| 1. |
- Graham, Jinko, et al.
(författare)
-
Negative association between type 1 diabetes and HLA DQB1*0602-DQA1*0102 is attenuated with age at onset
- 1999
-
Ingår i: European Journal of Immunogenetics. - : Wiley. - 0960-7420 .- 1365-2370. ; 26, s. 117-
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 2. |
- Jensen, Richard A., et al.
(författare)
-
Multiple factors affect the loss of measurable C-peptide over 6 years in newly diagnosed 15- to 35-year-old diabetic subjects
- 2007
-
Ingår i: Journal of diabetes and its complications. - : Elsevier BV. - 1056-8727 .- 1873-460X. ; 21:4, s. 205-213
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study is to identify risk factors for the loss of measurable plasma C-peptide in newly diagnosed 15- to 35-year-old diabetic subjects. Methods: This Swedish study included 778 subjects. C-peptide levels were obtained each year for 6 years after diagnosis. Loss of measurable C-peptide was defined as a level at or below the lower detection limit of the local assay (0.13 nmol/l). In addition to C-peptide, other baseline covariates included gender, age, body mass index, HLA genotype, and autoantibody levels. Results: Compared with autoantibody-negative subjects, autoantibody-positive subjects had lower median baseline C-peptide (0.27 vs. 0.50, P<001), their levels declined over the study period, and the risk of losing measurable C-peptide was significantly higher when more than one autoantibody was present [odds ratio (OR), 4.0; 95% confidence interval (CI), 2.13-7.54]. Among autoantibody-positive individuals, the presence of GAD65Ab (OR, 1.8; 95% Cl, 1.24-2.51) and islet cell antibodies (OR, 1.6; 95% CI, 1.19-2.18) conferred a higher risk for loss of measurable C-peptide as did female gender (OR, 1.6; 95% CI, 1.17-2.11) and time after diagnosis (OR, 1.5 for each additional year postdiagnosis; 95% CI, 1.41-1.57). Higher baseline C-peptide levels were protective (OR, 0.5 for each additional log nanomoles per liter; 95% CI, 0.36-0.58). Conclusions: This study identified autoantibody status, gender, and baseline C-peptide levels as factors that will be useful for predicting the disease course of 15- to 35-year-old diabetic individuals.
|
|
| 3. |
- Åkesson, Lina, et al.
(författare)
-
Decreased core temperature and Increased beta(3)-Adrenergic sensitivity in diabetes-prone BB rats
- 2007
-
Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert Inc. - 1520-9156 .- 1557-8593. ; 9:4, s. 354-362
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetes-prone (DP) congenic DR.lypllyp BioBreeding (BB) rats all develop Type I diabetes between 50 and 81 days of age, while DR. lyp/+ or DR.+/+ BB rats are diabetes resistant (DR). The DP rats display reduced weight gain prior to developing hyperglycemia, implying that metabolic events may precede diabetes onset. We tested the hypothesis that temperature measurements could serve as a physiological marker for the impending onset of hyperglycemia. Methods: Prior to the onset of hyperglycemia, brain, lower back, and intrascapular brown adipose tissue temperatures were analyzed by thermal signature analysis, , which measures infrared emission from tissues. A thermocoupled rectal probe measured core temperature. In addition we performed a beta 3-adrenergic receptor challenge test with the beta 3-adrenergic receptor agonist BRL37344. Results: DP rats displayed lower core temperature than DR rats prior to the onset of hyperglycemia. No temperature difference was detected in brain, lower back, or intrascapular brown adipose tissue between DP and DR rats. The beta 3-adrenergic challenge showed that the rate of temperature increase after administration of BRL37344 was significantly higher (0.005 +/- 0.002 degrees C/min) in DP than in DR rats (P = 0.044). Conclusions: These studies reveal that the prediabetic DP rats fail to maintain core temperature and that they display increased sensitivity to heat production induced by a beta 3-adrenergic receptor agonist. These studies suggest that body temperature as a measure of metabolic dysregulation is altered in the prediabetic DP rat prior to the onset of hyperglycemia.
|
|
