Increased risk of immune checkpoint inhibitor–induced type 1 diabetes mellitus with the new approved 6-week scheme of pembrolizumab in patients with melanoma?

Abstract Background The use of immune checkpoint inhibitor (ICI) therapy is becoming a standard of care for several cancers. Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) or its ligand (PD-L1) cause a broad spectrum of autoimmune adverse events. ICI-induced type 1 diabetes mellitus (T1DM) is extremely rare (< 1%) but potentially life-threatening. It appears to be more common with PD-1 blockade (or combination immunotherapy) than with anti-CTLA-4 therapy, often during the first three to six months of therapy. Cases presentation We report an acute onset T1DM with severe inaugural diabetic ketoacidosis (DKA) and remarkably elevated Glutamic Acid Decarboxylase antibody (GADA) titres following a single administration of combined ICI therapy with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) in two adult patients with advanced metastatic melanoma. In these cases, the time to diabetes onset was remarkably short (two and five weeks), and one presented with fulminous T1DM in a previous long-standing type 2 diabetes mellitus. Conclusions Oncological patients treated with combination therapy of anti-PD-1 and anti-CTLA-4 can develop a particular pattern of T1DM, with very rapid onset within a few weeks after starting ICI therapy, even in the presence of an existing type 2 diabetes. ICI-induced T1DM is a medical emergency in presence of severe inaugural DKA and requires a collaboration between specialists and primary care physicians, as well as patient education, for early diagnosis and supportive care.

Download Full-text

Pregnancy and delivery in a patient with a 40-year history of type 1 diabetes mellitus and antiphospholipid syndrome

Journal of obstetrics and women s diseases ◽

10.17816/jowd67693-99 ◽

2018 ◽

Vol 67 (6) ◽

pp. 93-99

Author(s):

Roman V. Kapustin ◽

Natalia V. Borovik ◽

Ekaterina V. Musina ◽

Olga N. Arzhanova ◽

Maria I. Yarmolinskaya ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Antiphospholipid Syndrome ◽

Perinatal Outcomes ◽

Increased Risk ◽

Pregnancy And Delivery ◽

Perinatal Center ◽

History Of

Type 1 diabetes mellitus is a condition associated with an increased risk of adverse perinatal outcomes such as spontaneous abortions, preterm birth, placental insufficiency, congenital malformations, and perinatal mortality. Diabetes mellitus combined with cardiovascular diseases in women during pregnancy often leads to hypertensive disorders and pre-eclampsia. The severity of the microvascular diabetic complications and frequency of hypoglycemic episodes, particularly in early pregnancy, are related to the risk of pre-eclampsia. We report the case of pregnancy and delivery of a live newborn in a 42-year-old woman with type 1 diabetes mellitus, pre-existing hypertension, heritable thrombophilia, and antiphospholipid syndrome. She had a 40-year history of type 1 diabetes mellitus with well-controlled diabetic nephropathy and retinopathy. The woman had been receiving continuous subcutaneous insulin therapy for the last five years, which allowed maintaining an appropriate glycemic control during pregnancy. Multidisciplinary supervision of course of pregnancy was carried out from the pre-gravidity stage until delivery and postpartum. In spite of the severe pre-eclampsia and preterm delivery by cesarean section at 36 weeks, she and newborn could avoid the intensive unit care and discharge from perinatal center without any complications.

Download Full-text

Risk of Urticaria in Children with Type 1 Diabetes Mellitus: A Nationwide Cohort Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17010176 ◽

2019 ◽

Vol 17 (1) ◽

pp. 176

Author(s):

Shih-Yi Lin ◽

Cheng-Li Lin ◽

Cheng-Chieh Lin ◽

Wu-Huei Hsu ◽

Chung-Y. Hsu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Hazard Ratio ◽

Control Group ◽

Case Group ◽

Research Database ◽

Increased Risk ◽

Type 1 Dm

Type 1 diabetes mellitus (T1DM) has been linked to many autoimmune problems. The association between T1DM and urticaria warrants investigation. Data were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. Participants with T1DM were recruited as the case group, and that group was matched by sex and age at a ratio of 1:4 to the control group comprising those without T1DM. The study period was 1998–2011. All participants were followed up to the diagnosis of urticaria, withdrawal from the insurance program, death, or the end of the study. A multivariable Cox proportional hazard model was used to calculate the adjusted and crude hazard ratios for urticaria. A total of 5895 participants (1179 in the case group and 4716 in the control group) were followed up in the study. The total incidence rate of urticaria in patients with type 1 DM was 26.6 per 1000 person-years, and that in controls was 6.85 per 1000 person-years. Compared with the control group, the hazard ratio of urticaria in the case group was 2.84 (95% CI = 2.27–3.56). Compared with age-matched participants without T1DM, patients with type 1 DM aged <18 years had a 3.62-fold higher risk of urticaria (95% CI = 2.85–4.59). The hazard ratio in patients with an adjusted Diabetes Complications Severity Index (aDCSI) score of 1.01–2.00 per year was 2.57 (95% CI = 1.18–5.57), and that in patients with an aDCSI score of >2.00 per year was 4.47 (95% CI = 2.68–7.47). T1DM patients aged <18 years had an increased risk of urticaria, but a similar phenomenon was not observed among T1DM patients older than 18 years.

Download Full-text