title: Pancreas-protective effect of rituximab for acute-onset type 1 diabetes in the honeymoon period: a case report.
abstract: A randomized controlled study of rituximab demonstrated that the drug protects pancreatic function in patients with acute-onset type 1 diabetes mellitus (AOT1DM). However, the mechanism of this protective effect is poorly understood. We examined the effects of rituximab in two patients with AOT1DM in the honeymoon period and the mechanism of these effects. Case 1 was a 40-year-old man and Case 2 was a 45-year-old man, both diagnosed with AOT1DM. Various tests indicated intact capacity for endogenous insulin secretion and that they were in the honeymoon phase of AOT1DM. Treatment with rituximab protected against pancreatic β-cell damage and maintained somewhat the endogenous insulin secretion. In Case 2, HbA1c level was maintained below 6.5% up to 24 months after treatment. However, in Case 1, the patient showed a gradual increase in HbA1c level starting around 9 months but fell at 12 months to >9.0% and required an insulin dose about twice greater than that of Case 2. High spleen tyrosine kinase (Syk) levels were recorded in the two patients before rituximab administration and after the treatment, the levels were further increased in Case 1, but decreased in Case 2. Both patients require continuous careful follow-up for glycemic control, insulin secretion capacity, and adverse reactions in the future. Although the clinical relevance of high Syk levels in AOT1DM patients remains unclear, the difference in the change in Syk level between the two patients may explain the different clinical courses.
  
  
  CONCLUSIONS
  We described the pancreas-protective effect of rituximab in two patients with acute-onset type 1 diabetes mellitus in the honeymoon period and investigated the possible mechanism of action.The present study demonstrated that treatment with rituximab maintained endogenous insulin secretion capacity for 2 years in the two patients.The phosphorylated-spleen tyrosine kinase (p-Syk) data suggest that the differences in HbA1c level and the required insulin dose between the two patients could be due to reactivation or nonreactivation of β-cells.
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health , Japan, Kitakyushu , Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kurozumi
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health , Japan, Kitakyushu , Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Okada
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan; Department of Internal Medicine, Japan Labour Health and Welfare Organization, Kyushu Rosai Hospital, Moji Medical Center, Kyushu, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Arao
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health , Japan, Kitakyushu , Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health , Japan, Kitakyushu , Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Yoshikawa
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health , Japan, Kitakyushu , Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Torimoto
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health , Japan, Kitakyushu , Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kubo
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health , Japan, Kitakyushu , Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakayamada
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health , Japan, Kitakyushu , Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka