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- Graham, Jinko, et al.
(author)
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Negative association between type 1 diabetes and HLA DQB1*0602-DQA1*0102 is attenuated with age at onset
- 1999
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In: European Journal of Immunogenetics. - : Wiley. - 0960-7420 .- 1365-2370. ; 26, s. 117-
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Journal article (peer-reviewed)abstract
- HLA-associated relative risks of type 1 (insulin-dependent) diabetes mellitus were analysed in population-based Swedish patients and controls aged 0-34 years. The age dependence of HLA-associated relative risks was assessed by likelihood ratio tests of regression parameters in separate logistic regression models for each HLA category. The analyses demonstrated an attenuation with increasing age at onset in the relative risk for the positively associated DQB1*0201-A1*0502/B1*0302-A1*0301 (DQ2/8) genotype (P = 0.02) and the negatively associated DQB1*0602-A1*0102 (DQ6.2) haplotype (P = 0.004). At birth, DQ6.2-positive individuals had an estimated relative risk of 0.03, but this increased to 1.1 at age 35 years. Relative risks for individuals with DQ genotype 8/8 or 8/X or DQ genotype 2/2 or 2/X, where X is any DQ haplotype ether than 2, 8 or 6.2, were not significantly age-dependent. An exploratory analysis of DQ haplotypes other than 2, 8 and 6.2 suggested that the risk of type 1 diabetes increases with age for DQB1*0604-A1*0102 (DQ6.4) and that the peak risk for the negatively associated DQB1*0301-A1*0501 haplotype is at age 18 years. There was also weak evidence that the risk for DQB1*0303-A1*0301 (DQ9), which has a positive association in the Japanese population, may decrease with age. We speculate that HLA-DQ alleles have a significant effect on the rate of beta cell destruction, which is accelerated in DQ2/8-positive individuals and inhibited, but not completely blocked, in DQ6.2-positive individuals.
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- Landin-Olsson, Mona, et al.
(author)
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Appearance of islet cell autoantibodies after clinical diagnosis of diabetes mellitus
- 1999
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In: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 29:1, s. 57-63
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Journal article (peer-reviewed)abstract
- Islet cell antibodies (ICA) and glutamic acid decarboxylase antibodies (GAD65Ab) are often present at diagnosis of insulin dependent diabetes mellitus (type I diabetes) and are supposed to decline in level and frequency during the first years of disease. We have analysed ICA and GAD65Ab at onset and after one gear in 395 population based randomly selected 15-34 year old patients newly diagnosed with diabetes mellitus, to study how these autoantibodies persist, disappear and appear and their relation to C-peptide levels. Of the 395 samples 212 (54%) were positive for ICA, 250 (63%) were positive for GAD65Ab and 170 (43%) were positive for both. At follow up after one year, 27/183 (15%) of the ICA negative patients and 25/145 (17%) of the GAD65Ab negative patients had converted to positivity. Among the 103 patients negative for both ICA and GAD65Ab, 16 turned positive for one or both antibodies after one year. Patients converting to positivity for one or the other antibody after one year, had lower C-peptide levels after one year than patients who initially were and remained negative, supporting the hypothesis that these patients have a genuine type I diabetes. In conclusion, newly diagnosed patients may be negative for autoantibodies at diagnosis but develop these antibodies later on during the disease.
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- Littorin, Bengt, et al.
(author)
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Islet cell and glutamic acid decarboxylase antibodies present at diagnosis of diabetes predict the need for insulin treatment : A cohort study in young adults whose disease was initially labeled as type 2 or unclassifiable diabetes
- 1999
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 22:3, s. 409-412
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Journal article (peer-reviewed)abstract
- OBJECTIVE:To clarify the predictive value of islet cell antibody (ICA) and GAD65 antibody (GADA) present at diagnosis with respect to the need for insulin treatment 6 years after diagnosis in young adults initially considered to have type 2 or unclassifiable diabetes.RESEARCH DESIGN AND METHODS:The patient material was representative of the entire Swedish population, consisting of patients who were 15-34 years old at diagnosis of diabetes in 1987-1988 but were not considered to have type 1 diabetes at onset. At follow-up, 6 years after the diagnosis, it was noted whether the patient was treated with insulin. The presence of ICA was determined by an immunofluorescence assay, and GADAs were measured by a radioligand assay.RESULTS:Six years after diagnosis, 70 of 97 patients were treated with insulin, and 27 of 97 patients were treated with oral drugs or diet alone. At diagnosis, ICAs and GADAs were present in 41 (59%) of 70 patients and 41 (60%) of 68 patients, respectively, of those now treated with insulin, compared with only 1 (4%) of 26 patients and 2 (7%) of 27 patients who were still not treated with insulin. For either ICA or GADA, the corresponding frequencies were 50 (74%) of 68 for patients who were later treated with insulin and 3 (12%) of 26 for those who were still not treated with insulin, respectively. The sensitivity for later insulin treatment was highest (74%) for the presence of ICA or GADA, and the specificity was highest (100%) for ICA and GADA. The positive predictive value was 100% for the combination of ICA and GADA, 98% for ICA alone, and approximately 95% for GADA alone.CONCLUSIONS:Determination of the presence of ICA and GADA at diagnosis of diabetes improves the classification of diabetes and predicts the future need of insulin in young adults.
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- Andersson, Agneta, et al.
(author)
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Effects of physical exercise on phospholipid fatty acid composition in skeletal muscle
- 1998
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In: American Journal of Physiology. Endocrinology and Metabolism. - 0193-1849 .- 1522-1555. ; 274:37, s. E432-E438
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Journal article (peer-reviewed)abstract
- The effects of low-intensity exercise on the fatty acid composition in skeletal muscle and in serum were studied in 19 sedentary, middle-aged Swedish men. During a 10-wk period, all subjects were given a standardized diet with an identical fat composition. After 4 wk on this diet, they were randomly allocated to a daily exercise program (55% peak oxygen uptake) or to continue to live a sedentary life for the remaining 6 wk. Aerobic capacity (submaximal bicycle test) and peripheral insulin sensitivity (hyperinsulinemic euglycemic clamp) improved with training, whereas the body weight as well as the body composition (underwater weighing and bioimpedance) were unchanged. The proportions of palmitic acid (16:0) and linoleic acid [18:2(n-6)] and the sum of n-6 fatty acids [18:2(n-6), 20:3(n-6), 20:4(n-6)] were decreased in skeletal muscle phospholipids, whereas the proportion of oleic acid [18:1(n-9)] was increased, by training. The fatty acid profile in skeletal muscle triglycerides remained unchanged. We conclude that regular low-intensity exercise influences the fatty acid composition of the phospholipids in skeletal muscle, which hypothetically may contribute to changes of the skeletal muscle membrane fluidity and influence the peripheral insulin sensitivity.
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