Rapid and slow progressors toward b-cell depletion and their predictors in type 1 diabetes: Prospective longitudinal study in Japanese type 1 diabetes (TIDE-J)

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posted on 2025-06-13, 00:10 authored by Shinsuke Noso, Daisuke Chujo, Akihisa Imagawa, Eiji Kawasaki, Takuya Awata, Kazuki Yasuda, Norio Abiru, Noriko Kodani, Yoichi Oikawa, Tomoyasu Fukui, Takeshi Katsuki, Junji Kozawa, Kan Nagasawa, Haruhiko Osawa, Kazuma Takahashi, Kyoichiro Tsuchiya, Masayuki Shimoda, Hisafumi Yasuda, Norikazu Maeda, Akira Shimada, Tetsuro Kobayashi, Toshiaki Hanafusa, Hiroshi Kajio, Hiroshi Ikegami

Objective

This study aimed to investigate the progression of β-cell dysfunction and its predictors in Japanese patients with type 1 diabetes, utilizing data from the nationwide, multicenter prospective longitudinal TIDE-J study.

Research Design and Methods

The TIDE-J study enrolled 314 Japanese individuals with type 1 diabetes, including 165 with acute-onset, 105 with slowly progressive, and 44 with fulminant type 1 diabetes. Clinical data, including C-peptide levels, glycemic control, and autoantibody status, were collected annually for up to 14 years. HLA genotypes were analyzed at study entry. The time to insulin depletion was analyzed using survival curves and Cox proportional hazards models to determine predictive factors.

Results

The rate of undetectable C-peptide varied significantly among subtypes: at 5 years post-onset, 43.1% (n=55) of acute-onset, 9.1% (n=7) of slowly progressive, and 93.2% (n=38) of fulminant type 1 diabetes patients reached undetectable C-peptide. Even within acute-onset type 1 diabetes, a marked interindividual variation was observed in the progression toward β-cell depletion. HLA genotypes influenced progression rates: DRB1*04:05-DQB1*04:01 /DRB1*04:05-DQB1*04:01 (DR4/DR4) carriers exhibited slower β-cell depletion, whereas DRB1*04:05-DQB1*04:01/DRB1*08:02-DQB1*03:02 (DR4/DR8) and DRB1*04:05-DQB1*04:01/DRB1*09:01-DQB1*03:03 (DR4/DR9) were associated with a rapid progression. For slowly progressive type 1 diabetes, low BMI, GADA positivity, and absence of the DRB1*15:01-DQB1*06:02 or DRB1*15:02-DQB1*06:01 (DR2) haplotype were predictive of progression to insulin dependence.

Conclusions

This study elucidates the heterogeneity in β-cell dysfunction among Japanese individuals with type 1 diabetes and identifies genetic and clinical predictors of disease progression. These findings provide insights for individualized management strategies and future therapeutic interventions.