Anti-programmed cell death-1 (PD-1) antibodies are regarded as a risk factor for insulindependent diabetes mellitus as a side-effect. While a small number of cases have been reported, evidence remains limited. This is the first report of an Asian patient developing insulin-dependent diabetes during anti-PD-1 therapy. A 55-year-old euglycemic woman receiving nivolumab for malignant melanoma showed abrupt onset of ketonuria, and elevated levels of plasma glucose (580 mg/dL) and hemoglobin A1c (7.0%). Over the next 2 weeks, serum C-peptide levels fell below the limit of detection. Islet autoantibodies were negative, and the patient showed a human leukocyte antigen haplotype associated with type 1 diabetes. Anti-PD-1 therapy can cause rapid onset of insulin-dependent diabetes, possibly because of inappropriate activation of T cells. Human leukocyte antigen haplotypes might be related to the onset of this disease. Physicians should be aware of this serious adverse event and carry out routine blood glucose testing during anti-PD-1 therapy.

To clarify the mechanism responsible for age-related changes in insulin action, the euglycemic clamp technique was performed with graded doses of insulin in conscious rats aged 2, 4, 10, and 20 mo. Insulin binding (IB) to muscle membranes was also studied. Maximal response of insulin-induced glucose disappearance rate (Rd) was decreased significantly between 2 and 4 mo of age. Dose-response curves shifted to the right progressively up to 20 mo of age. However, IB to the muscle membrane diminished between 1 and 4 mo of age without a decrease thereafter. When Rd was plotted against insulin bound to the membranes, the resulting curves shifted to the right with aging, suggesting a coupling defect between the binding and effector unit. In conclusion, insulin action alters in rats between 2 and 20 mo of age. The most pronounced impairment in IB and maximal response of insulin-induced Rd occurs during early life stage (through maturation) and then a coupling defect seems to be superimposed with further aging. However, we cannot exclude the possibility that these changes may be secondary to obesity or reduced physical activity, rather than aging per se.

The high prevalence of both ACA and ALF strongly suggests the involvement of autoimmunity against the exocrine pancreas as well as the endocrine pancreas in some type 1 diabetic patients. We propose that these conditions be referred to as autoimmune exocrinopathy and endocrinopathy of the pancreas.

The consumption and production of bismuth are increasing, however there is very little information about the direct toxic effect of bismuth. The present study aimed to characterize the potential toxic effects of bismuth through oral administration and observation for fourteen days following single dose of 0 and 2,000 mg/kg (acute oral toxicity study), and repeated oral administration for twenty-eight days at dose levels of 0, 40, 200, and 1,000 mg/kg daily (28-d repeated oral dose toxicity study) to male and female Crj:CD (SD) IGS rats (SPF). We found no deaths and no abnormalities in clinical signs, body weights, and necropsy findings for any of the animals in the acute oral toxicity study and no changes attributable to bismuth in either males or females in the dose group up to 1,000 mg/kg of the 28-d repeated-dose toxicity study. Therefore, we determined that the lethal dose with a 50% mortality rate (LD50) is greater than 2,000 mg/kg and the no-observed-adverse-effect level (NOAEL) of bismuth is 1,000 mg/kg in both sexes. We conclude that the adverse toxic effects of bismuth as a simple metal substance are low compared to lead toxicity under the conditions tested in our studies.

Autoimmune pancreatitis showed high signal intensity on DWI, which improved after steroid treatment. ADCs reflected disease activity. Thus, diffusion-weighted MRI might be useful for diagnosing AIP, determining the affected area, and evaluating the effect of treatment.