| 1. |
- Delli, Ahmed J, et al.
(författare)
-
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
-
Ingår i: Diabetes. - American Diabetes Association. - 1939-327X. ; 61:10, s. 2556-2564
-
Tidskriftsartikel (refereegranskat)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 (≥1 islet autoantibody) T1D type 1 diabetic patients (n = 2,964, <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.
|
|
| 2. |
- Elding Larsson, Helena, et al.
(författare)
-
Reduced Prevalence of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Young Children Participating in Longitudinal Follow-Up
- 2011
-
Ingår i: Diabetes Care. - American Diabetes Association. - 0149-5992. ; 34:11, s. 2347-2352
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Young children have an unacceptably high prevalence of diabetic ketoacidosis (DKA) at the clinical diagnosis of type I. diabetes. The aim of this study was to determine whether knowledge of genetic risk and close follow-up for development of islet autoantibodies through participation in The Environmental Determinants of Diabetes in the Young (TEDDY) study results in lower prevalence of DKA at diabetes onset in children aged andlt;2 and andlt;5 years compared with population-based incidence studies and registries. less thanbrgreater than less thanbrgreater thanRESEARCH DESIGN AND METHODS-Symptoms and laboratory data collected on TEDDY participants diagnosed with type 1 diabetes between 2004 and 2010 were compared with data collected during the similar periods from studies and registries in all TEDDY-participating countries (U.S., SEARCH for Diabetes in Youth Study; Sweden, Swediabkids; Finland, Finnish Pediatric Diabetes Register; and Germany, Diabetes Patienten Verlaufsdokumenation [DPV] Register). less thanbrgreater than less thanbrgreater thanRESULTS-A total of 40 children younger than age 2 years and 79 children younger than age 5 years were diagnosed with type 1 diabetes in TEDDY as of December 2010. In children andlt;2 years of age at onset, DKA prevalence in TEDDY participants was significantly lower than in all comparative registries (German DPV Register, P andlt; 0.0001; Swediabkids, P = 0.02; SEARCH, P andlt; 0.0001; Finnish Register, P andlt; 0.0001). The prevalence of DKA in TEDDY children diagnosed at andlt;5 years of age (13.1%) was significantly lower compared with SEARCH (36.4%) (P andlt; 0.0001) and the German DPV Register (32.2%) (P andlt; 0.0001) but not compared with Swediabkids or the Finnish Register. less thanbrgreater than less thanbrgreater thanCONCLUSIONS-Participation in the TEDDY study is associated with reduced risk of DMA at diagnosis of type 1 diabetes in young children.
|
|
| 3. |
- Gyllenberg, A, et al.
(författare)
-
Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes
- 2012
-
Ingår i: Genes and Immunity. - Nature Publishing Group. - 1466-4879. ; 13:8, s. 632-640
-
Tidskriftsartikel (refereegranskat)abstract
- The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P = 4 x 10(-5) and rs3087456, P = 0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P = 0.006, P = 0.007). We also detect association to T1D for both markers, rs11074932 (P = 0.004) and rs3087456 (P = 0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.
|
|
| 4. |
- Lundgren, Fredrik, et al.
(författare)
-
PTFE Bypass to Below-knee Arteries: : Distal Vein Collar or Not? A Prospective Randomised Multicentre Study
- 2010
-
Ingår i: European Journal of Vascular and Endovascular Surgery. - Elsevier Science B.V., Amsterdam. - 1078-5884. ; 39:6, s. 747-754
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Patency and limb salvage after synthetic bypass to the arteries below-knee are inferior to that which can be achieved with autologous vein. Use of a vein collar at the distal anastomosis has been suggested to improve patency and limb salvage, a problem that is analysed in this randomised clinical study. Methods: Patients with critical limb ischaennia undergoing polytetrafluoroethylene (PTFE) bypass to below-knee arteries were randomly either assigned a vein collar or not in two groups bypass to the popliteal artery below-knee (femoro-popliteal below-knee (FemPopBK)) and more distal bypass (femoro-distal bypass (FemDist)). Follow-up was scheduled until amputation, death or at most 5 years, whichever event occurred first. Results: In the FemPopBK and in the FemDist groups, 115/202 and 72/150 were randomised to have a vein collar, respectively. Information was available for 345 of 352 randomised patients (98%). At 3 years, primary patency was 26% (95% confidence interval (CI) 18-38) with a vein collar and 43 (33-58) without a vein collar for femoro-popliteal bypass and 20 (11-38), and 17 (9-33) for femoro-distal bypass, respectively. The corresponding figures for limb salvage were 64 (54-75) and 61(50-74) for femoro-popliteal bypass, and 59 (46-76) and 44 (32-61) for femoro-distal bypass with and without a vein collar, respectively. Log-rank-test for the whole Kaplan-Meier life table curve showed no statistically significant differences with or without vein collar primary patency: p = 0.0853, p = 0.228; secondary patency: p = 0.317, p = 0.280; limb salvage: p = 0.757, p = 0.187 for FemPopBK and FemDist, respectively. The use of a vein collar did not influence patency or limb salvage. Conclusion: This study failed to show any benefit for vein collar with PTFE bypass to a below-knee artery.
|
|
| 5. |
- Resic-Lindehammer, S., et al.
(författare)
-
Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
- 2008
-
Ingår i: Acta Diabetologica. - 0940-5429. ; 45:4, s. 231-5
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
|
|
| 6. |
- Samuelsson, U, et al.
(författare)
-
Residual beta cell function at diagnosis of type 1 diabetes in children and adolescents varies with gender and season
- 2013
-
Ingår i: Diabetes/Metabolism Research and Reviews. - Wiley-Blackwell Publishing. - 1520-7552. ; 29:1, s. 85-89
-
Tidskriftsartikel (refereegranskat)abstract
- Background There are seasonal variations and gender differences in incidence of type 1 diabetes (T1D), metabolic control and responses to immune interventions at onset of the disease. We hypothesized that there are seasonal and gender differences in residual insulin secretion already at diagnosis of T1D. Methods In 2005, a national study, the Better Diabetes Diagnosis, was started to classify all newly diagnosed children and adolescents with diabetes. About 95% (3824/4017) of the patients were classified as T1D, and our analyses are based on the patients with T1D. Results C-peptide was lower in younger children, 010 years of age (0.23 +/- 0.20 nmol/L) than in older children, 1118 years of age (0.34 +/- 0.28 nmol/L) (p < 0.000 ). There was a seasonal variation in non-fasting serum C-peptide, significantly correlated to the seasonal variation of diagnosis (p < 0.01). Most children were diagnosed in January, February and March as well as in October when C-peptide was highest, whereas fewer patients were diagnosed in April and May when serum C-peptide was significantly lower (p < 0.01). The seasonal variation of C-peptide was more pronounced in boys than in girls (p < 0.000 and p < 0.01, respectively). Girls had higher C-peptide than boys (p < 0.05), especially in early puberty. Conclusions Both seasonal and gender differences in residual beta cell function exist already at diagnosis of T1D. These observations have consequences for treatment and for randomizing patients in immune intervention clinical trials. Copyright (C) 2012 John Wiley & Sons, Ltd.
|
|
| 7. |
- Vaziri-Sani, Fariba, et al.
(författare)
-
A novel triple mix radiobinding assay for the three ZnT8 (ZnT8-RWQ) autoantibody variants in children with newly diagnosed diabetes.
- 2011
-
Ingår i: Journal of immunological methods. - 1872-7905. ; 371, s. 25-37
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Autoantibodies against the zinc transporter 8 (ZnT8A) are common in type 1 diabetes (T1D). ZnT8A analyses are complicated by the fact that there are three variants of the autoantigen at amino acid position 325 representing ZnT8-R (Arginine), ZnT8-W (Tryptophan) and ZnT8-Q (Glutamin). The aims of the study were: 1) to develop an autoantigen triple mix Radio-Binding Assay (RBA) for ZnT8A; 2) to identify the individual ZnT8-R,-W,-QA reactivity and 3) to validate the triple mix ZnT8A RBA in children with newly diagnosed T1D. METHODS: Serum samples were obtained from 2664 (56% males, n=1436) patients in the Swedish nationwide Better Diabetes Diagnosis (BDD) study representing patients with T1D (97%, n=2582), T2D (1.7%, n=46), MODY (1.0%, n=28) and secondary diabetes (0.3%, n=8). cDNA coding for the C-terminal end of each variant was prepared by site-directed mutagenesis and subcloned into a high efficiency in vitro transcription translation vector. The ZnT8 variants were labeled with 35S-methionine and used in a standard RBA separating free from autoantibody-bound autoantigen with Protein A-Sepharose. RESULTS: ZnT8-TripleA was detected in 1678 (65%) patients with T1D, 4 (9%) T2D, 3 (11%) MODY and in none (0%) of the patients with secondary diabetes. Among the T1D patients ZnT8-RA was detected in 1351 (52%) patients, ZnT8-WA in 1209 (47%) and ZnT8-QA in 790 (31%) demonstrating that 1661 (64%) had one or several ZnT8A. The ZnT8-TripleA assay showed a false positive rate of 1.9% (n=49). Only 1.2% (n=32) of the T1D patients were false negative for ZnT8-TripleA compared to 0/46 (0%) of the T2D patients. The precision (intra assay CV) and reproducibility (inter assay CV) of the ZnT8-TripleA assay did not differ from the RBA of the individual ZnT8 variants. CONCLUSION: We conclude that the ZnT8-TripleA assay had low false positive and false negative rates. The ZnT8-TripleA assay would therefore be highly suitable not only to analyze patient with newly diagnosed diabetes but also for screening the general population since this assay demonstrated high sensitivity and very high specificity.
|
|
