Plasma angiopoietin-like protein 2 levels and mortality risk among younger-old Japanese people: a population-based case-cohort study

Aging is important medical and social problem. Excessive angiopoietin-like protein (ANGPTL)-2 signaling causes chronic tissue inflammation, promoting development and progression of aging-related diseases. Moreover, circulating ANGPTL2 levels reportedly predict risk of some aging-related diseases and subsequent death. However, there are as yet no reports of whether circulating ANGPTL2 levels predict vital prognosis in younger-old, community-dwelling populations. This study investigated associations between plasma ANGPTL2 levels and all-cause and specific-cause mortality in this population. The case-cohort study was abstracted from an on-going, age-specific prospective cohort study: the New Integrated Suburban Seniority Investigation Project. This project enrolled 3073 participants aged 64 years at the beginning of the investigation from 1996 through 2005. A sub-cohort of 714 randomly sampled participants plus 387 cases representing deceased participants followed through 2015 underwent survival analysis. Plasma ANGPTL2 concentrations were positively associated with >80% and 100% higher risk of all-cause mortality and cancer mortality, respectively, after adjustment for gender, smoking, alcohol consumption, walking time, sleep duration, caloric intake, medical status, disease history, BMI, and triglyceride, creatinine, uric acid, and high sensitivity C-reactive protein levels. More robust association between ANGPTL2 levels and all-cause and cancer mortality was seen in subjects with either frailties or with lifestyles of heavier drinking or current smoking. Elevated plasma ANGPTL2 levels are associated with high all-cause and cancer mortality in a community-dwelling sample of younger-old adults. These findings expand our knowledge of human aging and associated diseases.

Quality Initiative to Reduce Extrauterine Growth Restriction in Very Low Birth Weight Infants

BACKGROUND: We report a statewide quality improvement initiative aimed to decrease the incidence of extrauterine growth restriction among very low birth weight infants cared for in Tennessee NICUs. METHODS: The cohort consisted of infants born appropriate for gestational age between May 2016 and December 2018 from 9 NICUs across Tennessee. The infants were 23 to 32 weeks gestation and 500 to 1499 g birth weight. The process measures were the hours of life (HOL) when parenteral protein and intravenous lipid emulsion were initiated, the number of days to first enteral feeding, and attainment of full enteral caloric intake (110–130 kcal/kg per day). The primary outcome was extrauterine growth restriction, defined as weight <10th percentile for weight at 36 weeks postmenstrual age. Statistical process control charts and the Shewhart control rules were used to find special cause variation. RESULTS: Although special cause variation was not indicated in the primary outcome measure, it was indicated for the reduction in specific process measures: HOL when parenteral protein was initiated, HOL when intravenous lipid emulsion was initiated, and the number of days to attainment of full enteral caloric intake (among the hospitals considered regional perinatal centers). CONCLUSIONS: A statewide quality improvement initiative led to earlier initiation of parenteral and enteral nutrition and improved awareness of the importance of postnatal nutrition.

To Improve the Initial Inpatient Management of Adolescents Admitted with Severe Anorexia Nervosa: A Narrative Review and a Convenient Protocol

Inadequate nutritional rehabilitation of severely malnourished adolescents with Anorexia Nervosa (AN) increases the risk of medical complications. There is no consensus on best practices for inpatient nutritional rehabilitation and medical stabilization for severe AN. This study aimed to elaborate an admission protocol for adolescents with severe AN based on a comprehensive narrative review of current evidence. A Pubmed search was conducted in July 2017 and updated in August 2020, using the keywords severe AN or eating disorders (ED), management guidelines and adolescent. Relevant references cited in these guidelines were retrieved. A secondary search was conducted using AN or ED and refeeding protocol, refeeding syndrome (RS), hypophosphatemia, hypoglycemia, cardiac monitoring or cardiac complications. Evidence obtained was used to develop the admission protocol. Selective blood tests were proposed during the first three days of nutritional rehabilitation. Higher initial caloric intake is supported by evidence. Continuous nasogastric tube feeding was proposed for patients with a BMI < 12 kg/m2. We monitor hypoglycemia for 72 h. Continuous cardiac monitoring for bradycardia <30 BPM and systematic phosphate supplementation should be considered. Developing protocols is necessary to improve standardization of care. We provide an example of an inpatient admission protocol for adolescents with severe AN.

Correlates of cardiorespiratory fitness among overweight or obese individuals with type 2 diabetes

IntroductionMechanistic studies suggest that type 2 diabetes is independently associated with low cardiorespiratory fitness (CRF). Little is known about the CRF profile in type 2 diabetes; we assessed the correlates of low CRF among overweight/obese adults with type 2 diabetes.Research design and methodsA total of 4215 participants with type 2 diabetes and without cardiovascular disease underwent maximal exercise testing in the Look AHEAD (Action for Health in Diabetes) study. Low CRF was defined based on the Aerobics Center Longitudinal Study reference standards. Calorie intake and physical activity were assessed using questionnaires. Body fat composition was assessed using dual-energy X-ray absorptiometry.ResultsWaist circumference, systolic blood pressure, glycemic measures, whole body fat, caloric intake, and fat-free mass were inversely associated with fitness across sex (all p<0.001). Comparing with moderate or high CRF groups, the low CRF group was associated with higher adjusted odds of obesity (OR 3.19 (95% CI 1.95 to 5.20) in men, 3.86 (95% CI 2.55 to 5.84)) in women), abdominal obesity (OR 3.99 (95% CI 2.00 to 7.96) in men, 2.28 (95% CI 1.08 to 4.79) in women), hypertension (OR 1.74 (95% CI 1.09 to 2.77) in men, 1.44 (95% CI 1.02 to 2.05) in women), metabolic syndrome (OR 5.52 (95% CI 2.51 to 12.14) in men, 2.25 (95% CI 1.35 to 3.76) in women), use of beta-blocker (1.22 (95% CI 0.86 to 1.73) in men, 1.33 (95% CI 1.03 to 1.73) in women), and ACE inhibitor/angiotensin-receptor blocker (1.86 (95% CI 1.39 to 2.50) in men, 1.07 (95% CI 0.86 to 1.32) in women). Women with low CRF had higher odds of current smoking (2.02 (95% CI 1.25 to 3.28)).ConclusionsLow CRF was associated with increased odds of cardiometabolic correlates in a large cohort of adults with type 2 diabetes.

The Effects of Caloric Restriction and/or Intermittent Fasting on Bone Health

This mini-review summarizes the available information regarding the impact of caloric restriction (CR) and/or intermittent fasting (IF) on bone health. CR and IF are dietary interventions used in rehabilitative healthcare for augmenting weight loss and also proposed for recovery of conditions such as stroke and heart failure. CR restricts the total number of calories rather than different food groups or periods of eating. In contrast, IF severely restricts caloric intake for a period of time followed by a period of ad libitum intake. Here, we discuss the available information regarding the impact of these rehabilitation diets on bone metabolism, highlighting areas of consistency and discrepancy and suggesting future areas of study to advance the understanding of CR and/or IF on bone health.

Malnutrition–Sarcopenia Syndrome and Self-Management Behaviors in Continuing-Care Retirement Community Residents

Malnutrition–sarcopenia syndrome (MSS) might put older adults at higher risk for disability, frailty, and mortality. This study examined the prevalence and association of the self-management-process factors (i.e., self-efficacy and aging expectations) and behaviors (protein and caloric intake and sedentary and physical-activity behaviors) to MSS among older adults living in continuing care retirement communities (CCRCs). Using a cross-sectional correlational design, data of 96 CCRC residents (82.4 ± 7.4 years) were analyzed. Muscle mass, strength, function, nutritional status, sedentary time, physical activity levels, protein and caloric intake, self-efficacy for physical activity, aging expectations, and physical and mental health-related quality of life were measured. Results show that 36 (37.5%) had sarcopenia, 21 (21.9%) had malnutrition risk, 13 (13.4%) had malnutrition, and 12 (12.5%) had MSS. We also found that high time spent in sedentary behaviors (OR = 1.041; 95% CI: 1.011–1.071) was associated with higher odds of having MSS and high expectations regarding aging (OR = 0.896; 95% CI: 0.806–0.997) was associated with less likelihood of having MSS. Findings suggest that CCRC residents should be screened for MSS. Self-management interventions that consider the self-management-process factors are needed to prevent MSS and mitigate its negative outcomes among CRCC residents.

Aerobic Fitness, B-Vitamins, and Weight Status Are Related to Selective Attention in Children

There is an increasing prevalence of poor health behaviors during childhood, particularly in terms of physical activity and nutrition. This trend has occurred alongside a growing body of evidence linking these behaviors to cognitive function. B-vitamins are thought to be particularly important in the neural development that occurs during pregnancy, as well as in healthy cognitive aging. However, much less is known regarding the role of B-vitamins during childhood. Given that preadolescent childhood is a critical period for cognitive development, this study investigated the relationship between specific aspects of nutrition, particularly B-vitamins, and related health factors (e.g., body mass, fitness) on selective attention in children. Children (n = 85; 8–11 years) completed a selective attention task to assess inhibition. Participant’s dietary intake was collected using the Automated Self-Administered 24-h dietary assessment tool. Correlations between specific nutrients, BMI, fitness, and task performance were investigated. After accounting for demographic variables and total caloric intake, increased B-vitamin intake (i.e., thiamin and folic acid) was associated with shorter reaction times (p’s < 0.05), fitness was associated with greater response accuracy (p < 0.05), and increased BMI was related to increased variability in reaction times (p < 0.05). Together, these findings suggest that aspects of health may have unique contributions on cognitive performance. Proper physical health and nutrition are imperative for effective cognitive functioning in preadolescent children. Targeted efforts aimed at health education amongst this population could ensure proper cognitive development during school-age years, providing a strong foundation throughout life.

Retention, Fasting Patterns, and Weight Loss With an Intermittent Fasting App: A Large-scale, 52-week Observational Study (Preprint)

BACKGROUND Intermittent Fasting (IF) is an increasingly popular approach to dietary control that focuses on the timing of eating rather than the quantity and content of caloric intake. IF practitioners typically seek to improve their weight and other health factors. Millions of practitioners have turned to purpose-built mobile applications to help them track and adhere to their fasts and monitor changes in their weight and other biometrics. OBJECTIVE This study aimed to quantify user retention, fasting patterns, and weight loss by users of two commonly used IF mobile apps. We aimed to describe starting BMI, amount of fasting, frequency of weight tracking, and other demographics as correlates of retention and weight change. METHODS We assembled height, weight, fasting and demographic data for adult users (age 18-100yo) of the LIFE Fasting Tracker and LIFE Extend apps from 2018-2020. Retention up to 52 weeks was quantified based on recorded fasts and correlated with user demographics. Users who provided height and at least two weights and whose first fast and weight records were contemporaneous were included in the weight loss analysis. Fasting was quantified as Extended Fasting Hours (hours beyond 12 in a fast) averaged per Day (EFH/Day). RESULTS 792,692 users were followed for retention based on 26 million recorded fasts. 132,775 (16.7%) of users were retained at 13 weeks, 54,881 (6.9%) at 26 weeks, and 16,478 (2.1%) at 52 weeks, allowing 4 consecutive weeks of inactivity. Weight loss in the qualifying cohort (n=161,346) was strongly correlated with starting BMI and EFH/Day. Users with BMI ≥ 40 lost 11.3% of their starting weight by 52 weeks versus a slight weight gain on average for users with starting BMI <23. Additionally, EFH/Day was an approximately linear predictor of weight loss for a given time point and starting BMI. By week 26, users lost over 1% of their starting weight per EFH/Day on average. Furthermore, users who recorded their weight monthly lost considerably more weight than those who did not (eg, 8.5% vs 3.7% weight loss at week 13 for users with BMI ≥25). By 26 weeks, 69.2% (2985/4313) of users with starting BMI ≥ 25 who recorded monthly weights lost at least 5% of their starting weight, and 39.9% (1722/4313) lost at least 10% body weight. CONCLUSIONS Intermittent Fasting with the LIFE mobile apps appears to be a sustainable approach to weight reduction in the overweight and obese population. Healthy weight and underweight individuals do not lose much weight on average, even with extensive fasting. Obese users lose substantial weight over time, with more weight loss in those who fast more and who record their weight more frequently.

Gut Metabolite Trimethylamine N-Oxide Protects INS-1 β-Cell and Rat Islet Function under Diabetic Glucolipotoxic Conditions

Serum accumulation of the gut microbial metabolite trimethylamine N-oxide (TMAO) is associated with high caloric intake and type 2 diabetes (T2D). Impaired pancreatic β-cell function is a hallmark of diet-induced T2D, which is linked to hyperglycemia and hyperlipidemia. While TMAO production via the gut microbiome-liver axis is well defined, its molecular effects on metabolic tissues are unclear, since studies in various tissues show deleterious and beneficial TMAO effects. We investigated the molecular effects of TMAO on functional β-cell mass. We hypothesized that TMAO may damage functional β-cell mass by inhibiting β-cell viability, survival, proliferation, or function to promote T2D pathogenesis. We treated INS-1 832/13 β-cells and primary rat islets with physiological TMAO concentrations and compared functional β-cell mass under healthy standard cell culture (SCC) and T2D-like glucolipotoxic (GLT) conditions. GLT significantly impeded β-cell mass and function by inducing oxidative and endoplasmic reticulum (ER) stress. TMAO normalized GLT-mediated damage in β-cells and primary islet function. Acute 40µM TMAO recovered insulin production, insulin granule formation, and insulin secretion by upregulating the IRE1α unfolded protein response to GLT-induced ER and oxidative stress. These novel results demonstrate that TMAO protects β-cell function and suggest that TMAO may play a beneficial molecular role in diet-induced T2D conditions.