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Diabetes is a rare, but potentially life‐threatening, adverse event of immune checkpoint inhibitors that requires prompt recognition and treatment. It usually occurs in the first 3 months of treatment and is typically related to programmed cell death‐1 antibodies, alone or in combined therapy. It has rarely been described developing after immunotherapy cessation. We present a 51‐year‐old man with metastatic melanoma, who developed acute‐onset diabetes 52 days after combined immunotherapy cessation with nivolumab and ipilimumab, and 25.6 months after receiving the first dose. He presented with acute hyperglycemic symptoms, ketosis, complete insulin depletion and negative autoimmunity, fulfilling the criteria of fulminant type 1 diabetes. The patient had previously developed hypophysitis with isolated adrenocorticotropic hormone deficiency during immunotherapy. We describe a case of late‐onset fulminant type 1 diabetes developing after immunotherapy cessation. Patient education and active follow up after immunotherapy discontinuation are crucial to warrant a timely intervention., We describe a case of immunotherapy‐related type 1 diabetes developing after combined immunotherapy cessation. The patient developed fulminant type 1 diabetes >2 years after the first immunotherapy dose, and had previously developed immune‐related hypophysitis.

Objective This study compares the patterns of visceral (VIS) and subcutaneous (SC) adipose tissue (AT)-derived metabolites from non-obese (BMI 24-26 kg/m2) and obese subjects (BMI > 40 kg/m2) with no major metabolic risk factors other than BMI. Methods SC- and VIS- AT obtained from obese (Ob) and non-obese (NOb) subjects during surgery were incubated to obtain their metabolites. Differences related to obesity or anatomical provenances of AT were assessed using an untargeted metabolomics approach based on gas chromatography-mass spectrometry. Results The overall effect of obesity on the metabolite profile resulted more remarkable than the effect of regional AT. Only the depletion of 2-ketoisocaproic (2-KIC) acid reached statistical significance for the SC-AT alone, although it was observed in both depots. Obesity induced more significant changes in several amino acids levels of the VIS-AT metabolites. On the one hand, higher released levels of glutamine and alanine were detected in the VIS- obese AT, whereas on the other, the VIS- obese AT presented a diminished uptake of essential amino acids (methionine, threonine, lysine), BCAAs, leucine, and serine. Conclusion This study shows that obesity markedly affects the amino acid metabolic signature of the AT before the clinical onset of other significant metabolic alterations aside from BMI.

Objective Persistent inflammation and impaired adipogenesis are frequent features of obesity and underlie the development of its complications. However, the factors behind adipose tissue dysfunction are not completely understood. Previously it was shown that histone demethylase KDM1A is required for adipogenesis. Design and Methods Kdm1a expression was knocked down in 3T3-L1 preadipocytes by siRNA transfection and whole-genome expression profiling was performed by microarray hybridization. The role of NF-κβ and C/EBPβ was analyzed by incubation with the inhibitor parthenolide and by cebpb knockdown, respectively. Results Knockdown of kdm1a or rcor2 in 3T3-L1 preadipocytes results in impaired differentiation and induction of inflammatory gene expression. Enhanced expression of il6 in kdm1a knocked down preadipocytes is associated with increased recruitment of C/EBPβ and the NF-κβ subunit RelA to the il6 promoter. Cebpb knockdown attenuates the induction of il6 expression in kdm1a knocked down cells, whereas simultaneous cebpb knockdown and NF-κβ inhibition abrogates it. Dietary-induced and genetic mouse models of obesity display decreased KDM1A in adipose tissue, and this correlates with increased expression of proinflammatory genes and C/EBPβ. Conclusion KDM1A represses the expression of inflammatory genes in preadipocytes. Dysregulated kdm1a expression in preadipocytes may thus participate in the development of obesity-associated inflammation.

Aim: Considering the poor long-term success of current dietary and pharmacological interventions, we aimed to evaluate the potential effect of sodium tungstate in the treatment of grade I and II obesity (ClinicalTrials.gov identifier: NCT00555074). Methods: Prospective, randomized, placebo-controlled, double-blind, proof-of-concept study was carried out. Following a 2-week lead-in period, 30 obese (body mass index, BMI 30.0–39.9 kg/m2), non-diabetic subjects were randomized to receive either sodium tungstate (100 mg bid) or placebo for 6 weeks. The primary study endpoint was the absolute change in body weight relative to the time of randomization. Results: Treatment with sodium tungstate [−0.135 ± 0.268 kg (95% CI −0.686 to +0.416 kg)] was not associated with a significant weight loss compared to placebo [−0.063 ± 0.277 kg (95% CI −0.632 to +0.507 kg)] (p = 0.854). Likewise, treatment with sodium tungstate was not associated with significant changes in fat mass (DEXA), resting energy expenditure (indirect calorimetry) or caloric consumption (3-day food records). Conclusion: Our data do not support sodium tungstate as a pharmacological agent in the treatment of human obesity.