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C-peptide response and HLA genotypes in subjects with recent-onset type 1 diabetes after immunotherapy with DiaPep277: an exploratory study.

Buzzetti R, Cernea S, Petrone A, Capizzi M, Spoletini M, Zampetti S, Guglielmi C, Venditti C, Pozzilli P, DiaPep Trialists Gro - Diabetes (2011)

Bottom Line: HLA genotypes were classified in high, moderate, and low risk categories.A total of 146 subjects (aged 4.3 to 58.5 years) were enrolled, including 76 children (<18 years old) and 70 adults.Children showed a decrease of the three parameters over time regardless of therapy and HLA genotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicina Interna e Specialità Mediche, Division of Diabetes, University Sapienza, Rome, Italy. raffaella.buzzetti@uniroma1.it

ABSTRACT

Objective: To investigate whether lower risk HLA class II genotypes would influence the efficacy of DiaPep277 therapy in protecting β-cell function evaluated by C-peptide secretion in recent-onset type 1 diabetic subjects.

Research design and methods: Data were collected from type 1 diabetic subjects enrolled in multicenter phase II studies with a randomized, double-blind, and placebo-controlled design in whom fasting and stimulated C-peptide levels were measured. HLA genotypes were classified in high, moderate, and low risk categories.

Results: A total of 146 subjects (aged 4.3 to 58.5 years) were enrolled, including 76 children (<18 years old) and 70 adults. At baseline, there was a significant increase in fasting, maximal, and area under the curve (AUC) C-peptide from high to moderate and low risk HLA genotypes in adults (P for trend <0.04) but not in children. Children showed a decrease of the three parameters over time regardless of therapy and HLA genotype. DiaPep277-treated adults with low risk genotype had significantly higher maximal and AUC C-peptide versus placebo at 12 months (0.04 ± 0.07 vs. -0.28 ± 0.09 nmol/L, P < 0.01, and 0.53 ± 1.3 vs. -4.59 ± 1.5 nmol/L, P < 0.05, respectively). In the moderate risk genotype group, Δmaximal and AUC C-peptide values were significantly higher in DiaPep277-treated versus placebo-treated patients (P < 0.01 and P < 0.05, respectively).

Conclusions: This exploratory study demonstrates that type 1 diabetic adults with low and moderate risk HLA genotypes benefit the most from intervention with DiaPep277; the only subgroup with an increase of C-peptide at 12 months after diagnosis was the low risk DiaPep277-treated subgroup.

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Related in: MedlinePlus

Difference in C-peptide values (fasting, maximal, and AUC) between visit 12 and baseline (visit 12 minus visit 1) for adults and children with type 1 diabetes treated with DiaPep277 or placebo. Black column, high/moderate risk genotype, placebo treated (n = 19 adults and n = 25 children); small checkered column, low risk genotype, placebo treated (n = 5 adults and n = 7 children); large checkered column, high/moderate risk genotype, DiaPep277 treated (n = 33 adults and n = 36 children); white column, low risk genotype, DiaPep277 treated (n = 13 adults and n = 8 children).
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Figure 2: Difference in C-peptide values (fasting, maximal, and AUC) between visit 12 and baseline (visit 12 minus visit 1) for adults and children with type 1 diabetes treated with DiaPep277 or placebo. Black column, high/moderate risk genotype, placebo treated (n = 19 adults and n = 25 children); small checkered column, low risk genotype, placebo treated (n = 5 adults and n = 7 children); large checkered column, high/moderate risk genotype, DiaPep277 treated (n = 33 adults and n = 36 children); white column, low risk genotype, DiaPep277 treated (n = 13 adults and n = 8 children).

Mentions: High/moderate and low risk HLA genotype patients were subdivided according to treatment. Placebo-treated (24 adults and 32 children) or DiaPep277-treated (46 adults and 44 children) subjects were followed up for C-peptide values up to 12 months after trial initiation (Fig. 1). Children with type 1 diabetes had a decrease of all three evaluated parameters over the observational period, and the differences between fasting, maximal, and AUC C-peptide values at 12 months versus baseline (ΔC-peptide = C-peptide at visit 12 – C-peptide at visit 1) did not differ significantly between the four subgroups (Figs. 1 and 2). In a similar manner, adults with high/moderate risk HLA genotype had a decrease of fasting, maximal, and AUC C-peptide values over time, regardless of therapy (placebo or DiaPep277). Of interest, the only subgroup that had an increase in C-peptide levels was adult subjects with low risk HLA genotype (Supplementary Table 1) who were treated with DiaPep277 compared with placebo (Figs. 1 and 2). There were statistically significant higher maximal C-peptide and AUC C-peptide values in subjects with low risk genotype treated with DiaPep277 versus placebo at 12 months compared with baseline: Δmaximal C-peptide 0.04 ± 0.07 nmol/L (DiaPep277) vs. −0.29 ± 0.1 nmol/L (placebo), P = 0.0093 (P = 0.01 after Bonferroni correction) and ΔAUC C-peptide 0.54 ± 1.3 nmol/L (DiaPep277) vs. −4.6 ± 1.5 nmol/L (placebo), P = 0.0158 (P = 0.02 after Bonferroni correction), respectively. The increase in fasting C-peptide values did not reach statistical significance: Δfasting C-peptide 0.03 ± 0.08 nmol/L (DiaPep277) vs. −0.14 ± 0.05 nmol/L (placebo), P = 0.09.


C-peptide response and HLA genotypes in subjects with recent-onset type 1 diabetes after immunotherapy with DiaPep277: an exploratory study.

Buzzetti R, Cernea S, Petrone A, Capizzi M, Spoletini M, Zampetti S, Guglielmi C, Venditti C, Pozzilli P, DiaPep Trialists Gro - Diabetes (2011)

Difference in C-peptide values (fasting, maximal, and AUC) between visit 12 and baseline (visit 12 minus visit 1) for adults and children with type 1 diabetes treated with DiaPep277 or placebo. Black column, high/moderate risk genotype, placebo treated (n = 19 adults and n = 25 children); small checkered column, low risk genotype, placebo treated (n = 5 adults and n = 7 children); large checkered column, high/moderate risk genotype, DiaPep277 treated (n = 33 adults and n = 36 children); white column, low risk genotype, DiaPep277 treated (n = 13 adults and n = 8 children).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198071&req=5

Figure 2: Difference in C-peptide values (fasting, maximal, and AUC) between visit 12 and baseline (visit 12 minus visit 1) for adults and children with type 1 diabetes treated with DiaPep277 or placebo. Black column, high/moderate risk genotype, placebo treated (n = 19 adults and n = 25 children); small checkered column, low risk genotype, placebo treated (n = 5 adults and n = 7 children); large checkered column, high/moderate risk genotype, DiaPep277 treated (n = 33 adults and n = 36 children); white column, low risk genotype, DiaPep277 treated (n = 13 adults and n = 8 children).
Mentions: High/moderate and low risk HLA genotype patients were subdivided according to treatment. Placebo-treated (24 adults and 32 children) or DiaPep277-treated (46 adults and 44 children) subjects were followed up for C-peptide values up to 12 months after trial initiation (Fig. 1). Children with type 1 diabetes had a decrease of all three evaluated parameters over the observational period, and the differences between fasting, maximal, and AUC C-peptide values at 12 months versus baseline (ΔC-peptide = C-peptide at visit 12 – C-peptide at visit 1) did not differ significantly between the four subgroups (Figs. 1 and 2). In a similar manner, adults with high/moderate risk HLA genotype had a decrease of fasting, maximal, and AUC C-peptide values over time, regardless of therapy (placebo or DiaPep277). Of interest, the only subgroup that had an increase in C-peptide levels was adult subjects with low risk HLA genotype (Supplementary Table 1) who were treated with DiaPep277 compared with placebo (Figs. 1 and 2). There were statistically significant higher maximal C-peptide and AUC C-peptide values in subjects with low risk genotype treated with DiaPep277 versus placebo at 12 months compared with baseline: Δmaximal C-peptide 0.04 ± 0.07 nmol/L (DiaPep277) vs. −0.29 ± 0.1 nmol/L (placebo), P = 0.0093 (P = 0.01 after Bonferroni correction) and ΔAUC C-peptide 0.54 ± 1.3 nmol/L (DiaPep277) vs. −4.6 ± 1.5 nmol/L (placebo), P = 0.0158 (P = 0.02 after Bonferroni correction), respectively. The increase in fasting C-peptide values did not reach statistical significance: Δfasting C-peptide 0.03 ± 0.08 nmol/L (DiaPep277) vs. −0.14 ± 0.05 nmol/L (placebo), P = 0.09.

Bottom Line: HLA genotypes were classified in high, moderate, and low risk categories.A total of 146 subjects (aged 4.3 to 58.5 years) were enrolled, including 76 children (<18 years old) and 70 adults.Children showed a decrease of the three parameters over time regardless of therapy and HLA genotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicina Interna e Specialità Mediche, Division of Diabetes, University Sapienza, Rome, Italy. raffaella.buzzetti@uniroma1.it

ABSTRACT

Objective: To investigate whether lower risk HLA class II genotypes would influence the efficacy of DiaPep277 therapy in protecting β-cell function evaluated by C-peptide secretion in recent-onset type 1 diabetic subjects.

Research design and methods: Data were collected from type 1 diabetic subjects enrolled in multicenter phase II studies with a randomized, double-blind, and placebo-controlled design in whom fasting and stimulated C-peptide levels were measured. HLA genotypes were classified in high, moderate, and low risk categories.

Results: A total of 146 subjects (aged 4.3 to 58.5 years) were enrolled, including 76 children (<18 years old) and 70 adults. At baseline, there was a significant increase in fasting, maximal, and area under the curve (AUC) C-peptide from high to moderate and low risk HLA genotypes in adults (P for trend <0.04) but not in children. Children showed a decrease of the three parameters over time regardless of therapy and HLA genotype. DiaPep277-treated adults with low risk genotype had significantly higher maximal and AUC C-peptide versus placebo at 12 months (0.04 ± 0.07 vs. -0.28 ± 0.09 nmol/L, P < 0.01, and 0.53 ± 1.3 vs. -4.59 ± 1.5 nmol/L, P < 0.05, respectively). In the moderate risk genotype group, Δmaximal and AUC C-peptide values were significantly higher in DiaPep277-treated versus placebo-treated patients (P < 0.01 and P < 0.05, respectively).

Conclusions: This exploratory study demonstrates that type 1 diabetic adults with low and moderate risk HLA genotypes benefit the most from intervention with DiaPep277; the only subgroup with an increase of C-peptide at 12 months after diagnosis was the low risk DiaPep277-treated subgroup.

Show MeSH
Related in: MedlinePlus