A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Effect of Oral Insulin on Prevention of Diabetes in Relatives of Patients With Type 1 Diabetes A Randomized Clinical Trial
Tekijät: Writing Committee for the Type 1 Diabetes TrialNet Oral Insulin Study Group
Kustantaja: AMER MEDICAL ASSOC
Julkaisuvuosi: 2017
Journal: JAMA: Journal of the American Medical Association
Tietokannassa oleva lehden nimi: JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
Lehden akronyymi: JAMA-J AM MED ASSOC
Vuosikerta: 318
Numero: 19
Aloitussivu: 1891
Lopetussivu: 1902
Sivujen määrä: 12
ISSN: 0098-7484
eISSN: 1538-3598
DOI: https://doi.org/10.1001/jama.2017.17070
Tiivistelmä
IMPORTANCE Type 1 diabetes requires major lifestyle changes and carries increased morbidity and mortality. Prevention or delay of diabetes would have major clinical effect.OBJECTIVE To determine whether oral insulin delays onset of type 1 diabetes in autoantibody-positive relatives of patients with type 1 diabetes.DESIGN, SETTING, AND PARTICIPANTS Between March 2, 2007, and December 21, 2015, relatives with at least 2 autoantibodies, including insulin autoantibodies and normal glucose tolerance, were enrolled in Canada, the United States, Australia, New Zealand, the United Kingdom, Italy, Sweden, Finland, and Germany. The main study group (n = 389) had first-phase insulin release on an intravenous glucose tolerance test thatwas higher than the threshold. The 55 patients in the secondary stratum 1 had an identical antibody profile as the main study group except they had first-phase insulin release thatwas lower than the threshold. Secondary strata 2 (n = 114) and strata 3 (n = 3) had different autoantibody profiles and first-phase insulin release threshold combinations. Follow-up continued through December 31, 2016.INTERVENTIONS Randomization to receive 7.5mg/d of oral insulin (n = 283) or placebo (n = 277), including participants in the main study group who received oral insulin (n = 203) or placebo (n = 186).MAIN OUTCOME AND MEASURES The primary outcomewas time to diabetes in the main study group. Significance was based on a 1-sided threshold of.05, and 1-sided 95% CIs are reported.RESULTS Of a total of 560 randomized participants (median enrollment age, 8.2 years; interquartile range [IQR], 5.7-12.1 years; 170 boys [60%]; 90.7% white non-Hispanic; 57.6% with a sibling with type 1 diabetes), 550 completed the trial including 389 participants (median age, 8.4 years; 245 boys [63%]), 382 (96%) in the main study group. During a median follow-up of 2.7 years (IQR, 1.5-4.6 years) in the main study group, diabetes was diagnosed in 58 participants (28.5%) in the oral insulin group and 62 (33%) in the placebo group. Time to diabetes was not significantly different between the 2 groups (hazard ratio [HR], 0.87; 95% CI, 0-1.2; P =.21). In secondary stratum 1 (n = 55), diabetes was diagnosed in 13 participants (48.1%) in the oral insulin group and in 19 participants (70.3%) in the placebo group. The time to diabetes was significantly longer with oral insulin (HR, 0.45; 95% CI, 0-0.82; P =.006). The HR for time to diabetes for the between-group comparisons for the 116 participants in the other secondary stratum was 1.03 (95% CI, 0-2.11; P =.53) and for the entire cohort of 560 participants was 0.83 (95% CI, 0-1.07; P =.11), which were not significantly different. The most common adverse event was infection (n = 254), with 134 events in the oral insulin group and 120 events in the placebo group, but no significant study-related adverse events occurred.CONCLUSIONS AND RELEVANCE Among autoantibody-positive relatives of patients with type 1 diabetes, oral insulin at a dose of 7.5mg/d, compared with placebo, did not delay or prevent the development of type 1 diabetes over 2.7 years. These findings do not support oral insulin as used in this study for diabetes prevention.
IMPORTANCE Type 1 diabetes requires major lifestyle changes and carries increased morbidity and mortality. Prevention or delay of diabetes would have major clinical effect.OBJECTIVE To determine whether oral insulin delays onset of type 1 diabetes in autoantibody-positive relatives of patients with type 1 diabetes.DESIGN, SETTING, AND PARTICIPANTS Between March 2, 2007, and December 21, 2015, relatives with at least 2 autoantibodies, including insulin autoantibodies and normal glucose tolerance, were enrolled in Canada, the United States, Australia, New Zealand, the United Kingdom, Italy, Sweden, Finland, and Germany. The main study group (n = 389) had first-phase insulin release on an intravenous glucose tolerance test thatwas higher than the threshold. The 55 patients in the secondary stratum 1 had an identical antibody profile as the main study group except they had first-phase insulin release thatwas lower than the threshold. Secondary strata 2 (n = 114) and strata 3 (n = 3) had different autoantibody profiles and first-phase insulin release threshold combinations. Follow-up continued through December 31, 2016.INTERVENTIONS Randomization to receive 7.5mg/d of oral insulin (n = 283) or placebo (n = 277), including participants in the main study group who received oral insulin (n = 203) or placebo (n = 186).MAIN OUTCOME AND MEASURES The primary outcomewas time to diabetes in the main study group. Significance was based on a 1-sided threshold of.05, and 1-sided 95% CIs are reported.RESULTS Of a total of 560 randomized participants (median enrollment age, 8.2 years; interquartile range [IQR], 5.7-12.1 years; 170 boys [60%]; 90.7% white non-Hispanic; 57.6% with a sibling with type 1 diabetes), 550 completed the trial including 389 participants (median age, 8.4 years; 245 boys [63%]), 382 (96%) in the main study group. During a median follow-up of 2.7 years (IQR, 1.5-4.6 years) in the main study group, diabetes was diagnosed in 58 participants (28.5%) in the oral insulin group and 62 (33%) in the placebo group. Time to diabetes was not significantly different between the 2 groups (hazard ratio [HR], 0.87; 95% CI, 0-1.2; P =.21). In secondary stratum 1 (n = 55), diabetes was diagnosed in 13 participants (48.1%) in the oral insulin group and in 19 participants (70.3%) in the placebo group. The time to diabetes was significantly longer with oral insulin (HR, 0.45; 95% CI, 0-0.82; P =.006). The HR for time to diabetes for the between-group comparisons for the 116 participants in the other secondary stratum was 1.03 (95% CI, 0-2.11; P =.53) and for the entire cohort of 560 participants was 0.83 (95% CI, 0-1.07; P =.11), which were not significantly different. The most common adverse event was infection (n = 254), with 134 events in the oral insulin group and 120 events in the placebo group, but no significant study-related adverse events occurred.CONCLUSIONS AND RELEVANCE Among autoantibody-positive relatives of patients with type 1 diabetes, oral insulin at a dose of 7.5mg/d, compared with placebo, did not delay or prevent the development of type 1 diabetes over 2.7 years. These findings do not support oral insulin as used in this study for diabetes prevention.
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