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Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach.
Huang, JY, Cai, S, Huang, Z, Tint, MT, Yuan, WL, Aris, IM, Godfrey, KM, Karnani, N, Lee, YS, Chan, JKY, et al
Nature communications. 2021;(1):5613
Abstract
Assisted reproductive technologies (ART) are increasingly used, however little is known about the long-term health of ART-conceived offspring. Weak selection of comparison groups and poorly characterized mechanisms impede current understanding. In a prospective cohort (Growing Up in Singapore Towards healthy Outcomes; GUSTO; Clinical Trials ID: NCT01174875) including 83 ART-conceived and 1095 spontaneously-conceived singletons, we estimate effects of ART on anthropometry, blood pressure, serum metabolic biomarkers, and cord tissue DNA methylation by emulating a pragmatic trial supported by machine learning-based estimators. We find ART-conceived children to be shorter (-0.5 SD [95% CI: -0.7, -0.2]), lighter (-0.6 SD [-0.9, -0.3]) and have lower skinfold thicknesses (e.g. -14% [-24%, -3%] suprailiac), and blood pressure (-3 mmHg [-6, -0.5] systolic) at 6-6.5 years, with no strong differences in metabolic biomarkers. Differences are not explained by parental anthropometry or comorbidities, polygenic risk score, breastfeeding, or illnesses. Our simulations demonstrate ART is strongly associated with lower NECAB3 DNA methylation, with negative control analyses suggesting these estimates are unbiased. However, methylation changes do not appear to mediate observed differences in child phenotype.
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Weight gain velocity and adequate amount of nutrition for infants with congenital diaphragmatic hernia.
Terui, K, Tazuke, Y, Nagata, K, Ito, M, Okuyama, H, Hayakawa, M, Taguchi, T, Sato, Y, Usui, N
Pediatric surgery international. 2021;(2):205-212
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PURPOSE Growth retardation is a severe morbidity in infants with congenital diaphragmatic hernia (CDH). This study aimed to determine when catch-up growth starts in infants with CDH and to determine the adequate amount of nutrition required during catch-up growth. METHODS This was a multicenter retrospective cohort study involving neonates with isolated CDH (born 2006-2010; n = 98). Weight gain velocity (WGV) was calculated using body weight Z-scores. The minimum required weight gain was defined as WGV ≥ 0. Patients were dichotomized into severe and non-severe cases according to diaphragmatic defects. RESULTS Average monthly WGV changed from < 0 to ≥ 0 at 2 months of age. Total caloric intake at 2 months of age was lower when the WGV between 1 and 3 months was < 0 in both severe cases [122 (95% confidence interval (CI) 116-128) vs. 97 (95% CI 84-110) kcal/kg/day, p = 0.02] and non-severe cases [115 (95% CI 110-120) vs. 99 (95% CI 87-111) kcal/kg/day, p < 0.001)]. CONCLUSION Catch-up growth started at approximately 2 months of age. During this period, total caloric intake of > 122 kcal/kg/day was needed to avoid decreases in the body weight Z-score in severe cases.
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Excess body weight is an independent risk factor for severe forms of COVID-19.
Pietri, L, Giorgi, R, Bégu, A, Lojou, M, Koubi, M, Cauchois, R, Grangeot, R, Dubois, N, Kaplanski, G, Valéro, R, et al
Metabolism: clinical and experimental. 2021;:154703
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BACKGROUND AND AIMS Few studies distinguished the independent role of overweight/obesity or their associated-comorbidities in the evolution towards severe forms of COVID-19. Obesity as a unifying risk factor for severe COVID-19 is an emerging hypothesis. The aim of this study was to evaluate whether excessive body weight per se, was a risk factor for developing a severe form of COVID-19. PATIENTS AND METHODS We included 131 patients hospitalized for COVID-19 pneumonia in a single center of the internal medicine department in Marseille, France. We recorded anthropometric and metabolic parameters such as fasting glycaemia, insulinemia, HOMA-IR, lipids, and all clinical criteria linked to SARS-CoV-2 infection at the admission. Excess body weight was defined by a BMI ≥ 25 kg/m2. The occurrence of a serious event was defined as a high-debit oxygen requirement over 6 L/min, admission into the intensive care unit, or death. RESULTS Among 113 patients, two thirds (n = 76, 67%) had an excess body weight. The number of serious events was significantly higher in excess body weight patients compared to normal weight patients (respectively 25% vs 8%, p = 0.03) although excess body weight patients were younger (respectively 63.6 vs 70.3 years old, p = 0.01). In multivariate analyses, the excess body weight status was the only predictor for developing a serious event linked to SARS-CoV-2 infection, with an odds ratio at 5.6 (95% CI: 1.30-23.96; p = 0.02), independently of previous obesity associated comorbidities. There was a trend towards a positive association between the BMI (normal weight, overweight and obesity) and the risk of serious events linked to COVID-19, with a marked increase from 8.1% to 20% and 30.6% respectively (p = 0.05). CONCLUSION Excess body weight was significantly associated with severe forms of the disease, independently of its classical associated comorbidities. Physicians and specialists in Public Health must be sensitized to better protect people with an excess body weight against SARS-CoV-2 infection.
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Changes in Firefighter Weight and Cardiovascular Disease Risk Factors over Five Years.
Mathias, KC, Bode, ED, Stewart, DF, Smith, DL
Medicine and science in sports and exercise. 2020;(11):2476-2482
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PURPOSE This study aimed to assess changes in cardiovascular disease (CVD) risk factors in firefighters who lost, maintained, or gained weight over 5 yr. METHODS Anthropometrics and biomarkers of CVD were measured during two occupational medical exams 4.8 yr apart in 656 career firefighters. Weight change subgroups were loss (decrease of >3% body weight), stable (within ±3% body weight), and gain (increase of >3% body weight). Changes in CVD risk factors in the total sample and within weight change subgroups were tested for statistical significance using paired t-tests. RESULTS After 5 yr, 12% of the sample lost weight, 38% maintained weight, and 50% gained weight. Firefighters on average had significant increases (P < 0.001) in body weight (2.5 ± 0.2 kg), body mass index (0.8 ± 0.1 kg·m), total cholesterol (5.5 ± 1.4 mg·dL), LDL cholesterol (5.2 ± 1.2 mg·dL), and blood glucose (2.1 ± 0.5 mg·dL). Firefighters who gained weight (6.6 ± 0.2 kg) had significant increases (P < 0.001) in total cholesterol (12.9 ± 1.8 mg·dL), LDL cholesterol (11.1 ± 1.6 mg·dL), and blood glucose (2.9 ± 0.7 mg·dL) with a significant decrease (P ≤ 0.01) in HDL cholesterol (-1.3 ± 0.4 mg·dL). Firefighters who lost weight (-7.2 ± 0.5 kg) had significant decreases (P < 0.05) in total cholesterol (-8.5 ± 3.9 mg·dL), LDL cholesterol (-6.7 ± 3.3 mg·dL), and blood pressure (systolic: -5.3 ± 1.3 mm Hg; diastolic -4.2 ± 1.0 mm Hg) with a significant increase (P < 0.05) in HDL cholesterol (2.3 ± 1.0 mg·dL). CONCLUSIONS Although improvements in cardiovascular health among firefighters who lost weight were found, 50% of the sample gained weight with adverse changes in measures of cardiovascular health. Given that sudden cardiac death is the most common cause of duty-related death among firefighters, with increased risk among obese firefighters, the amount of weight gain and the adverse changes in cardiovascular health suggest the need for improvements in health promotion programs for firefighters in the United States.
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The contribution of ascitic fluid to body weight in patients with liver cirrhosis, and its estimation using girth: a cross-sectional observational study.
Lamarti, E, Hickson, M
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2020;(3):404-413
Abstract
BACKGROUND There is a high prevalence of malnutrition among people with decompensated liver disease. Standard nutritional screening tools use weight and body mass index (BMI) to identify risk, although these are difficult to measure for those with ascites, often secondary to liver cirrhosis. Dietetic guidance suggests adjusting for ascitic weight by 2.2-14 kg, although there is a lack of evidence to substantiate these values. The present study aimed to measure the contribution of ascitic fluid weight and compare this with the current guidance, as well as to examine whether girth circumference can be used to estimate ascitic weight. METHODS A cross-sectional, observational study was conducted over 13 weeks. Participants attending for paracentesis were weighed, their girths measured, and BMI was calculated pre- and post-paracentesis. Fluid removed via paracentesis was recorded. Ethical approval was received (IRAS project ID: 218747). RESULTS Eighteen participants underwent paracentesis. The range of ascitic fluid drained was 3.8-19 L [mean (SD) = 8.7 (3.7) L]. Weight difference between pre- and post-paracentesis was in the range 4.5-20 kg [mean (SD) = 8.7 (3.9) kg]. Ascitic fluid weight is shown to be higher in each category (minimal, moderate, severe ascites) than the current guidance values. Weight difference was greater than 14 kg in 11% (n = 2) of participants. A strong, statistically significant relationship (rho = 0.68, P ≤ 0.01) between ascitic weight and pre-paracentesis girth was found. An equation was formulated to enable the estimation of ascitic fluid from pre-paracentesis girth. CONCLUSIONS Current dietetic guidance should be re-evaluated to reflect the greater weight differences identified. Measuring girth pre-paracentesis may help to inform dry weight estimation. Further research is required to verify the accuracy of estimating ascitic weight from pre-paracentesis girth.
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Relationship between sensory liking for fat, sweet or salt and cardiometabolic diseases: mediating effects of diet and weight status.
Lampuré, A, Adriouch, S, Castetbon, K, Deglaire, A, Schlich, P, Péneau, S, Fezeu, L, Hercberg, S, Méjean, C
European journal of nutrition. 2020;(1):249-261
Abstract
PURPOSE Previous works have been suggested that individual sensory liking is a predictor of dietary intake and weight status, and may consequently influence development of cardiometabolic diseases (CMDs). We investigated the association between sensory liking for fat-and-salt, fat-and-sweet, sweet or salt and the onset of hypertension, diabetes and cardiovascular diseases (CVDs) over 6 years in adults, and the mediating effects of dietary intake and body mass index (BMI). METHODS We examined the CMDs risk among 41,332 (for CVD and diabetes) and 37,936 (for hypertension) French adults (NutriNet-Santé cohort). Liking scores, individual characteristics, diet and anthropometry were assessed at baseline using questionnaires. Health events were collected during 6 years. Associations between sensory liking and CMDs risk, and the mediating effect of diet and BMI, were assessed using Cox proportional hazards models. RESULTS Sensory liking for fat-and-salt was associated with an increased risk of diabetes, hypertension and CVD [hazard ratios (HR) for 1-point increment of the sensory score: HR 1.30 (95% CI 1.18, 1.43), HR 1.08 (1.04, 1.13) and HR 1.10 (1.02, 1.19), respectively]. BMI and dietary intake both explained 93%, 98% and 70%, of the overall variation of liking for fat-and-salt liking in diabetes, hypertension and CVD, respectively. Liking for fat-and-sweet and liking for salt were also associated with an increased risk of diabetes [HR 1.09 (1.01, 1.17) and HR 1.09 (1.01, 1.18), respectively], whereas liking for sweet was associated with a decreased risk [HR 0.76 (0.69, 0.84)]. CONCLUSIONS Higher liking for fat-and-salt is significantly associated with CMDs risk, largely explained by dietary intake and BMI. Our findings may help to guide effective targeted measures in prevention.
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Outcomes in a digital weight management intervention with one-on-one health coaching.
Silberman, JM, Kaur, M, Sletteland, J, Venkatesan, A
PloS one. 2020;(4):e0232221
Abstract
BACKGROUND Some guidelines state that in-person weight management interventions are more efficacious than those delivered digitally. However, digital programs are more scalable and accessible. We hypothesized that one-on-one health coaching via app-based video chat would simulate an in-person experience and help achieve outcomes comparable to those of in-person interventions. METHODS A 12-month digital weight management intervention was provided to overweight or obese adults recruited from a large technology company. One-on-one health coaching sessions were offered during a 24-week intensive phase as well as subsequent maintenance phase. Focused on sustainable changes in activity and diet, the intervention incorporates SMART goals, in-app food and activity logs, Fitbit integration, as well as optional sleep and stress modules. Self-Determination Theory and the Transtheoretical Model are incorporated to drive behavior change. Multilevel mixed-effects models were used to analyze weight changes retrospectively. RESULTS Six hundred eighty-three participants reported 29,051 weights. At 12 months, mean percent changes in body weight were -7.2% and -7.6% for overweight and obese groups, respectively. A weight change of -5% is commonly targeted for in-person weight management interventions. Observed weight loss exceeded this target by 2.2% (95% CI, 0.7% to 3.8%; P < .01) for the overweight group and 2.6% (95% CI, 1.4% to 3.9%; P < .01) for the obese group. CONCLUSIONS Further research is needed with randomization to in-person or digital interventions. Though limited by an observational, retrospective design, preliminary results suggest that some digital weight management programs with one-on-one coaching may achieve outcomes comparable to those of robust, in-person interventions.
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Body weight changes and incidence of cachexia after stroke.
Scherbakov, N, Pietrock, C, Sandek, A, Ebner, N, Valentova, M, Springer, J, Schefold, JC, von Haehling, S, Anker, SD, Norman, K, et al
Journal of cachexia, sarcopenia and muscle. 2019;(3):611-620
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BACKGROUND Body weight loss is a frequent complication after stroke, and its adverse effect on clinical outcome has been shown in several clinical trials. The purpose of this prospective longitudinal single-centre observational study was to investigate dynamical changes of body composition and body weight after ischemic stroke and an association with functional outcome. METHODS Sixty-seven consecutive patients (age 69 ± 11 years, body mass index 27.0 ± 4.1 kg/m2 , 42% female patient, mean ± SD) with acute ischemic stroke with mild to moderate neurological deficit (National Institute of Health Stroke Scale median 4, ranged 0-12) were analysed in the acute phase (4 ± 2 days) and at 12 months (389 ± 26 days) follow-up. Body composition was examined by dual energy X-ray absorptiometry. Cachexia was defined according to the consensus definition by body weight loss ≥5% within 1 year and additional clinical signs. Lean tissue wasting was considered if a ratio of upper and lower limbs lean mass sum to squared height (kg/m2 ) was ≤5.45 kg/m2 for female patient and ≤7.25 kg/m2 for male patient. RESULTS According to the body weight changes after 12 months, 42 (63%) patients had weight gain or stable weight, 11 (16%) patients had moderate weight loss, and 14 (21%) patients became cachectic. A relative decline of 19% of fat tissue and 6.5% of lean tissue was observed in cachectic patients, while no changes of lean tissue were observed in non-cachectic patients after 12 months. The modified Rankin Scale was 48% higher (2.1 ± 1.6, P < 0.05), Barthel Index was 22% lower (71 ± 39, P < 0.01), and handgrip strength was 34% lower (21.9 ± 13.0, P < 0.05) in cachectic compared to non-cachectic patients after 12 months. The low physical performance if defined by Barthel Index <60 points was linked to the lean tissue wasting (OR 44.8, P < 0.01), presence of cachexia (OR 20.8, P < 0.01), and low body mass index <25 kg/m2 (OR 11.5, P < 0.05). After adjustment for cofounders, lean tissue wasting remained independently associated with the low physical performance at 12 months follow-up (OR 137.9, P < 0.05). CONCLUSIONS In this cohort study, every fifth patient with ischemic stroke fulfilled the criteria of cachexia within 12 months after index event. The incidence of cachexia was 21%. Cachectic patients showed the lowest functional and physical capacity.
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Longitudinal Phenotypes of Type 1 Diabetes in Youth Based on Weight and Glycemia and Their Association With Complications.
Kahkoska, AR, Nguyen, CT, Adair, LA, Aiello, AE, Burger, KS, Buse, JB, Dabelea, D, Dolan, LM, Malik, FS, Mottl, AK, et al
The Journal of clinical endocrinology and metabolism. 2019;(12):6003-6016
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CONTEXT Subclinical and clinical complications emerge early in type 1 diabetes (T1D) and may be associated with obesity and hyperglycemia. OBJECTIVE Test how longitudinal "weight-glycemia" phenotypes increase susceptibility to different patterns of early/subclinical complications among youth with T1D. DESIGN SEARCH for Diabetes in Youth observational study. SETTING Population-based cohort. PARTICIPANTS Youth with T1D (n = 570) diagnosed 2002 to 2006 or 2008. MAIN OUTCOME MEASURES Participants were clustered based on longitudinal body mass index z score and HbA1c from a baseline visit and 5+ year follow-up visit (mean diabetes duration: 1.4 ± 0.4 years and 8.2 ± 1.9 years, respectively). Logistic regression modeling tested cluster associations with seven early/subclinical diabetes complications at follow-up, adjusting for sex, race/ethnicity, age, and duration. RESULTS Four longitudinal weight-glycemia clusters were identified: The Referent Cluster (n = 195, 34.3%), the Hyperglycemia Only Cluster (n = 53, 9.3%), the Elevated Weight Only Cluster (n = 206, 36.1%), and the Elevated Weight With Increasing Hyperglycemia (EWH) Cluster (n = 115, 20.2%). Compared with the Referent Cluster, the Hyperglycemia Only Cluster had elevated odds of dyslipidemia [adjusted odds ratio (aOR) 2.22, 95% CI: 1.15 to 4.29], retinopathy (aOR 9.98, 95% CI: 2.49 to 40.0), and diabetic kidney disease (DKD) (aOR 4.16, 95% CI: 1.37 to 12.62). The EWH Cluster had elevated odds of hypertension (aOR 2.18, 95% CI: 1.19 to 4.00), dyslipidemia (aOR 2.36, 95% CI: 1.41 to 3.95), arterial stiffness (aOR 2.46, 95% CI: 1.09 to 5.53), retinopathy (aOR 5.11, 95% CI: 1.34 to 19.46), and DKD (aOR 3.43, 95% CI: 1.29 to 9.11). CONCLUSIONS Weight-glycemia phenotypes show different patterns of complications, particularly markers of subclinical macrovascular disease, even in the first decade of T1D.
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Safety and efficacy of tofogliflozin in Japanese patients with type 2 diabetes mellitus in real-world clinical practice: Results of 3-month interim analysis of a long-term post-marketing surveillance study (J-STEP/LT).
Utsunomiya, K, Senda, M, Kakiuchi, S, Kameda, H, Tamura, M, Kurihara, Y, Gunji, R, Fujii, S, Fujiwara, H, Kaku, K
Journal of diabetes investigation. 2019;(5):1272-1283
Abstract
AIMS/INTRODUCTION The present study analysis was carried out to evaluate the safety and efficacy of tofogliflozin, a sodium-glucose cotransporter 2 inhibitor, in Japanese patients with type 2 diabetes mellitus in real-world clinical practice. MATERIALS AND METHODS This was a 3-year non-interventional observational study of patients with type 2 diabetes mellitus newly administered tofogliflozin who were uncontrolled on current therapy. We carried out a 12-week interim analysis of tofogliflozin as part of 3-year post-marketing surveillance study. The incidence of adverse drug reactions was evaluated as a safety end-point. As efficacy end-points, glycated hemoglobin and bodyweight were evaluated. RESULTS A total of 6,897 patients were enrolled. Tofogliflozin significantly reduced mean changes from baseline glycated hemoglobin (-0.63%, P < 0.0001) and bodyweight (-2.02 kg, P < 0.0001). The change in glycated hemoglobin and bodyweight reductions in response to tofogliflozin was consistently observed in all body mass index subgroups. Adverse drug reactions occurred in 345 of 6,712 patients (5.14%). There was a low incidence of adverse drug reactions known to be associated with sodium-glucose cotransporter 2 inhibitors, and they were reported as non-serious. The incidences of polyuria/pollakiuria were higher in patients aged ≥65 years than <65 years, and were significantly different among estimated glomerular filtration rate subgroups. Urinary tract and genital infections occurred more frequently in women than in men. CONCLUSIONS Tofogliflozin was well tolerated, and no emerging new safety concerns were observed. Tofogliflozin significantly improved glycemic control with no impact on bodyweight gain. The short-term administration of tofogliflozin is considered to have a favorable benefit-risk profile in Japanese patients with type 2 diabetes mellitus.