Insulin therapy can cause various types of immune responses to it by the body’s immune system. Previous studies have reported three cases of type 1 diabetes triggered by insulin therapy in Japanese patients with type 2 diabetes. To characterize the immunological and genetic profile of insulin-triggered type 1 diabetes, Professor Hideichi Makino and his team from the Graduate School of Ehime University in Japan conducted a study to collect data from patients with insulin-triggered type 1 diabetes. The results of the study were published online in The Journal of Clinical Endocrinology and Metabolism on June 27, 2014. In this study, data were collected from six patients with insulin-triggered type 1 diabetes, four males and two females, aged 59.5 ± 12.8 y. Serum and urine C-peptide levels, islet-associated autoantibodies, insulin antibodies, HLA or insulin gene VNTR genotype were analyzed in these patients by Prof. Makino et al. The ELISPOT analyzer was also used to assess the Th1 or Th2 related responses in these patients. Prior to insulin treatment, none of these six patients had received previous insulin therapy and had no autoantibodies against GAD65. After insulin treatment, the glycemic control of these 6 patients deteriorated dramatically without any apparent reason, and the C-peptide levels decreased rapidly to insulin-deficient levels. The mean insulin treatment period from the initiation of insulin therapy to the onset of type 1 diabetes in these six patients was 7.7 ± 6.1 months. When islet-associated autoantibodies were negative to positive, insulin allergic reactions or high insulin antibody titers were observed in some cases. All six patients had type 1 diabetes high-risk susceptibility genes with IDDM1 in the HLA class II gene region and IDDM2 in the VNTR gene region of the insulin gene. two of the four patients were confirmed to have GAD-reactive Th1 cells and insulin C peptide-responsive Th1 cells, but no GAD-responsive Th2 cells or insulin C peptide-responsive Th2 cells. This study suggests that in patients with type 2 diabetes, insulin therapy may trigger type 1 diabetes, and that IDDM1, IDDM2, and self-reactive T cells may play a role in the development of type 1 diabetes.Professor Makino cautions clinicians who encounter patients in their clinical work who have a dramatic deterioration in glycemic control after insulin on therapy should carefully consider whether the occurrence of the possibility of insulin-triggered type 1 diabetes mellitus.