| 1. |
- Allen, David B, et al.
(author)
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GH Safety Workshop Position Paper: a critical appraisal of recombinant human growth hormone therapy in children and adults.
- 2016
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In: European Journal of Endocrinology. - 1479-683X. ; 174:2, s. 1-9
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Journal article (peer-reviewed)abstract
- Recombinant human growth hormone (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety including; cancer risk, impact on glucose homeostasis and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk and the need for longterm surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.
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| 5. |
- Beardsall, Kathryn, et al.
(author)
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Insulin and carbohydrate metabolism
- 2008
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In: Baillière's Best Practice & Research. Clinical Endocrinology & Metabolism. - : Elsevier BV. - 1521-690X .- 1532-1908. ; 22:1, s. 41-55
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Research review (peer-reviewed)abstract
- Fetal glucose exposure and consequent fetal insulin secretion is normally tightly regulated by glucose delivery from the mother during pregnancy. Maternal hyperglycaemia and gestational diabetes (GDM) are known to be detrimental to offspring, although defining the criteria for diagnosis of GDM is controversial. Recent data suggest that the risk of poor fetal outcome appears to be a continuous variable across the range of glucose control, and that the level of maternal blood glucose for a diagnosis of gestational diabetes needs to be reviewed. After birth, rapid adaptation is necessary for infants to be able to maintain independent glucose homeostasis. This adaptation is compromised in infants who are small for gestational age (SGA), premature, or large for gestational age (LGA). Interestingly, the infants who are born at the extremes of birth weight are also at increased risk of impaired glucose tolerance and diabetes in later life.
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| 6. |
- Ekelund, Ulf, et al.
(author)
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Association of weight gain in infancy and early childhood with metabolic risk in young adults
- 2007
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:1, s. 98-103
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Journal article (peer-reviewed)abstract
- CONTEXT: Early postnatal life has been suggested as an important window during which risks for long-term health may be influenced. OBJECTIVE: The aim of this study was to examine the independent associations between weight gain during infancy (0-6 months) and early childhood (3-6 yr) with components of the metabolic syndrome in young adults. DESIGN: This was a prospective cohort study (The Stockholm Weight Development Study). SETTING: The study was conducted in a general community. PARTICIPANTS: Subjects included 128 (54 males) singletons, followed from birth to 17 yr. MAIN OUTCOME MEASURE: None of these young adults met the full criteria for the metabolic syndrome. We therefore calculated a continuous clustered metabolic risk score by averaging the standardized values of the following components: waist circumference, blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, glucose, and insulin level. RESULTS: Clustered metabolic risk at age 17 yr was predicted by weight gain during infancy (standardized beta = 0.16; P < 0.0001) but not during early childhood (standardized beta = 0.10; P = 0.23), adjusted for birth weight, gestational age, current height, maternal fat mass, and socioeconomic status at age 17 yr. Further adjustment for current fat mass and weight gain during childhood did not alter the significant association between infancy weight gain with the metabolic risk score (standardized beta = 0.20; P = 0.007). CONCLUSIONS: Rapid weight gain during infancy (0-6 months) but not during early childhood (3-6 yr) predicted clustered metabolic risk at age 17 yr. Early interventions to moderate rapid weight gain even at very young ages may help to reduce adult cardiovascular disease risks.
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| 7. |
- Horsch, S., et al.
(author)
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Randomized Control Trial of Postnatal rhIGF-1/rhIGFBP-3 Replacement in Preterm Infants: Post-hoc Analysis of Its Effect on Brain Injury
- 2020
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In: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 8
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Journal article (peer-reviewed)abstract
- Background: Postnatal insulin-like growth factor-1 (IGF-1) replacement with recombinant human (rh)IGF-1 and IGF binding protein-3 (rhIGF-1/rhIGFBP-3) is being studied as a potential treatment to reduce comorbidities of prematurity. We have recently reported on a phase II, multicenter, randomized, controlled trial comparing postnatal rhIGF-1/rhIGFBP-3 replacement with standard of care (SOC) in extremely preterm infants (NCT01096784). Maximum severity of retinopathy of prematurity was the primary endpoint of the trial and presence of GMH-IVH/PHI one of the pre-specified secondary endpoints. Infants therefore received serial cranial ultrasound scans (CUS) between birth and term age. In this post-hoc analysis we present a detailed analysis of the CUS data of this trial and evaluate the effect of postnatal rhIGF-1/rhIGFBP-3 replacement on the incidence of different kinds of brain injury in extremely preterm infants. Methods: This report is an exploratory post-hoc analysis of a phase II trial in which infants <28 weeks gestational age were randomly allocated to rhIGF-1/rhIGFBP-3 or SOC. Serial cranial ultrasounds were performed between birth and term-equivalent age. Presence of germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH), periventricular hemorrhagic infarction (PHI), post-hemorrhagic ventricular dilatation, and white matter injury (WMI) were scored by two independent masked readers. Results: The analysis included 117 infants; 58 received rhIGF-1/rhIGFBP-3 and 59 received SOC. A trend toward less grade II-III GMH-IVH and PHI was observed in treated infants vs. SOC. A subanalysis of infants without evidence of GMH-IVH at study entry (n = 104) showed reduced progression to GMH-IVH in treated infants (25.0% [13/52] vs. 40.4% [21/52]; not significant). No effects of rhIGF-1/rhIGFBP-3 on WMI were observed. Conclusion: The potential protective effect of rhIGF-1/rhIGFBP-3 on the occurrence of GMH-IVH/PHI appeared most pronounced in infants with no evidence of GMH-IVH at treatment start.
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| 8. |
- Jensen, Rikke Beck, et al.
(author)
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Baseline IGF-I Levels Determine Insulin Secretion and Insulin Sensitivity during the First Year on Growth Hormone Therapy in Children Born Small for Gestational Age. Results from a North European Multicentre Study (NESGAS)
- 2013
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In: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 80:1, s. 38-46
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Journal article (peer-reviewed)abstract
- Objective: Developmental programming alters growth and metabolic outcome in children born small for gestational age (SGA). We explored insulin and glucose metabolism in SGA children treated with a fixed GH dose over 1 year. Methods: In the North European Small for Gestational Age Study (NESGAS), 110 short SGA children received GH at 67 mu g/kg/day for 1 year. Insulin secretion was assessed by acute insulin response (AIR), insulin sensitivity (IS) by HOMA and disposition index (DI) by insulin secretion adjusted for IS. Results: First-year GH therapy led to increases in height and IGF-I standard deviation score (SDS), and reductions in IS (p < 0.0001). Compensatory increases in AIR (p < 0.0001) were insufficient and resulted in reduced DI (p = 0.032). Children in the highest IGF-I SDS tertile at baseline were the least insulin sensitive at baseline (p = 0.024) and 1 year (p = 0.006). IGF-I responses after 1 year were positively related to AIR (r = 0.30, p = 0.007) and DI (r = 0.29, p = 0.005). Conclusion: In SGA children treated with a high GH dose for 1 year, baseline IGF-I levels were related to IS whilst gains in height and IGF-I responses were associated with insulin secretion. Defining heterogeneity in IGF-I in SGA children may be useful in predicting growth and metabolic response. Copyright (C) 2013 S. Karger AG, Basel
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| 9. |
- Jensen, Rikke Beck, et al.
(author)
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Genetic Markers of Insulin Sensitivity and Insulin Secretion Are Associated With Spontaneous Postnatal Growth and Response to Growth Hormone Treatment in Short SGA Children: the North European SGA Study (NESGAS)
- 2015
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:3, s. 503-507
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Journal article (peer-reviewed)abstract
- Purpose: The wide heterogeneity in the early growth and metabolism of children born small for gestational age (SGA), both before and during GH therapy, may reflect common genetic variations related to insulin secretion or sensitivity. Method: Combined multiallele single nucleotide polymorphism scores with known associations with insulin sensitivity or insulin secretion were analyzed for their relationships with spontaneous postnatal growth and first-year responses to GH therapy in 96 short SGA children. Results: The insulin sensitivity allele score (GS-InSens) was positively associated with spontaneous postnatal weight gain (regression coefficient [B]: 0.12 SD scores per allele; 95% confidence interval [CI], 0.01-0.23; P = .03) and also in response to GH therapy with first-year height velocity (B: 0.18 cm/y per allele; 95% CI, 0.02-0.35; P = .03) and change in IGF-1 (B: 0.17 SD scores per allele; 95% CI, 0.00-0.32; P = .03). The association with first-year height velocity was independent of reported predictors of response to GH therapy (adjusted P = .04). The insulin secretion allele score (GS-InSec) was positively associated with spontaneous postnatal height gain (B: 0.15; 95% CI, 0.01-0.30; P = .03) and disposition index both before (B: 0.02; 95% CI, 0.00-0.04; P = .04) and after 1 year of GH therapy (B: 0.03; 95% CI, 0.01-0.05; P = .002), but not with growth and IGF-1 responses to GH therapy. Neither of the allele scores was associated with size at birth. Conclusion: Genetic allele scores indicative of insulin sensitivity and insulin secretion were associated with spontaneous postnatal growth and responses to GH therapy in short SGA children. Further pharmacogenetic studies may support the rationale for adjuvant therapies by informing the mechanisms of treatment response.
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| 10. |
- Kimani-Murage, Elizabeth W., et al.
(author)
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Nutritional status and HIV in rural South African children
- 2011
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 11
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Journal article (peer-reviewed)abstract
- Background: Achieving the Millennium Development Goals that aim to reduce malnutrition and child mortality depends in part on the ability of governments/policymakers to address nutritional status of children in general and those infected or affected by HIV/AIDS in particular. This study describes HIV prevalence in children, patterns of malnutrition by HIV status and determinants of nutritional status.Methods: The study involved 671 children aged 12-59 months living in the Agincourt sub-district, rural South Africa in 2007. Anthropometric measurements were taken and HIV testing with disclosure was done using two rapid tests. Z-scores were generated using WHO 2006 standards as indicators of nutritional status. Linear and logistic regression analyses were conducted to establish the determinants of child nutritonal status.Results: Prevalence of malnutrition, particularly stunting (18%), was high in the overall sample of children. HIV prevalence in this age group was 4.4% (95% CI: 2.79 to 5.97). HIV positive children had significantly poorer nutritional outcomes than their HIV negative counterparts. Besides HIV status, other significant determinants of nutritional outcomes included age of the child, birth weight, maternal age, age of household head, and area of residence.Conclusions: This study documents poor nutritional status among children aged 12-59 months in rural South Africa. HIV is an independent modifiable risk factor for poor nutritional outcomes and makes a significant contribution to nutritional outcomes at the individual level. Early paediatric HIV testing of exposed or at risk children, followed by appropriate health care for infected children, may improve their nutritional status and survival.
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| 11. |
- Kimani-Murage, Elizabeth W, et al.
(author)
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The prevalence of stunting, overweight and obesity, and metabolic disease risk in rural South African children
- 2010
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In: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 10, s. 158-
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Journal article (peer-reviewed)abstract
- The study highlights that in transitional societies, early stunting and adolescent obesity may co-exist in the same socio-geographic population. It is likely that this profile relates to changes in nutrition and diet, but variation in factors such as infectious disease burden and physical activity patterns, as well as social influences, need to be investigated. As obesity and adult short stature are risk factors for metabolic syndrome and Type 2 diabetes, this combination of early stunting and adolescent obesity may be an explosive combination.
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| 12. |
- Looker, Helen C, et al.
(author)
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Biomarkers of rapid chronic kidney disease progression in type 2 diabetes.
- 2015
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In: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 88:4, s. 888-896
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Journal article (peer-reviewed)abstract
- Here we evaluated the performance of a large set of serum biomarkers for the prediction of rapid progression of chronic kidney disease (CKD) in patients with type 2 diabetes. We used a case-control design nested within a prospective cohort of patients with baseline eGFR 30-60 ml/min per 1.73 m(2). Within a 3.5-year period of Go-DARTS study patients, 154 had over a 40% eGFR decline and 153 controls maintained over 95% of baseline eGFR. A total of 207 serum biomarkers were measured and logistic regression was used with forward selection to choose a subset that were maximized on top of clinical variables including age, gender, hemoglobin A1c, eGFR, and albuminuria. Nested cross-validation determined the best number of biomarkers to retain and evaluate for predictive performance. Ultimately, 30 biomarkers showed significant associations with rapid progression and adjusted for clinical characteristics. A panel of 14 biomarkers increased the area under the ROC curve from 0.706 (clinical data alone) to 0.868. Biomarkers selected included fibroblast growth factor-21, the symmetric to asymmetric dimethylarginine ratio, β2-microglobulin, C16-acylcarnitine, and kidney injury molecule-1. Use of more extensive clinical data including prebaseline eGFR slope improved prediction but to a lesser extent than biomarkers (area under the ROC curve of 0.793). Thus we identified several novel associations of biomarkers with CKD progression and the utility of a small panel of biomarkers to improve prediction.Kidney International advance online publication, 22 July 2015; doi:10.1038/ki.2015.199.
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| 13. |
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| 14. |
- Ong, Ken K., et al.
(author)
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Pregnancy Insulin, Glucose, and BMI Contribute to Birth Outcomes in Nondiabetic Mothers
- 2008
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 31:11, s. 2193-2197
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Journal article (peer-reviewed)abstract
- OBJECTIVE - We investigated the effects of normal variations in maternal glycemia on birth size and other birth outcomes. RESEARCH DESIGN AND METHODS - Women in two unselected birth cohorts, one retrospective (n = 3,158) and one prospective (n = 668), underwent an oral glucose challenge at 28 weeks of gestation. In the retrospective study, glycemia was linked to routine birth records. In the prospective study, offspring adiposity was assessed by skinfold thickness from birth to age 24 months. RESULTS - In the retrospective study, within the nondiabetic range (2.1-7.8 mmol/l), each 1 mmol/l rise in the mother's 60-min glucose level was associated with a (mean +/- SEM) 2.1 +/- 0.8% (P = 0.006) rise in absolute risk of assisted vaginal delivery, a 3.4 +/- 0.8% (P < 0.0001) rise in emergency cesarean delivery, a 3.1 +/- 0.7% (P < 0.0001) rise in elective cesarean delivery, and a 46 +/- 8 g (P < 0.0001) increase in offspring birth weight. in the prospective study, fetal macrosomia (birth weight >90th centile) was independently related to the mother's fasting glucose (odds ratio 2.61 per + 1 mmol/l [95% CI 1.15-5.93]) and prepregnancy BMI (1.10 per +1 kg/m(2) [1.04-1.18]). The mother's higher fasting glycemia (P = 0.004), lower insulin sensitivity (P = 0.01), and lower insulin secretion (P = 0.02) were independently related to greater offspring adiposity at birth. During postnatal follow-up, the correlation between the mother's glycemia and offspring adiposity disappeared by 3 months, whereas prepregnancy BMI was associated with offspring adiposity that was only apparent at 12 and 24 months (both P < 0.05). CONCLUSIONS - Prepregnancy BMI, pregnancy glycemia, insulin sensitivity, and insulin secretion all contribute to offspring adiposity and macrosomia and may be separate targets for intervention to optimize birth outcomes and later offspring health.
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| 15. |
- Prioreschi, Alessandra, et al.
(author)
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Examining the relationships between body image, eating attitudes, BMI, and physical activity in rural and urban South African young adult females using structural equation modeling
- 2017
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In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:11
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Journal article (peer-reviewed)abstract
- The persistence of food insecurity, malnutrition, increasing adiposity, and decreasing physical activity, heightens the need to understand relationships between body image satisfaction, eating attitudes, BMI and physical activity levels in South Africa. Females aged 18-23 years were recruited from rural (n = 509) and urban (n = 510) settings. Body image satisfaction was measured using Stunkard's silhouettes, and the 26-item Eating Attitudes questionnaire (EAT-26) was used to evaluate participants' risk of disordered eating. Minutes per week of moderate to vigorous physical activity (MVPA) was assessed using the Global Physical Activity Questionnaire (GPAQ). Significant linear correlates were included in a series of regressions run separately for urban and rural participants. Structural equation modeling (SEM) was used to test the relationships between variables. Urban females were more likely to be overweight and obese than rural females (p = 0.02), and had a greater desire to be thinner (p = 0.02). In both groups, being overweight or obese was positively associated with a desire to be thinner (p<0.01), and negatively associated with a desire to be fatter (p<0.01). Having a disordered eating attitude was associated with body image dissatisfaction in the urban group (beta = 1.27, p<0.01, CI: 0.38; 2.16), but only with a desire to be fatter in the rural group (beta = 0.63, p = 0.04, CI: 0.03; 1.23). In the SEM model, body image dissatisfaction was associated with disordered eating (beta = 0.63), as well as higher MVPA participation (p<0.01). These factors were directly associated with a decreased risk of disordered eating attitude, and with a decreased desire to be thinner. Findings indicate a shift in both settings towards more Westernised ideals. Physical activity may provide a means to promote a healthy body image, while reducing the risk of disordered eating. Given the high prevalence of overweight and obesity in both rural and urban women, this study provides insights for future interventions aimed at decreasing adiposity in a healthy way.
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| 16. |
- Said-Mohamed, Rihlat, et al.
(author)
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Rural-urban variations in age at menarche, adult height, leg-length and abdominal adiposity in black South African women in transitioning South Africa
- 2018
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In: Annals of Human Biology. - : Taylor & Francis. - 0301-4460 .- 1464-5033. ; 45:2, s. 123-132
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Journal article (peer-reviewed)abstract
- Background: The pre-pubertal socioeconomic environment may be an important determinant of age at menarche, adult height, body proportions and adiposity: traits closely linked to adolescent and adult health.Aims: This study explored differences in age at menarche, adult height, relative leg-length and waist circumference between rural and urban black South African young adult women, who are at different stages of the nutrition and epidemiologic transitions.Subjects and methods: We compared 18-23 year-old black South African women, 482 urban-dwelling from Soweto and 509 from the rural Mpumalanga province. Age at menarche, obstetric history and household socio-demographic and economic information were recorded using interview-administered questionnaires. Height, sitting-height, hip and waist circumference were measured using standardised techniques.Results: Urban and rural black South African women differed in their age at menarche (at ages 12.7 and 14.5 years, respectively). In urban women, a one-year increase in age at menarche was associated with a 0.65 cm and 0.16% increase in height and relative leg-length ratio, respectively. In both settings, earlier age at menarche and shorter relative leg-length were independently associated with an increase in waist circumference.Conclusions: In black South African women, the earlier onset of puberty, and consequently an earlier growth cessation process, may lead to central fat mass accumulation in adulthood.
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| 17. |
- Sutton, Elizabeth F, et al.
(author)
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Developmental programming : State-of-the-science and future directions: Summary from a Pennington Biomedical symposium
- 2016
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In: Obesity. - : Wiley. - 1930-739X .- 1930-7381. ; 24:5, s. 1018-1026
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Research review (peer-reviewed)abstract
- OBJECTIVE: On December 8-9, 2014, the Pennington Biomedical Research Center convened a scientific symposium to review the state-of-the-science and future directions for the study of developmental programming of obesity and chronic disease. The objectives of the symposium were to discuss: (i) past and current scientific advances in animal models, population-based cohort studies, and human clinical trials, (ii) the state-of-the-science of epigenetic-based research, and (iii) considerations for future studies.RESULTS: This symposium provided a comprehensive assessment of the state of the scientific field and identified research gaps and opportunities for future research in order to understand the mechanisms contributing to the developmental programming of health and disease.CONCLUSIONS: Identifying the mechanisms which cause or contribute to developmental programming of future generations will be invaluable to the scientific and medical community. The ability to intervene during critical periods of prenatal and early postnatal life to promote lifelong health is the ultimate goal. Considerations for future research including the use of animal models, the study design in human cohorts with considerations about the timing of the intrauterine exposure, and the resulting tissue-specific epigenetic signature were extensively discussed and are presented in this meeting summary.
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| 18. |
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| 19. |
- Wegmann, Mathilde Gersel, et al.
(author)
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Increases in bioactive IGF do not parallel increases in total IGF-I during growth hormone treatment of children born SGA
- 2020
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 105:4, s. 1291-1298
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Journal article (peer-reviewed)abstract
- Background: Some children born small for gestational age (SGA) experience supra-physiological insulin-like growth factor-I (IGF-I) concentrations during GH treatment. However, measurements of total IGF-I concentrations may not reflect the bioactive fraction of IGF-I which reaches the IGF-I receptor at target organs. We examined endogenous IGF-bioactivity using an IGF-I kinase receptor activation (KIRA) assay that measures the ability of IGF-I to activate the IGF-IR in vitro. Aim: To compare responses of bioactive IGF and total IGF-I concentrations in short GH treated SGA children in the North European Small for Gestational Age Study (NESGAS). Material and method: In NESGAS, short SGA children (n = 101, 61 males) received GH at 67 µg/ kg/day for 1 year. IGF-I concentrations were measured by Immulite immunoassay and bioactive IGF by in-house KIRA assay. Results: Bioactive IGF increased with age in healthy pre-pubertal children (n = 94). SGA children had low-normal bioactive IGF levels at baseline (-0.12 (1.8 SD), increasing significantly after one year of high-dose GH treatment to 1.1 (1.4) SD, P < 0.01. Following high-dose GH, 68% (n = 65) of SGA children had a total IGF-I concentration >2SD (mean IGF-I 2.8 SDS), whereas only 15% (n = 15) had levels of bioactive IGF slightly above normal reference values. At baseline, bioactive IGF (SDS) was significantly correlated to height (SDS) (r = 0.29, P = 0.005), in contrast to IGF-I (SDS) (r = 0.17, P = 0.10). IGF-I (SDS) was inversely correlated to delta height (SDS) after one year of high-dose GH treatment (r = -0.22, P = 0.02). Conclusion: In contrast to total IGF-I concentrations, bioactive IGF stayed within the normal reference ranges for most SGA children during the first year of GH treatment.
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| 20. |
- Wegmann, Mathilde Gersel, et al.
(author)
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The exon3-deleted growth hormone receptor gene polymorphism (d3-GHR) is associated with insulin and spontaneous growth in short SGA children (NESGAS)
- 2017
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In: Growth Hormone and IGF Research. - : Elsevier BV. - 1096-6374. ; 35, s. 45-51
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Journal article (peer-reviewed)abstract
- Objective The effect of a common polymorphism in the Growth Hormone (GH) receptor (d3-GHR) gene on growth, metabolism and body composition was examined in short children born small for gestational age (SGA) on GH treatment. Design In 96 prepubertal, short SGA children treated with high-dose GH (67 μg/kg/day) in the NESGAS study, insulin sensitivity (IS), insulin secretion and disposition index (DI) were determined during the first year of treatment. Body composition was analysed by DXA. The d3-GHR locus was determined by simple multiplex PCR. Results At baseline, children in the d3-GHR group (d3/fl (n = 37), d3/d3 (n = 7)) had significantly lower IS (median (25–75 percentile)) (223.3% (154.4–304.8)) vs. (269.7% (185.1–356.7)) (p = 0.03) and higher concentrations of glucose (mean (SD)) (4.4 mmol/L (0.6) vs. 4.2 mmol/L (0.7)) (p = 0.03), C-peptide (232.1 pmol/L (168.8–304.1) vs. 185.1 pmol/L (137.7–253.9)) (p = 0.04) and insulin (19.2 pmol/L (11.8–32.2)) vs. (13.7 pmol/L (9.3–20.8)) (p = 0.04) compared to children homozygous for the full length allele (fl/fl-GHR (n = 52)). There were no differences in DI or insulin secretion. Postnatal, spontaneous growth was significantly greater in the d3-GHR group compared to the fl/fl-GHR group (p = 0.02). There were no significant differences in growth response, body composition or metabolism after one year of GH therapy. Conclusion Short SGA children carrying the d3-GHR polymorphism had increased spontaneous growth, lower IS and a compensatory increase in glucose, C-peptide and insulin before GH therapy compared to children homozygous for the full-length allele.
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