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- Agardh, Carl-David, et al.
(författare)
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Clinical evidence for the safety of GAD65 immunomodulation in adult-onset autoimmune diabetes.
- 2005
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Ingår i: Journal of Diabetes and its Complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 19:4, s. 238-246
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this Phase II study was to evaluate if alum-formulated human recombinant GAD65 is safe and does not compromise beta cell function. The study was conducted as a randomized, double blind, placebo-controlled, dose-escalation clinical trial in a total of 47 Latent Autoimmune Diabetes in Adults (LADA) patients who received either placebo or 4, 20, 100, or 500 μg Diamyd subcutaneously at Weeks 1 and 4. Safety evaluations, including neurology, beta cell function tests, diabetes status assessment, hematology, biochemistry, and cellular and humoral immunological markers, were repeatedly assessed over 24 weeks. None of the patients had significant study-related adverse events (AE). Fasting c-peptide levels at 24 weeks were increased compared with placebo (P=.0015) in the 20 μg but not in the other dose groups. In addition, both fasting (P=.0081) and stimulated (P=.0236) c-peptide levels increased from baseline to 24 weeks in the 20 μg dose group. GADA log levels clearly increased (P=.0002) in response to 500 μg Diamyd. The CD4+CD25+/CD4+CD25− cell ratio increased (P=.0128) at 24 weeks in the 20 μg group. No sudden increase in HbA1c or plasma glucose or decrease in beta cell function was observed in any of the dose groups. These positive findings for clinical safety further support the clinical development of Diamyd as a therapeutic to prevent autoimmune diabetes.
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| 3. |
- Cederlund, Ragnhild, et al.
(författare)
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Hand disorders, hand function, and activities of daily living in elderly men with type 2 diabetes.
- 2009
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Ingår i: Journal of Diabetes and its Complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 23, s. 32-39
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: This study aimed to examine hand disorders, symptoms, overall hand function, activities of daily living (ADLs), and life satisfaction in elderly men with type 2 diabetes mellitus (DM), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). METHODS: Subjects were interviewed and evaluated with a battery of clinical and laboratory tests, including hand assessment, and a questionnaire. RESULTS: HbA1c differed between groups (highest in DM, especially in long-term DM). Limited joint motion (LJM), for example, prayer sign and Dupuytren's contracture, was most common in individuals with DM, followed by individuals with IGT, as compared to those with NGT. Vibrotactile sense was impaired symmetrically in the index and little fingers in DM. However, there were no differences for sensibility, dexterity, grip strength, and cold intolerance between groups. Individuals with long-term (>15 years) DM were more affected regarding sensibility and ADL than individuals with short-term DM, who had more sleep disturbances. ADL difficulties were less among IGT subjects. Vibrotactile sense showed correlations with Semmes-Weinstein monofilament test and static two-point discrimination. CONCLUSIONS/INTERPRETATION: Dupuytren's contracture and impaired vibrotactile sense in finger pulps occurred in patients with DM but not in those with IGT, although LJM occurred in both IGT and DM patients. A longer duration of DM was associated with more severe neuropathy and ADL difficulties. Life satisfaction was high, and hand disorders did not have a significant impact on ADL.
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| 4. |
- Dotevall, Annika, 1957, et al.
(författare)
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Considerable disturbances of cardiovascular risk factors in women with diabetes and myocardial infarction
- 2005
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Ingår i: J Diabetes Complications. - : Elsevier BV. - 1056-8727. ; 19:1, s. 26-34
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate to which extent differences in cardiovascular risk factors explain the increased risk of myocardial infarction (MI) and complication rate in women with diabetes mellitus (DM). DESIGN: Case-control study. SUBJECTS: We compared women with diabetes and previous MI (n=29), diabetes but no MI (n=46), prior MI but no diabetes (n=64), and healthy controls (n=125). MEASUREMENTS: Smoking habits, physical activity, blood pressure (BP), body mass index (BMI), waist/hip ratio (WHR), serum lipids, plasma fibrinogen, and serum sex hormones. RESULTS: Despite the fact that diabetic women had similar BMI, those with a past MI, compared to diabetic women without MI, had significantly higher WHR (mean, 95% CI) [0.89 (0.87, 0.92) vs. 0.84 (0.81, 0.86) mmol/l, P=.001] and very high S-triglycerides [3.03 (2.23, 3.83) vs. 1.69, (1.39, 1.99) mmol/l, P=.001] and low HDL-cholesterol [1.09 (0.94, 1.24) vs. 1.56 (1.41, 1.71) mmol/l, P<.001], indicating pronounced metabolic disturbances. Women with MI but no diabetes had intermediate values for WHR, triglycerides, and HDL-cholesterol. Furthermore, women with diabetes and MI had significantly higher p-fibrinogen, were smokers, and lived a more sedentary life than the other women. Over half of all women with prior MI were on lipid-lowering therapy and tended to have nonsignificantly lower S-cholesterol than women without MI. CONCLUSIONS: Women with diabetes who have manifested an MI carry a very substantial cardiovascular risk factor burden, which probably explain their increased morbidity and mortality. In order to improve prognosis, studies targeted at investigating treatment modalities for these abnormalities are needed.
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| 7. |
- Gustavsson, Carin, et al.
(författare)
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TNF-alpha is an independent serum marker for proliferative retinopathy in type 1 diabetic patients.
- 2008
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Ingår i: Journal of Diabetes and its Complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 22, s. 309-316
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: This study aimed to determine if there are any associations between serum levels of inflammatory markers and proliferative retinopathy (PDR) in type 1 diabetic patients. DESIGN: A cross-sectional design was utilized for this study. METHODS: One hundred twenty-eight type 1 diabetic patients underwent stereo fundus photography according to the Early Treatment Diabetic Retinopathy Study and were divided into two retinopathy groups: no or nonproliferative retinopathy (NDR/NPDR; n=62) and PDR (n=66). Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, soluble vascular cellular adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), P-selectin, and high-sensitivity C-reactive protein (hsCRP) were analyzed. Statistical analysis was performed using nonparametric Mann-Whitney U test and multivariate logistic regression analysis. RESULTS: Patients with PDR had higher levels of TNF-alpha [7.0 pg/ml (<4-17) vs. 6.0 pg/ml (<4-25); P=.009], sVCAM-1 [860 ng/ml (360-2120) vs. 700 ng/ml (310-1820); P<.001], and P-selectin [180 ng/ml (39-400) vs. 150 ng/ml (42-440); P=.017; figures are expressed as median (range)]. There were no differences in serum levels of sICAM-1 or hsCRP. IL-1beta was not detectable in any patient, and IL-6 was detectable in only 22.7% of the patients. In multivariate logistic regression analysis, TNF-alpha was the single, persistent, independent determinant inflammatory marker for PDR. CONCLUSION: The association between TNF-alpha and PDR in type 1 diabetic patients suggests that inflammation might play a role in the pathogenesis of proliferative diabetic retinopathy.
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| 8. |
- Jensen, Richard A., et al.
(författare)
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Multiple factors affect the loss of measurable C-peptide over 6 years in newly diagnosed 15- to 35-year-old diabetic subjects
- 2007
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Ingår i: Journal of diabetes and its complications. - : Elsevier BV. - 1056-8727 .- 1873-460X. ; 21:4, s. 205-213
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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.
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| 9. |
- Leksell, Janeth, et al.
(författare)
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Self-perceived health and self-care among diabetic subjects with defective vision : A comparison between subjects with threat of blindness and blind subjects
- 2005
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Ingår i: Journal of diabetes and its complications. - : Elsevier BV. - 1056-8727 .- 1873-460X. ; 19:1, s. 54-59
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare self-perceived health among diabetic patients who experienced threat of blindness with those who had already gone blind. Another aim was to explore different aspects of self-care in relation to self-perceived health among the subjects. Twenty-one diabetic patients under threat of becoming blind and 23 with diabetes-related blindness agreed to participate in the study. The participants were compared with an age- and gender-matched nondiabetic reference group. Self-perceived health was measured using the 63-item Swedish Health-Related Quality of Life Survey (SWED-QUAL) questionnaire. Data on diabetes-related variables were collected from the patient's hospital records. An interview guide was created for measuring dimensions of self-care. Patients with threat of becoming blind showed better self-perceived health than blind patients, but no differences were found in comparison with the Swedish reference group. Blind patients scored lower in 6 of the 13 health domains and they reported more problems with diabetes self-care than patients with threat of becoming blind. One of the 13 health domains, role limitations due to physical health, seemed to be associated with impaired self-care although only a partial understanding could be demonstrated. The results show that blind patients need specific support to cope well with different self-care situations. A great challenge in future research in diabetes is to implement education programs suitable especially for patients who have gone blind because of diabetes. © 2005 Elsevier Inc. All rights reserved.
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| 10. |
- Ma, Jun, et al.
(författare)
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Genetic association analysis of the adiponectin polymorphisms in type 1 diabetes with and without diabetic nephropathy.
- 2007
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Ingår i: J Diabetes Complications. - : Elsevier BV. - 1056-8727. ; 21:1, s. 28-33
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Adiponectin [adipocyte C1q and collagen domain containing (ACDC)] is the most abundant adipose-specific protein. It is beneficial in that it improves insulin sensitivity and mitigates vascular damage, in addition to the possibility of it having anti-inflammatory properties. Clinical evidences demonstrate that serum adiponectin concentrations are increased in patients with type 1 diabetes (T1D) as well as in patients with microvascular complications. However, the genetic influence of the ACDC gene in T1D and diabetic microvascular complications is still unclear. The present study aims to evaluate the association of the ACDC genetic variation in T1D and diabetic nephropathy (DN). MATERIALS AND METHODS: Ten single nucleotide polymorphisms (SNPs) of the ACDC gene were genotyped in 432 T1D patients (of which, 196 had DN) and 187 nondiabetic control subjects, who were all Swedish Caucasians, by using dynamic allele specific hybridization. RESULTS: Single-marker association analysis demonstrated that SNPs +45G15G(T/G) and +276(G/T) were strongly associated with T1D [P=.002, OR=1.855 (1.266-2.717) and P=.001, OR=1.694 (1.337-2.147)]. Further analysis for haplotypes of these two SNPs indicated that one of the common haplotype (T_G) was strongly associated with T1D [P<.001, OR=1.769 (1.430-2.188)]. However, there was no significant difference in the allele frequencies of these two SNPs between the groups of T1D patients with nephropathy and the patients without nephropathy. CONCLUSIONS: The present study thus suggests that SNPs +45G15G(T/G) and +276(G/T) in the ACDC gene are associated with T1D but not with DN among Swedish Caucasians.
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