Why Is Diabetes Mellitus a Risk Factor for Contrast-Induced Nephropathy?

Contrast-induced nephropathy (CIN) remains a leading cause of iatrogenic acute kidney injury, as the usage of contrast media for imaging and intravascular intervention keeps expanding. Diabetes is an important predisposing factor for CIN, particularly in patients with renal functional impairment. Renal hypoxia, combined with the generation of reactive oxygen species, plays a central role in the pathogenesis of CIN, and the diabetic kidney is particularly susceptible to intensified hypoxic and oxidative stress following the administration of contrast media. The pathophysiology of this vulnerability is complex and involves various mechanisms, including a priori enhanced tubular transport activity, oxygen consumption, and the generation of reactive oxygen species. The regulation of vascular tone and peritubular blood flow may also be altered, particularly due to defective nitrovasodilation, enhanced endothelin production, and a particular hyperresponsiveness to adenosine-related vasoconstriction. In addition, micro- and macrovascular diseases and chronic tubulointerstitial changes further compromise regional oxygen delivery, and renal antioxidant capacity might be hampered. A better understanding of these mechanisms and their control in the diabetic patient may initiate novel strategies in the prevention of contrast nephropathy in these susceptible patients

Obesity, diabetes and zinc: A workshop promoting knowledge and collaboration between the UK and Israel, November 28–30, 2016 – Israel

Sponsored by the Friends of Israel Educational Foundation (FIEF) and Ben-Gurion University of the Negev and supported by the EU COST action Zinc-Net (COST TD1304), a three-day collaborative UK-Israel workshop was organized by Drs Assaf Rudich, Imre Lengyel and Arie Moran. Participants from the UK and Israel met at the Desert Iris Hotel, Yeruham, Israel between the 28-30th of November 2016 for in-depth discussions, rather than a lecture series, to set the stage for future collaborative grants and projects on diabetes and zinc. Two days of formal scientific sessions with dynamic and wide-ranging discussions was followed by a day of touring and informal networking in the Negev area. This format was previously recognized by our sponsors as both effective and enjoyable and all participants agreed at the end of the meeting that the 3-days provided an excellent basis for future scientific collaboration. The discussions were centered on diabetes and obesity, already at pandemic levels, and zinc homeostasis which is related to the clinical issues and themes of the meeting. The free-flowing discussions were based on short presentations setting the scene for the six main topics: ‘Diabetes and zinc transporters’, ‘Nutrition related factors’, ‘Biomarkers’, ‘Clinical epidemiology’, ‘the Microbiome and diabetes’, and ‘Related diseases’. The abstract style summary of the sessions is followed by the major discussion points raised by the Authors and other participants (UK: Patrik Rorsman, Oxford University; Alan Stewart, University of St Andrews and Israel: Assaf Rudich, Idit Liberty, Rahel Gol, Guy Las and Amos Katz, Ben-Gurion University; Sarah Zangen, Haddassa University). We hope that readers will find this discourse stimulating and some of the ideas might make their way into their research efforts

Overexpressing IRS1 in Endothelial Cells Enhances Angioblast Differentiation and Wound Healing in Diabetes and Insulin Resistance

The effect of enhancing insulin’s actions in endothelial cells (ECs) to improve angiogenesis and wound healing was studied in obesity and diabetes. Insulin receptor substrate 1 (IRS1) was overexpressed in ECs using the VE-cadherin promoter to create ECIRS1 TG mice, which elevated pAkt activation and expressions of vascular endothelial growth factor (VEGF), Flk1, and VE-cadherin in ECs and granulation tissues (GTs) of full-thickness wounds. Open wound and epithelialization rates and angiogenesis significantly improved in normal mice and high fat (HF) diet–induced diabetic mice with hyperinsulinemia in ECIRS1 TG versus wild type (WT), but not in insulin-deficient diabetic mice. Increased angioblasts and EC numbers in GT of ECIRS1 mice were due to proliferation in situ rather than uptake. GT in HF-fed diabetic mice exhibited parallel decreases in insulin and VEGF-induced pAkt and EC numbers by >50% without changes in angioblasts versus WT mice, which were improved in ECIRS1 TG mice on normal chow or HF diet. Thus, HF-induced diabetes impaired angiogenesis by inhibiting insulin signaling in GT to decrease the differentiation of angioblasts to EC, which was normalized by enhancing insulin’s action targeted to EC, a potential target to improve wound healing in diabetes and obesity

Autoimmune Thyroid Diseases and Thyroid Cancer in Pemphigus: A Big Data Analysis

There is a little consensus regarding the association of pemphigus with autoimmune thyroid diseases. While this association had been confirmed by some observational studies, others had refuted it. We aimed to study the association between pemphigus and Hashimoto's thyroiditis, Grave's disease, and thyroid cancer using a large-scale real-life computerized database. A cross-sectional study was performed to compare pemphigus patients with age-, sex-, and ethnicity-matched control subjects regarding the prevalence of overt thyroid diseases. Chi-square and t-tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study was performed using the computerized database of Clalit Healthcare Services ensuring 4.5 million individuals. A total of 1,985 pemphigus patients and 9,874 controls were included in the study. The prevalence of Hashimoto's thyroiditis (12.9 vs. 11.9%; P = 0.228), Graves's disease (0.7 vs. 0.7%; P = 0.986), and thyroid cancer (0.7 vs. 0.5%; P = 0.305) were comparable among patients with pemphigus and control subjects. In sex-stratified analysis, pemphigus associated significantly with Hashimoto's thyroiditis among male patients (OR, 1.36; 95% CI, 1.04–1.79). In multivariate analysis adjusting for potential confounding factors, no independent associations between the conditions were revealed. Study findings were robust to sensitivity analysis that included only patients under pemphigus-specific treatments. In conclusion, Hashimoto's thyroiditis was found to be associated with pemphigus only among male patients, but not among all patients. Physicians treating patients with pemphigus might be aware of this possible association. This study does not provide a clue for an association of pemphigus with Grave‘s disease or thyroid cancer