We here report a case of nivolumab-induced acute granulomatous tubulointerstitial nephritis in a patient with gastric cancer. A 68-year-old woman with recurrent gastric cancer developed acute kidney injury associated with kidney enlargement and urinary leukocytes after 38 cycles of nivolumab treatment. A diagnosis of acute granulomatous tubulointerstitial nephritis was made based on kidney biopsy findings. Immunohistochemistry revealed expression of programmed cell death-ligand 1 (PD-L1) in degenerated epithelial cells of collecting tubules. Among infiltrating immune cells, aggregation of T cells was more extensive than that of B cells, with CD4 T cells outnumbering CD8 T cells, consistent with the relative numbers of these cells in the circulation. Treatment with methylprednisolone (1.0 mg/kg daily) led to a rapid improvement in renal function and reduction in the number of circulating CD4 T cells. Prompt administration of high-dose corticosteroid is thus recommended after diagnosis of this adverse event of nivolumab treatment by kidney biopsy.

BackgroundThe study aimed to examine the relationship between levels of serum eicosapentaenoic acid (EPA), arachidonic acid (AA), as well as EPA/AA ratio and weight loss during hospitalization in participants considered to be overweight, with type 2 diabetes.MethodsThe study participants included 142 patients who were hospitalized for treatment of type 2 diabetes. We divided the participants into two groups depending on the achievenemt in reduction of bodyweight 3% or more during hospitalization and examined the relationship between serum levels of EPA and AA, as well as ratio of EPA/AA on admission and effectiveness of weight loss under strict dietary therapy during hospitalization, using Cox proportional hazard models.ResultsAfter adjustment was made for several confounders, the hazard ratio of effective weight loss for logarithmical serum EPA was 1.59 (95% CI 1.02–2.49, P = 0.04) and for logarithmical EPA/AA ratio 1.64 (1.03–2.61, P = 0.04), whereas the hazard ratio for effective weight loss for logarithmical serum AA was 1.11 (0.45–2.78, P = 0.82). In addition, after dividing EPA/AA ratio and serum EPA into quartiles based on participant number, the hazard ratio for the highest quartile of EPA/AA ratio was 2.33 (1.14–4.77, P = 0.02), and for the highest quartile of serum EPA 1.60 (0.80–3.19, P = 0.18) compared with the lowest quartile.ConclusionThese results suggest the possibility that EPA is involved in bodyweight change under a caloric-restriction regimen. In addition, EPA/AA ratio was found to be a better predictor of medical intervention for weight loss among overweight patients with type 2 diabetes, compared with serum EPA level.

Advances in insulin preparations and administration methods have produced a gradual improvement in glycemic control in patients with type 1 diabetes mellitus (DM). Nevertheless, glycated hemoglobin (HbA1c) levels in patients with type 1 DM are still poor compared to those in patients with type 2 DM. Here, we sought to assess the efficacy and safety of the sodium-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin (IPRA) in patients with type 1 DM. This study was retrospectively conducted with data from type 1 DM patients who had a history of IPRA therapy. The primary endpoint was HbA1c level at 24 weeks. The baseline characteristics of a total of 12 subjects were as follows: age, 50.1 ± 13.2 years; diabetes duration, 17.3 ± 10.5 years; body mass index (BMI), 22.9 ± 2.1 kg/m 2 ; HbA1c, 8.8 ± 1.3%; and daily insulin dose, 0.60 ± 0.21 units/kg. IPRA decreased HbA1c levels to 8.2 ± 1.2% (p < 0.05) and reduced insulin dose to 0.52 ± 0.17 units/kg (p < 0.01) after 24 weeks. HbA1c value was particularly reduced in subjects with preserved C-peptide index. IPRA significantly reduced body weight by -1.4 ± 1.4 kg (p < 0.01) 16 weeks after starting treatment, with no further weight loss after 24 weeks. There were no instances of diabetic ketoacidosis or severe hypoglycemia. IPRA exerted beneficial effects on glycemic control without any severe adverse effects, and should be safe and effective when used in patients with type 1 DM with understanding of correspondence in sick day.

Recently, dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors have been very often used in subjects with type 2 diabetes mellitus (T2DM). In addition, combination drugs of both inhibitors have attracted much attention in aspects of its cost-effectiveness and improvement of patients’ adherence. However, it is still poorly understood which factors are related to the efficacy of SGLT2 inhibitors as add-on therapy to DPP-4 inhibitors. Therefore, we aimed to elucidate in which type of individuals and/or under which conditions canagliflozin as add-on therapy to teneligliptin could exert more beneficial effects on glycemic control and/or renal protection. We retrospectively analyzed 56 Japanese subjects with T2DM in the real-world clinical practice. Three months after starting the combination therapy, the change of HbA1c (ΔHbA1c) was strongly related to HbA1c levels at baseline. As expected, serum glucagon level was increased after starting the combination therapy. Interestingly, however, the change of glucagon levels (Δglucagon) was not related to HbA1c levels at baseline, ΔHbA1c, and other parameters, which indicated that the increase of glucagon did not clinically affect the effectiveness of combination therapy. In addition, the change of urinary albumin excretion (ΔUAE) was negatively correlated with systolic blood pressure and HbA1c levels at baseline and positively correlated with the change of systolic blood pressure (ΔsBP) in univariate analysis. Furthermore, in multivariate analysis, only ΔsBP was the independent factor associated with ΔUAE. Taken together, canagliflozin as add-on therapy to teneligliptin improves glycemic control in a Δglucagon-independent manner and reduces UAE in a ΔsBP-dependent manner in Japanese subjects with T2DM.

Introduction: This study aimed to examine the association between severity of diabetic neuropathy and weight loss during hospitalization in overweight participants with type 2 diabetes. Patients and Methods: Participants of this study comprised 193 patients who were hospitalized for type 2 diabetes treatment. The participants were divided into two groups in the study, based on whether or not reduction of bodyweight was at least 3% during hospitalization. Using Cox models, the association between severity of neuropathy and effectiveness of weight loss under a controlled diet was analyzed. Autonomic neuropathy was assessed on patient admission by R-R interval, as measured in an electrocardiogram (CVRR), and sensory neuropathy was assessed using both 128-Hz tuning-fork vibration and Achilles tendon reflex (ATR). Results: The adjusted hazard ratio for weight loss of at least 3% for CVRR was 1.17 (95% confidence interval 1.07-1.28, P=0.0006) and for vibration time 1.93 (1.01-3.68, P=0.045). After dividing CVRR and vibration time into tertiles based on participant number, the adjusted hazard ratio for the high tertile of CVRR was 2.17 (1.29-3.62, P=0.003), and for the long tertile of vibration time 1.84 (1.10-3.08, P=0.02), compared with the low and short tertiles, respectively. No association was detected between ATR category and weight loss. Conclusion: Severity of diabetic neuropathy was found to be a determinant in weight loss under a caloric restriction regimen for patients with type 2 diabetes. The results of the study suggest that the peripheral nervous system is involved in responses to medical intervention for treatment for type 2 diabetes including bodyweight management.