| 1. |
- Lagou, Vasiliki, et al.
(författare)
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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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| 2. |
- Mathews, Divya M. M., et al.
(författare)
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The impact of prolonged, maternal iodine exposure in early gestation on neonatal thyroid function
- 2023
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Context: Hysterosalpingography (HSG) using oil-soluble contrast medium (OSCM) improves pregnancy rates but results in severe and persistent iodine excess, potentially impacting the fetus and neonate.Objective: To determine the incidence of thyroid dysfunction in newborns conceived within six months of OSCM HSG.Design: Offspring study of a prospective cohort of women who underwent OSCM HSG.Setting: Auckland region, New Zealand (2020-2022)Participants: Offspring from the SELFI (Safety and Efficacy of Lipiodol in Fertility Investigations) study cohort (n=57).Measurements: All newborns had a dried blood spot card for TSH measurement 48 hours after birth as part of New Zealand's Newborn Metabolic Screening Programme. Forty-one neonates also had a heel prick serum sample at one week to measure thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Maternal urine iodine concentration (UIC) and TSH in the six months after OSCM HSG were retrieved from the SELFI study for analyses.Primary outcome: Incidence of hypothyroidism in the neonatal period.Results: There was no evidence of primary hypothyroidism on newborn screening (TSH 2-10 mIU/L). All neonates tested at one week had normal serum TSH, FT4, and FT3 levels. However, increasing maternal peak UIC levels during pregnancy were associated with lower TSH levels (p= 0.006), although also associated with lower FT4 levels (p=0.032).Conclusions: While pre-conceptional OSCM HSG in women did not result in neonatal hypothyroidism, gestational iodine excess was associated with a paradoxical lowering of neonatal TSH levels despite lower FT4 levels. These changes likely reflect alterations in deiodinase activity in the fetal hypothalamic-pituitary axis from iodine excess.
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| 3. |
- Hop, Paul J., et al.
(författare)
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Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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| 4. |
- Adaikina, Alena, et al.
(författare)
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Vibration Therapy as an Early Intervention for Children Aged 2-4 Years with Cerebral Palsy : A Feasibility Study
- 2023
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Ingår i: Physical & Occupational Therapy in Pediatrics. - : Taylor & Francis. - 0194-2638 .- 1541-3144. ; 43:5, s. 564-581
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To evaluate the feasibility and acceptability of vibration therapy (VT) in preschool children with cerebral palsy (CP) and obtain preliminary data on its potential effectiveness.Methods: Nine children aged 2.5-4.8 years (4 boys) with CP GMFCS levels I-III participated in a single-group feasibility study, undergoing a 12-week control period without intervention, followed by 12 weeks of home-based VT (four times/week, 9 min/day, frequency 20 Hz). We assessed adherence to VT protocol, adverse events, and family acceptability of VT. Clinical assessments included motor function (GMFM-66), body composition (DXA), mobility (10-meter walk/run test), and health-related quality of life (PedsQL).Results: VT was well tolerated and acceptable to families, with high adherence levels reported (mean = 93%). There were no observed between-period differences (Delta Control vs Delta VT) except for an improvement in the PedsQL "Movement & Balance" dimension with VT (p = 0.044). Nonetheless, changes after the VT but not the Control period were suggestive of potential treatment benefits for mobility, gross motor function, and body composition (lean mass and legs bone mineral density).Conclusion: Home-based VT is feasible and acceptable for preschool children with CP. Our preliminary data suggest potential health benefits from VT for these children, supporting larger randomized trials to assess its effectiveness properly.
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| 5. |
- Power, Lisa C., et al.
(författare)
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Exercise Cardiac Magnetic Resonance Imaging in Boys With Duchenne Muscular Dystrophy Without Cardiac Disease
- 2021
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Ingår i: Pediatric Neurology. - : Elsevier. - 0887-8994 .- 1873-5150. ; 117, s. 35-43
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Tidskriftsartikel (refereegranskat)abstract
- Background: Duchenne muscular dystrophy is caused by mutations in the DMD gene, resulting in cardiomyopathy in all affected children by 18 years. Although cardiomyopathy is now the leading cause of mortality in these children, there is ongoing debate regarding timely diagnosis, secondary prevention, and treatment of this condition. The purpose of this study was to use exercise cardiac magnetic resonance imaging in asymptomatic young boys with Duchenne muscular dystrophy to describe their heart function and compare this with healthy controls.Methods: We studied 11 boys with Duchenne muscular dystrophy aged 8.6 to 13.9 years and 11 healthy age- and sex-matched controls.Results: Compared with the controls, boys with Duchenne muscular dystrophy had lower ejection fraction at rest (57% versus 63%; P = 0.004). During submaximal exercise, they reached similar peak tachycardia but increased their heart rate and cardiac output only half as much as controls (P = 0.003 and P = 0.014, respectively). End-systolic volume remained higher in boys with Duchenne muscular dystrophy both at rest and during exercise. When transthoracic echocardiography was compared with cardiac magnetic resonance imaging, 45% of the echocardiograms had suboptimal or poor views in the Duchenne muscular dystrophy group.Conclusions: Boys with Duchenne muscular dystrophy had abnormalities in left ventricular systolic function that were exaggerated by exercise stress. Exercise cardiac magnetic resonance imaging is feasible in a select population of children with Duchenne muscular dystrophy, and it has the potential to unmask early signs of cardiomyopathy.
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| 6. |
- West, Rachel, et al.
(författare)
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Newborn Screening TSH Values Less Than 15 mIU/L Are Not Associated With Long-term Hypothyroidism or Cognitive Impairment
- 2020
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 105:9, s. E3329-E3338
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is unclear whether newborns with mild thyrotropin elevation (mTSHe) are at risk of neurocognitive impairment. We assessed whether mTSHe at birth persists during childhood and compared neurocognitive functioning to siblings.Methods: This study encompassed children born in the Auckland region (New Zealand) with a newborn screen TSH level of 8 to 14 mIU/L blood, age 6.9 to 12.6 years at assessment, and their siblings. Thyroid function tests (serum TSH and free thyroxine) and neurocognitive assessments were performed, including IQ via the Wechsler Intelligence Scale for Children, fourth edition.Results: Ninety-six mTSHe individuals were studied, including 67 children recruited with 75 sibling controls. Mean mTSHe newborn TSH level was 10.1 mIU/L blood and 2.4 mIU/L at assessment (range, 0.8-7.0 mIU/L, serum). Although higher newborn TSH levels in the mTSHe group correlated with lower full-scale IQ scores (r = 0.25; P =.040), they were not associated with the magnitude of the IQ difference within sibling pairs (P =.56). Cognitive scores were similar for mTSHe and controls (full-scale IQ 107 vs 109; P =.36), with a minor isolated difference in motor coordination scores.Conclusions: Our data do not suggest long-term negative effects of neonatal mild TSH elevation. TSH elevation below the screen threshold appears largely transient, and midchildhood neurocognitive performance of these children was similar to their siblings. We propose that associations between neonatal mild TSH elevation and IQ are due to familial confounders. We caution against the practice of reducing screening CH cutoffs to levels at which the diagnosis may not offer long- term benefit for those detected.
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| 7. |
- Adaikina, Alena, et al.
(författare)
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Feasibility study on a longer side-alternating vibration therapy protocol (15 min per session) in children and adolescents with mild cerebral palsy
- 2023
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Ingår i: Frontiers in Pediatrics. - : Frontiers Media S.A.. - 2296-2360. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Previous studies on side-alternating vibration therapy (sVT) have usually used a 9 min intervention protocol. We performed a feasibility study aimed at assessing the safety, acceptability, and potential effectiveness of a longer sVT protocol (15 min per session) in children and adolescents with cerebral palsy (CP).Methods: Fifteen participants aged 5.2-17.4 years (median = 12.4 years) with CP GMFCS level II underwent 20 weeks of sVT consisting of 15 min sessions 4 days/week. Participants were assessed at baseline and after the intervention period, including mobility (six-minute walk-test; 6MWT), body composition (whole-body dual-energy x-ray absorptiometry scans), and muscle function (force plate).Results: Adherence level to the 15 min VT protocol was 83% on average. There were no adverse events reported. After 20 weeks, there was some evidence for an increase in the walking distance covered in 6MWT (+43 m; p = 0.0018) and spine bone mineral density (+0.032 g/cm(2); p = 0.012) compared to baseline.Conclusions: The 15 min sVT protocol is feasible and well tolerated. The results also suggest potential benefits of this protocol to mobility and bone health. Randomized controlled trials are needed to reliably ascertain the potential effectiveness of a longer sVT protocol on physical function and body composition in young people with CP.
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| 8. |
- Adaikina, Alena, et al.
(författare)
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Vibration therapy in young children with mild to moderate cerebral palsy : does frequency and treatment duration matter? A randomised-controlled study
- 2023
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Ingår i: BMC Pediatrics. - : BioMed Central (BMC). - 1471-2431 .- 1471-2431. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vibration therapy (VT) has been increasingly studied in children with cerebral palsy (CP) over the last years, however, optimal therapeutic VT protocols are yet to be determined. The present study compared the effects of side-alternating VT protocols varying in frequency and treatment duration on the health of young children with mild-to-moderate CP.Methods: Thirty-four participants aged 6.0 to 12.6 years with CP acted as their own controls and underwent two consecutive study periods: a 12-week lead-in (control) period prior to the intervention period of 20-week side-alternating VT (9 min/session, 4 days/week), with the frequency either 20 Hz or 25 Hz, determined by randomisation. Participants had 4 assessment visits: baseline, after the control period, after 12-week VT (12VT), and after further 8 weeks of VT (20VT). Assessments included 6-minute walk test (6MWT); dual-energy x-ray absorptiometry; gross motor function; muscle function testing on the Leonardo mechanography plate and by hand-held dynamometry, and a quality-of-life questionnaire (CP QOL). Analysis was carried out using linear mixed models based on repeated measures.Results: Side-alternating VT was well-tolerated, with occasional mild itchiness reported. The median compliance level was 99%. VT led to improvements in 6MWT (+ 23 m; p = 0.007 after 20VT), gross motor function in standing skills (+ 0.8 points; p = 0.008 after 12VT; and + 1.3 points; p = 0.001 after 20VT) and in walking, running and jumping skills (+ 2.5 points; p < 0.0001 after 12VT; and + 3.7 points; p < 0.0001 after 20VT), spine bone mineral density z-score (+ 0.14; p = 0.015 after 20VT), velocity rise maximum of the chair rising test (+ 0.14 m/s; p = 0.021 after 20VT), force maximum of the single two-leg jump test (+ 0.30 N/kg; p = 0.0005 after 12VT; and + 0.46 N/kg; p = 0.022 after 20VT) and in the health module of CP QOL (+ 7 points; p = 0.0095 after 20VT). There were no observed differences between the two VT frequencies (i.e., 20 Hz vs 25 Hz) on study outcomes.Conclusions: The study confirms that side-alternating VT has positive effects on mobility, gross motor function, body composition, muscle function, and quality of life, independent of VT frequencies tested. Long-term, 20VT appears to be a more efficient treatment duration than a short-term, 12VT.
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| 9. |
- Chiavaroli, Valentina, et al.
(författare)
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Lower insulin sensitivity remains a feature of children born very preterm
- 2021
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Ingår i: Pediatric Diabetes. - : John Wiley & Sons. - 1399-543X .- 1399-5448. ; 22:2, s. 161-167
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Tidskriftsartikel (refereegranskat)abstract
- Background: The first report of children born very preterm (<32 weeks of gestation) having insulin resistance was made 16 years ago. However, neonatal care has improved since. Thus, we aimed to assess whether children born very preterm still have lower insulin sensitivity than term controls.Methods: Participants were prepubertal children aged 5 to 11 years born very preterm (<32 weeks of gestation; n = 51; 61% boys) or at term (37-41 weeks; n = 50; 62% boys). Frequently sampled intravenous glucose tolerance tests were performed, and insulin sensitivity was calculated using Bergman's minimal model. Additional clinical assessments included anthropometry, body composition using whole-body dual-energy X-ray absorptiometry scans, clinic blood pressure, and 24-hour ambulatory blood pressure monitoring.Results: Children born very preterm were 0.69 standard deviation score (SDS) lighter (P < .001), 0.53 SDS shorter (P = .003), and had body mass index 0.57 SDS lower (P = .003) than children born at term. Notably, children born very preterm had insulin sensitivity that was 25% lower than term controls (9.4 vs 12.6 x 10(-4) minutes(-1)center dot[mU/L]; P = .001). Other parameters of glucose metabolism, including fasting insulin levels, were similar in the two groups. The awake systolic blood pressure (from 24-hour monitoring) tended to be 3.1 mm Hg higher on average in children born very preterm (P = .054), while the clinic systolic blood pressure was 5.4 mm Hg higher (P = .002).Conclusions: Lower insulin sensitivity remains a feature of children born very preterm, despite improvements in neonatal intensive care. As reported in our original study, our findings suggest the defect in insulin action in prepubertal children born very pretermis primarily peripheral and not hepatic.
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| 10. |
- Chiavaroli, Valentina, et al.
(författare)
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The associations between maternal BMI and gestational weight gain and health outcomes in offspring at age 1 and 7 years
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- In secondary analyses of a randomised controlled trial of exercise during pregnancy, we examined associations between mid-pregnancy maternal body mass index (BMI) and excessive gestational weight gain (GWG) with offspring health. Follow-up data were available on 57 mother-child pairs at 1-year and 52 pairs at 7-year follow-ups. Clinical assessments included body composition and fasting blood tests. At age 1 year, increased maternal BMI in mid-gestation was associated with greater weight standard deviation scores (SDS) in the offspring (p = 0.035), with no observed associations for excessive GWG. At age 7 years, greater maternal BMI was associated with increased weight SDS (p < 0.001), BMI SDS (p = 0.005), and total body fat percentage (p = 0.037) in their children. Irrespective of maternal BMI, children born to mothers with excessive GWG had greater abdominal adiposity (p = 0.043) and less favourable lipid profile (lower HDL-C and higher triglycerides). At 7 years, maternal BMI and excessive GWG had compounded adverse associations with offspring adiposity. Compared to offspring of mothers with overweight/obesity plus excessive GWG, children of normal-weight mothers with adequate and excessive GWG were 0.97 and 0.64 SDS lighter (p = 0.002 and p = 0.014, respectively), and 0.98 and 0.63 SDS leaner (p = 0.001 and p = 0.014, respectively). Both greater maternal BMI in mid-pregnancy and excessive GWG were independently associated with increased adiposity in offspring at 7 years.
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