| 1. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
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Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life
- 2015
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Ingår i: Cell Host & Microbe. - Cambridge : Elsevier BV. - 1931-3128 .- 1934-6069. ; 17:5, s. 690-703
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota is central to human health, but its establishment in early life has not been quantitatively and functionally examined. Applying metagenomic analysis on fecal samples from a large cohort of Swedish infants and their mothers, we characterized the gut microbiome during the first year of life and assessed the impact of mode of delivery and feeding on its establishment. In contrast to vaginally delivered infants, the gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers. Nutrition had a major impact on early microbiota composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life.
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| 2. |
- Beamish, A. J., et al.
(författare)
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Changes in adipose tissue distribution and relation to cardiometabolic risk factors after Roux-en-Y in adolescents
- 2023
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Ingår i: Surgery for Obesity and Related Diseases. - : ELSEVIER SCIENCE INC. - 1550-7289 .- 1878-7533. ; 19:10, s. 1154-1161
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Tidskriftsartikel (refereegranskat)abstract
- Background: Roux-en-Y gastric bypass (RYGB) among adolescents with obesity results in signif-icant weight loss; however, depot-specific changes have been understudied.Objective: We hypothesized that visceral adipose tissue (VAT) reduction in adolescents undergoing RYGB would be greater than other depots and associated with improvement in cardiometabolic risk factors.Setting: Three specialized treatment centers in Sweden. Methods: Fifty-nine adolescents underwent dual x-ray absorptiometry before surgery and at 1, 2, and 5 years after RYGB. Changes in body composition in multiple depots (total fat, lean body, gynoid fat, android fat, subcutaneous adipose tissue, and VAT) and cardiometabolic risk factors were assessed using multiple linear regression analysis and generalized estimating equations adjusting for age, sex, and baseline risk factor levels. Data are presented as percent change (95% CI) with regression models showing slopes and estimated P values.Results: At 1 year post-RYGB, a significant reduction was observed across all body composition measures (P , .001) with the greatest reduction observed in VAT (-65.1% [-68.7, -61.8]). From year 1 to 5 years post-RYGB, a regain was observed in all depots except lean body mass (1.2% [.3, 2.7], P 5 .105). A sex-specific difference in overall trajectories was only observed in lean body mass with males consistently having higher mean levels. Change in VAT at 1 year correlated with change in triglycerides (slope: .21 mg/dL/kg, P = .034) and fasting plasma insulin (slope: 44 pmol/L/kg, P = .027). Conclusions: Adiposity measures all decreased after RYGB but poorly predicted change in cardio-metabolic risk. Despite significant reductions at 1 year, a steady regain was observed out to 5 years, with values still well below baseline. Further research should consider control group comparison and extended follow-up.
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| 3. |
- Hokken-Koelega, A. C. S., et al.
(författare)
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International Consensus Guideline on Small for Gestational Age: Etiology and Management From Infancy to Early Adulthood
- 2023
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Ingår i: Endocrine Reviews. - : The Endocrine Society. - 0163-769X .- 1945-7189. ; 44:3, s. 539-565
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Tidskriftsartikel (refereegranskat)abstract
- This International Consensus Guideline was developed by experts in the field of small for gestational age (SGA) of 10 pediatric endocrine societies worldwide. A consensus meeting was held and 1300 articles formed the basis for discussions. All experts voted about the strengths of the recommendations. The guideline gives new and clinically relevant insights into the etiology of short stature after SGA birth, including novel knowledge about (epi)genetic causes. Further, it presents long-term consequences of SGA birth and also reviews new treatment options, including treatment with gonadotropin-releasing hormone agonist (GnRHa) in addition to growth hormone (GH) treatment, as well as the metabolic and cardiovascular health of young adults born SGA after cessation of childhood GH treatment in comparison with appropriate control groups. To diagnose SGA, accurate anthropometry and use of national growth charts are recommended. Follow-up in early life is warranted and neurodevelopment evaluation in those at risk. Excessive postnatal weight gain should be avoided, as this is associated with an unfavorable cardiometabolic health profile in adulthood. Children born SGA with persistent short stature < -2.5 SDS at age 2 years or < -2 SDS at 3 to 4 years of age, should be referred for diagnostic workup. In case of dysmorphic features, major malformations, microcephaly, developmental delay, intellectual disability, and/or signs of skeletal dysplasia, genetic testing should be considered. Treatment with 0.033 to 0.067 mg GH/kg/day is recommended in case of persistent short stature at age of 3 to 4 years. Adding GnRHa treatment could be considered when short adult height is expected at pubertal onset. All young adults born SGA require counseling to adopt a healthy lifestyle.
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| 4. |
- Stevens, A., et al.
(författare)
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Gene expression signatures predict response to therapy with growth hormone
- 2021
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Ingår i: Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 21, s. 594-607
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response are inexact. GHD (n = 71) and TS patients (n = 43) were recruited to study response to r-hGH over 5 years. Analysis was performed using 1219 genetic markers and baseline (pre-treatment) blood transcriptome. Random forest was used to determine predictive value of transcriptomic data associated with growth response. No genetic marker passed the stringency criteria for prediction. However, we identified an identical set of genes in both GHD and TS whose expression could be used to classify therapeutic response to r-hGH with a high accuracy (AUC > 0.9). Combining transcriptomic markers with clinical phenotype was shown to significantly reduce predictive error. This work could be translated into a single genomic test linked to a prediction algorithm to improve clinical management. Trial registration numbers: NCT00256126 and NCT00699855.
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| 5. |
- Friedrich, Nele, et al.
(författare)
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Age and sex specific reference intervals across life-span for insulin-like growth factor binding protein 3 (IGFBP-3) and the IGF-I/IGFBP-3 ratio measured by new automated chemiluminescence assays.
- 2014
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:5
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Tidskriftsartikel (refereegranskat)abstract
- Context: Measurement of IGFBP-3 can aid the diagnosis of growth hormone related diseases. Furthermore, epidemiological studies suggest that IGFBP-3 and the molar IGF-I/IGFBP-3 ratio are associated with clinical endpoints like cancer or cardiovascular disease. However, their clinical use is limited by the lack of validated reference intervals. Objectives: Establishment of age- and sex-specific reference intervals for IGFBP-3 and the molar IGF-I/IGFBP-3 ratio by newly developed automated immunoassays. Setting: Multicentre study with samples from 11 cohorts from the USA, Canada and Europe Participants: 14,970 subjects healthy subjects covering all ages from birth to senescence. Main outcome measures: Concentrations of IGFBP-3 and the IGF-I/IGFBP-3 ratio as determined by the IDS iSYS IGF-I and IGFBP-3 assays. Results: Both the concentration of IGFBP-3 and the IGF-I/IGFBP-3 ratio are mainly determined by age. IGFBP-3 concentrations increase until the age of 22 years, with a plateau being visible between 15 and 25 years. Determined by the high peripubertal peak in IGF-I, the peak in the IGF-I/IGFBP-3 ratio occurs already around the age of 15, with a slightly earlier and higher peak in females. Beyond the age of 60, IGFBP-3 concentrations remain higher in females, whereas IGF-I as well as the IGF-I/IGFBP-3 ratio remain significantly higher in males. Conclusions: We present an extensive set of assay specific, age and sex-adjusted normative data for concentrations of IGFBP-3 and the molar IGF-I/IGFBP-3 ratio and demonstrate distinct sex specific differences across lifespan.
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