1. |
- Bybrant, M. C., et al.
(author)
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Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes
- 2021
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In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 22:3, s. 417-424
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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.
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2. |
- Carlsson, Annelie, et al.
(author)
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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
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In: Diabetes Care. - Arlington, VA, United States : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:1, s. 82-89
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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.
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3. |
- Forsander, Gun, 1951, et al.
(author)
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Preferences for treatment among adolescents with Type 1 diabetes: a national study using a discrete choice experiment model
- 2018
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In: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 35:5, s. 621-629
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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.
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4. |
- Hedlund, Emma, et al.
(author)
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Month of birth and the risk of developing type 1 diabetes among children in the Swedish national Better Diabetes Diagnosis Study
- 2022
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In: Acta Paediatrica. - Chichester, United Kingdom : Wiley. - 0803-5253 .- 1651-2227. ; 111:12, s. 2378-2383
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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.
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5. |
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6. |
- Samuelsson, John, et al.
(author)
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Poor metabolic control in childhood strongly correlates to diabetes-related premature death in persons <30 years of age-A population-based cohort study
- 2020
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In: Pediatric Diabetes. - : Wiley-Blackwell Publishing Inc.. - 1399-543X .- 1399-5448. ; 21:3, s. 479-485
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Journal article (peer-reviewed)abstract
- Background/objectiveThe importance of metabolic control in childhood regarding excess risk of death in young persons has not been well studied. This registry‐based study aimed to investigate mortality rates and cause of death related to metabolic control in young persons (≤29 years) in Sweden with type 1 diabetes.MethodsAll 12 652 subjects registered in the Swedish pediatric diabetes quality register, from 2006 to 2014, were included. Data were merged with the Swedish Cause of Death Register. Standardized mortality rates were calculated using the official Swedish population register.ResultsOf 68 deaths identified, 38.2% of the deaths were registered as being due to diabetes whereof the major cause of death was acute complications. Overall standardized mortality ratio was 2.7 (2.1‐3.4, 95% CI). Subjects who died from diabetes had a mean HbA1c of 74 ± 19 mmol/mol (8.9 ± 1.7%) during childhood vs 62 ± 12 mmol/mol (7.8 ± 1.1%) in those still alive (P < .001).ConclusionsIn this nationwide cohort of young subjects with type 1 diabetes, there was a high mortality rate compared to the general population. Mean HbA1c in childhood was significantly higher in those who died from diabetes, compared to subjects who were still alive. To decrease mortality in young persons with type 1 diabetes it is essential not only to achieve but also to maintain a good metabolic control during childhood and adolescence.
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7. |
- Samuelsson, Ulf, 1951-, et al.
(author)
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Continued improvement of metabolic control in Swedish pediatric diabetes care.
- 2018
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In: Pediatric Diabetes. - : John Wiley & Sons. - 1399-543X .- 1399-5448. ; 19:1, s. 150-157
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Journal article (peer-reviewed)abstract
- BACKGROUND: To prospectively investigate if the grand mean HbA1c and the differences in mean HbA1c between centers in Sweden could be reduced, thereby improving care delivered by pediatric diabetes teams.METHODS: We used an 18-month quality improvement collaborative (QIC) together with the Swedish pediatric diabetes quality registry (SWEDIABKIDS). The first program (IQ-1), started in April 2011 and the second (IQ-2) in April 2012; together they encompassed 70% of Swedish children and adolescents with diabetes.RESULTS: The proportion of patients in IQ-1 with a mean HbA1c <7.4% (57 mmol/mol) increased from 26.4% before start to 35.9% at 36 months (P < .001), and from 30.2% to 37.2% (P < .001) for IQ-2. Mean HbA1c decreased in both participating and non-participating (NP) centers in Sweden, thereby indicating an improvement by a spatial spill over effect in NP centers. The grand mean HbA1c decreased by 0.45% (4.9 mmol/mol) during 36 months; at the end of 2014 it was 7.43% (57.7 mmol/mol) (P < .001). A linear regression model with the difference in HbA1c before start and second follow-up as dependent variable showed that QIC participation significantly decreased mean HbA1c both for IQ-1 and IQ-2. The proportion of patients with high HbA1c values (>8.7%, 72 mmol/mol) decreased significantly in both QICs, while it increased in the NP group.CONCLUSIONS: The grand mean HbA1c has decreased significantly in Sweden from 2010 to 2014, and QICs have contributed significantly to this decrease. There seems to be a spatial spill-over effect in NP centers.
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8. |
- Tojjar, Jasaman, et al.
(author)
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Sex Differences in Age of Diagnosis, HLA Genotype, and Autoantibody Profile in Children With Type 1 Diabetes
- 2023
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In: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 46:11, s. 1993-1996
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To examine sex differences in children with newly diagnosed type 1 diabetes (T1D) with respect to age at diagnosis, presence of autoantibodies (GAD antibody [GADA], insulinoma-associated protein 2 [IA-2A], insulin autoantibody [IAA], and zinc transporter 8 autoantibody), and HLA risk. RESEARCH DESIGN AND METHODS: A population-based nationwide sample of 3,645 Swedish children at T1D diagnosis was used. RESULTS: Girls were younger at T1D diagnosis (9.53 vs. 10.23 years; P < 0.001), more likely to be autoantibody-positive (94.7% vs. 92.0%; P = 0.002), more often positive for multiple autoantibodies (P < 0.001), more likely to be positive for GADA (64.9% vs. 49.0%; P < 0.001), and less likely to be positive for IAA (32.3% vs. 33.8%; P = 0.016). Small sex differences in HLA risk were found in children <9 years of age. CONCLUSIONS: The disease mechanisms leading to T1D may influence the immune system differently in girls and boys.
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9. |
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10. |
- Anderzén, Johan
(author)
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Differences in glycemic control in type 1 diabetes children and adolescents : in a national and international perspective and the effect on microvascular complications in young adults
- 2023
-
Doctoral thesis (other academic/artistic)abstract
- This thesis focuses on glycemic control measured as HbA1c in type 1 diabetes (T1D) patients during childhood and especially during adolescence, both in a Swedish and an international context, and relates the glycemic control to the risk of complications in young adults. In studies I and II, the Swedish Pediatric Diabetes Quality Register (SWEDIABKIDS) and the Swedish National Diabetes Register (NDR) were used. More than 4000 young adults with T1D and data on HbA1c in NDR both in 2011 and 2012 as well as data on HbA1c in SWEDIABKIDS were used. The T1D patients with poor glycemic control during their teenage period had a risk for retinopathy several times higher than those with good glycemic control. The risk for micro- and macroalbuminuria was also higher in those with poor glycemic control and was most pronounced in the T1D patients with high HbA1c in both registers. Females had worse glycemic control than males during the teenage period and an increased risk of retinopathy as young adults. In studies III and IV, pediatric diabetes quality register data from, respectively, eight and seven Western high-income countries were collected in the year 2013. Data on about 60 000 T1D patients were analyzed according to mean HbA1c levels in the countries and related to actual age and T1D duration to determine if there were differences in glycemic control between the countries. There were large differences in mean HbA1c between the countries, both when related to age and T1D duration. Despite the differences in mean HbA1c, the increase in mean HbA1c with increasing age and T1D duration was very similar in all countries. The overall picture of these studies is that good glycemic control is very important to avoid complications of T1D as young adults, and it seems particularly important to maintain a good glycemic control during adolescence. Furthermore large differences in glycemic control in T1D patients in Western high-income countries were found. Despite the differences in glycemic control, the pattern of rising HbA1c with increasing age and duration of T1D was very similar in all countries. Females have worse glycemic control than males during their teenage period, both in Sweden and internationally, and they also have more retinopathy as young adults. This thesis shows that it is of the utmost importance to treat T1D patients intensively directly after diagnosis, to treat the young T1D patients intensely and to reduce the rise in HbA1c with increasing age and duration of T1D in order to avoid complications early in life. Diabetes quality registers give the opportunity to compare results and share experiences, both within and between countries, so treatment of T1D can be designed in the best possible way and thereby minimize T1D complications.
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11. |
- Anderzen, J., et al.
(author)
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International benchmarking in type 1 diabetes: Large difference in childhood HbA1c between eight high-income countries but similar rise during adolescence-A quality registry study
- 2020
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In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 21:4, s. 621-627
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Journal article (peer-reviewed)abstract
- Objectives To identify differences and similarities in HbA1c levels and patterns regarding age and gender in eight high-income countries. Subjects 66 071 children and adolescents below18 years of age with type 1 diabetes for at least 3 months and at least one HbA1c measurement during the study period. Methods Pediatric Diabetes Quality Registry data from Austria, Denmark, England, Germany, Norway, Sweden, the United States, and Wales were collected between 2013 and 2014. HbA1c, gender, age, and duration were used in the analysis. Results Distribution of gender and age groups was similar in the eight participating countries. The mean HbA1c varied from 60 to 73 mmol/mol (7.6%-8.8%) between the countries. The increase in HbA1c between the youngest (0-9 years) to the oldest (15-17 years) age group was close to 8 mmol/mol (0.7%) in all countries (P < .001). Females had a 1 mmol/mol (0.1%) higher mean HbA1c than boys (P < .001) in seven out of eight countries. Conclusions In spite of large differences in the mean HbA1c between countries, a remarkable similarity in the increase of HbA1c from childhood to adolescence was found.
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12. |
- Boman, Krister K, et al.
(author)
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Serious illness in childhood : the different threats of cancer and diabetes from a parent perspective.
- 2004
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In: Journal of Pediatrics. - : Elsevier BV. - 0022-3476 .- 1097-6833. ; 145, s. 373-379
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Journal article (peer-reviewed)abstract
- Objectives To compare the incidence of disease-related distress symptoms in parents of children with cancer and diabetes. Study design A total of 675 parents of patients with cancer, patients with diabetes, and control subjects were assessed for 11 distress symptom clusters. Patient and control parent mean differences were tested by 2-tailed t tests, illness groups were compared by means of analysis of variance. Distress variations as a function of time since diagnosis were examined by regression analysis. Results The distress levels of patient parents exceeded those of control parents for global distress (P < .0001) and for most symptom subcategories. Distress levels of parents of patients with cancer (CP) significantly exceeded those of parents of patients with diabetes (DP) in anxiety (P < .0001), physical and psychologic distress (P < .0001), depression (P < .005), and loneliness (P < .05). Levels in DP matched those of CP in uncertainty, loss of control/the patient, self-esteem, disease-related fear, and sleep disturbances. Distress levels were lower in CP most distant hi time from diagnosis, whereas DP showed a reversed trend. Conclusions Parental distress patterns in childhood illness depend on illness type and time passed since diagnosis. Symptom profiles verify the need for psyehosocial attention at the initial shock after the cancer diagnosis and indicate long-term consequences for many parents. In pediatric diabetes, the persistence or intensification of distress over time is of specific clinical relevance.
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13. |
- Carlsson, Annelie, et al.
(author)
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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
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In: Läkartidningen. - 0023-7205. ; 115:11, s. 484-484
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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.
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14. |
- Delli, Ahmed, et al.
(author)
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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
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:10, s. 2556-2564
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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.
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15. |
- Ernerudh, Jan, 1952-, et al.
(author)
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Effect of photopheresis on lymphocyte population in children with newly diagnosed type 1 diabetes
- 2004
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In: Clinical and Diagnostic Laboratory Immunology. - 1071-412X. ; 11:5, s. 856-861
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Journal article (peer-reviewed)abstract
- In recent years photopheresis has been claimed to be an effective form of immunomodulation. It has also been shown to have an effect on the disease process at the onset of type 1 diabetes. In a double-blind, placebo-controlled randomized study, we analyzed if the effect of photopheresis in children with newly diagnosed diabetes is related to changes in the balance of lymhocyte populations. We also analyzed if lymphocyte subsets were related to recent infection, mild or aggressive disease manifestations, heredity, or gender. Nineteen children received active treatment with photopheresis, while 21 children received sham pheresis (placebo group). No influence of a history of previous infection, heredity, or certain clinical parameters on lymphocyte subsets was found. At the onset of type 1 diabetes, girls showed a higher proportion and a larger number of T cells (CD3+) and T-helper cells (CD4+) and a higher proportion of naïve CD4 +CD45RA+ cells. In the placebo group, an increase in the number of subsets with the activated phenotype in both the CD4 (CD29 +) and the CD8 (CD11a+) compartments was noted during the course of the study. These changes did not occur in the photopheresis group. No relation between lymphocyte subsets and clinical outcome was found 1 year after the treatment with photopheresis. In conclusion, we found no major effect of photopheresis on lymphocyte populations in a group of children with newly diagnosed type 1 diabetes. However, in the placebo group the proportions of activated CD4 and CD8 cells increased over time. Since these changes did not occur in the actively treated group, our findings suggest that photopheresis may have some suppressive effects.
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16. |
- Forsander, Gun, 1951, et al.
(author)
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Adolescent life with diabetes-Gender matters for level of distress. Experiences from the national TODS study
- 2017
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In: Pediatric Diabetes. - : WILEY. - 1399-543X .- 1399-5448. ; 18:7, s. 651-659
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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.
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17. |
- Fureman, Anna-Lena, et al.
(author)
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Comparing Continuous Subcutaneous Insulin Infusion and Multiple Daily Injections in children with type 1 diabetes in Sweden from 2011 to 2016 : a longitudinal study from the Swedish National Quality Register (SWEDIABKIDS)
- 2021
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In: Pediatric Diabetes. - : Blackwell Publishing. - 1399-543X .- 1399-5448. ; 22:5, s. 766-775
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Journal article (peer-reviewed)abstract
- OBJECTIVE: This study aimed to compare metabolic control measured as hemoglobin A1c (HbA1c), the risk of severe hypoglycemia, and body composition measured as BMI-SDS in a nationwide sample of children and adolescents with type 1 diabetes with continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI), respectively.METHODS: Longitudinal data from 2011-2016 were extracted from the Swedish National Quality Register (SWEDIABKIDS) with both cross-sectional (6 years) and longitudinal (4 years) comparisons. Main end points were changes in HbA1c, BMI-SDS, and incidence of severe hypoglycemia.RESULTS: <0.001) and the use of CSII increased in both sexes and all age groups. Mean HbA1c was 0.1% (0.7-1.5 mmol/mol) lower in the CSII treated group. Teenagers, especially girls, using CSII tended to have higher BMI-SDS. There was no difference in the number of hypoglycemias between CSII and MDI over the years 2011-2016.CONCLUSION: There was a small decrease in HbA1c with CSII treatment but of little clinical relevance. Overall, mean HbA1c decreased in both sexes and all age groups without increasing the episodes of severe hypoglycemia, indicating that other factors than insulin method contributed to a better metabolic control.
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18. |
- Fureman, Anna-Lena, et al.
(author)
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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
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In: Diabetes Technology & Therapeutics. - : Mary Ann Liebert. - 1520-9156 .- 1557-8593.
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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.
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19. |
- Hanberger, Lena, 1957-, et al.
(author)
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Type 1 diabetes during adolescence : International comparison between Germany, Austria, and Sweden.
- 2018
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In: Pediatric Diabetes. - : John Wiley & Sons. - 1399-543X .- 1399-5448. ; 19:3, s. 506-511
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Journal article (peer-reviewed)abstract
- OBJECTIVES: By using pediatric diabetes quality registries in Austria, Germany, and Sweden treatment of type 1 diabetes and the outcome of care during the vulnerable adolescence period were compared.METHODS: Data in DPV, broadly used in Austria and Germany, and Swediabkids used in Sweden, from clinical visits in the year 2013 on 14 383 patients aged 11 to 16 years regarding hemoglobin A1c (HbA1c), insulin regimen, body mass index (BMI)-SD score (SDS), blood pressure, hypoglycemia, ketoacidosis, and smoking habits were analyzed.RESULTS: Patients in Sweden had fewer clinical visits per year (P < .05), lower insulin dose per kg (P < .001), and lower proportion of fast acting insulin compared with Germany and Austria (P < .001). The proportion of pump users was higher in Sweden (P < .001). Patients in Sweden had lower mean HbA1c levels (Austria: 64 mmol/mol, Germany: 63 mmol/mol, and Sweden: 61 mmol/mol [8.0%, 7.9%, and 7.7%, respectively]; P < .001). The frequency of severe hypoglycemia was higher in Sweden while it was lower for ketoacidosis (3.3% and 1.1%, respectively) than in Austria (1.1% and 5.3%) and Germany (2.0% and 4.4%) (P < .001). Girls in all 3 countries had higher HbA1c and BMI-SDS than boys.CONCLUSIONS: Sharing data between diabetes registries and nations enables us to better understand differences in diabetes outcome between countries. In this particular comparison, pediatric patients with diabetes in Sweden were more often treated with insulin pump, had lower HbA1c levels and a higher rate of severe hypoglycemia. Patients in Austria and Germany used rapid acting insulin analogs more often and had a lower rate of ketoacidosis.
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20. |
- Holmqvist, Britt-Marie, 1952-, et al.
(author)
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A low incidence of Type 1 diabetes between 1977 and 2001 in south-eastern Sweden in areas with high population density and which are more deprived
- 2008
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In: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 25:3, s. 255-260
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Journal article (peer-reviewed)abstract
- Aims To explore how socioeconomic factors and population density may contribute to the geographical variation of incidence of Type 1 diabetes in children in south-eastern Sweden.Method All children diagnosed with Type 1 diabetes in south-eastern Sweden during 1977–2001 were defined geographically to their place of residence and were allocated x and y coordinates in the national grid. The population at risk and socioeconomic data were aggregated in 82 000 200-m squares and geocoded likewise. A socioeconomic index was calculated using a signed χ2 method. Rural–urban gradients were defined by overlay analysis in a geographic information system.Results The incidence during the past 25 years has been rising steadily, particularly in the last 6 years. The incidence was highest in areas with a high proportion of small families, of families with a high family income and better education, and this was found both at the time of diagnosis and at the time of birth. In the rural–urban analysis, the lowest incidence was found in the urban area with > 20 000 inhabitants, where there was also a higher frequency of deprivation.Conclusions Our findings indicate that geographical variations in incidence rates of Type 1 diabetes in children are associated with socioeconomic factors and population density, although other contributing factors remain to be explained.
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21. |
- Hyllienmark, Lars, et al.
(author)
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Nerve conduction defects are retarded by tight metabolic control in type I diabetes
- 2001
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In: Muscle and Nerve. - 0148-639X .- 1097-4598. ; 24:2, s. 240-246
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Journal article (peer-reviewed)abstract
- This follow-up study examines whether the development of nerve dysfunction is retarded by tight metabolic control in patients with type I diabetes mellitus. Seventy-one patients and 115 age-matched healthy control subjects underwent studies of nerve conduction in peroneal and sural nerves. The presence of diabetes was associated with a reduction in peroneal motor nerve conduction velocity (MCV) by 5.9 m/s, sural sensory nerve conduction velocity (SCV) by 3.4 m/s, and sural sensory nerve action potential (SNAP) amplitude by 22%. Dysfunction in peroneal MCV, sural SCV, and sural SNAP were related to long-term poor metabolic control. Eleven of 12 patients with HbA1c <6.5% had normal nerve conduction or abnormality in only one nerve as compared to 2 of 15 patients with HbA1c >8.0%. It is concluded that tight long-term metabolic control (HbA1c <6.5%) can retard nerve dysfunction in patients with type I diabetes mellitus and a mean disease duration of 12 years.
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22. |
- Jonsdottir, Berglind, et al.
(author)
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Thyroid and islet autoantibodies predict autoimmune thyroid disease already at Type 1 diabetes diagnosis
- 2017
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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.
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23. |
- Lindell, Nina, et al.
(author)
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Maternal obesity as a risk factor for early childhood type 1 diabetes : a nationwide, prospective, population-based case-control study
- 2018
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In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 61:1, s. 130-137
-
Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS: Genetic and environmental factors are believed to cause type 1 diabetes. The aim of this study was to investigate the influence of maternal BMI and gestational weight gain on the subsequent risk of childhood type 1 diabetes.METHODS: Children in the Swedish National Quality Register for Diabetes in Children were matched with control children from the Swedish Medical Birth Register. Children were included whose mothers had data available on BMI in early pregnancy and gestational weight gain, giving a total of 16,179 individuals: 3231 children with type 1 diabetes and 12,948 control children.RESULTS: Mothers of children with type 1 diabetes were more likely to be obese (9% [n = 292/3231] vs 7.7% [n = 991/12,948]; p = 0.02) and/or have diabetes themselves (2.8% [n = 90/3231] vs 0.8% [n = 108/12,948]; p < 0.001) compared with mothers of control children. Gestational weight gain did not differ significantly between the two groups of mothers. In mothers without diabetes, maternal obesity was a significant risk factor for type 1 diabetes in the offspring (p = 0.04). A child had an increased risk of developing type 1 diabetes if the mother had been obese in early pregnancy (crude OR 1.20; 95% CI 1.05, 1.38; adjusted OR 1.18; 95% CI 1.02, 1.36). Among children with type 1 diabetes (n = 3231) there was a difference (p < 0.001) in age at onset in relation to the mother's BMI. Among children in the oldest age group (15-19 years), there were more mothers who had been underweight during pregnancy, while in the youngest age group (0-4 years) the pattern was reversed.CONCLUSIONS/INTERPRETATION: Maternal obesity, in the absence of maternal diabetes, is a risk factor for type 1 diabetes in the offspring, and influences the age of onset of type 1 diabetes. This emphasises the importance of a normal maternal BMI to potentially decrease the incidence of type 1 diabetes.
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24. |
- Lindell, Nina, 1984-
(author)
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Perinatal risk factors for type 1 diabetes in children and adolescents
- 2021
-
Doctoral thesis (other academic/artistic)abstract
- Background Type 1 diabetes (T1D) is an autoimmune disease characterized by progressive loss of the insulin producing pancreatic β-cells. The disease process starts years before the clinical diagnosis. The cause of T1D is unknown, but it is believed to be a combination of genetic and environmental factors. Around 50% of the genetic risk is attributed to the human leucocyte antigen (HLA) genes and the strongest associations are with the HLA-DR3-DQ2 and HLA-DR4-DQ8 haplotypes. The highest risk genotype is the heterozygote form of the two, the HLA-DQ2/8 genotype. It may be that certain environmental factors pose a risk to individuals with a particular genetic susceptibility but not to others. In the last few decades T1D incidence has risen very quickly and due to the rate of the increase, it is believed to depend on environmental factors rather than genetic. In parallel with this increase, the incidence of several environmental factors has also risen i.e., the incidence of cesarean section (CS), overweight/obesity in the general population and birthweight. These environmental factors have been implicated as risk factors for T1D, but studies have had conflicting results.Objective The overall aim of this thesis was to increase knowledge regarding factors during pregnancy and the perinatal period that could increase or decrease the risk of T1D among children and adolescents. The environmental risk factors studied were mode of childbirth (study I), maternal BMI and gestational weight gain (GWG) (study II) and the child’s size for gestational age and birthweight (study III). In the last study the environmental risk factors were compared between children with different genetic risks of T1D.Material and methods The studies included in this thesis are population-based register studies, three case-control studies and one cohort study, using prospectively collected material from the Swedish medical birth registry (MBR) and the Swedish pediatric diabetes quality registry (SWEDIABKIDS), as well as information from the Swedish national cohort study Better Diabetes Diagnosis (BDD). The study population consists of children and adolescents (0–18/19 years) diagnosed with T1D Jan 2000-Oct 2012 and registered in SWEDIABKIDS (n=9,376). All children with T1D were matched with four control children from the MBR with the same year and day of birth, same sex, and born in the same region of Sweden (n=37,504). In study I, the entire study population was used but in study III twins were excluded (n=552). In study II, children for whom data on their mother’s BMI in early pregnancy and GWG were available were included (3,231 children with T1D and 12,948 control children). In study IV, children with T1D who also participated in the BDD study were included (4,533 children).Results and conclusions Maternal overweight and obesity were associated with an increased risk of T1D in the offspring but were not more common among children with high or low genetic risk. Maternal BMI was also inversely associated with the age at onset of T1D in children with HLADQ8/ X and/or HLA-DQ2/X. Neither GWG nor mode of childbirth had any obvious impact on the risk of developing T1D. Being born large for gestational age or with a birthweight ≥4000 g (macrosomia) was associated with an increased risk of T1D and being born small for gestational age or with a low birthweight (<2500 g) was associated with a decreased risk of T1D, irrespective of maternal BMI and diabetes. Comparing children with T1D and different HLA genotypes revealed a slight difference in birthweight between the genotype groups. Children with HLA-DQ2/8 were more often born with macrosomia compared to children with HLA-DQ8/X. Children without either HLA-DQ2 or HLADQ8 (HLA-DQX/X) were more often born with a low birthweight compared to those with HLADQ2/ 8 and HLA-DQ8/X. Size for gestational age did not differ between the genotype groups, and the effect of size for gestational age and birthweight on age at onset of T1D was ambiguous.The effects of the environmental risk factors identified in this thesis are generally weak and no clear conclusion on whether they are causative can be drawn. Yet since overweight/obesity and a high birthweight are common in the population, even a small increase in risk can result in many cases of T1D. Overweight/obesity and a high birthweight are also associated with other adverse health outcomes and they are, at least partly, modifiable. This motivates additional research regarding their involvement in T1D etiology as well as preventive actions against overweight and obesity in the population.
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25. |
- Lindell, Nina, 1984-, et al.
(author)
-
Size for gestational age affects the risk for type 1 diabetes in children and adolescents : a Swedish national case–control study
- 2021
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 64:5, s. 1113-1120
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Journal article (peer-reviewed)abstract
- Aim/hypothesis: Environmental factors are believed to contribute to the risk of developing type 1 diabetes. The aim of this study was to investigate how size for gestational age affects the risk of developing childhood type 1 diabetes. Methods: Using the Swedish paediatric diabetes quality register and the Swedish medical birth register, children with type 1 diabetes diagnosed between 2000 and 2012 (n = 9376) were matched with four control children (n = 37,504). Small for gestational age (SGA) and large for gestational age (LGA) were defined according to Swedish national standards. Data were initially analysed using Pearson’s χ2 and thereafter by single and multiple logistic regression models. Results: An equal proportion of children were born appropriate for gestational age, but children with type 1 diabetes were more often born LGA and less often born SGA than control children (4.7% vs 3.5% and 2.0% vs 2.6%, respectively, p < 0.001). In the multiple logistic regression analysis, being born LGA increased (adjusted OR 1.16 [95% CI 1.02, 1.32]) and SGA decreased (adjusted OR 0.76 [95% CI 0.63, 0.92]) the risk for type 1 diabetes, regardless of maternal BMI and diabetes. Conclusions/interpretation: Size for gestational age of Swedish children affects the risk of type 1 diabetes, with increased risk if the child is born LGA and decreased risk if the child is born SGA. Being born LGA is an independent risk factor for type 1 diabetes irrespective of maternal BMI and diabetes. Thus, reducing the risk for a child being born LGA might to some extent reduce the risk for type 1 diabetes. Graphical abstract: [Figure not available: see fulltext.].
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26. |
- Ljungkrantz, M, et al.
(author)
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Type 1 diabetes : Increased height and weight gains in early childhood
- 2008
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In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 9:3 PART 2, s. 50-56
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Journal article (peer-reviewed)abstract
- Objective: The accelerator/beta-cell stress hypothesis regards insulin resistance as one common basis for type 1 and type 2 diabetes and weight increase as an important trigger of type 1 diabetes. To test this hypothesis, we examined children's height and weight gain from birth to the time of diagnosis of type 1 diabetes. Method: Growth charts (n=316) from children 0-16yr old up to the time of diagnosis of type 1 diabetes were compared with growth charts from age- and sex-matched controls. Results: Compared with their controls, children who developed diabetes had experienced more pronounced gain in both weight and height. In the year of diagnosis, they were taller [0.5 vs. 0.36 standard deviation score (SDS), p<0.03] and heavier (0.7 vs. 0.45 SDS, p<0.01). Children who developed diabetes aged 5yr or less gained more weight during the period between their third month and third year of life (p<0.01). Children who were diagnosed between 6 and 10yr of age had gained more in height before they were 5yr old (p<0.05). Regression analysis showed that a high weight or a high body mass index (BMI) at 5yr of age indicated, more than the other measurements, a high risk for diabetes later during childhood, while height and weight at ages less than 5yr did not add any further information on diabetes risk. Conclusions: Rapid growth before 7yr of age and increased BMI in childhood are risk factors for later type 1 diabetes. These findings support the accelerator/beta-cell stress hypothesis. © 2008 The Author Journal compilation © 2008 Blackwell Munksgaard.
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27. |
- Ludvigsson, Johnny, et al.
(author)
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Combined Etanercept, GAD-alum and vitamin D treatment: an open pilot trial to preserve beta cell function in recent onset type 1 diabetes
- 2021
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In: Diabetes-Metabolism Research and Reviews. - : Wiley. - 1520-7552 .- 1520-7560.
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Journal article (peer-reviewed)abstract
- Aim We aimed to study the feasibility and tolerability of a combination therapy consisting of glutamic acid decarboxylase (GAD-alum), Etanercept and vitamin D in children and adolescents with newly diagnosed with type 1 diabetes (T1D), and evaluate preservation of beta cell function. Material and Methods Etanercept Diamyd Combination Regimen is an open-labelled multi-centre study pilot trial which enrolled 20 GAD antibodies positive T1D patients (7 girls and 13 boys), aged (mean +/- SD): 12.4 +/- 2.3 (8.3-16.1) years, with a diabetes duration of 81.4 +/- 22.1 days. Baseline fasting C-peptide was 0.24 +/- 0.1 (0.10-0.35) nmol/l. The patients received Day 1-450 Vitamin D (Calciferol) 2000 U/d per os, Etanercept sc Day 1-90 0.8 mg/kg once a week and GAD-alum sc injections (20 mu g, Diamyd (TM)) Day 30 and 60. They were followed for 30 months. Results No treatment related serious adverse events were observed. After 6 months 90-min stimulated C-peptide had improved in 8/20 patients and C-peptide area under the curve (AUC) after Mixed Meal Tolerance Test in 5 patients, but declined thereafter, while HbA1c and insulin requirement remained close to baseline. Administration of Etanercept did not reduce tumour necrosis factor (TNF) spontaneous secretion from peripheral blood mononuclear cells, but rather GAD65-induced TNF-alpha increased. Spontaneous interleukin-17a secretion increased after the administration of Etanercept, and GAD65-induced cytokines and chemokines were also enhanced following 1 month of Etanercept administration. Conclusions Combination therapy with parallel treatment with GAD-alum, Etanercept and vitamin D in children and adolescents with type 1 diabetes was feasible and tolerable but had no beneficial effects on the autoimmune process or beta cell function.
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28. |
- Ludvigsson, Johnny, 1943-, et al.
(author)
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Combined vitamin D, ibuprofen and glutamic acid decarboxylase-alum treatment in recent onset Type I diabetes: lessons from the DIABGAD randomized pilot trial.
- 2020
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In: Future science OA. - London, United Kingdom : Future Science Ltd. - 2056-5623. ; 6:7
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Journal article (peer-reviewed)abstract
- Double-blind placebo-controlled intervention using glutamic acid decarboxylase (GAD)-alum, vitamin D and Ibuprofen in recent onset Type I diabetes (T1D).64 patients (T1D since <4months, age 10-17.99, fasting sC-peptide ≥0.12nmol/l, GADA-positive) were randomized intoDay(D) 1-90 400mg/day Ibuprofen, D1-450 vitamin D 2000IU/day, D15, 45 sc. 20μg GAD-alum; as A but placebo instead of Ibuprofen; as B but 40μg GAD-alum D15, 45; placebo.Treatment was safe and tolerable. No C-peptide preservation was observed. We observed a linear correlation of baseline C-peptide, HbA1c and insulin/per kilogram/24h with change in C-peptide AUC at 15months (r=-0.776, p<0.0001).Ibuprofen, vitamin D + GAD-alum did not preserve C-peptide. Treatment efficacy was influenced by baseline clinical and immunological factors and vitamin D concentration. Clinical Trial Registration: NCT01785108 (ClinicalTrials.gov).
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29. |
- Ludvigsson, Johnny, 1943-, et al.
(author)
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Continuous insulin infusion (CSII) or modern type of multiple daily injections (MDI) in diabetic children and adolescents a critical review on a controversial issue
- 2007
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In: Pediatric Endocrinology Reviews. - 1565-4753. ; 5:2, s. 666-678
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Journal article (peer-reviewed)abstract
- OBJECTIVE:There is a common opinion that CSII is superior to MDI. CSII offers the most physiological insulin substitution.METHOD:Review of recent publications (Cochrane criteria), on modern multiple daily injections (MDI) based on insulin analogues, modern self-control and education.RESULTS:There is a lack of randomised controlled studies comparing CSII with modern MDI in children and adolescents. In some studies CSII seems to give a slight decrease of HbA1c, a slightly better quality of life, perhaps less hypoglycemia. However, serious hypoglycemia, sometimes fatal, occurs, DKA seems to increase, weight gain and local infections at injection sites may occur and CSII is more expensive than MDI.CONCLUSION:CSII is a useful tool. It is reasonable to use it when there are appropriate indications. CSII does not solve all problems but has to be combined with other important parts of diabetes treatment.
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30. |
- Ludvigsson, Johnny, et al.
(author)
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Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial
- 2021
-
In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:7, s. 1604-1612
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Journal article (peer-reviewed)abstract
- OBJECTIVE To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion in all patients with type 1 diabetes (T1D) or in a genetically prespecified subgroup. RESEARCH DESIGN AND METHODS In a multicenter, randomized, placebo-controlled, double-blind trial, 109 patients aged 12-24 years (mean +/- SD 16.4 +/- 4.1) with a diabetes duration of 7-193 days (88.8 +/- 51.4), elevated serum GAD65 autoantibodies, and a fasting serum C-peptide >0.12 nmol/L were recruited. Participants were randomized to receive either three intralymphatic injections (1 month apart) with 4 mu g GAD-alum and oral vitamin D (2,000 IE daily for 120 days) or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15 months. RESULTS Primary end point was not met in the full analysis set (treatment effect ratio 1.091 [CI 0.845-1.408]; P = 0.5009). However, GAD-alum-treated patients carrying HLA DR3-DQ2 (n = 29; defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557 [CI 1.126-2.153]; P = 0.0078) after 15 months compared with individuals receiving placebo with the same genotype (n = 17). Several secondary end points showed supporting trends, and a positive effect was seen in partial remission (insulin dose-adjusted HbA(1c) <= 9; P = 0.0310). Minor transient injection site reactions were reported. CONCLUSION Intralymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent-onset T1D carrying HLA DR3-DQ2. This constitutes a disease-modifying treatment for T1D with a precision medicine approach.
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31. |
- Ludvigsson, Johnny, 1943-, et al.
(author)
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Photopheresis at onset of type 1 diabetes : A randomised, double blind, placebo controlled trial
- 2001
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In: Archives of Disease in Childhood. - : BMJ. - 0003-9888 .- 1468-2044. ; 85:2, s. 149-154
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Journal article (peer-reviewed)abstract
- Background - In recent years photopheresis, an extracorporeal form of photochemotherapy using psoralen and ultraviolet A irradiation of leucocytes, has been claimed to be an effective form of immunomodulation. Aim - To evaluate its effect in type 1 diabetes we performed a double blind, controlled study using placebo tablets and sham pheresis in the control group. Methods - A total of 49 children, aged 10-18 years of age at diagnosis of type 1 diabetes were included, 40 fulfilled the study and were followed for three years (19 received active treatment with photopheresis and 21 placebo treatment). Results - The actively treated children secreted significantly more C peptide in urine during follow up than control children. C peptide values in serum showed corresponding differences between the two groups. The insulin dose/kg body weight needed to achieve satisfactory HbA1c values was always lower in the photopheresis group, there was no difference between the groups regarding HbAlc values during follow up. The treatment was well accepted except for nausea (n = 3) and urticaria (n = 1) in the actively treated group. There were no differences regarding weight or height, or episodes of infection between the two groups during follow up. Conclusion - Photopheresis does have an effect in addition to its possible placebo effect, shown as a weak but significant effect on the disease process at the onset of type 1 diabetes, an effect still noted after three years of follow up.
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32. |
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33. |
- Nordfeldt, Sam, 1957-, et al.
(author)
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Serum ACE predicts severe hypoglycemia in children and adolescents with type 1 diabetes
- 2003
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 26:2, s. 274-278
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Journal article (peer-reviewed)abstract
- OBJECTIVE - To investigate whether risk of severe hypoglycemia is related to serum (S) ACE level during intensive treatment in type 1 diabetic children. RESEARCH DESIGN AND METHODS - A cohort of 86 intensively treated type 1 diabetic patients was studied during 1999-2000. In 1999, the age range was 7-19 years (median 12.8), diabetes duration was 1.2-14.7 years (5.3), insulin dose was 0,4-1.7 units ╖ kg-1 ╖ 24 h-1 (1.0), and the HbA1c year mean was 4.7-10.2% (6.8). HbA1c, insulin doses, and events of severe hypoglycemia (needing assistance from another person) were prospectively registered at regular visits, scheduled quarterly. S-ACE was determined once. RESULTS - Severe hypoglycemia was correlated to S-ACE (r = 0.22, 95% CI 0.0I-0.41, P = 0.0093). The square root of severe hypoglycemia was correlated to S-ACE (r = 0.27, 95% CI 0.06-0.45, P = 0.0093). Patients with S-ACE at the median level or above (n = 44) reported a mean of 3.0 yearly events of severe hypoglycemia compared with 0.5 events in patients with S-ACE lower than the median (n = 42) (P = 0.0079). Of the patients with an S-ACE at the median level or above, 27 (61%) reported severe hypoglycemia, compared with 17 (40%) patients with an S-ACE lower than the median (P = 0.0527). Insulin dose, HbA1c, age, onset age, duration, C-peptide, and sex did not differ between these two groups. S-ACE was negatively correlated with age (r = -0.27, 95% CI -0.46 to 0.07, P = 0.0265) but not with HbA1c, duration, or blood pressure. CONCLUSIONS - The elevated rate of severe hypoglycemia among patients with higher S-ACE suggests, among other factors, that a genetic determinant for severe hypoglycemia exists. Further evaluation is needed before the clinical usefulness of this test can be elucidated.
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34. |
- Panagopoulos, Ioannis, et al.
(author)
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Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10,16)(q22,p13)
- 2001
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 10:4, s. 395-404
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Journal article (peer-reviewed)abstract
- The CBP gene at 16p 13 fuses to MOZ and MLL as a result of the t(8,16)(p11,p13) in acute (myelo)monocytic leukemias (AML M4/M5) and the t(11,16)(q23,p13) in treatment-related AML, respectively. We show here that a novel t(10,16)(q22,p13) in a childhood AML M5a leads to a MORF-CBP chimera. RT-PCR using MORF forward and CBP reverse primers amplified a MORF-CBP fusion in which nucleotide 3103 of MORF was fused in-frame with nucleotide 284 of CBP. Nested RT-PCR with CBP forward and MORF reverse primers generated a CBP-MORF transcript in which nucleotide 283 of CBP was fused in-frame with nucleotide 3104 of MORF. Genomic analyses revealed that the breaks were close to Alu elements in intron 16 of MORF and intron 2 of CBP and that duplications had occurred near the breakpoints. A database search using MORF cDNA enabled us to construct an exon-intron map of the MORF gene. The MORF-CBP protein retains the zinc fingers, two nuclear localization signals, the histone acetyltransferase (HAT) domain, a portion of the acidic domain of MORF and the CBP protein downstream of codon 29. Thus, the part of CBP encoding the RARA-binding domain, the CREB-binding domain, the three Cys/His-rich regions, the bromodomain, the HAT domain and the Glu-rich domains is present. In the reciprocal CBP-MORF, part of the acidic domain and the C-terminal Ser- and Met-rich regions of MORF are likely to be driven by the CBP promoter. Since both fusion transcripts were present, their exact role in the leukemogenic process remains to be elucidated.
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35. |
- Persson, M., et al.
(author)
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The Better Diabetes Diagnosis (BDD) study – A review of a nationwide prospective cohort study in Sweden
- 2018
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In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 140, s. 236-244
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Research review (peer-reviewed)abstract
- The incidence of type 1 diabetes (T1D) in Sweden is one of the highest in the world. However, the possibility of other types of diabetes must also be considered. In addition, individuals with T1D constitute a heterogeneous group. A precise classification of diabetes is a prerequisite for optimal outcome. For precise classification, knowledge on the distribution of genetic factors, biochemical markers and clinical features in individuals with new onset of diabetes is needed. The Better Diabetes Diagnosis (BDD), is a nationwide study in Sweden with the primary aim to facilitate a more precise classification and diagnosis of diabetes in order to enable the most adequate treatment for each patient. Secondary aims include identification of risk factors for diabetes-related co-morbidities. Since 2005, data on almost all children and adolescents with newly diagnosed diabetes in Sweden are prospectively collected and including heredity of diabetes, clinical symptoms, levels of C peptide, genetic analyses and detection of autoantibodies. Since 2011, analyses of HLA profile, autoantibodies and C peptide levels are part of clinical routine in Sweden for all pediatric patients with suspected diagnosis of diabetes. In this review, we present the methods and main results of the BDD study so far and discuss future aspects.
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36. |
- Ping Zhao, Lue, et al.
(author)
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Building and validating a prediction model for paediatric type 1 diabetes risk using next generation targeted sequencing of class II HLA genes
- 2017
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In: Diabetes/Metabolism Research Reviews. - : WILEY. - 1520-7552 .- 1520-7560. ; 33:8
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Journal article (peer-reviewed)abstract
- AimIt is of interest to predict possible lifetime risk of type 1 diabetes (T1D) in young children for recruiting high-risk subjects into longitudinal studies of effective prevention strategies. MethodsUtilizing a case-control study in Sweden, we applied a recently developed next generation targeted sequencing technology to genotype class II genes and applied an object-oriented regression to build and validate a prediction model for T1D. ResultsIn the training set, estimated risk scores were significantly different between patients and controls (P=8.12x10(-92)), and the area under the curve (AUC) from the receiver operating characteristic (ROC) analysis was 0.917. Using the validation data set, we validated the result with AUC of 0.886. Combining both training and validation data resulted in a predictive model with AUC of 0.903. Further, we performed a biological validation by correlating risk scores with 6 islet autoantibodies, and found that the risk score was significantly correlated with IA-2A (Z-score=3.628, Pamp;lt;0.001). When applying this prediction model to the Swedish population, where the lifetime T1D risk ranges from 0.5% to 2%, we anticipate identifying approximately 20 000 high-risk subjects after testing all newborns, and this calculation would identify approximately 80% of all patients expected to develop T1D in their lifetime. ConclusionThrough both empirical and biological validation, we have established a prediction model for estimating lifetime T1D risk, using class II HLA. This prediction model should prove useful for future investigations to identify high-risk subjects for prevention research in high-risk populations.
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37. |
- Sadauskaite-Kühne, Vaiva, 1970-, et al.
(author)
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Longer breastfeeding is an independent protective factor against development of type 1 diabetes mellitus in childhood
- 2004
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In: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 20:2, s. 150-157
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Journal article (peer-reviewed)abstract
- BackgroundEarly weaning diet, early introduction of breast milk substitution and cow's milk have been shown to increase the risk of type 1 diabetes later in life. It is also shown that older maternal age, maternal education, preeclampsia, prematurity, neonatal illness and neonatal icterus caused by blood group incompatibility, infections and stress might be risk factors for type 1 diabetes. We aimed to determine whether early nutrition is an independent risk factor for diabetes despite other life events.MethodsData from 517 children (268 boys and 249 girls) in south-east of Sweden and 286 children (133 boys and 153 girls) in Lithuania in the age group of 0 to 15 years with newly diagnosed type 1 diabetes mellitus were included into analysis. Three age- and sex-matched healthy controls were randomly selected. Response rate in control families in Sweden was 72.9% and in Lithuania 94.8%. Information was collected via questionnaires.ResultsExclusive breastfeeding longer than five months (odds ratio 0.54, 95% confidence interval 0.36–0.81) and total breastfeeding longer than 7 (0.56, 0.38–0.84) or 9 months (0.61, 0.38–0.84), breastfeeding substitution that started later than the third month (0.57, 0.33–0.98) among Swedish children 5 to 9 years old and later than the seventh month (0.24, 0.07–0.84) among all Swedish children is protective against diabetes when adjusted for all other above-listed risk factors. In Lithuania, exclusive breastfeeding longer than two months in the age group of 5 to 9 years is protective (0.58, 0.34–0.99) when adjusted for other factors.ConclusionsLonger exclusive and total breastfeeding appears as an independent protective factor against type 1 diabetes.
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38. |
- Saduaskaite-Kühne, Vaiva, 1970-, et al.
(author)
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Severity at onset of childhood type 1 diabetes in countries with high and low incidence of the condition
- 2002
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In: Diabetes Research and Clinical Practice. - 0168-8227 .- 1872-8227. ; 55:3, s. 247-254
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Journal article (peer-reviewed)abstract
- Severity of Type 1 diabetes mellitus (DM) at presentation was compared between south-east Sweden and Lithuania where incidence of childhood Type 1 diabetes is three times lower than in Sweden. New cases of diabetes at age 0–15 years from August 1995 to March 1999 in south-east Sweden and from August 1996 to August 2000 in Lithuania were included. Symptoms and clinical characteristics at diagnosis were recorded. Data about the close environment were collected using questionnaires. Lithuanian children were diagnosed in a more severe condition, mean pH 7.30 and HbA1c 11.5% compared with mean pH 7.36 and HbA1c 9.7% in Swedish children (P<0.0001). More Lithuanian than Swedish children were diagnosed in ketoacidosis (pH≤7.2, hyperglycaemia and ketonuria), 21.3 versus 7.3% (P<0.0001). Only 4.6% of Swedish children and 1.0% of Lithuanian children had no symptoms (P=0.007). Children in families with at least one first degree relative with diabetes (12.2% in Sweden and 8.4% in Lithuania, NS) had laboratory values at diagnosis closer to normal than sporadic cases in either country. Factors predicting ketoacidosis in Sweden were an unemployed mother and absence of infections in the 6 months before diagnosis. In Lithuania it was younger age and mother with less education. Additional educational activities for doctors are needed in countries with low incidence to reduce prevalence of ketoacidosis at onset.
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39. |
- Samuelsson, Ulf, 1951-, et al.
(author)
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A fourfold difference in the incidence of type 1 diabetes between Sweden and Lithuania but similar prevalence of autoimmunity
- 2004
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In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 66:2, s. 173-181
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Journal article (peer-reviewed)abstract
- We investigated whether other autoimmune disorders in addition to type 1 diabetes are more common in Sweden than Lithuania, and if there are any differences in inheritance patterns of both type 1 diabetes and other autoimmune disorders.Data from 517 children in southeast Sweden and 286 children in Lithuania aged 0–15 years were included in the study. Age- and sex-matched control children were randomly selected. Information was collected by questionnaire.Of the children with diabetes in Sweden, 13.2% had a family member with type 1 diabetes compared to 7% of children with diabetes in Lithuania (P<0.01) (OR=2.01). No such difference was seen for other autoimmune diseases in family members of children with diabetes (Sweden 12%, Lithuania 14%, n.s.). Control children in Lithuania had family members with autoimmunity more frequently (15.3%) than control children in Sweden (7.4%, P<0.001) (OR=2.26). This difference was most pronounced in mothers. The Lithuanian control children had an autoimmune disease more frequently than the controls in Sweden (4.7% versus 1.5%, respectively, P<0.001) (OR=3.21).There seem to be environmental factors that specifically contribute to the development of type 1 diabetes, factors which are less related to the development of autoimmunity in general.
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40. |
- Samuelsson, Ulf, 1951-, et al.
(author)
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Clinical characteristics at onset of Type 1 diabetes in children diagnosed between 1977 and 2001 in the south-east region of Sweden
- 2005
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In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 68:1, s. 49-55
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Journal article (peer-reviewed)abstract
- To survey clinical characteristics at diagnosis for children diagnosed with Type 1 diabetes during 25 years in the south-east part of Sweden we included all 1903 children <16 years of age and who had been diagnosed between 1977 and 2001 in the south-east region of Sweden. A nurse or doctor in the diabetes team obtained information from medical records. Over the 25 years the mean duration of symptoms prior to diagnosis was 17.8 ± 26.4 days and the mean glucose level at diagnosis was 23.6 ± 9.7 mmol/l. Three percent of the children (n = 50) had a pH value ≤ 7.1. The youngest children (0-5 years) had shorter duration of symptoms, lower blood-glucose levels and less often had ketonuria than the oldest children (11-15 years) but more often suffered from infections prior to diagnosis. The proportion of children diagnosed in the group 0-5 years of age increased over the study-period, apart from the last 5 years, while children with pH value ≤ 7.3 decreased significantly as did the proportion of children with ketonuria or infection. The clinical characteristics at diagnosis of diabetes are heterogeneous, especially in the oldest age group. Some characteristics varied with time. © 2004 Elsevier Ireland Ltd. All rights reserved.
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41. |
- Samuelsson, Ulf, 1951-, et al.
(author)
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Do high blood glucose peaks contribute to higher HbA1c? Results from repeated continuous glucose measurements in children
- 2008
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In: World Journal of Pediatrics. - : Springer Science and Business Media LLC. - 1708-8569. ; 4:3, s. 215-221
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Journal article (peer-reviewed)abstract
- Background: HbA1c levels are infl uenced by the glycemic control of previous 2-3 months. Sometimes patients have surprisingly low HbA1c in spite of many correctly measured high blood glucose values, which is diffi cult to explain. As glucose sensors give an objective picture based on glucose readings several times per minute over 24 hours, we used the area under the curve (AUC) of such subcutaneous glucose profi les to evaluate their relationship with HbA1c. Methods: Thirty-two patients were randomized into two study arms, one open and the other blinded. Both arms had 8 pump users and 8 patients with multiple daily injections (MDI). After three months the two arms crossed over. Both study arms wore a continuous glucose monitoring system (CGMS) for 3 days every 2 weeks. HbA1c was determined before and after each 3-month study period. Results: There was no relationship between HbA1c and s.c. glucose AUC or between HbA1c and the number of peaks >15.0 mmol/L when all CGMS profi les during the 6 months were taken together. Children on MDI showed a positive relationship between HbA1c and AUC (P<0.01) as well as the number of peaks (P<0.01). Children with a negative relationship between HbA1c and AUC generally had fewer fluctuations in blood glucose values, whereas children with a positive relationship had wide fluctuations. Conclusions: Although there was no relationship between s.c. glucose AUC and HbA1c, the results indicate that wide blood glucose fluctuations may be related to high HbA1c values. Therefore, complications and therapeutic interventions should aim at reducing such fluctuations. © Springer 2008.
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42. |
- Samuelsson, Ulf, 1951-, et al.
(author)
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Geographical mapping of type 1 diabetes in children and adolescents in south east Sweden
- 2004
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In: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 58:5, s. 388-392
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Journal article (peer-reviewed)abstract
- Study objective: As earlier studies have shown space-time clusters at onset of type 1 diabetes in the south east region of Sweden we investigated if there also has been any geographical clusters of diabetes in this region.Design: The place of residence (coordinates) at the time of diagnosis were geocoded in a geographical information system (GIS). All children diagnosed with type 1 diabetes up to 16 years of age at diagnosis between 1977–1995 were included. The population at risk was obtained directly from the population registry for the respective years and geographical area levels.Setting: South east region of Sweden containing 5 counties, 49 municipalities, and 525 parishes.Main results: A significant geographical variation in incidence rate were found between the municipalities (p<0.001) but not between the counties. The variation became somewhat weaker when excluding the six largest municipalities (p<0.02). In municipalities with increased risk (>35.1/100 000) the major contribution comes from children in age group 6–10 years of age at diagnosis. There were no obvious differences between the age groups in municipalities with decreased risk (<20.1/100 000). Boys and girls had about the same degree of geographical variation.Conclusions: Apart from chance, the most probable explanation for the geographical variation in the risk for children and adolescents to develop type 1 diabetes between the municipalities in the region is that local environmental factors play a part in the process leading to the disease.
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43. |
- Samuelsson, Ulf, 1951-, et al.
(author)
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Increased prevalence of malignant diseases in the close neighborhood of children with cancer
- 2001
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In: Journal of environmental health. - 0022-0892. ; 64:7, s. 18-22
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Journal article (peer-reviewed)abstract
- Clustering of cancer in families may be due to chance, inherited genetic mutations, common exposure to environmental agents, or a combination of these factors. The authors, to address a clinical impression that cancer occurs more often in the environment of a child with cancer, investigated whether the prevalence of cancer among children and adults in the neighborhood of children with cancer was higher than the prevalence in the neighborhood of healthy children. One hundred thirty-seven children diagnosed with a malignant disease between 1981 and 1992 at the Department of Pediatrics, University Hospital of Link÷ping, Sweden, were investigated and compared with 232 healthy control children. The control children were traced from the official Swedish population registry. It was found that 13 percent of the children with cancer and six percent of the control children were dose neighbors of other children diagnosed with cancer (p < .05). Cancer also was more common in the circles of acquaintances around the children with cancer than in circles of acquaintances around control children (p < .03). The frequency of cancer in the neighborhood or in the circle of acquaintances was significantly greater in older children than in younger children. These results support the hypothesis that environmental factors can initiate or precipitate cancer in children as well as in adults.
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44. |
- Samuelsson, Ulf, 1951-, et al.
(author)
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Islet autoantibodies in the prediction of diabetes in school children
- 2001
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In: Diabetes Research and Clinical Practice. - 1872-8227 .- 0168-8227. ; 51:1, s. 51-57
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Journal article (peer-reviewed)abstract
- In 1987 serum was collected from 1031 non-diabetic schoolchildren in the Southeast area of Sweden with the aim of evaluating islet autoantibody status (ICA, GADA and IA2-ab) in the prediction of diabetes in schoolchildren. The clinical development of Type 1 diabetes in the children was assessed in 1994 and 1997. The combination of ICA, GADA and IA2-ab were found in four subjects whereas six had two and 35 children one of these antibodies. After 10 years, six of the 1031 children had developed clinical diabetes and five of these six children were positive for islet antibodies. Two were positive for all three antibodies, two were positive for ICA and GADA, and one was positive for GADA. Among the individual autoantibodies, ICA showed the highest positive predictive value (29%) whereas the predictive value for the combination of two autoantibodies was highest for GADA and ICA (40%). Thus, GADA and ICA measurements may be a rational approach to detect schoolchildren at risk for developing diabetes.
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45. |
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46. |
- Samuelsson, Ulf, 1951-, et al.
(author)
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Seasonal variation in the diagnosis of type 1 diabetes in south-east Sweden
- 2007
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In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 76:1, s. 75-81
-
Journal article (peer-reviewed)abstract
- With the aim to survey the seasonal pattern of diagnosis of type 1 diabetes we included all 1903 children <16 years of age and who had been diagnosed with type 1 diabetes between 1977 and 2001 in the south-east of Sweden. To investigate the seasonal pattern a mixture of two cosine functions was included in a logistic regression model.There was a clear seasonal variation over the years (p < 0.001). Children in the oldest age group (11–15 years) showed the most obvious seasonal variation (p < 0.001). Children with a short duration of symptoms had about the same seasonal variation as children with a long duration. Both children with and without an infection 3 months prior to diagnosis showed significant seasonal variation (p < 0.001) although the seasonal pattern differed between the two groups (p < 0.001). As the incidence of diabetes increased during the 25 years the study period was divided into periods of 5 years and it was only during the two last periods that significant seasonal variation occurred.There is a clear seasonal variation in diagnosis of type 1 diagnosis in children and the results suggest that children with a less aggressive disease process at diagnosis were most responsible for this variation. Children with and without prior infection showed a different seasonal pattern.
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47. |
- Samuelsson, Ulf, 1951-, et al.
(author)
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Seasonal variation of birth month and breastfeeding in children with diabetes mellitus
- 2001
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In: Journal of Pediatric Endocrinology & Metabolism (JPEM). - 0334-018X .- 2191-0251. ; 14:1, s. 43-46
-
Journal article (peer-reviewed)abstract
- Objective: As breastfeeding is suggested to protect against diabetes mellitus we decided to investigate whether the seasonal variation of month of birth of diabetic children, with more diabetes in children born in summer, can be explained to some extent by a seasonal variation of exclusive breastfeeding. Patients: A population-based group of 297 children who had been diagnosed with diabetes mellitus before the age of 15 years was compared with 792 matched healthy subjects. Results: There was no difference in duration of breast-feeding between children who later got diabetes and the controls. Children (both diabetics and controls) born during the summer were exclusively breastfed for a mean period of 2.2 months. Corresponding figures for children born during winter were 2.8 months (p<0.04), spring 2.5 months (n.s.) and autumn 2.7 months (p<0.05). Seasonality was most pronounced in children who developed diabetes between the ages of 10 and 15 years. Conclusion: These results indicate that children born during the summer, who have increased risk of developing diabetes mellitus, have also been exclusively breastfed for a shorter time.
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48. |
- Samuelsson, Ulf, 1951-, et al.
(author)
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The concentrations of short-chain fatty acids and other microflora-associated characteristics in faeces from children with newly diagnosed Type 1 diabetes and control children and their family members
- 2004
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In: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 21:1, s. 64-67
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Journal article (peer-reviewed)abstract
- Aims: The gut flora is quantitatively the most important source of microbial stimulation and may provide a primary signal in the maturation of the immune system. We compared the microflora-associated characteristics (MACs) in 22 children with newly diagnosed diabetes, 27 healthy controls, and their family members to see if there were differences between the children and if there was a familial pattern. Methods: The MACs were assessed by determining the concentrations of eight short-chain fatty acids (SCFA), mucin, urobilin, b-aspartylglycine, coprastanol and faecal tryptic activity (FTA). Results: There were no statistically significant differences between the concentrations of SCFA in the diabetes and control children. Members of families with a diabetic child had a higher concentration of acetic acid (P < 0.02) and lower concentrations of several other SCFAs than control families (P < 0.05-0.02). The other MACs showed no differences between the children or between the two family groups. Conclusion: In this pilot study we saw no differences in the MACs between children with diabetes and their controls. There were, however, some differences between the family members of diabetic children and controls that may indicate a familial pattern regarding the production of SCFAs by the gut flora. The role of the gut flora in relation to the risk of developing Type 1 diabetes needs to be analysed in larger and/or prospective studies.
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49. |
- Samuelsson, Ulf, 1951-, et al.
(author)
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When should determination of ketonemia be recommended?
- 2002
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In: Diabetes Technology & Therapeutics. - : Mary Ann Liebert Inc. - 1520-9156 .- 1557-8593. ; 4:5, s. 645-650
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Journal article (peer-reviewed)abstract
- Diabetic ketoacidosis is a serious complication of type diabetes. β-Hydroxybutyrate (β-OHB) accounts for about 75% of ketones, and blood concentration can be determined with a sensor. The aim of this study was to investigate the frequency and degree of ketonemia in daily life of children with diabetes and to make a base for recommendations for determination of ketonemia in clinical practice. During 3 months 45 patients with type 1 diabetes since 1-10 years old (mean 4.4 ± 3.3 years old) at the pediatric clinic in Linköping, Sweden, performed 24-h profiles (eight determinations) in 2 weeks with blood glucose and β-OHB. The children performed 11,189 blood glucose and 7,057 β-OHB measurements. Only 0.3% (n = 21) of β-OHB measurements were ≥ 1.0 mmol/L. An β-OHB concentration > 0.2 mmol/L was more common in the morning than during the rest of the day (p < 0.001). Young children (4-7 years old) had values ≥ 0.2 mmol/L more often than adolescents (p < 0.001). Blood glucose values > 15 mmol/L were more often accompanied by β-OHB > 0.2 mmol/L (p < 0.001). High β-OHB concentrations are rare in diabetic children with reasonably good metabolic control. Already a value > 0.4 mmol/L seems abnormal, and we recommend that patients retest glucose and ketones with β-OHB > 0.4 mmol/L. Furthermore, we recommend that diabetic children and adolescents measure β-OHB when symptoms like nausea or vomiting occur to differentiate ketoacidosis from gastroenteritis, and during infections, during periods with high blood glucose (> 15 mmol/L), and if they notice ketonuria. Monitoring β-OHB should be routine for patients on pump therapy.
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50. |
- Samuelsson, Ulf, 1951-
(author)
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Why do children get diabetes? : A study on some genetical, immunological and environmental factors
- 1993
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Doctoral thesis (other academic/artistic)abstract
- Insulin dependent diabetes mellitus (IDDM) is one of the most common and serious chronic disorders of childhood. Despite advances in the knowledge about the cause of IDDM during the last decades the etiology still remains incompletely understood but is probably due to a complex network of genetic, immunological and environmental factors. The aim of the thesis was to elucidate some parts of this network and, if possible, identify riskfactors or markers for the development of IDDM in childhood.Background infonnation was received from questionnaires and/or medical records. Islet cell surface antibodies (ICSA) were analysed by a new radioimmunologic method with a specificity of 100 % and a sensitivity of 70 % for positive titers, while the other autoantibodies and C-peptide values were determined by wellknown and accepted methods.An international study on 745 HLA-typed children with diabetes indicated that IDDM is genetically heterogenous. Patients with HLA-DR3/nonDR4 generally have a milder form of diabetes than patients without this marker.Studies from the South-east region of Sweden showed that early weight gain seems to be more correlated to development of IDDM than breastfeeding resp. non-breastfeeding.Analysis of space-time clustering in all cases of childhood diabetes (n=584) diagnosed between 1977-1990 indicates clustering with maximal effect within 7 months and 15 km. The frequency of islet cell antibodies (!CA) among non-diabetic schoolchildren was 1,4 %. Corresponding figures for insulinautoantibodies) IAA) and ICSA were 4,0 % and 4,3 %respectively. Only !CA showed a relationship to C-peptide values. Children with low levels of ICA had high values and vice versa.An international family study showed that certain factors seem to cause not only a high incidence of diabetes in Finland and Sweden but also a more aggressive early disease process. ICSA was the only autoantibody which showed simultaneous positivity in all family members. ICSA had also a similar seasonality as incidence of IDDM and was most common in family members of patients with a short duration of symptoms before diagnosis (<8 days).In conclusion, early feeding may be of importance for future development of Type I diabetes not only because of degree of exposition to cow milk proteins but also because of effects on energy intake and early betacellstimulation. Environmental factors, probably infections, are of importance for eliciting the disease. High incidence areas have a moreaggressive disease process than areas with lower incidence. Although signs on an autoimmune attack on the beta cells are rather common in the general population such an attack seldom leads to IDDM. ICSA, contrary to ICA, may reflect an early ongoing disease process in genetically predisposed individuals.
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