-
1.
Decline in HbA1c during the first year of elexacaftor/tezacaftor/ivacaftor treatment in the Danish cystic fibrosis cohort: Short title: Decline in HbA1c after elexacaftor/tezacaftor/ivacaftor treatment.
Nielsen, BU, Olsen, MF, Mabuza Mathiesen, IH, Pressler, T, Ritz, C, Katzenstein, TL, Olesen, HV, Skov, M, Jensen-Fangel, S, Almdal, TP, et al
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2024;(1):103-108
Abstract
BACKGROUND Elexacaftor/tezacaftor/ivacaftor (ETI) has improved the clinical status of individuals with cystic fibrosis (CF), however, whether ETI impacts glucose tolerance remains unknown. We aimed to study the change in glycated hemoglobin (HbA1c) and CF related diabetes (CFRD) status after initiation of ETI. METHODS We included individuals ≥12 years treated with ETI in Denmark in a longitudinal observational study. HbA1c was measured at baseline, 3, 6, 9 and 12 months after treatment initiation. Change in HbA1c was assessed in mixed models adjusted for age, sex, glucose tolerance and prior CFTR modulator treatment. In a sub-population with CFRD, we assessed the change in insulin usage, hypoglycemic events and the 30-day continuous glucose monitoring (CGM) parameters (i.e., average blood glucose, time below (≤3.9 mM) and above (>10.0 mM) normal range, and the variation in glucose) after 12 months of treatment. RESULTS Among 321 individuals with CF, HbA1c declined by 2.1 mmol/mol [95 % confidence interval (CI): -2.6; -1.5 mmol/mol] after 3 months and by 2.3 mmol/mol [95 %CI: -2.8; -1.9 mmol/mol] after 12 months of ETI treatment. The decline was independent of glucose tolerance status at baseline. In 26 individuals with CFRD at baseline, the mean decline in HbA1c was 3.6 mmol/mol [95 %CI: -6.9; -0.4 mmol/mol] after 12 months, but we did not observe any change in insulin usage, weekly number of hypoglycemic events or CGM parameters. CONCLUSION In the Danish CF cohort, HbA1c declined over 12 months of ETI treatment, however, among a subset with CFRD, we observed no change in insulin usage and CGM glucose levels.
-
2.
Effect of lipid-based nutrient supplements on micronutrient status and hemoglobin among children with stunting: secondary analysis of a randomized controlled trial in Uganda.
Mutumba, R, Pesu, H, Mbabazi, J, Greibe, E, Nexo, E, Olsen, MF, Briend, A, Mølgaard, C, Michaelsen, KF, Ritz, C, et al
The American journal of clinical nutrition. 2024;(3):829-837
Abstract
BACKGROUND Micronutrient deficiencies and anemia are widespread among children with stunting. OBJECTIVES We assessed the effects of lipid-based nutrient supplements (LNS) containing milk protein (MP) and/or whey permeate (WP) on micronutrient status and hemoglobin (Hb) among children with stunting. METHODS This was a secondary analysis of a randomized controlled trial. Children aged 12-59 mo with stunting were randomly assigned to LNS (100 g/d) with milk or soy protein and WP or maltodextrin for 12 wk, or no supplement. Hb, serum ferritin (S-FE), serum soluble transferrin receptor (S-TfR), plasma cobalamin (P-Cob), plasma methylmalonic acid (P-MMA), plasma folate (P-Fol), and serum retinol-binding protein (S-RBP) were measured at inclusion and at 12 wk. Data were analyzed using linear and logistic mixed-effects models. RESULTS Among 750 children, with mean age ± SD of 32 ± 11.7 mo, 45% (n = 338) were female and 98% (n = 736) completed follow-up. LNS, compared with no supplementation, resulted in 43% [95% confidence interval (CI): 28, 60] greater increase in S-FE corrected for inflammation (S-FEci), 2.4 (95% CI: 1.2, 3.5) mg/L greater decline in S-TfR, 138 (95% CI: 111, 164) pmol/L greater increase in P-Cob, 33% (95% CI: 27, 39) reduction in P-MMA, and 8.5 (95% CI: 6.6, 10.3) nmol/L greater increase in P-Fol. There was no effect of LNS on S-RBP. Lactation modified the effect of LNS on markers of cobalamin status, reflecting improved status among nonbreastfed and no effects among breastfed children. LNS increased Hb by 3.8 (95% CI: 1.7, 6.0) g/L and reduced the odds of anemia by 55% (odds ratio: 0.45, 95% CI: 0.29, 0.70). MP compared with soy protein increased S-FEci by 14% (95% CI: 3, 26). CONCLUSIONS LNS supplementation increases Hb and improves iron, cobalamin, and folate status, but not vitamin A status among children with stunting. LNS should be considered for children with stunting. This trial was registered at ISRCTN as 13093195.
-
3.
Effect of milk protein and whey permeate in large quantity lipid-based nutrient supplement on linear growth and body composition among stunted children: A randomized 2 × 2 factorial trial in Uganda.
Mbabazi, J, Pesu, H, Mutumba, R, Filteau, S, Lewis, JI, Wells, JC, Olsen, MF, Briend, A, Michaelsen, KF, Mølgaard, C, et al
PLoS medicine. 2023;(5):e1004227
Abstract
BACKGROUND Despite possible benefits for growth, milk is costly to include in foods for undernourished children. Furthermore, the relative effects of different milk components, milk protein (MP), and whey permeate (WP) are unclear. We aimed to assess the effects of MP and WP in lipid-based nutrient supplement (LNS), and of LNS itself, on linear growth and body composition among stunted children. METHODS AND FINDINGS We performed a randomized, double-blind, 2 × 2 factorial trial among 12 to 59 months old stunted children in Uganda. Children were randomized to 4 formulations of LNS with MP or soy protein isolate and WP or maltodextrin (100 g/day for 12 weeks) or no supplementation. Investigators and outcome assessors were blinded; however, participants were only blinded to the ingredients in LNS. Data were analyzed based on intention-to-treat (ITT) using linear mixed-effects models adjusted for age, sex, season, and site. Primary outcomes were change in height and knee-heel length, and secondary outcomes included body composition by bioimpedance analysis (ISRCTN13093195). Between February and September 2020, we enrolled 750 children with a median age of 30 (interquartile range 23 to 41) months, with mean (± standard deviation) height-for-age z-score (HAZ) -3.02 ± 0.74 and 12.7% (95) were breastfed. The 750 children were randomized to LNS (n = 600) with or without MP (n = 299 versus n = 301) and WP (n = 301 versus n = 299), or no supplementation (n = 150); 736 (98.1%), evenly distributed between groups, completed 12-week follow-up. Eleven serious adverse events occurred in 10 (1.3%) children, mainly hospitalization with malaria and anemia, all deemed unrelated to the intervention. Unsupplemented children had 0.06 (95% confidence interval, CI [0.02, 0.10]; p = 0.015) decline in HAZ, accompanied by 0.29 (95% CI [0.20, 0.39]; p < 0.001) kg/m2 increase in fat mass index (FMI), but 0.06 (95% CI [-0.002; 0.12]; p = 0.057) kg/m2 decline in fat-free mass index (FFMI). There were no interactions between MP and WP. The main effects of MP were 0.03 (95% CI [-0.10, 0.16]; p = 0.662) cm in height and 0.2 (95% CI [-0.3, 0.7]; p = 0.389) mm in knee-heel length. The main effects of WP were -0.08 (95% CI [-0.21, 0.05]; p = 220) cm and -0.2 (95% CI [-0.7; 0.3]; p = 403) mm, respectively. Interactions were found between WP and breastfeeding with respect to linear growth (p < 0.02), due to positive effects among breastfed and negative effects among non-breastfed children. Overall, LNS resulted in 0.56 (95% CI [0.42, 0.70]; p < 0.001) cm height increase, corresponding to 0.17 (95% CI [0.13, 0.21]; p < 0.001) HAZ increase, and 0.21 (95% CI [0.14, 0.28]; p < 0.001) kg weight increase, of which 76.5% (95% CI [61.9; 91.1]) was fat-free mass. Using height-adjusted indicators, LNS increased FFMI (0.07 kg/m2, 95% CI [0.0001; 0.13]; p = 0.049), but not FMI (0.01 kg/m2, 95% CI [-0.10, 0.12]; p = 0.800). Main limitations were lack of blinding of caregivers and short study duration. CONCLUSIONS Adding dairy to LNS has no additional effects on linear growth or body composition in stunted children aged 12 to 59 months. However, supplementation with LNS, irrespective of milk, supports linear catch-up growth and accretion of fat-free mass, but not fat mass. If left untreated, children already on a stunting trajectory gain fat at the expense of fat-free mass, thus nutrition programs to treat such children should be considered. TRIAL REGISTRATION ISRCTN13093195.
-
4.
Effects of Mindful Eating and YogaDance among Overweight and Obese Women: An Exploratory Randomized Controlled Trial.
Henninger, SH, Fibieger, AY, Magkos, F, Ritz, C
Nutrients. 2023;(7)
Abstract
Many current treatment options for managing overweight and obesity consist of rather strict diet and exercise regimes that are difficult to implement as a lifelong routine. Therefore, alternative initiatives such as mindful eating and pleasure-oriented physical activity with more focus on implementation and enjoyment are needed to reverse the obesity epidemic. Mindful eating is an approach focusing on inner hunger and satiety signals. YogaDance is a novel exercise approach combining elements of yoga and dance. This study was a randomized controlled trial investigating the individual and combined effects of mindful eating and YogaDance. Participants were healthy, inactive women with overweight or obesity (body mass index ≥ 25 kg/m2 and/or waist circumference ≥ 80 cm) who were randomized to one of four groups for 8 weeks: mindful eating alone, YogaDance alone, the combination of mindful eating and YogaDance, or control. Fat mass was the primary outcome and secondary outcomes included body weight, waist circumference, and other physiological, behavioral, and quality-of-life outcomes. Sixty-one women were included in the study and randomized to mindful eating and YogaDance combined, YogaDance, mindful eating, or control. Fat mass was reduced by 1.3 kg (95% CI [-10.0, 7.3] kg; p = 0.77), 3.0 kg (95% CI [-11.1, 5.1] kg; p = 0.48), and 1.8 kg (95% CI [-10.1, 6.6] kg; p = 0.69) for the mindful eating, YogaDance, and combined mindful eating and YogaDance interventions, respectively, compared to the control, with corresponding effect sizes of 0.15, 0.34, and 0.21. In complete-case analyses, fat percent and waist circumference were reduced whereas mental quality of life and eating behavior were improved for mindful eating and mindful eating and YogaDance combined compared to the control. In conclusion, the study found modest benefits of an 8-week combination of mindful eating and YogaDance, corroborating findings in previous studies on mindful eating, yoga, and dance. However, the study had several limitations that should be taken into consideration, including low power due to a large drop-out as well as low to moderate training load and compliance. The trial was retrospectively registered (ISRCTN87234794).
-
5.
Associations between Stunting, Wasting and Body Composition: A Longitudinal Study in 6- to 15-Month-Old Kenyan Children.
Konyole, SO, Omollo, SA, Kinyuru, JN, Owuor, BO, Estambale, BB, Ritz, C, Michaelsen, KF, Filteau, SM, Wells, JC, Roos, N, et al
The Journal of nutrition. 2023;(4):970-978
Abstract
BACKGROUND Early growth and body composition may influence the risk of obesity and health in adulthood. Few studies have examined how undernutrition is associated with body composition in early life. OBJECTIVES We assessed stunting and wasting as correlates of body composition in young Kenyan children. METHODS Nested in a randomized controlled nutrition trial, this longitudinal study assessed fat and fat-free mass (FM, FFM) using deuterium dilution technique among children at age 6 and 15 months. This trial was registered at http://controlled-trials.com/ (ISRCTN30012997). Cross-sectional and longitudinal associations between z-score categories of length-for-age (LAZ) or weight-for-length (WLZ) and FM, FFM, fat mass index (FMI), fat-free mass index (FFMI), triceps, and subscapular skinfolds were analyzed by linear mixed models. RESULTS Among the 499 children enrolled, breastfeeding declined from 99% to 87%, stunting increased from 13% to 32%, and wasting remained at 2% to 3% between 6 and 15 mo. Compared with LAZ >0, stunted children had a 1.12 kg (95% CI: 0.88, 1.36; P < 0.001) lower FFM at 6 mo and increased to 1.59 kg (95% CI: 1.25, 1.94; P < 0.001) at 15 mo, corresponding to differences of 18% and 17%, respectively. When analyzing FFMI, the deficit in FFM tended to be less than proportional to children's height at 6 mo (P ≤ 0.060) but not at 15 mo (P > 0.40). Stunting was associated with 0.28 kg (95% CI: 0.09, 0.47; P = 0.004) lower FM at 6 mo. However, this association was not significant at 15 mo, and stunting was not associated with FMI at any time point. A lower WLZ was generally associated with lower FM, FFM, FMI, and FFMI at 6 and 15 mo. Differences in FFM, but not FM, increased with time, whereas FFMI differences did not change, and FMI differences generally decreased with time. CONCLUSIONS Overall, low LAZ and WLZ among young Kenyan children were associated with reduced lean tissue, which may have long-term health consequences.
-
6.
Multidimensional individualized nutritional therapy for individuals with severe chronic obstructive pulmonary disease: study protocol for a registry-based randomized controlled trial.
Hegelund, MH, Ritz, C, Nielsen, TL, Olsen, MF, Søborg, C, Braagaard, L, Mølgaard, C, Krogh-Madsen, R, Lindegaard, B, Faurholt-Jepsen, D
Trials. 2023;(1):86
Abstract
BACKGROUND Individuals with severe chronic obstructive pulmonary disease (COPD) are often at risk of undernutrition with low health-related quality of life (HRQoL). Undernutrition can worsen COPD and other comorbidities, be an independent predictor of morbidity and functional decline resulting in increased healthcare consumption and increased risk of death. Especially exacerbations and acute infections result in unintentional weight loss. The aim is to investigate the effect of an individualized nutritional intervention among individuals with severe COPD. METHODS An open-label randomized controlled trial with two parallel groups. Participants are recruited from the pulmonary outpatient clinic at the Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital, North Zealand, Denmark, and randomly allocated to either the intervention (intervention + standard of care) or control group (standard of care). The intervention has a duration of 3 months and combines individual nutritional care with adherence support and practical tools. It contains 4 elements including an individual nutritional plan, regular contacts, adherence support, and weight diary. The primary outcome is a difference in HRQoL (EQ-5D-5L) between the intervention and control group 3 months after baseline. Difference in functional capacity (grip strength, 30-s stand chair test, and physical activity), disease-specific quality of life (COPD Assessment Test), anxiety and depression (Hospital Anxiety and Depression Scale), nutritional parameters (energy and protein intake), anthropometry (weight, body mass index, waist, hip, and upper arm circumference), body composition (total fat-free and fat mass and indices), and prognosis (exacerbations, oxygen therapy, hospital contacts, and mortality) 3 months after baseline will be included as secondary outcomes. Data will be collected through home visits at baseline and 1 and 3 months after baseline. DISCUSSION Currently, nutritional care is a neglected area of outpatient care among individuals with severe COPD. If this patient-centered approach can demonstrate a positive impact on HRQoL, mortality, and hospital contacts, it should be recommended as part of end-of-life care for individuals with severe COPD. TRIAL REGISTRATION ClinicalTrials.gov NCT04873856 . Registered on May 3, 2021.
-
7.
Individual participant data (IPD)-level meta-analysis of randomised controlled trials to estimate the vitamin D dietary requirements in dark-skinned individuals resident at high latitude.
Cashman, KD, Kiely, ME, Andersen, R, Grønborg, IM, Tetens, I, Tripkovic, L, Lanham-New, SA, Lamberg-Allardt, C, Adebayo, FA, Gallagher, JC, et al
European journal of nutrition. 2022;(2):1015-1034
-
-
Free full text
-
Abstract
CONTEXT AND PURPOSE There is an urgent need to develop vitamin D dietary recommendations for dark-skinned populations resident at high latitude. Using data from randomised controlled trials (RCTs) with vitamin D3-supplements/fortified foods, we undertook an individual participant data-level meta-regression (IPD) analysis of the response of wintertime serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among dark-skinned children and adults residing at ≥ 40° N and derived dietary requirement values for vitamin D. METHODS IPD analysis using data from 677 dark-skinned participants (of Black or South Asian descent; ages 5-86 years) in 10 RCTs with vitamin D supplements/fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D intake estimates across a range of 25(OH)D thresholds. RESULTS To maintain serum 25(OH)D concentrations ≥ 25 and 30 nmol/L in 97.5% of individuals, 23.9 and 27.3 µg/day of vitamin D, respectively, were required among South Asian and 24.1 and 33.2 µg/day, respectively, among Black participants. Overall, our age-stratified intake estimates did not exceed age-specific Tolerable Upper Intake Levels for vitamin D. The vitamin D intake required by dark-skinned individuals to maintain 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L was 66.8 µg/day. This intake predicted that the upper 2.5% of individuals could potentially achieve serum 25(OH)D concentrations ≥ 158 nmol/L, which has been linked to potential adverse effects in older adults in supplementation studies. CONCLUSIONS Our IPD-derived vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25, 30 and 50 nmol/L are substantially higher than the equivalent estimates for White individuals. These requirement estimates are also higher than those currently recommended internationally by several agencies, which are based predominantly on data from Whites and derived from standard meta-regression based on aggregate data. Much more work is needed in dark-skinned populations both in the dose-response relationship and risk characterisation for health outcomes. TRAIL REGISTRATION PROSPERO International Prospective Register of Systematic Reviews (Registration Number: CRD42018097260).
-
8.
Sample size calculations for continuous outcomes in clinical nutrition.
Ritz, C, Olsen, MF, Grenov, B, Friis, H
European journal of clinical nutrition. 2022;(12):1682-1689
Abstract
In nutrition research, sample size calculations for continuous outcomes are important for the planning phase of many randomized trials and could also be relevant for some observational studies such as cohort and cross-sectional studies. However, only little literature dedicated to this topic exists within nutritional science. This article reviews the most common methods for sample size calculations in nutrition research. Approximate formulas are used for explaining concepts and requirements and for working through examples from the literature. Sample size calculations for the various study designs, which are covered, may all be seen as extensions of the sample size calculation for the basic two-group comparison through the application of suitable scaling factors and, possibly, modification of the significance level. The latter is needed for sample size calculations for multi-group designs and designs involving multiple primary outcomes. Like cluster-randomized designs, these types of study designs may be more challenging than standard sample size calculations. In such non-standard scenarios, there may be a need for consulting a biostatistician. Finally, it should be stressed that there may be many ways to plan a study. The final sample size calculation provided for a grant applicant, study protocol, or publication will often not only depend on considerations and input information as described in this article but will also involve restrictions in terms of logistics and/or resources.
-
9.
Vitamin D biomarkers for Dietary Reference Intake development in children: a systematic review and meta-analysis.
Cashman, KD, Ritz, C, Carlin, A, Kennedy, M
The American journal of clinical nutrition. 2022;(2):544-558
-
-
Free full text
-
Abstract
BACKGROUND Circulating 25-hydroxyvitamin D [25(OH)D] has been the accepted vitamin D exposure/intake biomarker of choice within recent DRI exercises, but use of other vitamin D-related biomarkers as well as functional markers has been suggested. These may be of value in future vitamin D DRI exercises, such as the FAO/WHO's one for young children. OBJECTIVES To systematically review the usefulness of circulating 25(OH)D, parathyroid hormone (PTH), free and bioavailable 25(OH)D, C3-epimer of 25(OH)D, vitamin D3, 24,25-dihydroxyvitamin D [24,25(OH)2D], and bone turnover markers and calcium absorption as vitamin D biomarkers for DRI development in children. METHODS Methods included structured searches of published articles, full-text reviews, data extraction, quality assessment, meta-analysis, and random-effects meta-regression. RESULTS Fifty-nine vitamin D supplementation randomized controlled trials (RCTs) were included (39 in infants/children as the priority group and the remainder in adults since pediatric studies were absent/limited). Vitamin D supplementation significantly raised circulating 25(OH)D in infants and children, but the response was highly heterogeneous [weighted mean difference (WMD): 27.7 nmol/L; 95% CI: 22.9, 32.5; 27 RCTs; I2 = 93%]. Meta-regression suggested an increase by 1.7 nmol/L (95% CI: 0.7, 2.6) in serum 25(OH)D per each 100-IU increment in vitamin D intake (P = 0.0005). Vitamin D supplementation had a significant effect on circulating 24,25(OH)2D (WMD: 3.4 nmol/L; 95% CI: 2.4, 4.5; 13 RCTs; I2 = 95%), with a dose-response relation (+0.15 nmol/L per 100 IU; 95% CI: -0.01, 0.29). With circulating PTH, although there was a significant effect of vitamin D on WMD (P = 0.05), there was no significant dose-response relation (P = 0.32). Pediatric data were too limited in relation to the usefulness of the other biomarkers. CONCLUSIONS Circulating 25(OH)D may be a useful biomarker of vitamin D exposure/intake for DRI development in infants and children. Circulating 24,25(OH)2D also showed some promise, but further data are needed, especially in infants and children.
-
10.
A high-protein low-glycemic index diet attenuates gestational weight gain in pregnant women with obesity: the "An optimized programming of healthy children" (APPROACH) randomized controlled trial.
Geiker, NRW, Magkos, F, Zingenberg, H, Svare, J, Chabanova, E, Thomsen, HS, Ritz, C, Astrup, A
The American journal of clinical nutrition. 2022;(3):970-979
-
-
Free full text
-
Abstract
BACKGROUND Prepregnancy overweight and excessive gestational weight gain (GWG) increase the risk of complications and offspring obesity. OBJECTIVES We aimed to investigate the effect of a high-protein low-glycemic index (HPLGI) diet on GWG, birth weight, and risk of gestational complications in pregnant women with obesity. METHODS A total of 279 women with prepregnancy overweight or obesity (BMI: 28-45 kg/m2), between 18 and 45 y old, and in their late first trimester with singleton pregnancies, were randomly assigned to 1 of 2 ad libitum diets: a high-protein low-glycemic index diet (HPLGI 25%-28% of energy from protein and glycemic index ≤ 55) and a moderate-protein moderate-glycemic index diet (MPMGI 15%-18% of energy from protein and glycemic index ∼60). Diets were consumed from gestational week 15 and throughout pregnancy. Participants received dietary guidance by a clinical dietician 9 times to facilitate adherence. RESULTS Out of 141 and 138 women randomly assigned to the HPLGI and MPMGI diets, 105 and 104 completed the intervention, respectively (75%). In the available case analyses, GWG was 6.8 ± 1.3 kg among women assigned the HPLGI diet and this was significantly lower, by -1.7 kg (95% CI: -2.8, -0.5 kg; P = 0.004), than the GWG of 8.5 ± 1.3 kg among women assigned the MPMGI diet. There were no significant differences between diets on major neonatal outcomes (birth weight and other anthropometric measures). The incidence of composite pregnancy complications was lower for the HPLGI than for the MPMGI diet (35.4% compared with 53.7%, respectively; P = 0.009), including cesarean delivery (15.4% compared with 28.8%, respectively; P = 0.03). There were no reported maternal, fetal, or neonatal deaths. Incidence of miscarriages (1%-2%) did not differ between groups. CONCLUSIONS A moderate increase in dietary protein in conjunction with a reduction in glycemic index during the last 2 trimesters of pregnancy reduced GWG and limited complications and cesarean deliveries among women with overweight or obesity.