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Metformin action over gut microbiota is related to weight and glycemic control in gestational diabetes mellitus: A randomized trial.
Molina-Vega, M, Picón-César, MJ, Gutiérrez-Repiso, C, Fernández-Valero, A, Lima-Rubio, F, González-Romero, S, Moreno-Indias, I, Tinahones, FJ
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112465
Abstract
BACKGROUND Metformin, which is known to produce profound changes in gut microbiota, is being increasingly used in gestational diabetes mellitus (GDM). The aim of this study was to elucidate the differences in gut microbiota composition and function in women with GDM treated with metformin compared to those treated with insulin. METHODS From May to December 2018, 58 women with GDM were randomized to receive insulin (INS; n = 28) or metformin (MET; n = 30) at the University Hospital Virgen de la Victoria, Málaga, Spain. Basal visits, with at least 1 follow-up visit and prepartum visit, were performed. At the basal and prepartum visits, blood and stool samples were collected. The gut microbiota profile was determined through 16S rRNA analysis. RESULTS Compared to INS, women on MET presented a lower mean postprandial glycemia and a lower increase in weight and body mass index (BMI). Firmicutes and Peptostreptococcaceae abundance declined, while Proteobacteria and Enterobacteriaceae abundance increased in the MET group. We found inverse correlations between changes in the abundance of Proteobacteria and mean postprandial glycemia (p = 0.023), as well as between Enterobacteriaceae and a rise in BMI and weight gain (p = 0.031 and p = 0.036, respectively). Regarding the metabolic profile of gut microbiota, predicted metabolic pathways related to propionate degradation and ubiquinol biosynthesis predominated in the MET group. CONCLUSION Metformin in GDM affects the composition and metabolic profile of gut microbiota. These changes could mediate, at least in part, its clinical effects. Studies designed to assess how these changes influence metabolic control during and after pregnancy are necessary.
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Effects of Early Weight Gain Velocity, Diet Quality, and Snack Food Access on Toddler Weight Status at 1.5 Years: Follow-Up of a Randomized Controlled Infant Formula Trial.
Mennella, JA, Smethers, AD, Decker, JE, Delahanty, MT, Stallings, VA, Trabulsi, JC
Nutrients. 2021;(11)
Abstract
This study followed children who participated in a feeding trial in which the type of randomized infant formula fed from 2 weeks significantly affected weight gain velocity during the first 4 months and weight-for-length Z (WLZ) scores up to 11.5 months. We focused on measures of anthropometry, dietary intakes, and parenting related to the provision of snack foods that were collected at the end of the trial (1 year) and the 1.5 years follow-up visit. We not only describe what toddlers are eating, but we also determined the independent and/or interactive effects of randomized formula group, early weight gain velocity, the nutrient content of the post-formula diet, and maternal snack food practices, on toddlers' weight status. Diet quality underwent drastic changes during this 6-month period. As infant formula disappeared from the diet, fruit and 100% fruit juice intake increased slightly, while intake of "What We Eat in America" food categories sweetened beverages and snacks and sweets more than doubled. Added sugars accounted for 5% of energy needs at 1 year and 9% at 1.5 years. Generalized linear mixed models revealed that, independent of the randomized formula group, greater velocities of weight gain during early infancy and lower access to snacks as toddlers predicted higher WLZ and a greater proportion of toddlers with overweight at 1.5 years. Energy and added sugar intake had no significant effects. These findings add to the growing body of evidence that unhealthy dietary habits are formed even before formula weaning and that, along with improving early diet, transient rapid weight gain and parental feeding practices are modifiable determinants that may reduce risks for obesity.
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The Effect of High Glucose Intake on Weight Gain in Very Low Birth Weight Neonates: A Randomized Controlled Trial.
Choobdar, F, Mazouri, A, Firuzian, F, Ghasemzadeh, M, Vahedi, Z
Clinical pediatrics. 2021;(14):577-585
Abstract
This study aims at evaluating the effect of high glucose intake as a component of total parenteral nutrition on birth weight (BW) regain in very low birth weight neonates. Ninety newborns with BW <1500 g were randomized to control or experimental groups. Both groups received the same total parenteral nutrition regimens except glucose intake provided by dextrose water (DW) serum: 7 to 15 g/kg/d (10% DW) in the former versus 8.75 to 18.75 g/kg/d (12.5% DW) in the latter. Body weight as the primary outcome was monitored until the BW was regained. Results revealed that neonates who received 12.5% DW regained BW significantly faster (10.98 ± 2.46 vs 13.24 ± 4.03 days, P = .024) and needed lesser duration of respiratory support (5.34 ± 2.11 vs 7.17 ± 3.19 days, P = .003). As the proposed intervention can reduce neonatal intensive care unit admission duration, it mitigates risks of health care-associated infections, while favorably affecting the health economy.
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Effects of the Dual Endothelin Receptor Antagonist Aprocitentan on Body Weight and Fluid Homeostasis in Healthy Subjects on a High Sodium Diet.
Gueneau de Mussy, P, Sidharta, PN, Wuerzner, G, Maillard, MP, Guérard, N, Iglarz, M, Flamion, B, Dingemanse, J, Burnier, M
Clinical pharmacology and therapeutics. 2021;(3):746-753
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Abstract
Aprocitentan is a novel, oral, dual endothelin receptor antagonist (ERA) in development in difficult-to-control hypertension. As fluid retention and edema are concerns with ERAs, we investigated whether aprocitentan causes weight gain in healthy subjects on a high sodium diet and explored potential mechanisms if occurring. This double-blind, randomized, placebo-controlled, crossover study enrolled 28 subjects. Three doses of aprocitentan (10, 25, or 50 mg/day for 9 days) were compared with placebo. Increases in body weight were observed with aprocitentan (placebo-corrected mean weight gains [90% confidence interval]) of 0.43 [0.05-0.80], 0.77 [0.03-1.51], and 0.83 [0.33-1.32] kg at 10 mg, 25 mg, and 50 mg, respectively. Decreases in hemoglobin and uric acid were observed. Plasma volume increased at most by 5.5% without dose-response relationship. Urinary sodium excretion decreased at 10 mg and 25 mg but not at 50 mg. Therefore, aprocitentan produced moderate weight increases in healthy subjects on high sodium diet, without obvious sodium retention.
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Effect of pentoxifylline on colon cancer patients treated with chemotherapy (Part I).
Meirovitz, A, Baider, L, Peretz, T, Stephanos, S, Barak, V
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2021;(1):341-349
Abstract
BACKGROUND Cancer progression is associated with significant systemic clinical manifestations including cachexia induced weight loss and anorexia. Pentoxifylline (PTX) is a drug that has been shown to have multiple beneficial effects in cancer patients through its anti-inflammatory properties. MAIN OBJECTIVE To evaluate PTX effects on colon cancer patients treated with chemotherapy. PATIENTS AND METHODS Forty metastatic colon cancer patients receiving chemotherapy were enrolled in this randomized study. 17 patients were treated with a full dose of PTX (400 mg TID), 9 patients with a reduced dose PTX (200 mg TID) and 23 served as controls (no PTX). RESULTS Follow-up evaluations of patients included the following: physical examination; leukopenia determination; weight determination; stomatitis determination; and survival rate. Patients treated with PTX (both full and reduced doses), experienced a significant increase in weight and a reduction in stomatitis relative to the control group. Treatment with PTX also significantly increased patient survival rate. All patients treated with PTX, had a median overall survival (OS) rate of 20.4 months as compared to 13.2 months in the control group. CONCLUSIONS PTX treatment of colon cancer patients, in addition to chemotherapy, significantly improved survival rates, induced weight gain and reduced stomatitis occurrence -all important parameters of cachexia.
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Individualized target fortification of breast milk with protein, carbohydrates, and fat for preterm infants: A double-blind randomized controlled trial.
Rochow, N, Fusch, G, Ali, A, Bhatia, A, So, HY, Iskander, R, Chessell, L, El Helou, S, Fusch, C
Clinical nutrition (Edinburgh, Scotland). 2021;(1):54-63
Abstract
BACKGROUND & AIMS In preterm infants, natural variation of breast milk composition makes it difficult to achieve recommended macronutrient intakes with standard fortification. Evidence suggests that nutritional deficiency induces poor postnatal growth. This study investigates impacts of target fortification on preterm growth and metabolism by adjusting breast milk macronutrients. METHODS This study was conducted as a single-centre, double-blind, randomized controlled trial for infants <30 gestational weeks. The control group received standard fortification and the intervention group received standard plus target fortification adding modular protein, lipids, and carbohydrates. Breast milk content was measured 3x/week using a validated near-infrared bedside spectrometer (NIRS). Modulars were added to achieve recommended values. To assess total nutrient intake, all 2810 native breast milk samples were analyzed - protein and fat using bedside-NIRS, lactose using tandem mass spectrometry (UPLC-MS/MS). Body composition was measured using air displacement plethysmography. Primary outcome was weight gain during the first 21 days of intervention. RESULTS Baseline characteristics, morbidities, and total fluid intake were not different between groups (intervention n = 52, control n = 51). The intervention group infants had higher macronutrient intakes, weight gain (21.2 ± 2.5 vs 19.3 ± 2.4 g/kg/d, mean difference: 1.9 g/kg/d, 95% CI: 0.9 - 2.9), and body weight. Infants in the intervention group from mothers with below-average breast milk protein content showed greatest impact on weight at 36 weeks (2580 ± 280 g vs 2210 ± 300 g), length, head circumference, fat, and fat-free mass. Also, feeding intolerance was less frequent, blood urea was higher, and triglycerides were lower. CONCLUSIONS This study provides evidence that target fortification of breast milk with low macronutrient content enhances the quality of nutrition and growth and is feasible in clinical routine.
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Flexible vs. rigid dieting in resistance-trained individuals seeking to optimize their physiques: A randomized controlled trial.
Conlin, LA, Aguilar, DT, Rogers, GE, Campbell, BI
Journal of the International Society of Sports Nutrition. 2021;(1):52
Abstract
BACKGROUND The purpose of this study was to compare a flexible vs. rigid diet on weight loss and subsequent weight regain in resistance-trained (RT) participants in a randomized, parallel group design. METHODS Twenty-three males and females (25.6 ± 6.1 yrs; 170 ± 8.1 cm; 75.4 ± 10.3 kg) completed the 20-week intervention (consisting of a 10-week diet phase and a 10-week post-diet phase). Participants were randomized to a flexible diet (FLEX) comprised of non-specific foods or a rigid diet (RIGID) comprised of specific foods. Participants adhered to an ~20%kcal reduction during the first 10-weeks of the intervention and were instructed to eat ad libitum for the final 10-weeks. Body composition and resting metabolic rate were assessed 5 times: (baseline, 5, 10 [end of diet phase], 16, and 20 weeks). RESULTS During the 10-week diet phase, both groups significantly reduced bodyweight (FLEX: baseline = 76.1 ± 8.4kg, post-diet = 73.5 ± 8.8 kg, ▲2.6 kg; RIGID baseline = 74.9 ± 12.2 kg, post-diet = 71.9 ± 11.7 kg, ▲3.0 kg, p < 0.001); fat mass (FLEX: baseline = 14.8 ± 5.7 kg, post-diet = 12.5 ± 5.0 kg, ▲2.3 kg; RIGID baseline = 18.1 ± 6.2 kg, post-diet = 14.9 ± 6.5 kg, ▲3.2 kg p < 0.001) and body fat% (FLEX: baseline = 19.4 ± 8.5%, post-diet = 17.0 ± 7.1%, ▲2.4%; RIGID baseline = 24.0 ± 6.2%, post-diet = 20.7 ± 7.1%, ▲3.3%; p < 0.001). There were no significant differences between the two groups for any variable during the diet phase. During the post-diet phase, a significant diet x time interaction (p < 0.001) was observed for FFM with the FLEX group gaining a greater amount of FFM (+1.7 kg) in comparison with the RIGID group (-0.7 kg). CONCLUSIONS A flexible or rigid diet strategy is equally effective for weight loss during a caloric restriction diet in free-living, RT individuals. While post-diet FFM gains were greater in the FLEX group, there were no significant differences in the amount of time spent in resistance and aerobic exercise modes nor were there any significant differences in protein and total caloric intakes between the two diet groups. In the absence of a clear physiological rationale for increases in FFM, in addition to the lack of a standardized diet during the post-diet phase, we refrain from attributing the increases in FFM in the FLEX group to their diet assignment during the diet phase of the investigation. We recommend future research investigate additional physiological and psychological effects of flexible diets and weight regain in lean individuals.
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Changes in Cardiovascular Risk Factors Over 6 Years in Young Adults in a Randomized Trial of Weight Gain Prevention.
Wing, RR, Espeland, MA, Tate, DF, Perdue, LH, Bahnson, J, Polzien, K, Ferguson Robichaud, E, LaRose, JG, Gorin, AA, Lewis, CE, et al
Obesity (Silver Spring, Md.). 2020;(12):2323-2330
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Abstract
OBJECTIVE This study aimed to determine the impact of weight gain prevention interventions on changes in cardiovascular risk factors over 6 years. METHODS The Study of Novel Approaches to Weight Gain Prevention (SNAP) randomized 599 participants (ages 18-35; 46% with BMI 21-25; 54% with BMI 25-30) to Large Changes (produce buffer by losing 5-10 pounds initially), Small Changes (daily small changes in intake and activity) or Control and followed 355 participants with ongoing intervention and assessments through 6 years. RESULTS There were no significant differences among interventions for changes in weight or cardiovascular disease (CVD) risk factors from baseline to 6 years. However, 44% of participants gained ≥5%, and only 14% lost ≥5% over 6 years. Weight changes, from baseline to year 6, were significantly associated with changes in risk factors, especially insulin and high-density lipoprotein cholesterol. Earlier weight changes (e.g., weight cycling) had no beneficial or adverse effect on changes in CVD risk factors at 6 years, independent of 6-year weight changes. CONCLUSIONS Despite participation in a weight gain prevention trial, almost half of these young adults gained ≥5% or more over 6 years, with significant worsening in CVD risk factors. Greater attention to long-term weight gain prevention in young adults is needed.
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Impaired Metabolic Flexibility to High-Fat Overfeeding Predicts Future Weight Gain in Healthy Adults.
Begaye, B, Vinales, KL, Hollstein, T, Ando, T, Walter, M, Bogardus, C, Krakoff, J, Piaggi, P
Diabetes. 2020;(2):181-192
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Abstract
The ability to switch fuels for oxidation in response to changes in macronutrient composition of diet (metabolic flexibility) may be informative of individuals' susceptibility to weight gain. Seventy-nine healthy, weight-stable participants underwent 24-h assessments of energy expenditure and respiratory quotient (RQ) in a whole-room calorimeter during energy balance (EBL) (50% carbohydrate, 30% fat) and then during 24-h fasting and three 200% overfeeding diets in a crossover design. Metabolic flexibility was defined as the change in 24-h RQ from EBL during fasting and standard overfeeding (STOF) (50% carbohydrate, 30% fat), high-fat overfeeding (HFOF) (60% fat, 20% carbohydrate), and high-carbohydrate overfeeding (HCOF) (75% carbohydrate, 5% fat) diets. Free-living weight change was assessed after 6 and 12 months. Compared with EBL, RQ decreased on average by 9% during fasting and by 4% during HFOF but increased by 4% during STOF and by 8% during HCOF. A smaller decrease in RQ, reflecting a smaller increase in lipid oxidation rate, during HFOF but not during the other diets predicted greater weight gain at both 6 and 12 months. An impaired metabolic flexibility to acute HFOF can identify individuals prone to weight gain, indicating that an individual's capacity to oxidize dietary fat is a metabolic determinant of weight change.
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Evaluation of antenatal risk factors for postpartum depression: a secondary cohort analysis of the cluster-randomised GeliS trial.
Johar, H, Hoffmann, J, Günther, J, Atasoy, S, Stecher, L, Spies, M, Hauner, H, Ladwig, KH
BMC medicine. 2020;(1):227
Abstract
BACKGROUND Maternal weight variables are important predictors of postpartum depression (PPD). While preliminary evidence points to an association between pre-pregnancy obesity and PPD, the role of excessive gestational weight gain (GWG) on PPD is less studied. In this secondary cohort analysis of the German 'healthy living in pregnancy' (GeliS) trial, we aimed to investigate associations between weight-related variables and PPD and to assess the influence of GWG on the risk for PPD. METHODS We included women with normal weight, overweight, and obesity (BMI 18.5-40.0 kg/m2). Symptoms of PPD were assessed 6-8 weeks postpartum using the Edinburgh Postnatal Depression Scale. Pre-pregnancy BMI was self-reported. During the course of pregnancy, weight was measured at gynaecological practices within regular check-ups. GWG was defined as the difference between the last measured weight before delivery and the first measured weight at the time of recruitment (≤ 12th week of gestation). Excessive GWG was classified according to the Institute of Medicine. Multiple logistic regression analyses were used to estimate the odds of PPD in relation to pre-pregnancy BMI, GWG, and excessive GWG adjusting for important confounders. RESULTS Of the total 1583 participants, 45.6% (n = 722) showed excessive GWG and 7.9% (n = 138) experienced PPD. Pre-pregnancy BMI (per 5-unit increase; OR = 1.23, 95% CI 1.08-1.41, p = 0.002) and pre-pregnancy overweight or obesity were significantly positively associated with the odds of developing PPD, particularly among women with an antenatal history of anxiety or depressive symptoms (overweight: OR = 1.93, 95% CI = 1.15-3.22, p = 0.01; obesity: OR = 2.11, 95% CI = 1.13-3.96, p = 0.02). Sociodemographic or lifestyle factors did not additively influence the odds of having PPD. In fully adjusted models, there was no significant evidence that GWG or the occurrence of excessive GWG increased the odds of experiencing PPD (excessive vs. non-excessive: OR = 3.48, 95% CI 0.35-34.94; GWG per 1 kg increase: OR = 1.16, 95% CI 0.94-1.44). CONCLUSION Pre-pregnancy overweight or obesity is associated with PPD independent of concurrent risk factors. History of anxiety or depressive symptoms suggests a stress-induced link between pre-pregnancy weight and PPD. TRIAL REGISTRATION NCT01958307 , ClinicalTrials.gov, retrospectively registered on 9 October 2013.