Treatment with antioxidants at onset of type 1 diabetes in children: a randomized, double-blind placebo-controlled study

Ludvigsson, Johnny; Samuelsson, Ulf; Johansson, Christer; Stenhammar, Lars

doi:10.1002/dmrr.176

Cited by 37 publications

(21 citation statements)

References 49 publications

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“…A limited number of patients participated during this period in early intervention studies [15][16][17][18]. None of these studies showed any significant effect on remission rate, apart from the plasmapheresis study [15] in [1979][1980].…”

Section: Patientsmentioning

confidence: 99%

Clinical manifestations and beta cell function in Swedish diabetic children have remained unchanged during the last 25 years

Nordwall

Ludvigsson

2008

Diabetes Metabolism Res

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Section: Patientsmentioning

confidence: 99%

Clinical manifestations and beta cell function in Swedish diabetic children have remained unchanged during the last 25 years

Nordwall

Ludvigsson

2008

Diabetes Metabolism Res

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“…Residual insulin secretion facilitates metabolic control and decreases the risk of keto-acidosis [3], and even modest beta cell function, with stimulated C-peptide above 0.2 nmol/l, may reduce long-term complications [4]. Type 1 diabetes is an autoimmune disease [5]; however, most attempts to use immune intervention to preserve residual beta cell function have achieved limited benefits or have been associated with adverse effects [6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Treatment with anti-CD3 monoclonal antibodies appears to be the most promising treatment to date, but several patients treated in this way, as well as with anti-CD20 monoclonal antibodies, have experienced treatment-related adverse events [20,21].…”

Section: Introductionmentioning

confidence: 99%

Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial

et al. 2010

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Aims/hypothesis The aim of this study was to investigate the safety and efficacy of alum formulated glutamic acid decarboxylase GAD 65 (GAD-alum) treatment of children and adolescents with type 1 diabetes after 4 years of follow-up. Methods Seventy children and adolescents aged 10-18 years with recent onset type 1 diabetes participated in a phase II, double-blind, randomised placebo-controlled clinical trial. Patients identified as possible participants attended one of eight clinics in Sweden to receive information about the study and for an eligibility check, including a medical history. Participants were randomised to one of the two treatment groups and received either a subcutaneous injection of 20 μg of GAD-alum or placebo at baseline and 1 month later. The study was blinded to participants and investigators until month 30. The study was unblinded at 15 months to the sponsor and statistician in order to evaluate the data. At follow-up after 30 months there was a significant preservation of residual insulin secretion, as measured by C-peptide, in the group receiving GAD-alum compared with placebo. This was particularly evident in patients with <6 months disease duration at baseline. There were no treatment-related serious adverse events. We have now followed these patients for 4 years. Overall, 59 patients, 29 who had been treated with GAD-alum and 30 who had received placebo, gave their informed consent. Results One patient in each treatment group experienced an episode of keto-acidosis between months 30 and 48. There were no treatment-related adverse events. The primary efficacy endpoint was the change in fasting C-peptide concentration from baseline to 15 months after the prime injection for all participants per protocol set. In the GADalum group fasting C-peptide was 0.332±0.032 nmol/l at day 1 and 0.215 ± 0.031 nmol/l at month 15. The corresponding figures for the placebo group were 0.354± 0.039 and 0.184±0.033 nmol/l, respectively. The decline in fasting C-peptide levels between day 1 and month 1, was smaller in the GAD-alum group than the placebo group. The difference between the treatment groups was not statistically significant. In those patients who were treated within 6 months of diabetes diagnosis, fasting C-peptide had decreased significantly less in the GADalum group than in the placebo-treated group after 4 years.

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“…Furthermore, vitamin E has been shown to be effective in preventing severe complications in long-standing type 1 diabetic patients (15). Vitamin E was used in one previous trial at diagnosis of type 1 diabetes with modest results (16).…”

Section: Introductionmentioning

confidence: 99%

A randomized trial of nicotinamide and vitamin E in children with recent onset type 1 diabetes (IMDIAB IX)

Crinó

Schiaffini

Manfrini

et al. 2004

European Journal of Endocrinology

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Objective: Various adjuvant therapies have been introduced along with intensive insulin therapy in patients with recent onset type 1 diabetes. Nicotinamide (NA), administered at diagnosis of the disease, can have beneficial effects on the clinical remission rate, improve metabolic control and preserve or slightly increase beta-cell function, probably by reducing toxicity due to free oxygen radicals. Vitamin E, a known antioxidant, inhibits lipid peroxidation; this can lead to protection of islet beta cells from the combined effects of interleukin 1, tumor necrosis factor and gamma interferon. The aim of the present study was to investigate whether the addition of vitamin E to NA could improve metabolic control and the residual beta-cell function, as measured by C-peptide secretion, in children and adolescents with recent onset type 1 diabetes; patients were followed-up for 2 years after diagnosis. Patients and study design: Recent onset type 1 diabetes patients (n ¼ 64, mean age 8.8 years) were recruited by participating centres of the IMDIAB group. Thirty-two patients were randomized to NA (25 mg/kg body weight) plus vitamin E (15 mg/kg body weight); 32 patients acted as controls and received NA only at the same dose as above. Intensive insulin therapy was applied to both treatment groups. Results: There were three drop outs during the 2-year follow-up period. Overall, patients assigned to the NA þ vitamin E group or the NA group did not significantly differ in terms of glycated hemoglobin (HbA1c) levels, insulin requirement or baseline C-peptide secretion. Patients diagnosed at an age of less than 9 years showed significantly reduced C-peptide levels compared with those aged over 9 years at diagnosis and at the 2-year follow-up but there were no differences between the NA and NA þ vitamin E treated groups. However at 6 months, patients over 9 years of age treated with NA þ vitamin E showed significantly higher C-peptide compared with the NA group (P , 0.003). In both age groups and in the different treatment groups, C-peptide levels found at diagnosis were preserved 2 years later. Conclusions: The use of NA alone, or in combination with vitamin E, along with intensive insulin therapy is able to preserve baseline C-peptide secretion for up to 2 years after diagnosis. This finding is of particular interest for pre-pubertal children with type 1 diabetes and has never been reported before.

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Treatment with antioxidants at onset of type 1 diabetes in children: a randomized, double-blind placebo-controlled study

Abstract: At diagnosis of type 1 diabetes in children, high doses of antioxidative agents have no effect either on the preservation of beta cell function or on metabolic balance.

Cited by 37 publications

References 49 publications

Clinical manifestations and beta cell function in Swedish diabetic children have remained unchanged during the last 25 years

Clinical manifestations and beta cell function in Swedish diabetic children have remained unchanged during the last 25 years

Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial

A randomized trial of nicotinamide and vitamin E in children with recent onset type 1 diabetes (IMDIAB IX)

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