| 1. |
- Gullstrand, Camilla, 1977-, et al.
(författare)
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Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study
- 2008
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 9:3 PART 1, s. 182-190
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Tidskriftsartikel (refereegranskat)abstract
- Background: Autoantibodies against beta-cell antigens together with human leukocyte antigen (HLA)-risk genotypes are used as predictive markers for type 1 diabetes (T1D). In this study, we have investigated the role of HLA-risk and -protective genotypes for development of beta-cell autoantibodies and progression to T1D in healthy children. Methods: T1D-related HLA genotypes and autoantibodies against glutamic acid decarboxylase [glutamic acid decarboxylase antibodies (GADA)] and islet antigen-2 (IA-2A) were studied at 1, 2.5 and 5 yr of age in unselected healthy children and children with T1D participating in the All Babies In Southeast Sweden (ABIS) study. Results: GADA or IA-2A positivity at 5 yr of age was associated with DR4-DQ8 haplotype and DR3-DQ2/DR4-DQ8 genotype. By the age of 6-7 yr, we identified 32 children with T1D among the 17 055 participants in the ABIS study. Eight of 2329 (0.3%) non-diabetic children had permanent autoantibodies, and 143 of 2329 (6%) children had transient autoantibodies. HLA-risk genotypes associated with T1D, whereas protective genotypes were seldom found in children with T1D. Children with permanent autoantibodies had more often risk-associated DR4-DQ8 haplotype than autoantibody-negative children. No associations with HLA-risk or -protective genotypes were found for transient autoantibodies. Conclusions: The strong relation between HLA-risk alleles and T1D once again confirmed that HLA-risk genotypes play an important role for development of T1D. However, HLA genotypes seem not to explain induction of autoantibodies, especially transient autoantibodies, in the general population, emphasizing the role of environmental factors in the initiation of autoimmunity. It seems that HLA-risk genotypes are responsible for maturation of the permanent autoantibody response. © 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard.
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| 2. |
- Holmberg, Hanna, et al.
(författare)
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Short duration of breast-feeding as a risk-factor for β-cell autoantibodies in 5-year-old children from the general population
- 2007
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Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 97:1, s. 111-116
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Tidskriftsartikel (refereegranskat)abstract
- Breast-feeding has been suggested to have a protective effect against the development of type 1 diabetes. In the present study, we investigated the relation between duration of breast-feeding and β-cell autoantibodies in 5-year-old non-diabetic children who participated in a prospective population-based follow-up study (the All Babies in Southeast Sweden study). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tyrosine phosphatase-like IA-2 (IA-2A) were measured by radiobinding assays. A short duration of total breast-feeding was associated with an increased risk of GADA and/or IAA above the ninety-fifth percentile at 5 years of age (OR 2-09, 95% CI 1-45, 3-02; P<0-000) as well as with an increased risk of IAA above the ninety-fifth percentile at this age (OR 2-89, 95% CI 1-81, 4-62; P<0-000). A short duration of exclusive breast-feeding was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 2-01, 95% CI 1-08, 3-73; P = 0-028) as well as with an increased risk of IA-2A above the ninety-ninth percentile (OR 3-50, 95% CI 1-38, 8-92; P = 0-009) at 5 years of age. An early introduction of formula was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 1-84, 95% CI 1-01, 3-37; P = 0-047) at 5 years of age. The positive association between a short duration of both total and exclusive breast-feeding, as well as an early introduction of formula, and positivity for β-cell autoantibodies in children from the general population suggests that breast-feeding modifies the risk of β-cell autoimmunity, even years after finishing breast-feeding.
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| 3. |
- Hyllienmark, Lars, et al.
(författare)
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Early Electrophysiological Abnormalities and Clinical Neuropathy A prospective study in patients with type 1 diabetes
- 2013
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:10, s. 3187-3194
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEThe aim of this study was to elucidate whether subclinical nerve dysfunction as reflected by neurophysiological testing predicts the development of clinical neuropathy in patients with type 1 diabetes.RESEARCH DESIGN AND METHODSFifty-nine patients were studied twice with neurophysiological measurements at baseline and at follow-up. At baseline, patients were 15.5 3.22 years (range 7-22 years) of age, and duration of diabetes was 6.8 3.3 years. At follow-up, patients were 20-35 years of age, and disease duration was 20 +/- 5.3 years (range 10-31 years).RESULTSAt baseline, patients showed modestly reduced nerve conduction velocities and amplitudes compared with healthy subjects, but all were free of clinical neuropathy. At follow-up, clinical neuropathy was present in nine (15%) patients. These patients had a more pronounced reduction in peroneal motor nerve conduction velocity (MCV), median MCV, and sural sensory nerve action potential at baseline (P andlt; 0.010-0.003). In simple logistic regression analyses, the predictor with the strongest association with clinical neuropathy was baseline HbA(1c) (R-2 = 48%, odds ratio 7.9, P andlt; 0.002) followed by peroneal MCV at baseline (R-2 = 38%, odds ratio 0.6, P andlt; 0.006). With the use of a stepwise forward analysis that included all predictors, first baseline HbA(1c) and then only peroneal MCV at baseline entered significantly (R-2 = 61%). Neuropathy impairment assessment showed a stronger correlation with baseline HbA(1c) ( = 0.40, P andlt; 0.002) than with follow-up HbA(1c) ( = 0.034, P andlt; 0.007).CONCLUSIONSEarly defects in nerve conduction velocity predict the development of diabetic neuropathy. However, the strongest predictor was HbA(1c) during the first years of the disease.
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| 4. |
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| 5. |
- Landberg, Eva, 1966-, et al.
(författare)
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Detection of molecular variants of prolactin in human serum, evaluation of a method based on ultrafiltration
- 2007
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981 .- 1873-3492. ; 376:1-2, s. 220-225
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn human blood, there are several molecular variants of prolactin with different biological effects. There is a need for new methods to detect and quantify these variants in order to fully understand the pathophysiological role of prolactin.MethodsA method based on ultrafiltration was optimized, validated and compared to PEG precipitation. Serum samples from 84 patients were analyzed before and after pre treatment on two immunoassays, Elecsys (Roche) and Access (Beckman). Protein G precipitation was used to confirm presence of macroprolactin.ResultsThe recovery of prolactin after ultrafiltration was lower than after PEG precipitation. A limit of 40% recovery after PEG precipitation corresponded to 27% recovery after ultrafiltration. Using these limits there were total agreement regarding detection of macroprolactin (rs = 0.96). In contrast, recovery of prolactin in samples without macroprolactin showed a considerable disagreement between ultrafiltration and PEG precipitation (rs = 0.48). Within-run CV was 4% for the ultrafiltration method. The correlation coefficient (r) between the immunoassays was 0.96 after ultrafiltration.ConclusionsUltrafiltration can be used to compare different prolactin immunoassays and to detect macroprolactin in assays with interference from PEG. For samples without macroprolactin ultrafiltration may give additional information reflecting individual variations of other molecular variants of prolactin.
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| 6. |
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| 7. |
- Nilsson, Anna G, 1968, et al.
(författare)
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Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study.
- 2017
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Ingår i: European journal of endocrinology. - : BIOSCIENTIFICA LTD. - 1479-683X .- 0804-4643. ; 176:6, s. 715-725
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI).Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden.Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires.Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6-5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P < 0.0001) and HDL cholesterol (0.2 mmol/L; P < 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008).In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment.
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| 8. |
- Onnestam, Lisa, et al.
(författare)
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National Incidence and Prevalence of TSH-Secreting Pituitary Adenomas in Sweden
- 2013
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 98:2, s. 626-635
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Tidskriftsartikel (refereegranskat)abstract
- Context: TSH-secreting pituitary adenomas (TSHomas) are rare. Epidemiological data are scant and there are no reports on national incidence. less thanbrgreater than less thanbrgreater thanObjective: The objective of the study was to estimate the national Swedish incidence and prevalence of TSHomas. less thanbrgreater than less thanbrgreater thanDesign: This was an observational study. less thanbrgreater than less thanbrgreater thanSetting: The study was conducted at tertiary referral centers. less thanbrgreater than less thanbrgreater thanPatients: The Swedish Pituitary Registry and World Health Organization International Statistical Classification of Diseases and Related Health Problems coding at all university hospitals were used to identify patients diagnosed with TSHomas 1990-2010. The identified patients medical records were studied until the latest follow-up [median 5.0 years (range andlt; 1-20 years)]. less thanbrgreater than less thanbrgreater thanMain Outcome Measurements: Incidence, prevalence, demographics, tumor characteristics, treatment outcome, and thyroid hormone level at diagnosis were measured. less thanbrgreater than less thanbrgreater thanResults: The age-standardized national incidence of 28 TSHoma patients was 0.15 per 1 million inhabitants per year, with an increasing incidence over time (0.05 per 1 million per year in 1990-1994 to 0.26 per 1 million per year in 2005-2009). The national prevalence in 2010 was 2.8 per 1 million inhabitants, in which 0.85 per 1 million had active disease. Most patients (n = 22) underwent pituitary surgery, 5 had radiotherapy, and 6 had somatostatin analogues. Eighteen patients were considered cured at the latest follow-up; 25% remained uncontrolled. Subjects treated for putative primary hyperthyroidism prior to diagnosis had TSH levels more than double those with intact thyroid at diagnosis (P = .013). The median time to diagnosis was longer for women than men (4 vs andlt; 1 year, P = .026). More women than men were treated surgically (94.1% vs 54.5%, P = .022). less thanbrgreater than less thanbrgreater thanConclusion: This is the first estimate of a national incidence of TSHoma. Additional epidemiological studies are needed to compare these results with other geographical areas. This study suggests an increased incidence of TSHomas, in agreement with reports on other pituitary adenomas. (J Clin Endocrinol Metab 98: 626-635, 2013)
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| 9. |
- Svanberg, Christina, et al.
(författare)
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Cephalometric analysis of adults with Turner syndrome
- 2016
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Ingår i: Swedish Dental Journal. - : SWEDISH DENTAL JOURNAL. - 0347-9994. ; 40:1, s. 33-41
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Tidskriftsartikel (refereegranskat)abstract
- Turner syndrome (TS) is a genetic disorder of females with a prevalence of 1/2000-3000 live female births. The aim of this study was to compare cephalometric variables from adult women diagnosed with TS to a standardized reference group of 31-year old healthy women, and to evaluate the possible effects of human growth hormone (hGH) therapy in women with TS. Registered TS subjects in the Southeast region of Sweden were invited to take part in the study. Twenty-one women aged 36 +/- 13(18-57) years accepted participation. Lateral radiographs of the head were analyzed using standard cephalometric methods (Hasund analysis) and with the commercially available soft-ware program FACAD. Comparisons were made with roentgen-cephalometric standards from a reference group of nineteen 31-year old Swedish women. Analysis of the cephalometric radiographs from the TS subjects showed a more retrognathic maxilla (SNA 80.3 +/- 5.4) (p=0.0460) and mandible (SNB 77.0 +/- 5.2) (p=0.0014), and a correspondingly backward position of the chin (SN/Pg 78.9 +/- 5.5) (p=0.0046) as compared to the reference values of 31-year old women (SNA 83.2 +/- 3.0, SNB 81.5 +/- 2.3 and SNPg 83.0 +/- 2.3, respectively). In addition there was an increased posterior inclination of the maxilla (SN/NL 8.6 +/- 4.1), as compared to the reference values (SN/NL 5,3 +/- 2.7) (p=0.0048). There were no significant differences regarding sagittal or vertical jaw relations, mandibular inclination or cranial base angle between the TS-group and the 31-year olds with the reference values. No significant difference was seen in jaw relationship, as measured by the ANB value, however the Wits(index) (3.3 +/- 3.5) was higher (p=0.0001) than the reference values (-0.1 +/- 1.8). Subjects with or without previous hGH administration did not show any significant differences in cephalometric values. In conclusion, women with TS had a significantly more retrognathic maxilla (SNA) and mandible (SNB) and a correspondingly significantly posterior position of the chin (SN/Pg), a significantly increased posterior inclination of the maxilla (SN/NL) and a significantly increased Witsindex as compared to the reference group of 31-year old women. No craniofacial variables differed significantly between previously hGH-treated and not hGH-treated women with TS.
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| 10. |
- Wahlberg Topp, Jeanette, et al.
(författare)
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Effects of prolactin on platelet activation and blood clotting
- 2013
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa Healthcare. - 0036-5513 .- 1502-7686. ; 73:3, s. 221-228
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Tidskriftsartikel (refereegranskat)abstract
- Increased levels of prolactin often coincide with an increased risk for thromboembolic events, but it is unclear whether a direct causal relation exists. Our aim was to examine the effect of prolactin on platelet function. In addition to using recombinant prolactin for experiments in vitro, we analyzed platelet function by flow cytometry in a group of 13 females with hyperprolactinaemia and 18 healthy female controls. Platelet activation was measured by P-selectin expression and by the amount of platelet-bound fibrinogen after stimulation with adenosine diphosphate (ADP), collagen-related peptide and the protease activated receptor (thrombin receptor) (PAR)-activating peptides PAR4-AP and PAR1-AP. Free oscillation rheometry was used to measure clotting time in whole blood. No significant effect on platelet activation or clotting time could be seen in in vitro experiments by adding recombinant prolactin. However, significantly lower P-selectin expression was found in the hyperprolactinemic group when platelets were activated by ADP (5 and 10 mu M) or PAR4-AP. The expression of fibrinogen did not differ between the two groups for any of the activators used. For all samples, inverse significant correlations between P-selectin expression and prolactin concentration were found for both 5 mu M ADP (r = 0.61, p andlt; 0.01), 10 mu M ADP (r = -0.62, p andlt; 0.001) and PAR4-AP (r = -0.69, p andlt; 0.001). Thrombin cleavage of recombinant prolactin resulting in a 16 kDa C-terminal fragment did not alter the P-selectin expression upon activation. We found an indirect inhibitory effect of prolactin on platelets in hyperprolactinemic patients, suggesting that prolactin might have a protective role in thromboembolic disease.
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