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Gustafsson, Jan
Alternative names
Publications (10 of 87) Show all publications
Johnsson, I. W., Naessén, T., Ahlsson, F. & Gustafsson, J. (2018). High birth weight was associated with increased radial artery intima thickness but not with other investigated cardiovascular risk factors in adulthood.. Acta Paediatrica
Open this publication in new window or tab >>High birth weight was associated with increased radial artery intima thickness but not with other investigated cardiovascular risk factors in adulthood.
2018 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227Article in journal (Refereed) Epub ahead of print
Abstract [en]

AIM: This study investigated whether a high birth weight was associated with increased risk factors for cardiovascular disease when Swedish adults reached 34-40.

METHODS: We studied 27 subjects born at Uppsala University Hospital in 1975-1979, weighing at least 4500 g, and compared them with 27 controls selected by the Swedish National Board of Welfare with birth weights within ±1 standard deviations scores and similar ages and gender. The study included body mass index (BMI), blood pressure, lipid profile, haemoglobin A1c (HbA1c), C-reactive protein (CRP) and high-frequency ultrasound measurements of intima-media thickness, intima thickness (IT) and intima:media ratio of the carotid and radial arteries.

RESULTS: Subjects with a high birth weight did not differ from controls with regard to BMI, blood pressure, lipid profile, high-sensitivity CRP, HbA1c or carotid artery wall dimensions. However, their radial artery intima thickness was 37% greater than the control group and their intima:media ratio was 44% higher.

CONCLUSION: Our findings indicate that a high birth weight was associated with increased radial artery intima thickness, but not with other investigated cardiovascular risk factors, at 34-40 years of age. The clinical implications of these findings should be investigated further, especially in subjects born with a very high birth weight.

Keywords
Cardiovascular risk factors, High birth weight, Intima thickness, Intima:media ratio, Large for gestational age
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-364690 (URN)10.1111/apa.14414 (DOI)29791055 (PubMedID)
Available from: 2018-10-31 Created: 2018-10-31 Last updated: 2018-12-12
Gyllenhammar, I., Diderholm, B., Gustafsson, J., Berger, U., Ridefelt, P., Benskin, J. P., . . . Glynn, A. (2018). Perfluoroalkyl acid levels in first-time mothers in relation to offspring weight gain and growth. Environment International, 111, 191-199
Open this publication in new window or tab >>Perfluoroalkyl acid levels in first-time mothers in relation to offspring weight gain and growth
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2018 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 111, p. 191-199Article in journal (Refereed) Published
Abstract [en]

We investigated if maternal body burdens of perfluoroalkyl acids (PFAAs) at the time of delivery are associated with birth outcome and if early life exposure (in utero/nursing) is associated with early childhood growth and weight gain. Maternal PFAA body burdens were estimated by analysis of serum samples from mothers living in Uppsala County, Sweden (POPUP), sampled three weeks after delivery between 1996 and 2011. Data on child length and weight were collected from medical records and converted into standard deviation scores (SDS). Multiple linear regression models with appropriate covariates were used to analyze associations between maternal PFAA levels and birth outcomes (n=381). After birth Generalized Least Squares models were used to analyze associations between maternal PFAA and child growth (n=200). Inverse associations were found between maternal levels of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), and birth weight SDS with a change of -0.10 to -0.18 weight SDS for an inter-quartile range (IQR) increase in ng/g PFAA. After birth, weight and length SDS were not significantly associated with maternal PFAA. However, BMI SDS was significantly associated with PFOA, PFNA, and PFHxS at 3 and 4years of age, and with PFOS at 4 and 5years of age. If causal, these associations suggest that PFAA affects fetal and childhood body development in different directions.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-343486 (URN)10.1016/j.envint.2017.12.002 (DOI)000423441500020 ()29223808 (PubMedID)
Funder
Swedish Environmental Protection Agency, 219 1202Swedish Research Council Formas, 2010-1300Swedish Civil Contingencies Agency, dnr 1637/2012
Available from: 2018-02-27 Created: 2018-02-27 Last updated: 2018-03-07Bibliographically approved
Nylander, C., Tindberg, Y., Haas, J., Swenne, I., Torbjörnsdotter, T., Åkesson, K., . . . Fernell, E. (2018). Self- and parent-reported executive problems in adolescents with type 1 diabetes are associated with poor metabolic control and low physical activity.. Pediatric Diabetes, 19(1), 98-105
Open this publication in new window or tab >>Self- and parent-reported executive problems in adolescents with type 1 diabetes are associated with poor metabolic control and low physical activity.
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2018 (English)In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 1, p. 98-105Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Management of diabetes is demanding and requires efficient cognitive skills, especially in the domain of executive functioning. However, the impact of impaired executive functions on diabetes control has been studied to a limited extent. The aim of the study is to investigate the association between executive problems and diabetes control in adolescents with type 1 diabetes.

MATERIALS AND METHODS: Two hundred and forty-one of 477 (51%) of 12- to 18-year-old adolescents, with a diabetes duration of >2 years in Stockholm, Uppsala, and Jönköping participated. Parents and adolescents completed questionnaires, including Behavioral Rating Inventory of Executive Function (BRIEF), Attention-Deficit/Hyperactivity Disorder (ADHD)-Rating Scale (ADHD-RS) and demographic background factors. Diabetes-related data were collected from the Swedish Childhood Diabetes Registry, SWEDIABKIDS. Self-rated and parent-rated executive problems were analyzed with regard to gender, glycosylated hemoglobin (HbA1c), frequency of outpatient visits, and physical activity, using chi-square tests or Fisher's test, where P-values <.05 were considered significant. Furthermore, adjusted logistic regressions were performed with executive problems as independent variable.

RESULTS: Executive problems, according to BRIEF and/or ADHD-RS were for both genders associated with mean HbA1c >70 mmol/mol (patient rating P = .000, parent rating P = .017), a large number of outpatient visits (parent rating P = .015), and low physical activity (patient rating P = .000, parent rating P = .025). Self-rated executive problems were more prevalent in girls (P = .032), while parents reported these problems to a larger extent in boys (P = .028).

CONCLUSION: Executive problems are related to poor metabolic control in adolescents with type 1 diabetes. Patients with executive problems need to be recognized by the diabetes team and the diabetes care should be organized to provide adequate support for these patients.

Keywords
HbA1c, adolescents, neurodevelopmental problems, type 1 diabetes mellitus
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-332701 (URN)10.1111/pedi.12520 (DOI)000423397600014 ()28318073 (PubMedID)
Funder
Swedish Child Diabetes Foundation
Available from: 2017-10-31 Created: 2017-10-31 Last updated: 2018-03-07Bibliographically approved
Dalin, F., Nordling Eriksson, G., Dahlqvist, P., Hallgren, Å., Wahlberg, J., Ekwall, O., . . . Bensing, S. (2017). Clinical and immunological characteristics of Autoimmune Addison's disease: a nationwide Swedish multicenter study. Journal of Clinical Endocrinology and Metabolism, 102(2), 379-389
Open this publication in new window or tab >>Clinical and immunological characteristics of Autoimmune Addison's disease: a nationwide Swedish multicenter study
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2017 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, no 2, p. 379-389Article in journal (Refereed) Published
Abstract [en]

CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.

OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.

DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.

MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.

RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).

CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.

National Category
Medical and Health Sciences Endocrinology and Diabetes
Research subject
Endocrinology and Diabetology
Identifiers
urn:nbn:se:uu:diva-318344 (URN)10.1210/jc.2016-2522 (DOI)27870550 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 201167Novo Nordisk, NNF13OC0005975 NNF15OC0015922 NNF14OC0011003Åke Wiberg FoundationTore Nilsons Stiftelse för medicinsk forskningMarianne and Marcus Wallenberg FoundationSwedish Society of MedicineTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseSwedish Research CouncilThe Karolinska Institutet's Research FoundationSwedish Society for Medical Research (SSMF)Stockholm County Council
Available from: 2017-03-24 Created: 2017-03-24 Last updated: 2018-09-21Bibliographically approved
Tidblad, A., Gustafsson, J., Marcus, C., Ritzen, M. & Ekstrom, K. (2017). Comparison of Lipid And Glucose Metabolism Between Short Prepubertal Children And Healthy Children of Normal Height. Hormone Research in Paediatrics, 88, 303-304
Open this publication in new window or tab >>Comparison of Lipid And Glucose Metabolism Between Short Prepubertal Children And Healthy Children of Normal Height
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2017 (English)In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 88, p. 303-304Article in journal, Meeting abstract (Other academic) Published
National Category
Pediatrics
Identifiers
urn:nbn:se:uu:diva-346842 (URN)000412595403190 ()
Available from: 2018-03-28 Created: 2018-03-28 Last updated: 2018-03-28Bibliographically approved
Norlin, M., Lundqvist, J., Ellfolk, M., Hellström Pigg, M., Gustafsson, J. & Wikvall, K. (2017). Drug-mediated gene regulation of vitamin D3 metabolism in primary human dermal fibroblasts. Basic & Clinical Pharmacology & Toxicology, 120(1), 59-63
Open this publication in new window or tab >>Drug-mediated gene regulation of vitamin D3 metabolism in primary human dermal fibroblasts
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2017 (English)In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 120, no 1, p. 59-63Article in journal (Refereed) Published
Abstract [en]

Vitamin D metabolism was studied in primary human dermal fibroblasts with focus on drug-mediated gene regulation related to adverse side effects of antiretroviral drugs used in HIV therapy. The fibroblasts expressed mRNA for cytochrome P450 (CYP) enzymes catalysing bioactivating (CYP2R1, CYP27A1 and CYP27B1) and catabolic reactions (CYP24A1). The cells produced both 25-hydroxyvitamin D3 and 1a,25-dihydroxyvitamin D3. The results demonstrate that primary dermal fibroblasts have an active vitamin D3 metabolising system. High incidence of low bone mineral density is a concern for HIV-infected patients treated with antiretroviral drugs. Osteomalacia and severe vitamin D deficiency have been reported. We investigated whether drug-mediated gene regulation could be a possible mechanism behind these adverse drug effects. Fibroblasts were treated with different drugs used in HIV therapy and the 1a,25-dihydroxyvitamin D3 levels and relative mRNA-levels for crucial enzymes were determined. Efavirenz, stavudine and ritonavir significantly downregulated the bioactivating CYP2R1 and upregulated the catabolic CYP24A1. The drugs reduced bioactivating enzyme activities and cellular levels of 1a,25-dihydroxyvitamin D3. The current results indicate that effects on gene expression may lead to disturbed vitamin D-metabolism and decreased cellular levels of active vitamin D3. The data are consistent with the impaired bone health in patients treated with certain antiretroviral drugs.

National Category
Basic Medicine
Research subject
Biochemistry
Identifiers
urn:nbn:se:uu:diva-319044 (URN)10.1111/bcpt.12641 (DOI)000394527200009 ()27404500 (PubMedID)
Available from: 2017-03-30 Created: 2017-03-30 Last updated: 2018-01-13Bibliographically approved
Proos, L. A., Arnell, K., Gustafsson, J. & Dahl, M. (2017). Early/Precocious Puberty in Children with Pre/Perinatal Hydrocephalus. Hormone Research in Paediatrics, 88, 180-181
Open this publication in new window or tab >>Early/Precocious Puberty in Children with Pre/Perinatal Hydrocephalus
2017 (English)In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 88, p. 180-181Article in journal, Meeting abstract (Other academic) Published
National Category
Pediatrics
Identifiers
urn:nbn:se:uu:diva-346841 (URN)000412595402162 ()
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-03Bibliographically approved
Smith-Anttila, C. J. A., Bensing, S., Alimohammadi, M., Dalin, F., Oscarson, M., Zhang, M.-D., . . . Kämpe, O. (2017). Identification of endothelin-converting enzyme-2 as an autoantigen in autoimmune polyendocrine syndrome type 1. Autoimmunity, 50(4), 223-231
Open this publication in new window or tab >>Identification of endothelin-converting enzyme-2 as an autoantigen in autoimmune polyendocrine syndrome type 1
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2017 (English)In: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 50, no 4, p. 223-231Article in journal (Refereed) Published
Abstract [en]

Autoimmune polyendocrine syndrome type 1 (APS1) is a rare monogenic autoimmune disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies are a characteristic feature of APS1 and are often associated with particular disease manifestations. Pituitary deficits are reported in up to 7% of all APS1 patients, with immunoreactivity to pituitary tissue frequently reported. We aimed to isolate and identify specific pituitary autoantigens in patients with APS1. Immunoscreening of a pituitary cDNA expression library identified endothelin-converting enzyme (ECE)-2 as a potential candidate autoantigen. Immunoreactivity against ECE-2 was detected in 46% APS1 patient sera, with no immunoreactivity detectable in patients with other autoimmune disorders or healthy controls. Quantitative-PCR showed ECE-2 mRNA to be most abundantly expressed in the pancreas with high levels also in the pituitary and brain. In the pancreas ECE-2 was co-expressed with insulin or somatostatin, but not glucagon and was widely expressed in GH producing cells in the guinea pig pituitary. The correlation between immunoreactivity against ECE-2 and the major recognized clinical phenotypes of APS1 including hypopituitarism was not apparent. Our results identify ECE-2 as a specific autoantigen in APS1 with a restricted neuroendocrine distribution.

Keywords
APS1, endothelin-converting enzyme-2, ECE-2, pituitary autoantibodies, pancreas
National Category
Immunology
Identifiers
urn:nbn:se:uu:diva-333619 (URN)10.1080/08916934.2017.1332183 (DOI)000407564500005 ()28557628 (PubMedID)
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2017-11-16Bibliographically approved
Diderholm, B., Beardsall, K., Murgatroyd, P., Lees, C., Gustafsson, J. & Dunger, D. (2017). Maternal rates of lipolysis and glucose production in late pregnancy are independently related to foetal weight. Clinical Endocrinology, 87(3), 272-278
Open this publication in new window or tab >>Maternal rates of lipolysis and glucose production in late pregnancy are independently related to foetal weight
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2017 (English)In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 87, no 3, p. 272-278Article in journal (Refereed) Published
Abstract [en]

Objective: Associations between maternal glucose levels and increased foetal growth are well established, and independent relationships with maternal weight, weight gain and insulin resistance are also observed. The relative roles of lipolysis and glucose production in the determination of these observations remain unclear. Design: We examined, through detailed physiological studies, the relationship between maternal late gestational energy substrate production (glucose and glycerol), maternal weight and weight gain, and estimated foetal size in the third trimester. Patients: Twenty-one nulliparous pregnant women, without gestational diabetes (GDM) assessed at 28 weeks with oral glucose tolerance test, were recruited. Measurements: Rates of hepatic glucose production (GPR) and rates of glycerol production (reflecting lipolysis) using [C-13(6)]-glucose and [H-2(5)]-glycerol were measured at 34-36 weeks of gestation. Respiratory quotient was assessed by indirect calorimetry and body composition by measurements of total body water (TBW; (H2O)-O-18) and body density (BODPOD). Foetal weight was estimated from ultrasound measures of biparietal diameter, femoral length and abdominal circumference. Results: At 34-36 weeks, bivariate analyses showed that GPR and lipolysis correlated with estimated foetal weight (r=.71 and .72, respectively) as well as with maternal weight, fat mass and fat-free mass, but not maternal weight gain. In multivariate analyses, rates of both glucose production (r=.42) and lipolysis (r=.47) were independently associated with foetal size explaining 63% of the variance. Conclusions: Both maternal rates of lipolysis and hepatic glucose production in late gestation are strongly related to estimated foetal weight.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
foetal weight, glucose production, lipolysis, maternal glycaemia, resting energy expenditure
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-335650 (URN)10.1111/cen.13359 (DOI)000409271100008 ()28434207 (PubMedID)
Available from: 2017-12-07 Created: 2017-12-07 Last updated: 2017-12-07Bibliographically approved
Tidblad, A., Gustafsson, J., Marcus, C., Ritzen, M. & Ekström, K. (2017). Metabolic differences between short children with GH peak levels in the lower normal range and healthy children of normal height. Growth Hormone & IGF Research, 34, 22-27
Open this publication in new window or tab >>Metabolic differences between short children with GH peak levels in the lower normal range and healthy children of normal height
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2017 (English)In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 34, p. 22-27Article in journal (Refereed) Published
Abstract [en]

Objective: Severe growth hormone deficiency (GHD) leads to several metabolic effects in the body ranging from abnormal body composition to biochemical disturbances. However, less is known regarding these parameters in short children with GH peak levels in the lower normal range during provocation tests. Our aim was to study the metabolic profile of this group and compare it with that of healthy children of normal height.

Design: Thirty-five pre-pubertal short children (< - 2.5 SDS) aged between 7 and 10 years, with peak levels of GH between 7 and 14 mu g/L in an arginine insulin tolerance test (AITT), were compared with twelve age- and sex-matched children of normal height. The metabolic profile of the subjects was analysed by blood samples, DEXA, frequently sampled intravenous glucose tolerance test, microdialysis and stable isotope examinations of rates of glucose production and lipolysis.

Results: There were no overall significant metabolic differences between the groups. However, in the subgroup analysis, the short children with GH peaks < 10 mu g/L had significantly lower fasting insulin levels which also correlated to other metabolic parameters.

Conclusion: The short pre-pubertal children with GH peak levels between 7 and 14 mu g/L did not differ significantly from healthy children of normal height but subpopulations within this group show significant metabolic differences.

Place, publisher, year, edition, pages
CHURCHILL LIVINGSTONE, 2017
Keywords
Growth hormone, Short stature, Childhood, Metabolism, Insulin sensitivity
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-330744 (URN)10.1016/j.ghir.2017.04.001 (DOI)000405048700004 ()28482270 (PubMedID)
Available from: 2017-10-09 Created: 2017-10-09 Last updated: 2017-10-09Bibliographically approved
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