Search

Adipose tissue (AT) represents a plastic organ that can undergo significant remodeling in response to metabolic demands. With its numerous checkpoints, the incretin system seems to play a significant role in controlling glucose homeostasis and energy balance. The importance of the incretin hormones, namely the glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic peptide (GIP), in controlling the function of adipose cells has been brought to light by recent studies. Notably, a "paradigm shift" in reevaluating the role of the incretin system in AT as a potential target to treat obesity-linked metabolic disorders resulted from the demonstration that a disruption of the GIP and GLP-1 signaling axis in fat is associated with adiposity-induced insulin-resistance (IR) and/or type 2 diabetes mellitus (T2D). We will briefly discuss the (patho)physiological functions of GLP-1 and GIP signaling in AT in this review, emphasizing their potential impacts on lipid storage, adipogenesis, glucose metabolism and inflammation. We will also address the conundrum with the perturbation of the incretin axis in white or brown fat tissue and the emergence of metabolic disorders. In order to reduce or avoid adiposity-related metabolic complications, we will finally go over a potential scientific rationale for suggesting AT as a novel target for GLP-1 and GIP receptor agonists and co-agonists. [ABSTRACT FROM AUTHOR]

Background: Elevated plantar pressures represent a significant risk factor for neuropathic diabetic foot (NDF) ulceration. Foot offloading, through custom-made insoles, is essential for prevention and healing of NDF ulcerations. Objective quantitative evaluation to design custom-made insoles is not a standard method. Aims: 1) to develop a novel quantitative-statistical framework (QSF) for the evaluation and design of the insoles' offloading performance through in-shoe pressure measurement; 2) to compare the pressure-relieving efficiency of traditional shape-based total contact customised insoles (TCCI) with a novel CAD-CAM approach by the QSF. Methods: We recruited 30 neuropathic diabetic patients in cross-sectional study design. The risk-regions of interest (R-ROIs) and their areas with in-shoe peak pressure statistically ≥200kPa were identified for each patients' foot as determined on the average of peak pressure maps ascertained per each stance phase. Repeated measures Friedman test compared R-ROIs' areas in three different walking condition: flat insole (FI); TCCI and CAD-CAM insoles. Results: As compared with FI (20.6±12.9 cm2), both the TCCI (7±8.7 cm2) and the CAD-CAM (5.5±7.3 cm2) approaches provided a reduction of R-ROIs mean areas (p<0.0001). The CAD-CAM approach performed better than the TCCI with a mean pressure reduction of 37.3 kPa (15.6%) vs FI. Conclusions: The CAD-CAM strategy achieves better offloading performance than the traditional shape-only based approach. The introduced QSF provides a more rigorous method to the direct 200kPa cut-off approach outlined in the literature. It provides a statistically sound methodology to evaluate the offloading insoles design and subsequent monitoring steps. QSF allows the analysis of the whole foot's plantar surface, independently from a predetermined anatomical identification/masking. QSF can provide a detailed description about how and where custom-made insole redistributes the underfoot pressure respect to the FI. Thus, its usefulness extends to the design step, helping to guide the modifications necessary to achieve optimal offloading insole performances. [ABSTRACT FROM AUTHOR]

Aim: Peripheral artery disease (PAD) is one of the most common cardiovascular (CV) complications in patients with type 2 diabetes (T2D). Low dose rivaroxaban (2.5 mg twice daily) combined with aspirin ("dual pathway inhibition", DPI) reduces major adverse CV (MACE) and limb (MALE) events in patients with PAD, independently of the presence of T2D. However, the implementation of DPI in patients with a "diabetic foot syndrome" has not been widely evaluated. The aims of this survey were to ascertain the use of DPI and the possible outcomes in a population of T2D with PAD in a real word setting. Method: Italian multicenter survey from 24 outpatient clinics was carried out by using clinical questionnaires. Baseline clinical characteristics and changes in different outcomes were evaluated. Results / Discussion: We recruited 347 patients with T2D and PAD, in six months. Almost all the participants exhibited multiple CV risk factors, 68% of the patients exhibited foot ulceration, 49% had undergone revascularization, and 31% had a previous minor amputation. All the patients were treated with DPI. After 6 months follow-up, clinical changes in different outcomes were observed, such as reduction of pain at rest (63%), improvement in claudication (83%) and transcutaneous oximetry (71%), as well as a reduction >50% (79%) or healing (57%) of foot ulcerations. None had clinically relevant bleeding. Conclusion: The results of this survey suggest that, in patients with T2D and PAD, a population with very high risk of limb amputation, DPI should be offered as an important therapeutic strategy to improve prognosis. [ABSTRACT FROM AUTHOR]