restriction, moderate-intensity physical activity, and the DASH (dietary approaches to stop hypertension) dietary pattern. Weight-loss predictors with missing data were replaced by multiple imputation. Results Participants were 44% African American and 67% women; 79% were obese (BMI≥30), 87% were taking anti-hypertensive medications, and 38% were taking antidyslipidemia medications. Participants attended an average of 72% of 20 group sessions. They self-reported 117 minutes of moderate-intensity physical activity per week, kept 3.7 daily food records per week, and consumed 2.9 servings of fruits and vegetables per day. The Phase-I follow-up rate was 92%. Mean (SD) weight change was −5.8 kg (4.4), and 69% lost at least 4 kg. All race–gender subgroups lost substantial weight: African-American men (−5.4 kg ± 7.7); African-American women (−4.1 kg ± 2.9); non–African-American men (−8.5 kg ± 12.9); and non–African-American women (−5.8 kg ± 6.1). Behavioral measures (e.g., diet records and physical activity) accounted for most of the weight-loss variation, although the association between behavioral measures and weight loss differed by race and gender groups. Conclusions The WLM behavioral intervention successfully achieved clinically significant short-term weight loss in a diverse population of high-risk patients.
To evaluate racial and ethnic differences in communication quality during family centered rounds.
We conducted an observational study of family-centered rounds on hospital day 1. All enrolled ...caregivers completed a survey following rounds and a subset consented to audio record their encounter with the medical team. We applied a priori defined codes to transcriptions of the audio-recorded encounters to assess objective communication quality, including medical team behaviors, caregiver participatory behaviors, and global communication scores. The surveys were designed to measure subjective communication quality. Incident Rate Ratios (IRR) were calculated with regression models to compare the relative mean number of behaviors per encounter time minute by race and ethnicity.
Overall, 202 of 341 eligible caregivers completed the survey, and 59 had accompanying audio- recorded rounds. We found racial and ethnic differences in participatory behaviors: English-speaking Latinx (IRR 0.5; 95% confidence interval CI 0.3-0.8) Black (IRR 0.6; 95% CI 0.4-0.8), and Spanish-speaking Latinx caregivers (IRR 0.3; 95% CI 0.2-0.5) participated less than white caregivers. Coder-rated global ratings of medical team respect and partnership were lower for Black and Spanish-speaking Latinx caregivers than white caregivers (respect 3.1 and 2.9 vs 3.6, P values .03 and .04, respectively: partnership 2.4 and 2.3 vs 3.1, P values .03 and .04 respectively). In surveys, Spanish-speaking caregivers reported lower subjective communication quality in several domains.
In this study, Black and Latinx caregivers were treated with less partnership and respect than white caregivers.
Patients with CKD are at elevated risk of metabolic acidosis due to impaired net acid excretion (NAE). Identifying early markers of acidosis may guide prevention in chronic kidney disease (CKD). This ...study compared NAE in participants with and without CKD, as well as the NAE, blood pressure (BP), and metabolomic response to bicarbonate supplementation.
Randomized order, cross-over study with controlled feeding.
Participants consisted of 8 patients with CKD (estimated glomerular filtration rate 30-59mL/min/1.73m2 or 60-70mL/min/1.73m2 with albuminuria) and 6 patients without CKD. All participants had baseline serum bicarbonate concentrations between 20 and 28 mEq/L; they did not have diabetes mellitus and did not use alkali supplements at baseline.
Participants were fed a fixed–acid-load diet with bicarbonate supplementation (7 days) and with sodium chloride control (7 days) in a randomized order, cross-over fashion.
Urine NAE, 24-hour ambulatory BP, and 24-hour urine and plasma metabolomic profiles were measured after each period.
During the control period, mean NAE was 28.3±10.2 mEq/d overall without differences across groups (P=0.5). Urine pH, ammonium, and citrate were significantly lower in CKD than in non-CKD (P<0.05 for each). Bicarbonate supplementation reduced NAE and urine ammonium in the CKD group, increased urine pH in both groups (but more in patients with CKD than in those without), and increased; urine citrate in the CKD group (P< 0.2 for interaction for each). Metabolomic analysis revealed several urine organic anions were increased with bicarbonate in CKD, including 3-indoleacetate, citrate/isocitrate, and glutarate. BP was not significantly changed.
Small sample size and short feeding duration.
Compared to patients without CKD, those with CKD had lower acid excretion in the form of ammonium but also lower base excretion such as citrate and other organic anions, a potential compensation to preserve acid-base homeostasis. In CKD, acid excretion decreased further, but base excretion (eg, citrate) increased in response to alkali. Urine citrate should be evaluated as an early and responsive marker of impaired acid-base homeostasis.
National Institute of Diabetes and Digestive and Kidney Diseases and the Duke O’Brien Center for Kidney Research.
Registered at ClinicalTrials.gov with study number NCT02427594.
Recent studies have found low-normal potassium (K) to be associated with increased diabetes risk. We sought to verify these associations in a multi-ethnic US cohort; and to determine if these ...associations extend to US Hispanics and Asian-Americans.
We analyzed data from Multi-Ethnic Study of Atherosclerosis (MESA) participants who were free-of-diabetes at baseline. We examined cross-sectional associations between measures of K-serum, dietary, and urine-with fasting glucose and HOMA-IR. We examined longitudinal associations between K and diabetes risk over 8 years.
In multivariable models, compared to those with higher serum K (≥4.5mmol/L), those with lower serum K (<4.0mmol/L) had significantly higher fasting glucose 1.3 mg/dL (95%CI 0.2, 2.4), P-value = 0.03. Incident diabetes developed in 1281 of 5415 at-risk participants. In minimally-adjusted models, we found inverse associations between serum and dietary K and diabetes risk. Compared to those with higher serum K, those with lower serum K had an HR (95% CI) of incident diabetes of 1.23 (1.04, 1.47), P-value = 0.02. However, these associations were attenuated in fully-adjusted models. We found no significant interaction between potassium and ethnicity.
In this multi-ethnic cohort, we found a significant inverse association between serum K and fasting glucose but no significant association with longer-term diabetes risk. This inverse association between potassium and glucose must be studied further to understand the physiology and its potential impact on chronic health.
The Dietary Approaches to Stop Hypertension (DASH) diet has been proven to effectively lower blood pressure (BP), and associate with a lower cardiovascular disease and stroke risk in mainly ...non-Asians. Further, it is unclear if adhering to the DASH target nutrients has similar BP impact as adhering to the recommended DASH food groups. Associations between adherence to DASH foods or nutrients and BP or stroke risk were assessed in 1420 and 2061 Taiwanese adults from 1989 to 2002, respectively. The DASH food score (p=0.053), dairy (p=0.030) and calcium (p=0.020) intake were significantly and inversely associated with follow up systolic BP change in univariate analyses. Both dairy (p=0.020) and calcium (p=0.001) also showed a consistent inverse association with systolic BP change in multivariate analysis. None of the factors examined was associated with diastolic BP change. Both DASH nutrient score and magnesium intakes were significantly associated with the hazard ratio (HR) for total stroke in an inverse relationship. The HR of total stroke comparing the highest to the lowest tertile was 0.63 (95% CI: 0.41-0.98, p=0.037) for the DASH nutrient score, and 0.62 (95% CI: 0.40-0.97, p=0.030) for magnesium intake. Similar findings were observed for DASH nutrient score (p=0.011) and magnesium intake (p=0.043) with the HR for ischemic stroke. The HR for total and ischemic stroke for calcium intake also showed a borderline trend (p=0.071 and 0.051, respectively). In conclusion, adhering to the DASH diet is beneficial for long term BP control and reduction of stroke risk in this Chinese population.
BACKGROUND: Consumption of liquid calories from beverages has increased in parallel with the obesity epidemic in the US population, but their causal relation remains unclear. OBJECTIVE: The objective ...of this study was to examine how changes in beverage consumption affect weight change among adults. DESIGN: This was a prospective study of 810 adults participating in the PREMIER trial, an 18-mo randomized, controlled, behavioral intervention trial. Measurements (weight, height, and 24-h dietary recall) were made at baseline, 6 mo, and 18 mo. RESULTS: Baseline mean intake of liquid calories was 356 kcal/d (19% of total energy intake). After potential confounders and intervention assignment were controlled for, a reduction in liquid calorie intake of 100 kcal/d was associated with a weight loss of 0.25 kg (95% CI: 0.11, 0.39; P < 0.001) at 6 mo and of 0.24 kg (95% CI: 0.06, 0.41; P = 0.008) at 18 mo. A reduction in liquid calorie intake had a stronger effect than did a reduction in solid calorie intake on weight loss. Of the individual beverages, only intake of sugar-sweetened beverages (SSBs) was significantly associated with weight change. A reduction in SSB intake of 1 serving/d was associated with a weight loss of 0.49 kg (95% CI: 0.11, 0.82; P = 0.006) at 6 mo and of 0.65 kg (95% CI: 0.22, 1.09; P = 0.003) at 18 mo. CONCLUSIONS: These data support recommendations to limit liquid calorie intake among adults and to reduce SSB consumption as a means to accomplish weight loss or avoid excess weight gain. This trial was registered at clinicaltrials.gov as NCT00000616.
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