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A randomized controlled trial contrasting the effects of 4 low-calorie sweeteners and sucrose on body weight in adults with overweight or obesity.
Higgins, KA, Mattes, RD
The American journal of clinical nutrition. 2019;(5):1288-1301
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Abstract
BACKGROUND Low-calorie sweeteners (LCSs) provide sweetness with little or no energy. However, each LCS's unique chemical structure has potential to elicit different sensory, physiological, and behavioral responses that affect body weight. OBJECTIVE The purpose of this trial was to compare the effects of consumption of 4 LCSs and sucrose on body weight, ingestive behaviors, and glucose tolerance over a 12-wk intervention in adults (18-60 y old) with overweight or obesity (body mass index 25-40 kg/m2). METHODS In a parallel-arm design, 154 participants were randomly assigned to consume 1.25-1.75 L of beverage sweetened with sucrose (n = 39), aspartame (n = 30), saccharin (n = 29), sucralose (n = 28), or rebaudioside A (rebA) (n = 28) daily for 12 wk. The beverages contained 400-560 kcal/d (sucrose treatments) or <5 kcal/d (LCS treatments). Anthropometric indexes, energy intake, energy expenditure, appetite, and glucose tolerance were measured at baseline. Body weight was measured every 2 wk with energy intake, expenditure, and appetite assessed every 4 wk. Twenty-four-hour urine collections were completed every 4 wk to determine study compliance via para-aminobenzoic acid excretion. RESULTS Of the participants enrolled in the trial, 123 completed the 12-wk intervention. Sucrose and saccharin consumption led to increased body weight across the 12-wk intervention (Δweight = +1.85 ± 0.36 kg and +1.18 ± 0.36 kg, respectively; P ≤ 0.02) and did not differ from each other. There was no significant change in body weight with consumption of the other LCS treatments compared with baseline, but change in body weight for sucralose was negative and significantly lower compared with all other LCSs at week 12 (weight difference ≥ 1.37 ± 0.52 kg, P ≤ 0.008). Energy intake decreased with sucralose consumption (P = 0.02) and ingestive frequency was lower for sucralose than for saccharin (P = 0.045). Glucose tolerance was not significantly affected by any of the sweetener treatments. CONCLUSIONS Sucrose and saccharin consumption significantly increase body weight compared with aspartame, rebA, and sucralose, whereas weight change was directionally negative and lower for sucralose compared with saccharin, aspartame, and rebA consumption. LCSs should be categorized as distinct entities because of their differing effects on body weight. This trial was registered at clinicaltrials.gov as NCT02928653.
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The effect of prepregnancy body mass index on the risk of gestational diabetes mellitus: A systematic review and dose-response meta-analysis.
Najafi, F, Hasani, J, Izadi, N, Hashemi-Nazari, SS, Namvar, Z, Mohammadi, S, Sadeghi, M
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2019;(3):472-486
Abstract
This study was conducted to investigate the effect of the prepregnancy BMI on the risk of gestational diabetes mellitus (GDM). Five electronic databases, including PubMed, Scopus, Embase, Web of Science, and Google Scholar, were searched for literature published until 1 January 2018. The two-stage, random effect meta-analysis was performed to compare the dose-response relationship between BMI and GDM. As well as studies with categorized BMI, studies that treat BMI as a continuous variable were analysed. A total of 33 observational studies with an overall sample size of 962 966 women and 42 211 patients with GDM were included in analysis. The pooled estimate of GDM risk in the underweight, overweight, and obese pregnant women was 0.68, 2.01, and 3.98 using the adjusted OR and 0.34, 1.52, and 2.24 using the adjusted RR. The GDM risk increased 4% per unit of increase in BMI with both the crude and adjusted OR/RR models. Also, the risk of GDM increased 19% with the crude model and 14% with the adjusted model. The existence of dose-response relationship between the pre-pregnancy BMI and GDM can strengthen the scientific background for vigorous public health interventions for the control of pre-pregnancy BMI as well as the weight gain during pregnancy.
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Antenatal Magnesium Sulfate Exposure and Ponderal Index in Preterm Infants.
Deihl, TE, Simhan, HN
American journal of perinatology. 2019;(3):329-334
Abstract
OBJECTIVE Antenatal magnesium sulfate (MgSO4) is known to affect the central nervous system of preterm infants, and there is biologic rationale for influence on other phenotypes. This study investigated the effect of MgSO4 exposure on the trajectory of ponderal index (PI, kg/m3) from birth to 2 years of age. STUDY DESIGN A secondary analysis of a U.S. randomized controlled trial investigating MgSO4 versus placebo administration among women at high risk for preterm delivery was performed. Multivariable logistic regression was used to assess the relationship between PI from birth to 2 years of age and exposure to MgSO4 versus placebo. RESULTS There was a larger decrement in PI from birth to 2 years of age in infants exposed to MgSO4 compared with placebo (p = 0.032). There was a statistically significant one-way interaction between newborn sex and treatment group (p = 0.019). Change in PI in males exhibited a greater decrement in those exposed to MgSO4 versus placebo (p = 0.227), whereas female infants exposed to MgSO4 had a smaller decrement (p = 0.04). CONCLUSION MgSO4 exposure in preterm infants is associated with a larger decrease in PI from birth to 2 years of age. In addition, the direction of effect of MgSO4 on the change in PI over the first 2 years of life is different by sex.
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Examining Childhood Obesity From Infancy: The Relationship Between Tummy Time, Infant BMI-z, Weight Gain, and Motor Development-An Exploratory Study.
Koren, A, Kahn-D'angelo, L, Reece, SM, Gore, R
Journal of pediatric health care : official publication of National Association of Pediatric Nurse Associates & Practitioners. 2019;(1):80-91
Abstract
INTRODUCTION This exploratory study investigated the infant time spent in tummy time (TT) in relation to body mass index z score (BMI-z), weight gain, and motor development in infants from birth to 4 months. METHOD Mothers and their infants were telephone surveyed at 2 and 4 months. Mother demographics; TT; feeding practices; and infant length, and height, and development were collected each time. RESULTS Results from Cochran-Mantel-Haenszel and single logistic regression showed a significant association between development, level of BMI-z, and time spent in TT at 2 months of age (p < .0001). The threshold model showed there was a decline in BMI-z at 4 months as daily time in TT increases past the threshold value of approximately 12 minutes per day. Mother education and TT at 2 months were significant predictors of BMI-z at 4 months. DISCUSSION Study outcomes suggest that infant positioning and time in TT promote infant motor development and may moderate rapid infant weight gain.
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Optimized protein intakes in term infants support physiological growth and promote long-term health.
Koletzko, B, Demmelmair, H, Grote, V, Totzauer, M
Seminars in perinatology. 2019;(7):151153
Abstract
Breastfeeding is associated with a reduced later obesity risk, relative to feeding convention infant formula. Breastfeeding induces less weight gain during the first two years of life, which predicts less obesity up to adulthood. We tested the hypothesis that a high infant protein supply promotes weight gain and obesity risk, mediated by increased plasma amino acids and growth factors, insulin and insulin like growth factor 1 (IGF-1). A large multi-centre double blind trial randomized formula-fed infants to conventional bottle milk with a high protein content, or an intervention formula with a reduced protein content more similar to levels provided with human milk. Protein-reduced formula normalized weight, body mass index and body fatness up to 6 years, relative to a breastfed reference group, and reduced the adjusted odds for obesity 2.6-fold. Available data indicate potential underlying mechanisms. We conclude that infant feeding has very marked long-term programming effects on later BMI, obesity and adiposity, with major public health implications. Breastfeeding lowers the risk for later obesity and adiposity. This provides additional motivation for proactively and enthusiastically promoting, protecting and supporting breastfeeding. A high milk protein intake in infancy increases the long-term risk for obesity and adiposity. Infants not or not fully breastfed should receive infant formula delivering protein in amounts more similar to human milk contents, with high protein quality. Other sources of very high infant protein intakes, particular drinking unmodified cows' milk, should be avoided in infancy.
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Metabolic Determinants of Weight Gain in Humans.
Piaggi, P
Obesity (Silver Spring, Md.). 2019;(5):691-699
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Abstract
One of the fundamental challenges in obesity research is to identify subjects prone to weight gain so that obesity and its comorbidities can be promptly prevented or treated. The principles of thermodynamics as applied to human body energetics demonstrate that susceptibility to weight gain varies among individuals as a result of interindividual differences in energy expenditure and energy intake, two factors that counterbalance one another and determine daily energy balance and, ultimately, body weight change. This review focuses on the variability among individuals in human metabolism that determines weight change. Conflicting results have been reported about the role of interindividual differences in energy metabolism during energy balance in relation to future weight change. However, recent studies have shown that metabolic responses to acute, short-term dietary interventions that create energy imbalance, such as low-protein overfeeding or fasting for 24 hours, may reveal the underlying metabolic phenotype that determines the degree of resistance to diet-induced weight loss or the propensity to spontaneous weight gain over time. Metabolically "thrifty" individuals, characterized by a predilection for saving energy in settings of undernutrition and dietary protein restriction, display a minimal increase in plasma fibroblast growth factor 21 concentrations in response to a low-protein overfeeding diet and tend to gain more weight over time compared with metabolically "spendthrift" individuals. Similarly, interindividual variability in the causal relationship between energy expenditure and energy intake ("energy sensing") and in the metabolic response to cold exposure (e.g., brown adipose tissue activation) seems, to some extent, to be indicative of individual propensity to weight gain. Thus, an increased understanding and the clinical characterization of phenotypic differences in energy metabolism among individuals (metabolic profile) may lead to new strategies to prevent weight gain or improve weight-loss interventions by targeted therapies on the basis of metabolic phenotype and susceptibility to obesity in individual persons.
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Effects of antidepressant and antipsychotic use on weight gain: A systematic review.
Alonso-Pedrero, L, Bes-Rastrollo, M, Marti, A
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2019;(12):1680-1690
Abstract
Weight gain is an adverse effect of antidepressants and antipsychotics. This side effect can lead to numerous comorbidities and reduces life expectancy. The use of these drugs is increasing worldwide, and the weight gain produced by them represents a common clinical challenge. The goal of this systematic review was to evaluate the potential association of antidepressant and antipsychotic therapy with body weight gain in cohort studies. A search of cohort studies investigating the association between weight gain and the use of antidepressants and antipsychotics in individuals was conducted through the PubMed database from 1 January 2008 to 31 January 2019 following the PRISMA statement. We found 27 independent eligible cohort studies that included children (2-18 years old) and adult (18-103 years old) subjects. Most of the included studies showed a 5% weight gain in individuals using antidepressant therapy. However, Quetiapine, Haloperidol, Trifluoperazine, Risperidone, Aripiprazole, Olanzapine, and Clozapine increased body weight ≥7% from baseline, which is considered a clinically significant result. Weight loss was found in individuals treated with Bupropion. Further cohort studies with higher sample sizes and longer durations of treatment are needed to confirm our observations.
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An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2-5 years (KLIMB).
Rosenfeld, M, Cunningham, S, Harris, WT, Lapey, A, Regelmann, WE, Sawicki, GS, Southern, KW, Chilvers, M, Higgins, M, Tian, S, et al
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2019;(6):838-843
Abstract
BACKGROUND KIWI (NCT01705145) was a 24-week, single-arm, pharmacokinetics, safety, and efficacy study of ivacaftor in children aged 2 to 5 years with cystic fibrosis (CF) and a CFTR gating mutation. Here, we report the results of KLIMB (NCT01946412), an 84-week, open-label extension of KIWI. METHODS Children received age- and weight-based ivacaftor dosages for 84 weeks. The primary outcome was safety. Other outcomes included sweat chloride, growth parameters, and measures of pancreatic function. RESULTS All 33 children who completed KIWI enrolled in KLIMB; 28 completed 84 weeks of treatment. Most adverse events were consistent with those reported during KIWI. Ten (30%) children had transaminase elevations >3 × upper limit of normal (ULN), leading to 1 discontinuation in a child with alanine aminotransferase >8 × ULN. Improvements in sweat chloride, weight, and body mass index z scores and fecal elastase-1 observed during KIWI were maintained during KLIMB; there was no further improvement in these parameters. CONCLUSIONS Ivacaftor was generally well tolerated for up to 108 weeks in children aged 2 to 5 years with CF and a gating mutation, with safety consistent with the KIWI study. Improvements in sweat chloride and growth parameters during the initial 24 weeks of treatment were maintained for up to an additional 84 weeks of treatment. Prevalence of raised transaminases remained stable and did not increase with duration of exposure during the open-label extension.
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Change in Cardiometabolic Risk Factors Associated With Magnitude of Weight Regain 3 Years After a 1-Year Intensive Lifestyle Intervention in Type 2 Diabetes Mellitus: The Look AHEAD Trial.
Berger, SE, Huggins, GS, McCaffery, JM, Jacques, PF, Lichtenstein, AH
Journal of the American Heart Association. 2019;(20):e010951
Abstract
Background Weight regain after weight loss is common. The impact on cardiometabolic risk factors is not well established. Methods and Results Publicly available data were analyzed from participants of the Look AHEAD (Action for Health in Diabetes) trial with ≥3% initial weight loss (n=1561) during a 1-year intensive lifestyle intervention and with year 4 follow-up data. Participants who regained (regainers) or maintained (maintainers) weight loss were defined with 5 dichotomized cut points (0%, 25%, 50%, 75%, and 100%) of percentage weight loss regained (weight change from years 1-4 as percentage of first year weight loss). Change in cardiometabolic risk factors after initial weight loss was compared in maintainers and regainers, after controlling for demographics, medications, and baseline and year 1 change in body mass index. The effect was assessed separately in participants with <10% and ≥10% initial weight loss, and women and men. Maintainers exhibited significant improvements to the cardiometabolic risk factors assessed compared with regainers. No weight regain cut point maximized risk difference between maintainers and regainers across risk factors or sex/initial weight loss subgroups. For many risk factors, allowing more regain as part of maintenance (increasing cut point) diminished the cardiometabolic benefit among maintainers. Conclusions Maintaining weight loss was better than regain for all risk factors. No single cut point maximized the risk difference between maintainers and regainers. Maintainers who kept off ≥75% of weight lost had the greatest benefit. These findings emphasize the importance of intervention programs focusing not only on weight loss but weight loss maintenance, given the adverse consequences of the latter. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00017953.
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Extensive Phenotyping for Potential Weight-Inducing Factors in an Outpatient Population with Obesity.
Savas, M, Wester, VL, Visser, JA, Kleinendorst, L, van der Zwaag, B, van Haelst, MM, van den Akker, ELT, van Rossum, EFC
Obesity facts. 2019;(4):369-384
Abstract
BACKGROUND Obesity has been associated with miscellaneous weight-inducing determinants. A comprehensive assessment of known obesity-related factors other than diet and physical activity within one cohort is currently lacking. OBJECTIVES To assess the prevalence of potential contributors to obesity and self-reported triggers for marked weight gain in an adult population with obesity and between obesity classes. METHODS In this observational cohort study, we assessed 408 persons with obesity (aged 41.3 ± 14.2 years, BMI 40.5 ± 6.2) visiting our obesity clinic. They were evaluated for use of weight-inducing drugs, hormonal abnormalities, menarcheal age, (high) birth weight, sleep deprivation, and obstructive sleep apnea syndrome (OSAS). We additionally assessed self-reported triggers for marked weight gain and performed genetic testing in patients suspected of genetic obesity. RESULTS Nearly half of the patients were using a potentially weight-inducing drug, which was also the most reported trigger for marked weight gain. For the assessed hormonal conditions, a relatively high prevalence was found for hypothyroidism (14.1%), polycystic ovary syndrome (12.0%), and male hypogonadism (41.7%). A relatively low average menarcheal age (12.6 ± 1.8 years) was reported, whereas there was a high prevalence of a high birth weight (19.5%). Sleep deprivation and OSAS were reported in, respectively, 14.5 and 13.7% of the examined patients. Obesity class appeared to have no influence on the majority of the assessed factors. Of the genetically analyzed patients, a definitive genetic diagnosis was made in 3 patients (1.9%). CONCLUSIONS A thorough evaluation of patients with obesity yields a relatively high prevalence of various potentially weight-inducing factors. Diagnostic screening of patients with obesity could therefore benefit these patients by potentially reducing the social stigma and improving the outcomes of obesity treatment programs by tackling, where possible, the weight-inducing factors in advance.