The Development of Fulminant Type 1 Diabetes during Chemotherapy for Rectal Cancer

Adachi, Junichiro; Mimura, Makiyo; Gotyo, Naoki; Watanabe, Takayuki

doi:10.2169/internalmedicine.54.3413

Cited by 11 publications

(8 citation statements)

References 18 publications

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“…5-fluorouracil, leading to dTTP depletion, is commonly used for cancer chemotherapy (47,48). Both myelosuppression and secondary diabetes are common side effects of 5-fluorouracil therapy (49,50), and a case of fulminant T1D following 5-fluorouracil treatment has recently been reported (51). Although a recent first-phase study of a dUTPase inhibitor indicates good tolerance (52), our findings warrant close monitoring of hematological and metabolic adverse events in these patients.…”

Section: Discussionmentioning

confidence: 68%

dUTPase (DUT) Is Mutated in a Novel Monogenic Syndrome With Diabetes and Bone Marrow Failure

et al. 2017

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We describe a new syndrome characterized by early-onset diabetes associated with bone marrow failure, affecting mostly the erythrocytic lineage. Using whole-exome sequencing in a remotely consanguineous patient from a family with two affected siblings, we identified a single homozygous missense mutation (chr15.hg19:g.48,626,619A>G) located in the dUTPase () gene (National Center for Biotechnology Information Gene ID 1854), affecting both the mitochondrial (DUT-M p.Y142C) and the nuclear (DUT-N p.Y54C) isoforms. We found the same homozygous mutation in an unrelated consanguineous patient with diabetes and bone marrow aplasia from a family with two affected siblings, whereas none of the >60,000 subjects from the Exome Aggregation Consortium (ExAC) was homozygous for this mutation. This replicated observation probability was highly significant, thus confirming the role of this mutation in this syndrome. DUT is a key enzyme for maintaining DNA integrity by preventing misincorporation of uracil into DNA, which results in DNA toxicity and cell death. We showed that DUT silencing in human and rat pancreatic β-cells results in apoptosis via the intrinsic cell death pathway. Our findings support the importance of tight control of DNA metabolism for β-cell integrity and warrant close metabolic monitoring of patients treated by drugs affecting dUTP balance.

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Section: Discussionmentioning

confidence: 68%

dUTPase (DUT) Is Mutated in a Novel Monogenic Syndrome With Diabetes and Bone Marrow Failure

et al. 2017

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“…Moreover, the destruction of the exocrine part of the pancreatic tissue leads to digestive disorders, and necrosis of the pancreatic islets may bring about glucose intolerance. What is more, chemotherapy may induce diabetes [2], as cancer chemotherapy may decrease insulin sensibility or increase gluconeogenesis. Prognosis of patients with cancer and diabetes is poorer and more complicated, therefore, chemotherapy patients need to be frequently tested for glycaemia [10].…”

Section: Introductionmentioning

confidence: 99%

A comparison of caspase 3 expression in the endocrine and exocrine parts of the pancreas after cladribine application according to the "leukemic" schema

Jasinski

Chylińska-Wrzos

Lis-Sochocka

et al. 2017

Current Issues in Pharmacy and Medical Sciences

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The therapeutic effects of the immunosuppressive agent, cladribine, have been demonstrated by its toxicity to cells. However, its effects on healthy cells of the body is poorly understood. The aim of study was, hence, to, firstly, evaluate the morphology of the endocrine and exocrine pancreas after the administration of cladribine according to the "leukemic" schema, and, secondly, to assess its impact on the intensity of apoptosis. The experiment was carried out on female Wistar rats which were placed within the control group KA, and the experimental groups: A and A-bis. In the experimental groups, Cladribine was administered according to the cycle used to treat human hairy cell leukemia. In group A, the material was taken 24 hours after administration of the last dose of the drug, while in group A-bis, this was done after a 4 weeks break. The reaction was assessed to be average in 80% of all cells in group A, and in 64% of all acinar cells in group KA, while in group A-bis, the majority of the exocrine cells demonstrated a lack of immunohistochemical response (72%). Moreover, most endocrine cells (60%) in group A-bis revealed a strong reaction, while in Group A, the corresponding figure is a little over 34%. A comparison of the severity of the caspase 3 expression in both the exocrine and endocrine pancreas showed significant differentiation results between the group KA and group A-bis, and between group A and A-bis (p < 0.0001). In can be concluded that endocrine cells are more sensitive to cladribine than are exocrine cells.

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“…To the best of our knowledge, only one case with FT1D during chemotherapy with UFT has been reported to date. Adachi et al (20) suggested two possible mechanisms for this development. The first is via immune suppression or immunological reaction, and the second is via the effects of thymidine phosphorylase.…”

Section: Discussionmentioning

confidence: 99%

Diabetic ketoacidosis caused by fulminant type 1 diabetes during adjuvant chemotherapy for colon cancer: A case report

et al. 2019

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Development of diabetic ketoacidosis (DKA) caused by fulminant type 1 diabetes (FT1D) during administration of uracil-tegafur (UFT) with leucovorin (LV) as adjuvant chemotherapy is extremely rare. Here, we report a case of DKA caused by FT1D during administration of UFT with LV as adjuvant chemotherapy for colon cancer. A woman in her 60s was transferred to the emergency medical center of our hospital with complaints of impaired consciousness and vomiting. She had undergone left hemicolectomy and D3 lymph node dissection for transverse colon cancer 8 months earlier. She was provided UFT with LV as adjuvant chemotherapy. Laboratory analysis revealed hyperglycemia, high anion gap metabolic acidosis and urinary ketones. She was diagnosed with DKA and was started on intravenous infusion of fluid and continuous subcutaneous insulin injections. Following admission, she was examined and diagnosed with FT1D. The present case describes an extremely rare case of DKA caused by FT1D during adjuvant chemotherapy with UFT + LV for colon cancer.

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The Development of Fulminant Type 1 Diabetes during Chemotherapy for Rectal Cancer

Cited by 11 publications

References 18 publications

dUTPase (DUT) Is Mutated in a Novel Monogenic Syndrome With Diabetes and Bone Marrow Failure

dUTPase (DUT) Is Mutated in a Novel Monogenic Syndrome With Diabetes and Bone Marrow Failure

A comparison of caspase 3 expression in the endocrine and exocrine parts of the pancreas after cladribine application according to the "leukemic" schema

Diabetic ketoacidosis caused by fulminant type 1 diabetes during adjuvant chemotherapy for colon cancer: A case report

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