Objective: To investigate the role of the Pro12Ala peroxisome proliferator-activated receptor (PPAR) g-2 polymorphism in the susceptibility to the insulin resistance syndrome and its metabolic complications in a population-based nationwide multicenter study in Spain. Design: 464 unrelated adults (45.3% men and 54.7% women) aged between 35 and 64 years were randomly chosen from a nationwide population-based survey of obesity and related conditions including insulin resistance and cardiovascular risk factors. Methods: Anthropometric determinations included: body mass index (BMI), waist-to-hip ratio, sagittal abdominal diameter; biochemical determinations included: fasting plasma glucose concentration and concentration 2 h after an oral glucose tolerance test (OGTT), total cholesterol, high and low density lipoprotein-cholesterol, triglycerides, leptin and insulin. Systolic and diastolic blood pressure were also measured. Genotyping of the PPARg-2 Pro12Ala polymorphism was determined by polymerase chain reaction and single strand conformation polymorphism analysis. Results: The Ala12 allele frequency was higher in obese men than in lean men (0.15 vs 0.08, P ¼ 0:03). Men carriers of the Ala12 allele had a higher BMI than non-carriers (38.9% vs 21.3%; adjusted odds ratio 2.36, 95% confidence interval 1.10 -5.05, P ¼ 0:03). However, despite higher BMI obese men carriers of the Ala12 allele had lower sagittal abdominal diameter than Pro12 homozygotes ð24:1^3:2 vs 26:3^2:5 cm; P ¼ 0:01Þ: The Ala12 allele was associated with lower total triglycerides levels in the overall population and it was also associated with lower fasting insulin levels and a higher insulin sensitivity by homeostasis model assessment (HOMA) in women. Conclusions: Our results suggest that the Pro12Ala polymorphism of the PPARg-2 gene promotes peripheral deposition of adipose tissue and increased insulin sensitivity for a given BMI. The results in women might be due to their different adipose tissue distribution.
We present a series of ten patients with non-reconstructable peripheral vascular disease (PVD), secondary to arteriosclerosis (AS) and/or diabetes mellitus (DM), treated with local injection of non-expanded autologous, adipose-derived stromal vascular fraction (SVF) cells for the purposes of enhancing neovascularization and chronic wound healing. Adipose tissue was surgically harvested and processed to yield the heterogeneous SVF cells for immediate point-of-care injection. The gastrocnemius muscles and ulcers or wounds where present were locally injected with the resulting SVF. Response to treatment was evaluated both clinically based on pain-free ambulation, wound healing capacity over time and ankle/brachial index (ABI) measurements, and by imaging using MRI-based angiography. All patients exhibited clinical improvement (reduction in rest pain and claudication and improvements in ABI), with imaging signs of neovascularization in the majority (5 of 6) of patients in whom the evaluation was feasible. Similarly, 5 of 6 chronic wounds healed without further surgical intervention. This series highlights the utility of non-expanded adipose-derived heterogeneous SVF cell population processed at the point-of-care, to treat patients with end-stage PVD as an alternative to palliation or amputation.
Adipose-derived mesenchymal stem cells (ASCs) have been shown to produce vascular endothelial growth factor (VEGF) and can increase perfusion in patients with critical limb ischemia. We will show that this concept can be applied to augment blood flow in zones of flap ischemia. We presented a case study of a 26-year-old man with a complex hand injury covered by a reverse radial perforator fasciocutaneous flap, which developed ischemic necrosis and was treated by debridement, transplantation of ASCs to enhance vascular support, and saline dressings. ASCs are found in the stromal vascular fraction (SVF), a heterogeneous collection of cells, including pericytes and endothelial cells, that is prepared from lipoaspirate using collagenase digestion followed by centrifugation. These were injected into the flap, the palmar tissues both subjacent and peripheral to the flap, and the skin-grafted donor site. The case was documented with photography, measurements at hand therapy, and follow-up angiography MRI. At 72 hours, new vessels appeared diffusely; at 1 week, the remaining tissues of flap were bleeding. The wound, 11 cm × 4 cm, contracted spontaneously and was healed at 21 days. The skin graft over the donor site demonstrated unusual suppleness and elasticity. 3D CT angiography disclosed a new layer of vascularity in the superficial tissues of the palm when compared with the normal side. The patient regained full composite flexion, pinch, opposition, and wrist extension. Application of ASCs into the supporting tissues surrounding the ischemic flap, and into the flap itself, constituted a form of in-situ revascularization (ISR) that was subjectively and objectively effective for this patient.Level of Evidence: 5
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