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BackgroundObesity is a well-recognized risk factor for insulin resistance and type 2 diabetes (T2D), although the precise mechanisms underlying the relationship remain unknown. In this study we identified alterations of DNA methylation influencing T2D pathogenesis, in subcutaneous and visceral adipose tissues, liver, and blood from individuals with obesity.MethodsThe study included individuals with obesity, with and without T2D. From these patients, we obtained samples of liver tissue (n = 16), visceral and subcutaneous adipose tissues (n = 30), and peripheral blood (n = 38). We analyzed DNA methylation using Illumina Infinium Human Methylation arrays, and gene expression profiles using HumanHT-12 Expression BeadChip Arrays.ResultsAnalysis of DNA methylation profiles revealed several loci with differential methylation between individuals with and without T2D, in all tissues. Aberrant DNA methylation was mainly found in the liver and visceral adipose tissue. Gene ontology analysis of genes with altered DNA methylation revealed enriched terms related to glucose metabolism, lipid metabolism, cell cycle regulation, and response to wounding. An inverse correlation between altered methylation and gene expression in the four tissues was found in a subset of genes, which were related to insulin resistance, adipogenesis, fat storage, and inflammation.ConclusionsOur present findings provide additional evidence that aberrant DNA methylation may be a relevant mechanism involved in T2D pathogenesis among individuals with obesity.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0542-8) contains supplementary material, which is available to authorized users.

This paper reviews our experience with the Mitrofanoff principle as applied in eight patients. Of four patients with post-traumatic urethral stricture, three required the appendix as continent catheterizable conduit, with a modified appendicovesical anastomosis technique-that is, without a submucosal tunnel- and in one patient, the remnant ureter of a previous simple nephrectomy was used. Of the four remaining patients, one with a hypotonic bladder and three with urethral stricture, a complete laparoscopic approach was used to perform the same modified Mitrofanoff procedure with the appendix. With a mean follow-up of 19.5 months, all patients were completely dry. Only three patients had persistently positive urine cultures, but without evidence of renal function impairment. The modified direct appendicovesical anastomosis technique reduces the operative time, has a lower complication rate, and allows us to use a laparoscopic approach with the resulting benefits of a minimally invasive surgical procedure. As shown in urodynamic tests, urinary continence is preserved.

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