| 41. |
- Lehtisalo, Jenni, et al.
(författare)
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Diabetes, glycaemia, and cognitiona secondary analysis of the Finnish Diabetes Prevention Study
- 2016
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 32:1, s. 102-110
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Tidskriftsartikel (refereegranskat)abstract
- Background: Type 2 diabetes is linked with cognitive dysfunction and dementia in epidemiological studies, but these observations are limited by lack of data on the exact timing of diabetes onset. We investigated diabetes, dysglycaemia, and cognition in the Finnish Diabetes Prevention Study, in which the timing and duration of diabetes are well documented.Methods: The Finnish Diabetes Prevention Study comprised middle-aged, overweight participants with impaired glucose tolerance but no diabetes at baseline (n=522), randomized to lifestyle intervention or a control group. After an intervention period (mean duration 4years) and follow-up (additional 9years), cognitive assessment with the CERAD test battery and Trail Making Test A (TMT) was executed twice within a 2-year interval. Of the 364 (70%) participants with cognitive assessments, 171 (47%) had developed diabetes.Results: Cognitive function did not differ between those who developed diabetes and those who did not. Lower mean 2-h glucose at an oral glucose tolerance test (OGTT) and HbA(1C) during the intervention period predicted better performance in the TMT (p=0.012 and 0.024, respectively). Those without diabetes or with short duration of diabetes improved in CERAD total score between the two assessments (p=0.001) whereas those with long duration of diabetes did not (p=0.844).Conclusions: Better glycemic control among persons with baseline impaired glucose tolerance predicted better cognitive performance 9years later in this secondary analysis of the Finnish Diabetes Prevention Study population. In addition, learning effects in cognitive testing were not evident in people with long diabetes duration.
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| 42. |
- Lindahl, Emma, et al.
(författare)
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Early transcriptional regulation by C-peptide in freshly isolated rat proximal tubular cells
- 2011
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 27:7, s. 697-704
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Clinical studies have shown that proinsulin C-peptide exerts renoprotective effects in type 1 diabetes, although the underlying mechanisms are poorly understood. As C-peptide has been shown to induce several intracellular events and to localize to nuclei, we aimed to determine whether gene transcription is affected in proximal tubular kidney cells, and if so, whether genes with altered transcription include those related to protective mechanisms. METHODS: The effect of C-peptide incubation (2h) on gene expression was investigated in freshly isolated proximal tubular cells from streptozotocin-diabetic Sprague-Dawley rats using global gene expression profiling and RT-qPCR. Protein expression was assayed using western blotting. Different bioinformatic strategies were employed. RESULTS: Gene transcription profiling demonstrated differential transcription of 492 genes (p<0.01) after 2h of C-peptide exposure, with the majority of these genes repressed (83%). RT-qPCR validation supported a trend of several GPCR's being activated, and certain transcription factors to be repressed. Also, C-peptide repressed the transcription of genes associated with pathways of circulatory and inflammatory diseases. CONCLUSIONS: This study shows that C-peptide exerts early effects on gene transcription in proximal tubular cells. The findings also bring further knowledge to the renoprotective mechanisms of C-peptide in type I diabetes, and supports a transcriptional activity for C-peptide. It is suggested that C-peptide may play a regulatory role in the gene expression of proximal tubular cells.
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| 43. |
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| 44. |
- Loseth, Sissel, et al.
(författare)
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Polyneuropathy in type 1 and type 2 diabetes : comparison of nerve conduction studies, thermal perception thresholds and intraepidermal nerve fibre densities
- 2010
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 26:2, s. 100-106
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Tidskriftsartikel (refereegranskat)abstract
- Background To evaluate possible differences in distal polyneuropathy (PN) characteristics and degree of abnormalities for various small and large fibre parameters in diabetes type 1 (DM1) and type 2 (DM2). Methods Sixty-six DM1 and 57 DM2 patients with or without PN symptoms were included. Nerve conduction studies (NCS), quantitative sensory testing (QST) and quantification of intraepidermal nerve fibres (IENFs) were performed. Z-scores were calculated from reference materials. Results In both groups, 42% had abnormal NCS classification, 42% (DM1) and 39% (DM2) abnormal QST, as well as 40% (DM1) and 32% (DM2) abnormal IENF density. Seventy percent (DM1) and 65% (DM2) had one of the three tests abnormal (differences not significant). Correlations were found between most Z-score parameters and disease duration and HbAlc in DM1, but fewer in DM2. In multivariate analysis, some NCS and QST Z-scores were more abnormal in DM2. Symptom scoring correlated better with NCS and QST parameters in DM1. Conclusions The differences could be referred to disease duration, glycaemic control and possibly patient age. The various parameters from NCS, QST and IENF analysis contribute differently in the assessment of polyneuropathy. Copyright (C) 2009 John Wiley & Sons, Ltd.
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| 45. |
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| 46. |
- Ludvigsson, Johnny, et al.
(författare)
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Combined Etanercept, GAD-alum and vitamin D treatment: an open pilot trial to preserve beta cell function in recent onset type 1 diabetes
- 2021
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Ingår i: Diabetes-Metabolism Research and Reviews. - : Wiley. - 1520-7552 .- 1520-7560.
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Tidskriftsartikel (refereegranskat)abstract
- Aim We aimed to study the feasibility and tolerability of a combination therapy consisting of glutamic acid decarboxylase (GAD-alum), Etanercept and vitamin D in children and adolescents with newly diagnosed with type 1 diabetes (T1D), and evaluate preservation of beta cell function. Material and Methods Etanercept Diamyd Combination Regimen is an open-labelled multi-centre study pilot trial which enrolled 20 GAD antibodies positive T1D patients (7 girls and 13 boys), aged (mean +/- SD): 12.4 +/- 2.3 (8.3-16.1) years, with a diabetes duration of 81.4 +/- 22.1 days. Baseline fasting C-peptide was 0.24 +/- 0.1 (0.10-0.35) nmol/l. The patients received Day 1-450 Vitamin D (Calciferol) 2000 U/d per os, Etanercept sc Day 1-90 0.8 mg/kg once a week and GAD-alum sc injections (20 mu g, Diamyd (TM)) Day 30 and 60. They were followed for 30 months. Results No treatment related serious adverse events were observed. After 6 months 90-min stimulated C-peptide had improved in 8/20 patients and C-peptide area under the curve (AUC) after Mixed Meal Tolerance Test in 5 patients, but declined thereafter, while HbA1c and insulin requirement remained close to baseline. Administration of Etanercept did not reduce tumour necrosis factor (TNF) spontaneous secretion from peripheral blood mononuclear cells, but rather GAD65-induced TNF-alpha increased. Spontaneous interleukin-17a secretion increased after the administration of Etanercept, and GAD65-induced cytokines and chemokines were also enhanced following 1 month of Etanercept administration. Conclusions Combination therapy with parallel treatment with GAD-alum, Etanercept and vitamin D in children and adolescents with type 1 diabetes was feasible and tolerable but had no beneficial effects on the autoimmune process or beta cell function.
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| 47. |
- Ludvigsson, Johnny, et al.
(författare)
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Does modern high standard life style cause type 1 diabetes in children?
- 2013
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Ingår i: Diabetes/Metabolism Research Reviews. - : John Wiley and Sons. - 1520-7552 .- 1520-7560. ; 29:2, s. 161-165
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Tidskriftsartikel (refereegranskat)abstract
- Background Type 1 diabetes is a serious disease which, in spite of intensive treatment, causes serious complications and increased mortality. The incidence is increasing, but the aetiology is unknown. As part of modern lifestyle, increased hygiene has been suspected as one contributing cause but so far there is no evidence. Several large epidemiological studies, mainly restricted to children with increased genetic risk for type 1 diabetes, have so far given no clue. Methods All Babies in Southeast Sweden is unique in its design as it has followed an unselected group of children from birth 19971999 and onwards with regular follow-ups. This report is based on questionnaires from initially 16051 children of whom 80 have later on developed type 1 diabetes. The parents answered questionnaires at the birth of their child and then after 1, 23, 56 and 8years. A number of parameters possibly related to hygiene were analysed with several statistical methods, both with univariate and in regression models. Results Our study cannot identify any crucial environmental factor. This indicates that hygiene-related parameters traditionally regarded as part of modern life style do not play any important role for the aetiology of type 1 diabetes. Conclusions There is no reason to recommend a change of that part of our lifestyle. We find weak associations to previous gastrointestinal infections, which gives a hint that development of type 1 diabetes may be related to problems in the gut and maybe one should look closer into the microbes living in the gut.
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| 48. |
- Ludvigsson, Johnny, et al.
(författare)
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GAD-treatment of children and adolescents with recent-onset Type 1 diabetes preserves residual insulin secretion after 30 months
- 2014
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley-Blackwell. - 1520-7552 .- 1520-7560. ; 30:5, s. 405-414
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study aimed to analyse data from two different studies (Phase II and Phase III) regarding the safety and efficacy of treatment with alum formulated glutamic acid decarboxylase GAD65 (GAD-alum), 30 months after administration to children and adolescents with Type 1 diabetes (T1D).METHODS: The Phase II trial was a double-blind, randomized placebo-controlled study, including 70 children and adolescents which were followed for 30 months. Participants received a subcutaneous injection of either 20 µg of GAD-alum or placebo at baseline and one month later. During a subsequent larger European Phase III trial including three treatment arms, participants received two or four subcutaneous injections of either 20 µg of GAD-alum and/or placebo at baseline, 1, 3 and 9 months. The Phase III trial was prematurely interrupted at 15 months, but of the 148 Swedish patients, a majority completed the 21 months follow-up and 45 patients completed the trial at 30 months. Both studies included GADA-positive patients with fasting C-peptide ≥0.10 nmol/l. We have now combined the results of these two trials.RESULTS: There were no treatment related adverse events. In patients treated with 2 GAD-alum doses, stimulated C-peptide AUC had decreased significantly less (9 m: p < 0.037; 15 m p < 0.032; 21 m p < 0.003 and 30 m p < 0.004) and a larger proportion of these patients were also able to achieve a peak stimulated C-peptide >0.2 nmol/l (p < 0.05), as compared to placebo.CONCLUSION: Treatment with two doses of GAD-alum in children and adolescents with recent-onset T1D shows no adverse events and preserves residual insulin secretion. This article is protected by copyright. All rights reserved.
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| 49. |
- Ludvigsson, Johnny
(författare)
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Therapy with GAD in diabetes
- 2009
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Ingår i: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 25:4, s. 307-315
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Forskningsöversikt (refereegranskat)abstract
- The enzyme glutamic acid decarboxylase (GAD) is of great importance for the neurotransmission in the central nervous system, and therefore of interest for treatment of pain and neurological disease. However, it is also released in pancreas although its role is not quite clear. GAD is a major auto-antigen in the process leading to type 1 diabetes with both a clear cell-mediated immune response to GAD and auto-antibodies to GAD (GADA), which call be used as a predictor of diabetes. Administration of the isoform GAD65 can prevent autoimmune destruction of pancreatic beta cells in non-obese diabetic (NOD) mice and the subsequent need for exogenous insulin replacement. In Phase I and II studies an alum-formulated vaccine (Diamyd) has shown to be safe, and in a dose-finding study in Latent Autoimmune Diabetes in Adults (LADA) patients 20-mu g was given subcutaneously one month apart indicating preservation of residual insulin secretion. A double-blind randomized Phase II trial in 70 patients (10-18 years old) with recent-onset type 1 diabetes showed significant preservation of residual insulin secretion and a GAD-specific immune response, both humoral and cell-mediated, but no treatment-related adverse events. With this promising background further studies are on their way, both intervention in newly diagnosed type 1 diabetic patients, and trials to prevent the disease.
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