Favorable Effect of Anti-TNF Therapy on Insulin Sensitivity in Nonobese, Nondiabetic Patients with Inflammatory Bowel Disease

Background. The aim of this study was to investigate the effect of anti-TNF therapy on glucose and lipid metabolism in nondiabetic, nonobese patients with inflammatory bowel disease (IBD). Patients and Methods. We studied 44 patients with IBD, without a known history of diabetes. Three of the patients were diagnosed with overt diabetes and were excluded. Eighteen of the remaining patients (9 M/9 F, 33.6 ± 8.8 years) were on anti-TNF therapy for longer than 1 year, while 23 patients (16 M/7 F, 38.7 ± 12.5 years) were treated with aminosalicylates (AMSs). Twelve of the patients from the second group were then treated with anti-TNF and reassessed 6 months later. Fasting glucose, insulin, c-peptide, HbA1c, lipid, CRP, and fibrinogen levels were determined, and HOMA-IR index was calculated in all patients. Results. Patients from the two therapy groups were matched for age and BMI and were not obese. We did not find any differences between patients from the two therapy groups regarding fasting glucose, c-peptide, HbA1c, total cholesterol, HDL, LDL, triglycerides, CRP, and HOMA-IR index. In patients who were treated for 6 months with anti-TNF, a statistically significant decrease in insulin (before 15.5 ± 5.9 versus after 9.9 ± 2.9 μIU/ml, p=0.042) and c-peptide (before 2.4 ± 1 versus after 1.3 ± 0.4 ng/ml, p=0.030) levels as well as the HOMA-IR index (before 4.2 ± 1.9 versus after 2.2 ± 0.9, p=0.045) was observed, without any changes in weight, BMI, glucose, HbA1c, lipid, CRP, and fibrinogen levels. Conclusion. Anti-TNF therapy exerts a favorable effect on insulin sensitivity, while it has no effect on lipid levels in nondiabetic, nonobese patients with inflammatory bowel disease

From the (Epi)Genome to Metabolism and Vice Versa; Examples from Hematologic Malignancy

Hematologic malignancies comprise a heterogeneous group of neoplasms arising from hematopoietic cells or their precursors and most commonly presenting as leukemias, lymphomas, and myelomas. Genetic analyses have uncovered recurrent mutations which initiate or accumulate in the course of malignant transformation, as they provide selective growth advantage to the cell. These include mutations in genes encoding transcription factors and epigenetic regulators of metabolic genes, as well as genes encoding key metabolic enzymes. The resulting alterations contribute to the extensive metabolic reprogramming characterizing the transformed cell, supporting its increased biosynthetic needs and allowing it to withstand the metabolic stress that arises as a consequence of increased metabolic rates and changes in its microenvironment. Interestingly, this cross-talk is bidirectional, as metabolites also signal back to the nucleus and, via their widespread effects on modulating epigenetic modifications, shape the chromatin landscape and the transcriptional programs of the cell. In this article, we provide an overview of the main metabolic changes and relevant genetic alterations that characterize malignant hematopoiesis and discuss how, in turn, metabolites regulate epigenetic events during this process. The aim is to illustrate the intricate interrelationship between the genome (and epigenome) and metabolism and its relevance to hematologic malignancy