| 1. |
- Bakhtadze, Ekaterine, et al.
(författare)
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Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15-34 years) but not in middle-aged (40-59 years) diabetic patients
- 2008
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:12, s. 2224-2232
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes in children is characterised by autoimmune destruction of pancreatic beta cells and the presence of certain risk genotypes. In adults the same situation is often referred to as latent autoimmune diabetes in adults (LADA). We tested whether genetic markers associated with type 1 or type 2 diabetes could help to discriminate between autoimmune and non-autoimmune diabetes in young (15-34 years) and middle-aged (40-59 years) diabetic patients. In 1,642 young and 1,619 middle-aged patients we determined: (1) HLA-DQB1 genotypes; (2) PTPN22 and INS variable-number tandem repeat (VNTR) polymorphisms; (3) two single nucleotide polymorphisms (rs7903146 and rs10885406) in the TCF7L2 gene; (4) glutamic acid decarboxylase (GAD) and IA-2-protein tyrosine phosphatase-like protein (IA-2) antibodies; and (5) fasting plasma C-peptide. Frequency of risk genotypes HLA-DQB1 (60% vs 25%, p =9.4x10(-34); 45% vs 18%, p= 1.4x10(-16)), PTPN22 CT/TT (34% vs 26%, p=0.0023; 31% vs 23%, p=0.034), INS VNTR class I/I (69% vs 53%, p=1.3x10(-8); 69% vs 51%, p=8.5x10(-5)) and INS VNTR class IIIA/IIIA (75% vs 63%, p=4.3x10(-6); 73% vs 60%, p=0.008) was increased in young and middle-aged GAD antibodies (GADA)-positive compared with GADA-negative patients. The type 2 diabetes-associated genotypes of TCF7L2 CT/TT of rs7903146 were significantly more common in young GADA-negative than in GADA-positive patients (53% vs 43%; p=0.0004). No such difference was seen in middle-aged patients, in whom the frequency of the CT/TT genotypes of TCF7L2 was similarly increased in GADA-negative and GADA-positive groups (55% vs 56%). Common variants in the TCF7L2 gene help to differentiate young but not middle-aged GADA-positive and GADA-negative diabetic patients, suggesting that young GADA-negative patients have type 2 diabetes and that middle-aged GADA-positive patients are different from their young GADA-positive counterparts and share genetic features with type 2 diabetes.
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| 2. |
- Henricsson, Marianne, et al.
(författare)
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The incidence of retinopathy 10 years after diagnosis in young adult people with diabetes: results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS).
- 2003
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 26:2, s. 349-354
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—To estimate the prevalence and severity of diabetic retinopathy (DR) 10 years after diagnosis in a nationwide population-based cohort study of young adult diabetic patients in Sweden. RESEARCH DESIGN AND METHODS—The Diabetes Incidence Study in Sweden (DISS) aims to register all incident cases of diabetes aged 15–34 years in Sweden. In 1987–1988, 806 cases were reported, and 627 (78%) of them were followed up with regard to retinopathy 8–10 years later. The assessment was based on retinal photographs in most cases (86%). RESULTS—Ten years after diagnosis, retinopathy was found in 247 patients (39%). The retinopathy was mild in 206 (33%), whereas 30 (4.8%) patients had moderate nonproliferative DR (NPDR) and 11 (1.8%) had proliferative DR (PDR). Patients with retinopathy had worse glycemic control during the years than patients without (HbA1c 8.1 ± 1.5% and 6.8 ± 1.2%, respectively; P < 0.001). In a Cox regression analysis, time to retinopathy was related to high HbA1c (P < 0.001) and high BMI (P = 0.001). Patients with type 2 diabetes had an increased prevalence of severe retinopathy (NPDR or PDR) compared with those with type 1 diabetes (14 of 93 [15%] versus no or mild 24 of 471 [5%], respectively; P < 0.001). CONCLUSIONS—Despite modern diabetes management, 39% of young adult diabetic patients developed retinopathy within the first 10 years of the disease. Nevertheless, compared with the prevalence of retinopathy (63%), after a similar duration of diabetes before the Diabetes Control and Complications Trial, this prevalence was clearly lower. Current treatment aimed to achieve strict glycemic control has reduced the risk for developing retinopathy.
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| 3. |
- Littorin, Bengt, et al.
(författare)
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Family characteristics and life events before the onset of autoimmune type 1 diabetes in young adults : A nationwide study
- 2001
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 24:6, s. 1033-1037
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - To elucidate whether family characteristics and stressful life events were associated with onset of autoimmune type 1 diabetes in young adults. RESEARCH DESIGN AND METHODS - This investigation was based on a nationwide study (Diabetes Incidence Study in Sweden) of newly diagnosed patients aged 15-34 years. Patients clinically classified as type 1 diabetic with antibodies to islet cells and/or to GAD65 were compared with age- and sex-matched control subjects via questionnaire. The questionnaire covered diabetes heredity, social environment, educational level, and life events experienced during the 12 months before diagnosis. RESULTS - The rate of response was 82% for the diabetic patients and 65% for the control subjects. Questionnaires from 349 diabetic patients and 979 control subjects were considered. Diabetes in relatives was more frequent in the patients (odds ratio [OR] 2.6) who were born in Sweden and whose mothers were of Swedish origin. No major stress factors were detected in the diabetic patients, however, in comparison with the control subjects, the diabetic patients had experienced fewer conflicts with their parents and had less often broken contacts with friends. CONCLUSIONS - Young adults with recent-onset type 1 diabetes were more exposed to heredity for diabetes, but no major prediabetic stress factors were detected. Our study does not directly support the concept that psychosocial stressful life events are involved in the development of autoimmune type 1 diabetes in young adults.
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| 4. |
- Littorin, Bengt, et al.
(författare)
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Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects : results from the nationwide Diabetes Incidence Study in Sweden (DISS)
- 2006
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 49:12, s. 2847-2852
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Tidskriftsartikel (refereegranskat)abstract
- Low plasma vitamin D concentrations may promote the development of type 1 diabetes. To test this hypothesis, we measured plasma 25-hydroxyvitamin D (25OHD) in young adults with type 1 diabetes.The nationwide Diabetes Incidence Study in Sweden (DISS) covers 15- to 34-year-old people with newly diagnosed diabetes. Blood samples at diagnosis were collected during the 2-year period 1987/1988. Patients with islet antibodies (islet cell antibodies, GAD antibodies or tyrosine phosphatase-like protein antibodies) were defined as having autoimmune type 1 diabetes. Plasma 25OHD was measured in samples taken from 459 patients at the time of diagnosis, and in 138 of these subjects 8 years later. The results were compared with age- and sex-matched control subjects (n=208).At diagnosis, plasma 25OHD levels were significantly lower in patients with type 1 diabetes than in control subjects (82.5 +/- 1.3 vs 96.7 +/- 2.0 nmol/l; p < 0.0001). Eight years later, plasma 25OHD had decreased in patients (81.5 +/- 2.6 nmol/l; p=0.04). Plasma 25OHD levels were significantly lower in diabetic men than in diabetic women at diagnosis (77.9 +/- 1.4 vs 90.1 +/- 2.4 nmol/l; p < 0.0001) and at follow-up (77.1 +/- 2.8 nmol/l vs 87.2 +/- 4.5 nmol/l; p=0.048). 81.5 +/- 2.6 nmol/l; p=0.04). Plasma 25OHD levels were significantly lower in diabetic men than in diabetic women at diagnosis (77.9 +/- 1.4 vs 90.1 +/- 2.4 nmol/l; p < 0.0001) and at follow-up (77.1 +/- 2.8 nmol/l vs 87.2 +/- 4.5 nmol/l; p=0.048). Conclusions/interpretation The plasma 25OHD level was lower at diagnosis of autoimmune type 1 diabetes than in control subjects, and may have a role in the development of type 1 diabetes. Plasma 25OHD levels were lower in men than in women with type 1 diabetes. This difference may be relevant to the high incidence of type 1 diabetes among young adult men.
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| 7. |
- Schölin, Anna, et al.
(författare)
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Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults : a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden
- 2004
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 255:3, s. 384-391
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- ObjectivesTo establish the prevalence of remaining β-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later.DesignPopulation-based cohort study.SettingNationwide from all Departments of Medicine and Endocrinology in Sweden.SubjectsA total of 312 young (15–34 years old) adults diagnosed with diabetes during 1987–88.Main outcome measurePlasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved β-cell function was defined as measurable C-peptide levels. Three islet antibodies – cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies – were measured.ResultsAmongst 269 islet antibody positives (ab+) at diagnosis, preserved β-cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m−2, respectively; P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively; P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively; P = 0.007) at diagnosis compared with ab+ without remaining β-cell function. Amongst the 241 patients without detectable β-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up.ConclusionsSixteen per cent of patients with autoimmune type 1 diabetes had remaining β-cell function 8 years after diagnosis whereas 5.8% with β-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up.
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| 8. |
- Schölin, Anna, et al.
(författare)
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Normal weight promotes remission and low number of islet antibodies prolong the duration of remission in Type 1 diabetes
- 2004
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 21:5, s. 447-455
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Aim To identify clinical, immunological and biochemical factors that predict remission, and its duration in a large cohort of young adults with Type 1 diabetes mellitus (DM).Methods In Sweden, 362 patients (15–34 years), classified as Type 1 DM were included in a prospective, nation-wide population-based study. All patients were followed at local hospitals for examination of HbA1c and insulin dosage over a median period after diagnosis of 5 years. Duration of remission, defined as an insulin maintenance dose ≤ 0.3 U/kg/24 h and HbA1c within the normal range, was analysed in relation to characteristics at diagnosis.Results Remissions were seen in 43% of the patients with a median duration of 8 months (range 1–73). Sixteen per cent had a remission with a duration > 12 months. Among patients with antibodies (ab+), bivariate analysis suggested that adult age, absence of low BMI, high plasma C-peptide concentrations, lack of ketonuria or ketoacidosis at diagnosis and low insulin dose at discharge from hospital were associated with a high possibility of achieving remission. Multiple regression showed that normal weight (BMI of 20–24.9 kg/m2) was the only factor that remained significant for the possibility of entering remission. In survival analysis among ab+ remitters, a low number of islet antibodies, one or two instead of three or four, were associated with a long duration of remissions.Conclusion In islet antibody-positive Type 1 DM, normal body weight was the strongest factor for entering remission, whilst a low number of islet antibodies was of importance for the duration.
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