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Diabetes mellitus is a complex chronic disease, considered as one of the most common metabolic disorders worldwide, posing a major threat to global public health. Ferroptosis emerges as a novel mechanism of programmed cell death, distinct from apoptosis, necrosis, and autophagy, driven by iron-dependent lipid peroxidation accumulation and GPx4 downregulation. A mounting body of evidence highlights the interconnection between iron metabolism, ferroptosis, and diabetes pathogenesis, encompassing complications like diabetic nephropathy, cardiomyopathy, and neuropathy. Moreover, ferroptosis inhibitors hold promise as potential pharmacological targets for mitigating diabetes-related complications. A better understanding of the role of ferroptosis in diabetes may lead to an improvement in global diabetes management. In this review, we delve into the intricate relationship between ferroptosis and diabetes development, exploring associated complications and current pharmacological treatments. [ABSTRACT FROM AUTHOR]

Nicotinamide adenine dinucleotide (NAD.sup.+) is a co-substrate for several enzymes, including the sirtuin family of NAD.sup.+-dependent protein deacylases. Beneficial effects of increased NAD.sup.+ levels and sirtuin activation on mitochondrial homeostasis, organismal metabolism and lifespan have been established across species. Here we show that [alpha]-amino-[beta]-carboxymuconate-[epsilon]-semialdehyde decarboxylase (ACMSD), the enzyme that limits spontaneous cyclization of [alpha]-amino-[beta]-carboxymuconate-[epsilon]-semialdehyde in the de novo NAD.sup.+ synthesis pathway, controls cellular NAD.sup.+ levels via an evolutionarily conserved mechanism in Caenorhabditis elegans and mouse. Genetic and pharmacological inhibition of ACMSD boosts de novo NAD.sup.+ synthesis and sirtuin 1 activity, ultimately enhancing mitochondrial function. We also characterize two potent and selective inhibitors of ACMSD. Because expression of ACMSD is largely restricted to kidney and liver, these inhibitors may have therapeutic potential for protection of these tissues from injury. In summary, we identify ACMSD as a key modulator of cellular NAD.sup.+ levels, sirtuin activity and mitochondrial homeostasis in kidney and liver.Genetic or pharmacological inhibition of [alpha]-amino-[beta]-carboxymuconate-[epsilon]-semialdehyde decarboxylase increases NAD.sup.+ and improves mitochondrial function in nematodes and mice, and may have therapeutic potential in kidney and liver disease., Author(s): Elena Katsyuba [sup.1] , Adrienne Mottis [sup.1] , Marika Zietak [sup.2] [sup.3] , Francesca De Franco [sup.4] , Vera van der Velpen [sup.5] , Karim Gariani [sup.1] [sup.11] , [...]

Background: Acute Charcot foot can be difficult to diagnose, especially because of other alternate diagnoses that can mimic this condition, particularly stress fracture and acute bone and joint infections, which are 2 conditions that require immediate management. Here, we present the case of a patient who received kidney-pancreas-transplantation for type 1 diabetes mellitus, who consulted for right foot pain after walking. Case Report: Our patient was a 47-year-old man who had benefited from a kidney-pancreas transplantation in 2014 for type 1 diabetes and terminal kidney failure and was recently followed for a right foot plantar ulcer that was fully healed. He later presented for right foot pain after walking. Clinical examination showed a red, swollen, and warm foot. Blood test results were unremarkable. Imaging (X-ray/MRI) revealed features compatible with acute Charcot foot. The management consisted of prompt right-foot offloading followed by physiotherapy and adapted orthopedic insoles. Conclusions: This case shows the successful treatment of an active phase of Charcot foot, which avoided the classic transition to chronic Charcot foot with severe osteoarticular destruction. Arguments were developed to rule out other possible diagnoses. The underlying mechanisms of Charcot foot in diabetic patients are related to the neurological and micro-vascular complications induced by poor glycemic control, but the mechanisms are unclear. This case report may help clinicians to better understand and consider another less known and less frequent diagnosis when faced with these clinical features. [ABSTRACT FROM AUTHOR]

Sarcopenic obesity is defined as the coexistence of sarcopenia and obesity in the same individual, characterized by of the co-presence of body fat accumulation and muscle loss. This condition is currently a major concern as it is associated with frailty and disabilities such as cardiovascular disease, fractures, dementia, cancer, and increased all-cause mortality. Particularly, older individuals remain at risk of sarcopenic obesity. Progress at several levels is needed to improve the global prognostic outlook for this condition, including the elaboration and implementation of a more uniform definition that may favor the identification and specification of prevalence by age group. Furthermore, improvements in the understanding of the pathogenesis of sarcopenic obesity may lead to the development of more specific therapeutic interventions to improve prognosis. We reviewed the knowledge on sarcopenic obesity and its associations with cardiovascular diseases and mortality. [ABSTRACT FROM AUTHOR]