| 1. |
|
|
| 2. |
- Asad, Samina, et al.
(author)
-
HTR1A a Novel Type 1 Diabetes Susceptibility Gene on Chromosome 5p13-q13
- 2012
-
In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:5
-
Journal article (peer-reviewed)abstract
- Background: We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD less than= 2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D susceptibility genes. Methodology/Principal Findings: Microsatellites were genotyped in the Scandinavian families to fine-map the previously linked region. Further, SNPs were genotyped in Swedish and Danish families as well as Swedish sporadic cases. In the Swedish families we detected genome-wide significant linkage to the 5-hydroxytryptamine receptor 1A (HTR1A) gene (LOD 3.98, pless than9.8x10(-6)). Markers tagging two separate genes; the ring finger protein 180 (RNF180) and HTR1A showed association to T1D in the Swedish and Danish families (pless than0.002, pless than0.001 respectively). The association was not confirmed in sporadic cases. Conditional analysis indicates that the primary association was to HTR1A. Quantitative PCR show that transcripts of both HTR1A and RNF180 are present in human islets of Langerhans. Moreover, immunohistochemical analysis confirmed the presence of the 5-HTR1A protein in isolated human islets of Langerhans as well as in sections of human pancreas. Conclusions: We have identified and confirmed the association of both HTR1A and RFN180, two genes in high linkage disequilibrium (LD) to T1D in two separate family materials. As both HTR1A and RFN180 were expressed at the mRNA level and HTR1A as protein in human islets of Langerhans, we suggest that HTR1A may affect T1D susceptibility by modulating the initial autoimmune attack or either islet regeneration, insulin release, or both.
|
|
| 3. |
- Bixo Ottosson, Anna, et al.
(author)
-
Self-care management of type 1 diabetes has improved in Swedish schools according to children and adolescents
- 2017
-
In: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 106:12, s. 1987-1993
-
Journal article (peer-reviewed)abstract
- Aim: Age-appropriate support for diabetes self-care is essential during school time, and we investigated the perceived quality of support children and adolescents received in 2015 and 2008.Methods: This national study was based on questionnaires answered by children and adolescents aged 6–15 years of age with type 1 diabetes attending schools or preschools in 2008 (n = 317) and 2015 (n = 570) and separate parental questionnaires. The subjects were recruited by Swedish paediatric diabetes units, with 41/44 taking part in 2008 and 41/42 in 2015.Results: Fewer participants said they were treated differently in school because of their diabetes in 2015 than 2008. The opportunity to perform insulin boluses and glucose monitoring in privacy increased (80% versus 88%; p < 0.05). Most (83%) adolescents aged 13–15 years were satisfied with the support they received, but levels were lower in girls (p < 0.05). More subjects had hypoglycaemia during school hours (84% versus 70%, p < 0.001), but hypoglycaemia support did not increase and was lower for adolescents than younger children (p < 0.001).Conclusion: Children and adolescents received more support for type 1 diabetes in Swedish schools in 2015 than 2008, but more support is needed by girls and during hypoglycaemia.
|
|
| 4. |
|
|
| 5. |
- Boman, Åse, 1957-, et al.
(author)
-
Conceptions of Diabetes and Diabetes Care in Young People With Minority Backgrounds.
- 2015
-
In: Qualitative Health Research. - : SAGE Publications. - 1049-7323 .- 1552-7557. ; 25:1, s. 5-15
-
Journal article (peer-reviewed)abstract
- Adolescents with type 1 diabetes (T1DM) need stable self-care routines for good metabolic control to minimize future cardiovascular health complications. These routines are demanding, and might be particularly challenging in underprivileged groups. The aim of this study was to gain in-depth knowledge on the experience of adolescents with T1DM and a non-Swedish background regarding factors that might influence their ability to take care of themselves; in particular, factors that might influence diabetes management routines, their social situation, and the support they receive from caregivers. We interviewed 12 adolescents with T1DM and minority backgrounds. The results indicated resources and constraints in the adolescents' social context and in the health care organization. The adolescents developed conceptions that helped to explain and excuse their self-care failures, and their successes. These findings highlight the importance of integrating T1DM as part of the individual's personal prerequisites. We discuss implications for the organization of diabetes care for adolescents.
|
|
| 6. |
- Boman, Åse, 1957-, et al.
(author)
-
Health care to empower self-care in adolescents with type 1 diabetes mellitus and an immigrant minority background
- 2017
-
In: Sage Open medicine. - : SAGE Publications. - 2050-3121 .- 2050-3121. ; 5
-
Journal article (peer-reviewed)abstract
- Background: The pediatric diabetes team aims to support health, quality of life, and normal growth and development among adolescents with type 1 diabetes mellitus. Adolescents with an immigrant background have been found less successful in self-care. Previous research indicated that adolescents who had integrated the disease as a part of their self-image reasoned differently about their self-care to those who had not. Objective: The aim of this study was to identify elements in the patient–pediatrician consultations that might influence such integration of the disease among adolescents with type 1 diabetes mellitus. Methods: A total of 12 pediatrician–adolescent consultations were video-recorded and analyzed. The adolescents all had an immigrant background. Results: Integration of the disease appeared enabled when responsibility was shared; when hope, autonomy, and emotions were confirmed; and when the pediatrician asked probing questions. Letting objective data dominate the adolescent’s experiences, using risk as a motivator, neutralizing emotions in relation to having diabetes, and confirming forgetfulness, may instead inhibit disease integration. Conclusion: An extended person-centered approach with focus on the adolescent’s experiences of everyday life with a chronic disease and less attention on physical parameters in the pediatrician–adolescent consultations may increase integration of the disease.
|
|
| 7. |
|
|
| 8. |
- Bybrant, M. C., et al.
(author)
-
Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes
- 2021
-
In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 22:3, s. 417-424
-
Journal article (peer-reviewed)abstract
- Objectives Children with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti-tTG) that were >= 10 times the upper limit of normal (10x ULN) predicted CD in T1D. Methods Data from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005-2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti-tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti-tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh-Oberhuber classification. Results All of the 60 children with anti-tTG >= 10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti-tTG levels. Among 2003 screened children, 6.9% had positive anti-tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA-DQ2 and/or DQ8. Conclusions As all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method.
|
|
| 9. |
- Bybrant, M. C., et al.
(author)
-
Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study
- 2018
-
In: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 51:5, s. 221-227
-
Journal article (peer-reviewed)abstract
- Objectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).Patients and methods: Dried blood spots and serum samples were taken at diagnosis from children <18years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p=.00001) and those with DQX/X (p.00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p=.018).Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.
|
|
| 10. |
- Carlsson, Annelie, et al.
(author)
-
10 år med BDD-studien har gett bättre diabetesdiagnos hos barn : Studiens analysbatteri är nu klinisk rutin och kunskapen om olika diabetessjukdomar har ökat
- 2018
-
In: Läkartidningen. - 0023-7205. ; 115:11, s. 484-484
-
Journal article (peer-reviewed)abstract
- The Swedish study Better Diabetes Diagnosis (BDD) has now been ongoing for ten years and detailed information and blood samples have been collected from more than 8000 children and adolescents with newly diagnosed diabetes. We have been able to demonstrate that by means of HLA diabetes antibodies and C-peptide the discrimination between type one and type 2 diabetes is improved. These analyses are therefore included in the clinical check-up for all children and adolescents in Sweden who are diagnosed with diabetes. Type 1 diabetes is by far the most prevalent type of diabetes among Swedish children and adolescents. Type 2 diabetes is still relatively rare in Sweden but it is urgent to obtain a correct diagnosis as the long-term prognosis depends on a prompt pharmacological treatment. Monogenic diabetes (MODY) is also important to identify early. We therefore recommend that sequencing of MODY genes should be performed if an individual with newly-diagnosed diabetes is auto-antibody negative and has an HLA pattern associated with low risk for type 1 diabetes. However, despite these analytical tools it can be difficult to make the correct diabetes diagnosis initially. It is therefore prudent to re-evaluate the diabetes diagnosis after one year.
|
|
| 11. |
- Carlsson, Annelie, et al.
(author)
-
A multicenter observational safety study in Swedish children and adolescents using insulin detemir for the treatment of type 1 diabetes
- 2013
-
In: Pediatric Diabetes. - : Wiley-Blackwell. - 1399-543X .- 1399-5448. ; 14:5, s. 358-365
-
Journal article (peer-reviewed)abstract
- This 26-wk observational study in children and adolescents with type 1 diabetes (T1D) in Sweden investigated the safety and efficacy of insulin detemir (IDet) in newly diagnosed (ND) patients and those with established diabetes (ED) switching to IDet. A total of 159 patients initiated IDet as part of basal-bolus therapy, 59 in the ND stratum (mean age 9.7yr) and 97 in the ED stratum (mean age 12.5 yr). The primary outcome measure was the incidence of severe adverse drug reactions; just one major hypoglycemic event occurred in a patient in the ND stratum during the study and one patient was withdrawn due to injection-site reactions. All other events were classified as mild. In the ED stratum, there was a reduction in hypoglycemic events in the 4wk prior to study end from baseline (mean reduction of 2.46 events, not significant) and a significant reduction in nocturnal hypoglycemia (mean reduction of 2.24 events, p=0.0078). Glycemic control improved in the ND stratum as expected and, in the ED stratum, there was no significant change in HbA1c from baseline (mean reduction of -0.45%). At study end, mean daily IDet doses were 0.39U/kg (ND) and 0.54U/kg (ED). Weight increased by 5.7 and 2.0kg in the ND and ED strata, respectively, and was within the normal limits for growing children. IDet provided good glycemic control and was well tolerated, with a reduced risk of nocturnal hypoglycemia in a heterogeneous cohort of children and adolescents with T1D.
|
|
| 12. |
- Carlsson, Annelie, et al.
(author)
-
Absence of Islet Autoantibodies and Modestly Raised Glucose Values at Diabetes Diagnosis Should Lead to Testing for MODY : Lessons From a 5-Year Pediatric Swedish National Cohort Study
- 2020
-
In: Diabetes Care. - Arlington, VA, United States : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:1, s. 82-89
-
Journal article (peer-reviewed)abstract
- OBJECTIVE Identifying maturity-onset diabetes of the young (MODY) in pediatric populations close to diabetes diagnosis is difficult. Misdiagnosis and unnecessary insulin treatment are common. We aimed to identify the discriminatory clinical features at diabetes diagnosis of patients with glucokinase (GCK), hepatocyte nuclear factor-1A (HNF1A), and HNF4A MODY in the pediatric population.RESEARCH DESIGN AND METHODS Swedish patients (n = 3,933) aged 1–18 years, diagnosed with diabetes May 2005 to December 2010, were recruited from the national consecutive prospective cohort Better Diabetes Diagnosis. Clinical data, islet autoantibodies (GAD insulinoma antigen-2, zinc transporter 8, and insulin autoantibodies), HLA type, and C-peptide were collected at diagnosis. MODY was identified by sequencing GCK, HNF1A, and HNF4A, through either routine clinical or research testing.RESULTS The minimal prevalence of MODY was 1.2%. Discriminatory factors for MODY at diagnosis included four islet autoantibody negativity (100% vs. 11% not-known MODY; P = 2 × 10−44), HbA1c (7.0% vs. 10.7% [53 vs. 93 mmol/mol]; P = 1 × 10−20), plasma glucose (11.7 vs. 26.7 mmol/L; P = 3 × 10−19), parental diabetes (63% vs. 12%; P = 1 × 10−15), and diabetic ketoacidosis (0% vs. 15%; P = 0.001). Testing 303 autoantibody-negative patients identified 46 patients with MODY (detection rate 15%). Limiting testing to the 73 islet autoantibody-negative patients with HbA1c <7.5% (58 mmol/mol) at diagnosis identified 36 out of 46 (78%) patients with MODY (detection rate 49%). On follow-up, the 46 patients with MODY had excellent glycemic control, with an HbA1c of 6.4% (47 mmol/mol), with 42 out of 46 (91%) patients not on insulin treatment.CONCLUSIONS At diagnosis of pediatric diabetes, absence of all islet autoantibodies and modest hyperglycemia (HbA1c <7.5% [58 mmol/mol]) should result in testing for GCK, HNF1A, and HNF4A MODY. Testing all 12% patients negative for four islet autoantibodies is an effective strategy for not missing MODY but will result in a lower detection rate. Identifying MODY results in excellent long-term glycemic control without insulin.
|
|
| 13. |
- Carlsson, Annelie, et al.
(author)
-
Diabetes
- 2012. - 4
-
In: Barnmedicin. - 9789144076096 ; , s. 531-541
-
Book chapter (peer-reviewed)
|
|
| 14. |
|
|
| 15. |
- Delli, Ahmed, et al.
(author)
-
Type 1 diabetes patients born to immigrants to Sweden increase their native diabetes risk and differ from Swedish patients in HLA types and islet autoantibodies
- 2010
-
In: Pediatric Diabetes. - : Blackwell Publishing Ltd. - 1399-543X .- 1399-5448. ; 11:8, s. 513-520
-
Journal article (peer-reviewed)abstract
- Aim: To determine whether type 1 diabetes mellitus (T1DM) patients, having parents who immigrated to Sweden, have increased T1DM risk before 18 yr compared with countries of origin. We also determined whether they have different human leukocyte antigen (HLA) genetic markers and islet autoantibodies at diagnosis compared with Swedish patients. Methods: A total of 1988 (53% males) newly diagnosed and confirmed T1DM patients less than 18 yr registered within the Better Diabetes Diagnosis (BDD) study (May 2005 to September 2008) were included. Participants were classified into three groups: Swedish, non-Swedish, and Mixed-origin patients according to country of origin of two generations (parents and grandparents). These groups were compared with respect to T1DM HLA markers and islet autoantibodies [glutamic acid decarboxylase autoantibodies (GAD65Ab), insulin autoantibodies (IAA), and islet antigen-2 autoantibodies (IA-2Ab)]. Results: Only 30 (1.5%) patients were born outside Sweden. Swedish patients constituted 66%, non-Swedish patients 8%, Mixed origins 17%, and 9% were of uncertain origin. Confirmed T1DM in patients within the study was 22 (95% CI: 21-23) patients/105/yr rate for Swedish patients compared with 14 (95% CI: 13-15) among non-Swedish patients. The HLA-DQ8 haplotype (p less than 0.0001) and DQ2/8 genotype (p less than 0.02) predominated among Swedish compared with non-Swedish patients. In contrast, DQ2 was the most frequent haplotype among non-Swedish patients [OR = 1.5 (95% CI: 1.0-2.0), p less than 0.04]. Multiple (greater than= 2) autoantibodies (p less than 0.04) and specifically IA-2Ab (p less than 0.001) were most prevalent among the Swedish patients. Multiple autoantibodies were associated with DQ8 among the Swedish patients only (p less than 0.001). Conclusion: Patients born to parents who had immigrated to the high T1DM incidence environment of Sweden have, compared with Swedish patients, more frequent HLA-DQ2 genetic markers and are diagnosed more often with GAD65Ab.
|
|
| 16. |
- Delli, Ahmed, et al.
(author)
-
Zinc Transporter 8 Autoantibodies and Their Association With SLC30A8 and HLA-DQ Genes Differ Between Immigrant and Swedish Patients With Newly Diagnosed Type 1 Diabetes in the Better Diabetes Diagnosis Study
- 2012
-
In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:10, s. 2556-2564
-
Journal article (peer-reviewed)abstract
- We examined whether zinc transporter 8 autoantibodies (ZnT8A; arginine ZnT8-RA, tryptophan ZnT8-WA, and glutamine ZnT8-QA variants) differed between immigrant and Swedish patients due to different polymorphisms of SLC30A8, HLA-DQ, or both. Newly diagnosed autoimmune (andgt;= 1 islet autoantibody) type 1 diabetic patients (n = 2,964, andlt;18 years, 55% male) were ascertained in the Better Diabetes Diagnosis study. Two subgroups were identified: Swedes (n = 2,160, 73%) and immigrants (non-Swedes; n = 212, 7%). Non-Swedes had less frequent ZnT8-WA (38%) than Swedes (50%), consistent with a lower frequency in the non-Swedes (37%) of SLC30A8 CT+TT (RW+WW) genotypes than in the Swedes (54%). ZnT8-RA (57 and 58%, respectively) did not differ despite a higher frequency of CC (RR) genotypes in non-Swedes (63%) than Swedes (46%). We tested whether this inconsistency was due to HLA-DQ as 2/X (2/2; 2/y; y is anything but 2 or 8), which was a major genotype in non-Swedes (40%) compared with Swedes (14%). In the non-Swedes only, 2/X (2/2; 2/y) was negatively associated with ZnT8-WA and ZnT8-QA but not ZnT8-RA. Molecular simulation showed nonbinding of the relevant ZnT8-R peptide to DQ2, explaining in part a possible lack of tolerance to ZnT8-R. At diagnosis in non-Swedes, the presence of ZnT8-RA rather than ZnT8-WA was likely due to effects of HLA-DQ2 and the SLC30A8 CC (RR) genotypes.
|
|
| 17. |
- Enander, Rebecka, et al.
(author)
-
Beta cell function after intensive subcutaneous insulin therapy or intravenous insulin infusion at onset of type 1 diabetes in children without ketoacidosis.
- 2018
-
In: Pediatric diabetes. - : Hindawi Limited. - 1399-5448 .- 1399-543X. ; 19:6, s. 1079-1085
-
Journal article (peer-reviewed)abstract
- Our aim was to see if IV insulin therapy at diagnosis preserves beta-cell function better than multiple subcutaneous (SC) injections.Fifty-four children 9.9 ± 3.5years (range 2.8-14.9) without ketoacidosis were included in a 2years, randomized multicenter study with insulin SC or 48 to 72hours IV initially. Thirty-three (61%) were boys, 22 (41%) were pubertal. Forty-eight subjects completed 12 months follow-up and 43 completed 24 months. At 1, 6, 12, and 24 months, hemoglobin A1c (HbA1c), C-peptide and insulin/kg/24 h were measured. At 24 months, a mixed-meal tolerance test (MMTT) was performed.HbA1c at diagnosis was 10.7%, (93mmol/mol) for IV, 10.7%, (94mmol/mol) for SC. During the first 2 full days of insulin therapy, mean plasma glucose was 8.2 mmol/L for IV, 9.5 for SC (P =.025). Mean insulin dose was 1.5 U/kg/d for IV vs 1.0 for SC (P =.001). Sixteen (7 in IV, 9 in SC group) started with insulin pumps during the follow-up. At 24 months, we saw no significant differences: HbA1c (7.5%, 58mmol/mol, for IV, 7.2%, 55mmol/mol, for SC; ns), insulin doses (0.79 vs 0.88U/kg/d; ns), fasting C-peptide (0.08 vs 0.12nmol/L; ns), maximal MMTT response (0.19 vs 0.25nmol/L; ns) and AUC (18.26 vs 23.9 nmol/L*min; ns). Peak C-peptide >0.2 nmol/L in the combined IV and SC groups correlated significantly with HbA1c and C-peptide at onset in a multiple regression.Residual beta cell function at 2years seems to be independent from initial insulin regimens but related to HbA1c and C-peptide at onset.
|
|
| 18. |
- Forsander, Gun, 1951, et al.
(author)
-
Adolescent life with diabetes-Gender matters for level of distress. Experiences from the national TODS study
- 2017
-
In: Pediatric Diabetes. - : WILEY. - 1399-543X .- 1399-5448. ; 18:7, s. 651-659
-
Journal article (peer-reviewed)abstract
- Objective: To examine the relationship between diabetes distress and gender, and the association with glycemic control, social support, health behaviors, and socio-economic status. Methods: All adolescents, aged 15 to 18 years, in the national, pediatric diabetes registry SWE-DIABKIDS with type 1 diabetes were invited to complete an online questionnaire. A total of 2112 teenagers were identified. Results: 453 complete responses were valid for analyses. Young women scored significantly higher on the distress-screening instrument DDS-2. Almost half of the female respondents exhibited moderate to severe diabetes distress-more than twice the proportion than among male respondents (44% vs 19%). Females reported twice as high scores on the fear of hypoglycemia scale (P amp;lt; 0.0001) and had a higher HbA1c value than males (P amp;lt; 0.0001). Gender was highly correlated with distress level even when controlling for multiple factors that may affect distress (parameter(female) = 0.4, P = 0.0003). Particular social problems were highly significant, that is, those who trust that their parents can handle their diabetes when necessary were significantly less distressed than others (P = 0.018). Higher HbA1c levels were associated with higher distress scores (P = 0.0005 [female], P = 0.0487 [male]). Conclusions: Diabetes-related distress is a great burden for adolescents living with diabetes. Actively involved family and friends may reduce diabetes distress, but female adolescents appear to be particularly vulnerable and may need extra focus and support. Our findings indicate that pediatric diabetes teams working with teenagers must intensify the care during this vulnerable period of life in order to reduce the risk of both psychological and vascular complications in young adults.
|
|
| 19. |
- Forsander, Gun
(author)
-
Clinical management of children with type I diabetes mellitus : a prospective, randomized psycho-educational intervention trial
- 2000
-
Doctoral thesis (other academic/artistic)abstract
- The basic question addressed in this investigation was: is it possible to exert a significant influence on the course of diabetes mellitus in children by the use of a specific initial management regimen? The conventionally, hospital care treatment regimen (control group) was compared to a multi-disciplinary programme for family-oriented crises intervention with a learn-by-doing pedagogy and care in a therapeutic environment (study group). The reactions and the adjustment to the new family situation with a diabetic child were elucidated. The long-term (i.e., 5y) metabolic control and factors with influence on poor long-term glycaemic control were explored. The social situation and relationships between the family's social situation and the long-term requirement for in- and out-patient services was studied. The dietary habits were compared to treatment received, the recommended nutritional intake, age, sex and degree of glycaemic control. 38 children, 3-15 years old at diagnosis, were followed prospectively 5 years. The conclusion is that several important aspects of the course of diabetes mellitus in children could be influenced. Family satisfaction with the treatment received was significantly higher in the study group. Two years after diagnosis, the subjective, emotional climate of the family was significantly improved in the case of the mothers and fathers in the study group, but not for the parents in the control group. Long-term glycaemic control was not influenced by the initial treatment regimen. Five years after diagnosis, the overall mean HbA1c value was 7.2% and. 30% of the children had HbA1c values of < 6.3%. An early increase of HbA1c values, large variations in blood glucose levels, the emotional responses and level of formal education of the father and whether or not the child lived in a single-parent family, a higher fat consumption and more pronounced day-to day variance in their intake of energy and certain nutrients characterised children in poorer control. At least as high frequency of divorce as in the general population was observed and younger age and living in a single parent family were associated with a longer total length of readmission to the hospital. The children in both treatment groups complied well with recommendations concerning nutritional intake. Children demonstrating poorer glycaemic control had a higher intake of fat. Factors concerning age, sex and social situation, did not significantly influence the dietary habits of our subjects.
|
|
| 20. |
|
|
| 21. |
- Forsander, Gun, 1951
(author)
-
European Mastercourse in Pediatrics.
- 2011
-
In: Alfred Tenore, Malcolm Levene. Chapter 35.. - : Churchill Livingstone Elsevier.. ; , s. 466-491
-
Book chapter (other academic/artistic)
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Forsander, Gun, 1951, et al.
(author)
-
Influence of the initial management regimen and family social situation on glycemic control and medical care in children with type I diabetes mellitus.
- 2000
-
In: Acta paediatrica (Oslo, Norway : 1992). - 0803-5253. ; 89:12, s. 1462-8
-
Journal article (other academic/artistic)abstract
- It is well known that social family factors are of importance in diabetes care, but it is not clear whether the initial management regimen can buffer these factors. In a prospective, randomized intervention study, 36 children with diabetes mellitus (type I) were followed, the aim being to study if a family psychosocial intervention at diagnosis could improve glycemic control and minimize hospital admissions. The control group was treated initially in a hospital ward, while the study group received problem-based learning and family-therapeutic and social support in an out-hospital training apartment. A number of family social variables were evaluated at the time of diagnosis and 6, 12 and 24 mo later. Family function was assessed using the self-estimated Family Climate Test at these same time-points. HbAlc values and information concerning in- and out-hospital visits to the pediatric clinic were collected for the 5-y period following diagnosis. We found no association between the offered management regimen and glycemic control or rate of readmission. In the study group only, both parents reported a significant improvement of the family climate. An increased risk for poor glycemic control was recorded in children living in one-parent families (p = 0.03) or in families where the father had a low level of education (p = 0.04). Younger age (p = 0.05), a single-parent family (p = 0.05) and poor glycemic control (p = 0.02) were associated with more days of rehospitalization. The rate of divorce in the whole group was at least as high as in the normal population but, surprisingly, maternal dysfunction was associated with lower HbAlc value. The conclusion is that even with an initial management regimen designed to offer a family-individual care regimen based on accurate estimation of the psychological and pedagogical needs, the social family background is a most important factor for the glycemic control and need for readmission.
|
|
| 26. |
- Forsander, Gun, 1951, et al.
(author)
-
Metabolic control in children with insulin-dependent diabetes mellitus 5 y after diagnosis. Early detection of patients at risk for poor metabolic control.
- 1998
-
In: Acta paediatrica (Oslo, Norway : 1992). - 0803-5253. ; 87:8, s. 857-64
-
Journal article (peer-reviewed)abstract
- Children (n = 38) aged 3-15 y were randomly chosen, at the time of diabetes diagnosis, for conventional management at a hospital ward, or for treatment partly in a training apartment where the family was offered problem-based education and special therapeutic support. HbA1c, blood glucose stability, urinary C-peptide excretions and incidence of hypoglycaemic attacks and diabetes ketoacidosis (DKA) were monitored and some standardized, self-estimated psychological tests were performed during the first 2 y after diagnosis. During the 3 y thereafter, HbA1c, presence of DKA, microalbuminuria, retinopathy and hypertension were monitored. None of the patients demonstrated signs of diabetes microangiopathy or DKA. The overall mean HbA1c level was 7.2% 5 y after diagnosis and 30% of the children had HbA1c values <6.3%. There were no differences in the HbA1c values for the patients treated by the different management regimens. Blood glucose variability (SD) was also similar, with 75% of the values in the range of 3-10 mmol/l. Patients with poor glycaemic control (mean HbA1c >8.3%) year 5 after diagnosis had already the second year after diagnosis significantly higher HbA1c values and blood glucose variability. The fathers of these patients demonstrated a higher degree of maladjustment. On the basis of increasing HbA1c values, high blood glucose variability and psychosocial risk factors such as their fathers' emotional responses, patients at risk for poor metabolic control in the future can be identified within 2 y after diagnosis. Efforts and resources can thus be focused at an early stage on this group.
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
- Forsander, Gun, 1951, et al.
(author)
-
Preferences for treatment among adolescents with Type 1 diabetes: a national study using a discrete choice experiment model
- 2018
-
In: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 35:5, s. 621-629
-
Journal article (peer-reviewed)abstract
- AimTo test the possibility of using a discrete choice experiment model, on a national level in adolescents with Type 1 diabetes, in order to obtain a better understanding of drivers of and barriers to diabetes self-care. MethodsA survey instrument was constructed and tested on a small group of the target population: adolescents aged 15 to <18 years with Type 1 diabetes. All individuals in Sweden belonging to this target group (N=2112) were then identified via the Swedish paediatric diabetes quality registry SWEDIABKIDS, and were sent an invitation to answer an online questionnaire. A valid response for the discrete choice experiment analyses was achieved from 431 individuals. ResultsThe included respondents were not statistically different from non-participants in terms of age and duration of diabetes, but more young women entered the study and the participants had (on average) a significantly lower HbA(1c) value than the non-participants. Participants regarded as undesirable both non-severe hypoglycaemic events (day and night) and hyperglycaemic events. Avoiding weight gain and even achieving weight loss were the most important aspects among female respondents, who were willing to trade off a substantial level of glycaemic control [13 mmol/mol (1.2%)] to avoid a weight gain of 3 kg. Hypothetical equipment improvements were desired. ConclusionsThe responses may provide useful indications of the aspects that the respondents would prioritize given a real-life dilemma. For treatment effects, stratification along gender lines was important, whereas the treatment administration aspects were stratified according to treatment type because these aspects are closely related.
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
- Fureman, Anna-Lena, et al.
(author)
-
Partial clinical remission of Type 1 diabetes in Swedish children : A longitudinal study from the Swedish National Quality Register (SWEDIABKIDS) and the Better Diabetes Diagnosis (BDD) study
- 2024
-
In: Diabetes Technology & Therapeutics. - : Mary Ann Liebert. - 1520-9156 .- 1557-8593.
-
Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS: To investigate the frequency and characteristics of partial remission in Swedish children with type 1 diabetes and whether insulin delivery method, i.e., continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) affect incidence and duration of this period 2007-2011. Factors that increase the proportion of subjects that enter partial remission and extend this period can improve long-term metabolic control and reduce the risk of severe hypoglycemia, improve quality of life and in the long run reduce late complications.METHODS: Longitudinal data from 2007-2020 were extracted from the Swedish National Quality Register (SWEDIABKIDS) with all reported newly diagnosed children. Data on C-peptide from the participants in the Better Diabetes Diagnosis study (BDD) from 2007-2010 were used. The definition of partial remission was Insulin Dose Adjusted HbA1c (IDAA1c): HbA1c (%)+(4 x total daily insulin dose (U/kg/day)) ≤9.RESULTS: Of the 3,887 patients, 56% were boys. More boys than girls were in partial remission throughout the follow-up period until 24 months after diabetes onset. Fewer children 0-6 years old had partial remission at 3 and 12 months but not at 24 months compared to older age groups. A larger proportion of patients using CSII at 12 and 24 months remained in partial remission compared to those with MDI (37% vs 33%, p=0.02 and 31% vs 27%, p<0.01 respectively). The level of C-peptide was higher in the group with partial remission and mean HbA1c was lower, both p<0.001. Partial remission at 12 months after diabetes onset was associated with CSII (OR:1.39 CI:1.13, 1.71), shorter diabetes duration (OR:0.80 CI:0.76, 0.84) and male sex (OR:1.23 CI:1.04, 1.46)Conclusions/interpretation: Insulin through MDI, longer duration of diabetes, and female sex were associated with lower frequency of partial remission. Use of CSII seem to contribute to longer partial remission among Swedish children with type 1 diabetes.
|
|
| 33. |
- Garonzi, C., et al.
(author)
-
Impact of Fat Intake on Blood Glucose Control and Cardiovascular Risk Factors in Children and Adolescents with Type 1 Diabetes
- 2021
-
In: Nutrients. - : MDPI AG. - 2072-6643. ; 13:8
-
Journal article (peer-reviewed)abstract
- Nutrition therapy is a cornerstone of type 1 diabetes (T1D) management. Glycemic control is affected by diet composition, which can contribute to the development of diabetes complications. However, the specific role of macronutrients is still debated, particularly fat intake. This review aims at assessing the relationship between fat intake and glycemic control, cardiovascular risk factors, inflammation, and microbiota, in children and adolescents with T1D. High fat meals are followed by delayed and prolonged hyperglycemia and higher glycated hemoglobin A1c levels have been frequently reported in individuals with T1D consuming high amounts of fat. High fat intake has also been associated with increased cardiovascular risk, which is higher in people with diabetes than in healthy subjects. Finally, high fat meals lead to postprandial pro-inflammatory responses through different mechanisms, including gut microbiota modifications. Different fatty acids were proposed to have a specific role in metabolic regulation, however, further investigation is still necessary. In conclusion, available evidence suggests that a high fat intake should be avoided by children and adolescents with T1D, who should be encouraged to adhere to a healthy and balanced diet, as suggested by ISPAD and ADA recommendations. This nutritional choice might be beneficial for reducing cardiovascular risk and inflammation.
|
|
| 34. |
- Gerhardsson, P., et al.
(author)
-
The SWEET Project 10-Year Benchmarking in 19 Countries Worldwide Is Associated with Improved HbA1c and Increased Use of Diabetes Technology in Youth with Type 1 Diabetes
- 2021
-
In: Diabetes Technology & Therapeutics. - : Mary Ann Liebert Inc. - 1520-9156 .- 1557-8593. ; 23:7
-
Journal article (peer-reviewed)abstract
- Objective: The international SWEET registry (NCT04427189) was initiated in 2008 to improve outcomes in pediatric diabetes. A 10-year follow-up allowed studying time trends of key quality indicators in 22 centers from Europe, Australia, Canada, and India in youth with type 1 diabetes (T1D). Methods: Aggregated data per person with T1D <25 years of age were compared between 2008-2010 and 2016-2018. Hierarchic linear and logistic regression models were applied. Models were adjusted for gender, age-, and diabetes duration groups. Results: The first and second time periods included 4930 versus 13,654 persons, 51% versus 52% male, median age 11.3 [Q1; Q3: 7.9; 14.5] versus 13.3 [9.7; 16.4] years, and T1D duration 2.9 [0.8; 6.4] versus 4.2 [1.4; 7.7] years. The adjusted hemoglobin A1C (HbA1c) improved from 68 (95% confidence interval [CI]: 66-70) to 63 (60; 65) mmol/mol (P<0.0001) or 8.4 (95% CI: 8.2-8.6) to 7.9 (7.6; 8.1) % (P<0.0001). Across all age groups, HbA1c was significantly lower in pump and sensor users. Severe hypoglycemia declined from 3.8% (2.9; 5.0) to 2.4% (1.9; 3.1) (P<0.0001), whereas diabetic ketoacidosis events increased significantly with injection therapy only. Body mass index-standard deviation score also showed significant improvements 0.55 (0.46; 0.64) versus 0.42 (0.33; 0.51) (P<0.0001). Over time, the increase in pump use from 34% to 44% preceded the increase in HbA1c target achievement (<53mmol/mol) from 21% to 34%. Conclusions: Twice yearly benchmarking within the SWEET registry was associated with significantly improved HbA1c on a background of increasing pump and sensor use for 10 years in young persons with T1D.
|
|
| 35. |
- Grönberg, Annika, 1970-
(author)
-
Predictors of long-term glycemic control, pancreatic function and BMI trajectory in children with type 1 diabetes
- 2023
-
Doctoral thesis (other academic/artistic)abstract
- Background: The maintenance of normal metabolic control underpins all management of insulin dependent diabetes whether in terms of preserved beta-cell function, body composition, or family support. The hypothesis of this work was that preserved C-peptide predicts better glycemic control and lowers risk of severe hypoglycemia. It was additionally investigated whether Body Mass Index (BMI) and family structure contributes to the prediction of long-term glycemic control. Objectives: This thesis aimed to 1) identify the factors associated with residual C peptide production at least 10 years after diagnosis, 2) evaluate the association of BMI trajectory and long-term glycemic control, 3) identify early characteristics associated with rapid or slow decline of beta-cell function and how it affects the clinical course, and 4) investigate the relations of family structure at diagnosis and long-term glycemic control. Methods: Data from four cohorts were used: In the Uppsala cohort, measurement of long-term residual C-peptide was undertaken using ultrasensitive C-peptide ELISA in 73 children and adolescents <25 years, BMI trajectory prior diagnosis was evaluated in 295 children, while family structure at diagnosis was evaluated in 215 children in relation to glycemic control. In the Linköping cohort, stimulated C-peptide was assessed by mixed meal tolerance test in 50 children. Results: The cohort studies showed that better early glycemic control predicted long term residual C-peptide and that long term residual C-peptide, in turn, was protective against severe hypoglycemia. Additionally, BMI trajectory was predicted by BMI prior to the presentation of type 1 diabetes. There was no association with glycemic outcome. Children living in a whole family had a lower probability of long-term dysglycemia. Conclusions: Residual C-peptide is important for better glycemic control and to reduce complications in children with type 1 diabetes. Family structure, but not BMI trajectory, contributes to the prediction of long-term glycemic control. However, more research is needed to understand how to preserve the beta-cell function in children and to target and support families in those children with early deteriorating glycemic control to reduce future complications.
|
|
| 36. |
- Gyllenberg, A, et al.
(author)
-
Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes
- 2012
-
In: Genes and Immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 76:2, s. 202-203
-
Journal article (peer-reviewed)abstract
- The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.
|
|
| 37. |
|
|
| 38. |
- Gyllenberg, A, et al.
(author)
-
Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
-
In: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
-
Journal article (peer-reviewed)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
|
|
| 39. |
|
|
| 40. |
- Hartvigsson, Thomas, 1985, et al.
(author)
-
Error trawling and fringe decision competence: Ethical hazards in monitoring and addressing patient decision capacity in clinical practice
- 2018
-
In: Clinical Ethics. - : SAGE Publications. - 1477-7509 .- 1758-101X. ; 13:3, s. 126-136
-
Journal article (peer-reviewed)abstract
- This article addresses how health professionals should monitor and safeguard their patients’ ability to participate in making clinical decisions and making subsequent decisions regarding the implementation of their treatment plan. Patient participation in clinical decision-making is essential, e.g. in self-care, where patients are responsible for most ongoing care. We argue that one common, fact-oriented patient education strategy may in practice easily tend to take a destructive form that we call error trawling. Illustrating with empirical findings from a video study of consultations between clinicians and adolescent patients with diabetes, we argue on independent grounds that this strategy not only risks to overlook significant weaknesses in patient decision competence, but also to undermine patient capacity for decision-making and implementing care. In effect, this strategy for clinically monitoring and addressing the problem of fragile decision-making capacity brings hazards in need of address. We close by suggesting complementary and alternative strategies, and comment on how these may call for broadened competency among clinical health professionals.
|
|
| 41. |
- Hedlund, Emma, et al.
(author)
-
Month of birth and the risk of developing type 1 diabetes among children in the Swedish national Better Diabetes Diagnosis Study
- 2022
-
In: Acta Paediatrica. - Chichester, United Kingdom : Wiley. - 0803-5253 .- 1651-2227. ; 111:12, s. 2378-2383
-
Journal article (peer-reviewed)abstract
- Aim Previous studies have reported an association between month of birth and incidence of type 1 diabetes. Using population-based data, including almost all newly diagnosed children with type 1 diabetes in Sweden, we tested whether month of birth influences the risk of type 1 diabetes. Methods For 8761 children diagnosed with type 1 diabetes between May 2005 and December 2016 in the Better Diabetes Diagnosis study, month of birth, sex and age were compared. Human leucocyte antigen (HLA) genotype and autoantibodies at diagnosis were analysed for a subset of the cohort (n = 3647). Comparisons with the general population used data from Statistics Sweden. Results We found no association between month of birth or season and the incidence of type 1 diabetes in the cohort as a whole. However, boys diagnosed before 5 years were more often born in May (p = 0.004). We found no correlation between month of birth and HLA or antibodies. Conclusion In this large nationwide study, the impact of month of birth on type 1 diabetes diagnosis was weak, except for boys diagnosed before 5 years of age, who were more likely born in May. This may suggest different triggers for different subgroups of patients with type 1 diabetes.
|
|
| 42. |
- Herlitz, Anders, 1981, et al.
(author)
-
The Counseling, Self-care, Adherence Approach to Person-centered Care and Shared Decision Making: Moral Psychology, Executive Autonomy, and Ethics in Multi-dimensional Care Decisions
- 2016
-
In: Health Communication. - : Informa UK Limited. - 1041-0236 .- 1532-7027. ; 31:8, s. 964-973
-
Journal article (peer-reviewed)abstract
- This article argues that standard models of person-centred care (PCC) and shared decision making (SDM) rely on simplistic, often unrealistic assumptions of patient capacities that entail that PCC/SDM might have detrimental effects in many applications. We suggest a complementary PCC/SDM approach to ensure that patients are able to execute rational decisions taken jointly with care professionals when performing self-care. Illustrated by concrete examples from a study of adolescent diabetes care, we suggest a combination of moral and psychological considerations to support the claim that standard PCC/SDM threatens to systematically undermine its own goals. This threat is due to a tension between the ethical requirements of SDM in ideal circumstances and more long-term needs actualized by the context of self-care handled by patients with limited capacities for taking responsibility and adhere to their own rational decisions. To improve this situation, we suggest a counseling, self-care, adherence approach to PCC/SDM, where more attention is given to how treatment goals are internalized by patients, how patients perceive choice situations, and what emotional feedback patients are given. This focus may involve less of a concentration on autonomous and rational clinical decision making otherwise stressed in standard PCC/SDM advocacy.
|
|
| 43. |
- Jonsdottir, Berglind, et al.
(author)
-
Thyroid and islet autoantibodies predict autoimmune thyroid disease already at Type 1 diabetes diagnosis
- 2017
-
In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 102:4, s. 1277-1285
-
Journal article (peer-reviewed)abstract
- CONTEXT: Screening of autoimmune thyroid disease in children and young adults with Type 1 diabetes is important but vary greatly between clinics.OBJECTIVE: The aim was to determine the predictive value of thyroid autoantibodies, thyroid function, islet autoantibodies, and HLA- DQ at diagnosis of Type 1 diabetes for autoimmune thyroid disease during subsequent follow-up.SETTING: 43 Paediatric Endocrinology units Sweden. Design, patients and main outcome measures: At diagnosis of Type 1 diabetes, samples from 2433 children were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), and the three variants of the zinc transporter 8 (ZnT8W/R/QA) as well as HLA-DQA1-B1 genotypes and thyroid function. After 5.1-9.5 years disease duration, children treated with thyroxine were identified in the Swedish National Board of Health and Welfare Prescribed Drug Register.RESULTS: Thyroxine had been prescribed to 6% (147/2433; 66% girls). In patients below 5 years, female gender (HR=4.60, p=0.008) and GADA (HR=5.80, p=0.02) were significant predictors. In patients 5-10 years, TPOAb (HR=20.56, p<0.0001), TGAb (HR=3.40, p=0.006) and TSH outside the reference limit (HR=3.64, p<0.001) were predictors while in the 10-15 year olds, TPOAb (HR=17.00, p<0.001) and TSH outside the reference limit (HR=4.11, p<0.001) predicted future thyroxine prescription.CONCLUSION: In addition to TPOAb and TSH, positive GADA tested at the diagnosis of type 1 diabetes is important for the prediction of autoimmune thyroid disease in children below 5 years of age.
|
|
| 44. |
- Kollberg, Gittan, 1963, et al.
(author)
-
Cardiomyopathy and exercise intolerance in muscle glycogen storage disease 0.
- 2007
-
In: The New England journal of medicine. - 1533-4406. ; 357:15, s. 1507-14
-
Journal article (peer-reviewed)abstract
- Storage of glycogen is essential for glucose homeostasis and for energy supply during bursts of activity and sustained muscle work. We describe three siblings with profound muscle and heart glycogen deficiency caused by a homozygous stop mutation (R462-->ter) in the muscle glycogen synthase gene. The oldest brother died from sudden cardiac arrest at the age of 10.5 years. Two years later, an 11-year-old brother showed muscle fatigability, hypertrophic cardiomyopathy, and an abnormal heart rate and blood pressure while exercising; a 2-year-old sister had no symptoms. In muscle-biopsy specimens obtained from the two younger siblings, there was lack of glycogen, predominance of oxidative fibers, and mitochondrial proliferation. Glucose tolerance was normal.
|
|
| 45. |
- Korsgren, Olle, et al.
(author)
-
Imagining a better future for all people with type 1 diabetes mellitus
- 2019
-
In: Nature Reviews Endocrinology. - : Springer Science and Business Media LLC. - 1759-5029 .- 1759-5037. ; 15:11, s. 623-624
-
Journal article (other academic/artistic)abstract
- For a person with type 1 diabetes mellitus, lifelong insulin treatment is the only therapeutic option. However, increased blood levels of glucose are just a symptom of impaired beta-cell function. Approaching the centenary of the first insulin injection, broadening of international therapeutic guidelines to improve diagnostics, as well as monitor and preserve beta-cell function, is warranted.
|
|
| 46. |
- Lindehammer, Sabina, et al.
(author)
-
Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
- 2008
-
In: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-5
-
Journal article (peer-reviewed)abstract
- The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
|
|
| 47. |
- Lindgren, Marie, et al.
(author)
-
Prevalence and Predictive Factors for Celiac Disease in Children With Type 1 Diabetes : Whom and When to Screen? A Nationwide Longitudinal Cohort Study of Swedish Children
- 2024
-
In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 47:4, s. 756-760
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To examine the prevalence and predictive factors for celiac disease (CD) after a diagnosis of type 1 diabetes (T1D) in children and adolescents, to improve the current screening guidelines.RESEARCH DESIGN AND METHODS: The association between sex, age at T1D diagnosis, HLA, and diabetes autoantibodies, and a diagnosis of CD was examined in 5,295 children with T1D from the Better Diabetes Diagnosis study in Sweden.RESULTS: The prevalence of biopsy-proven CD was 9.8%, of which 58.2% already had a CD diagnosis before or at T1D onset. Almost all, 95.9%, were diagnosed with CD within 5 years after the T1D diagnosis. Younger age at the T1D diagnosis and being homozygote for DQ2 increased the risk of CD after T1D, but neither sex nor diabetes-related autoantibodies were associated with the risk.CONCLUSIONS: Age at and time after diabetes diagnosis should be considered in screening guidelines for CD in children with T1D.
|
|
| 48. |
- Ludvigsson, Johnny, et al.
(author)
-
Decline of C-peptide during the first year after diagnosis of Type 1 diabetes in children and adolescents
- 2013
-
In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 100:2, s. 203-209
-
Journal article (peer-reviewed)abstract
- Aims/hypothesis: We studied the decline of C-peptide during the first year after diagnosis of Type 1 diabetes (T1D), and its relation to various factors. less thanbrgreater than less thanbrgreater thanMethods: 3824/4017 newly diagnosed patients (95%) were classified as T1D in a national study. In a non-selected subgroup of 1669 T1D patients we determined non-fasting C-peptide both at diagnosis and after 1 year, and analyzed decline in relation to clinical symptoms and signs, initial C-peptide and occurrence of auto-antibodies. less thanbrgreater than less thanbrgreater thanResults: Younger children lost more C-peptide (p andlt; 0.001) and the higher the C-peptide at diagnosis the larger the decline during the first year (p andlt; 0.0000). Patients with higher BMI had higher C-peptide at diagnosis but lost more (p andlt; 0.01), and those with lower HbA1c, without symptoms and signs at diagnosis, and with higher BMI, had higher C-peptide at diagnosis, but lost more during the first year (p andlt; 0.001). Finally, patients diagnosed during autumn had higher C-peptide at diagnosis, but lost more during the coming year (p andlt; 0.001). Occurrence of auto-antibodies did not correlate with C-peptide decline, except possibly for a more rapid loss in IAA-positive patients. less thanbrgreater than less thanbrgreater thanConclusions/interpretation: Even in a restricted geographical area and narrow age range (andlt; 18 years), the natural course of Type 1 diabetes is heterogeneous. This should be considered in clinical trials.
|
|
| 49. |
- Ludvigsson, Johnny, 1943-, et al.
(author)
-
GAD treatment and insulin secretion in recent-onset type 1 diabetes
- 2008
-
In: New England Journal of Medicine. - Boston, Mass : Massachusetts medical society. - 0028-4793 .- 1533-4406. ; 359:18, s. 1909-1920
-
Journal article (peer-reviewed)abstract
- Background The 65-kD isoform of glutamic acid decarboxylase (GAD) is a major autoantigen in patients with type 1 diabetes mellitus. This trial assessed the ability of alum-formulated GAD (GAD-alum) to reverse recent-onset type 1 diabetes in patients 10 to 18 years of age. Methods We randomly assigned 70 patients with type 1 diabetes who had fasting C-peptide levels above 0.1 nmol per liter (0.3 ng per milliliter) and GAD autoantibodies, recruited within 18 months after receiving the diagnosis of diabetes, to receive subcutaneous injections of 20 μg of GAD-alum (35 patients) or placebo (alum alone, 35 patients) on study days 1 and 30. At day 1 and months 3, 9, 15, 21, and 30, patients underwent a mixed-meal tolerance test to stimulate residual insulin secretion (measured as the C-peptide level). The effect of GAD-alum on the immune system was also studied. Results Insulin secretion gradually decreased in both study groups. The study treatment had no significant effect on change in fasting C-peptide level after 15 months (the primary end point). Fasting C-peptide levels declined from baseline levels significantly less over 30 months in the GAD-alum group than in the placebo group (−0.21 vs. −0.27 nmol per liter [−0.62 vs. −0.81 ng per milliliter], P = 0.045), as did stimulated secretion measured as the area under the curve (−0.72 vs. −1.02 nmol per liter per 2 hours [−2.20 vs. −3.08 ng per milliliter per 2 hours], P = 0.04). No protective effect was seen in patients treated 6 months or more after receiving the diagnosis. Adverse events appeared to be mild and similar in frequency between the two groups. The GAD-alum treatment induced a GAD-specific immune response. Conclusions GAD-alum may contribute to the preservation of residual insulin secretion in patients with recent-onset type 1 diabetes, although it did not change the insulin requirement. (ClinicalTrials.gov number, NCT00435981.)
|
|
| 50. |
- Ludvigsson, Johnny, et al.
(author)
-
GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus
- 2012
-
In: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 366:5, s. 433-442
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes.METHODS: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels.RESULTS: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences.CONCLUSIONS: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period.
|
|
