589-P: Effect of Oral Insulin (OI) on Combined Glucose and C-Peptide Endpoints in Individuals at High-Risk for Type 1 Diabetes (T1D)

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 589-P
Author(s):  
LAURA M. JACOBSEN ◽  
DAVID D. CUTHBERTSON ◽  
EMILY K. SIMS ◽  
HEBA M. ISMAIL ◽  
LINDA DIMEGLIO ◽  
...  
2020 ◽  
Author(s):  
Ada Admin ◽  
Jay M. Sosenko ◽  
Jay S. Skyler ◽  
Kevan C. Herold ◽  
Desmond A. Schatz ◽  
...  

We assessed whether oral insulin slowed metabolic decline after 1 year of treatment in individuals at high risk for type 1 diabetes.<b> </b>Two oral insulin trials that were negative overall with type 1 diabetes as the primary endpoint were analyzed: the Diabetes Prevention Trial-Type 1 (DPT-1) and TrialNet oral insulin trials. Oral glucose tolerance tests at baseline and after 1 year of treatment were analyzed. Among those at high risk [Diabetes Prevention Trial Risk Score (DPTRS)≥6.75], the AUC C-peptide increased significantly from baseline to 1 year in each oral insulin group, whereas AUC glucose increased significantly in each placebo group. At 1 year, AUC C-peptide/AUC glucose was significantly higher (p<0.05) in the oral insulin group than in the placebo group in each trial (p=0.057 with age adjustment in the TrialNet trial; p<0.01 for trials combined with or without age adjustment). For DPTRS<6.75, oral insulin groups did not differ from placebo groups. <a>The findings suggest that 1 year of treatment with oral insulin slows metabolic deterioration in individuals at high risk for type 1 diabetes.</a> Moreover, the findings further suggest that metabolic endpoints can be useful adjuncts to the diagnostic endpoint in assessments of preventive treatments for the disorder.


2020 ◽  
Author(s):  
Ada Admin ◽  
Jay M. Sosenko ◽  
Jay S. Skyler ◽  
Kevan C. Herold ◽  
Desmond A. Schatz ◽  
...  

We assessed whether oral insulin slowed metabolic decline after 1 year of treatment in individuals at high risk for type 1 diabetes.<b> </b>Two oral insulin trials that were negative overall with type 1 diabetes as the primary endpoint were analyzed: the Diabetes Prevention Trial-Type 1 (DPT-1) and TrialNet oral insulin trials. Oral glucose tolerance tests at baseline and after 1 year of treatment were analyzed. Among those at high risk [Diabetes Prevention Trial Risk Score (DPTRS)≥6.75], the AUC C-peptide increased significantly from baseline to 1 year in each oral insulin group, whereas AUC glucose increased significantly in each placebo group. At 1 year, AUC C-peptide/AUC glucose was significantly higher (p<0.05) in the oral insulin group than in the placebo group in each trial (p=0.057 with age adjustment in the TrialNet trial; p<0.01 for trials combined with or without age adjustment). For DPTRS<6.75, oral insulin groups did not differ from placebo groups. <a>The findings suggest that 1 year of treatment with oral insulin slows metabolic deterioration in individuals at high risk for type 1 diabetes.</a> Moreover, the findings further suggest that metabolic endpoints can be useful adjuncts to the diagnostic endpoint in assessments of preventive treatments for the disorder.


Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 344-OR
Author(s):  
JAY SOSENKO ◽  
JERRY P. PALMER ◽  
MICHAEL J. HALLER ◽  
JAY S. SKYLER ◽  
ALBERTO PUGLIESE ◽  
...  

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 12-OR
Author(s):  
MARIA J. REDONDO ◽  
JAY SOSENKO ◽  
EMILY K. SIMS ◽  
DAVID D. CUTHBERTSON ◽  
EDDIE A. JAMES ◽  
...  

Author(s):  
Anna Giovenzana ◽  
Federica Vecchio ◽  
Federica Cugnata ◽  
Alessandro Nonis ◽  
Alessandra Mandelli ◽  
...  

Abstract Aims Alterations of the exocrine pancreas have been reported in type 1 diabetes, but their contribution to the pathogenesis of the disease is poorly understood. Here, we investigated markers of exocrine pancreas dysfunction in individuals at-risk of developing type 1 diabetes. Methods Serum P-amylase and lipase levels were assessed in samples obtained from healthy controls, patients with new onset type 1 diabetes, relatives participating to the TrialNet Pathway to Prevention who were, at blood collection, autoantibody negative or positive for a single autoantibody (low-risk individuals), and positive for multiple autoantibodies (high-risk individuals). Linear mixed models were adopted to estimate variation of pancreatic enzymes among the groups and to evaluate the influence of high-risk HLA genotypes and residual beta cell function on exocrine pancreas function. Results In adults, but not children, reduced levels of P-amylase and lipase were shown in at-risk individuals, including (for P-amylase levels only) those at low-risk, and in T1Dnew. Furthermore, while high-risk HLA genotypes negatively affected P-amylase levels in autoantibody negative adult individuals, fasting C-peptide levels did not correlate with pancreatic enzyme levels. Conclusions Exocrine pancreas dysfunction precedes the onset of type 1 diabetes in adult at-risk individuals and may be unrelated to fasting C-peptide levels.


2021 ◽  
Author(s):  
Emily K. Sims ◽  
David Cuthbertson ◽  
Kevan C. Herold ◽  
Jay M. Sosenko

Endpoints that provide an early identification of treatment effects are needed to implement type 1 diabetes prevention trials more efficiently. To this end, we assessed whether metabolic endpoints can be used to detect a teplizumab effect on rapid β-cell decline within 3 months after treatment in high-risk individuals in the TrialNet teplizumab trial. Glucose and C-peptide response curves (GCRCs) were constructed by plotting mean glucose and C-peptide values from 2-hour oral glucose tolerance tests on a 2-dimensional grid. Groups were compared visually for changes in GCRC shape and movement. GCRC changes reflected marked metabolic deterioration in the placebo group within 3 months of randomization. By 6 months, GCRCs resembled typical GCRCs at diagnosis. In contrast, GCRC changes in the teplizumab group suggested metabolic improvement. Quantitative comparisons, including two novel metabolic endpoints that indicate GCRC changes, the Within Quadrant Endpoint (WQE) and the Ordinal Directional Endpoint (ODE), were consistent with visual impressions of an appreciable treatment effect at 3 and 6-month timepoints. In conclusion, an analytic approach combining visual evidence with novel endpoints, demonstrated that Teplizumab delays rapid metabolic decline, and improves the metabolic state within 3 months after treatment; this effect extends for at least 6 months.


2013 ◽  
Vol 148 (1) ◽  
pp. 4-15 ◽  
Author(s):  
Linda Åkerman ◽  
Johnny Ludvigsson ◽  
Rosaura Casas
Keyword(s):  

2021 ◽  
Author(s):  
Emily K. Sims ◽  
David Cuthbertson ◽  
Kevan C. Herold ◽  
Jay M. Sosenko

Endpoints that provide an early identification of treatment effects are needed to implement type 1 diabetes prevention trials more efficiently. To this end, we assessed whether metabolic endpoints can be used to detect a teplizumab effect on rapid β-cell decline within 3 months after treatment in high-risk individuals in the TrialNet teplizumab trial. Glucose and C-peptide response curves (GCRCs) were constructed by plotting mean glucose and C-peptide values from 2-hour oral glucose tolerance tests on a 2-dimensional grid. Groups were compared visually for changes in GCRC shape and movement. GCRC changes reflected marked metabolic deterioration in the placebo group within 3 months of randomization. By 6 months, GCRCs resembled typical GCRCs at diagnosis. In contrast, GCRC changes in the teplizumab group suggested metabolic improvement. Quantitative comparisons, including two novel metabolic endpoints that indicate GCRC changes, the Within Quadrant Endpoint (WQE) and the Ordinal Directional Endpoint (ODE), were consistent with visual impressions of an appreciable treatment effect at 3 and 6-month timepoints. In conclusion, an analytic approach combining visual evidence with novel endpoints, demonstrated that Teplizumab delays rapid metabolic decline, and improves the metabolic state within 3 months after treatment; this effect extends for at least 6 months.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1678-P
Author(s):  
LAURA M. JACOBSEN ◽  
MARK A. CLEMENTS ◽  
MARIA JOSE REDONDO ◽  
BRANDON M. NATHAN ◽  
DESMOND SCHATZ ◽  
...  

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