OBJECTIVE -To study the effect of systemic hyperbaric oxygenation (HBO) therapy on the healing course of nonischemic chronic diabetic foot ulcers. RESEARCH DESIGN AND METHODS-From 1999 to 2000, 28 patients (average age 60.2 Ϯ 9.7 years, diabetes duration 18.2 Ϯ 6.6 years), of whom 87% had type 2 diabetes, demonstrating chronic Wagner grades I-III foot ulcers without clinical symptoms of arteriopathy, were studied. They were randomized to undergo HBO because their ulcers did not improve over 3 months of full standard treatment. All the patients demonstrated signs of neuropathy. HBO was applied twice a day, 5 days a week for 2 weeks; each session lasted 90 min at 2.5 ATA (absolute temperature air). The main parameter studied was the size of the foot ulcer measured on tracing graphs with a computer. It was evaluated before HBO and at day 15 and 30 after the baseline.RESULTS -HBO was well tolerated in all but one patient (barotraumatic otitis). The transcutaneous oxygen pressure (TcPO 2 ) measured on the dorsum of the feet of the patients was 45.6 Ϯ 18.1 mmHg (room air). During HBO, the TcPO 2 measured around the ulcer increased significantly from 21.9 Ϯ 12.1 to 454.2 Ϯ 128.1 mmHg (P Ͻ 0.001). At day 15 (i.e., after completion of HBO), the size of ulcers decreased significantly in the HBO group (41.8 Ϯ 25.5 vs. 21.7 Ϯ 16.9% in the control group [P ϭ 0.037]). Such a difference could no longer be observed at day 30 (48.1 Ϯ 30.3 vs. 41.7 Ϯ 27.3%). Four weeks later, complete healing was observed in two patients having undergone HBO and none in the control group.CONCLUSIONS -In addition to standard multidisciplinary management, HBO doubles the mean healing rate of nonischemic chronic foot ulcers in selected diabetic patients. The time dependence of the effect of HBO warrants further investigations. Diabetes Care 26:2378 -2382, 2003L ower-extremity ulcers are responsible for 20% of the hospital admissions of diabetic patients; the incidence of amputation is 6 per 1,000(1). Foot ulcer represents one of the major causes of lower-extremity injuries in the 220 million people suffering from diabetes worldwide, 2.5% of whom will develop a foot ulcer each year (2). Moreover, duration of hospitalization attests to the high morbidity of this condition (3), which has been shown to require as long as ϳ26 weeks for full recovery (4) despite a multidisciplinary approach (associating glycemia control, daily local care, foot offloading antibiotic therapy, and surgical revascularization).The diabetic foot is characterized by sensory, motor, and autonomic neuropathies leading to alteration of pressure distribution, foot deformities, and ulcerations. Metabolic control and infection treatments are of primary importance to control the evolution of the diabetic foot. Hyperbaric oxygenation (HBO) has previously been proposed as an adjunctive treatment for the diabetic foot because it improves in vitro the complex processes underlying healing (5-7). It has also been reported that HBO reduces the incidence of major amputation in diabetic patient...

BackgroundAs a result of the increased consumption of sugar-rich and fatty-products, and the increase in preference for such products, metabolic disorders are becoming more common at a younger age. Fructose is particularly used in prepared foods and carbonated beverages. We investigated the impact of regular consumption of fructose, in combination or not with fatty food, on the onset of metabolic syndrome and type 2 diabetes (T2D). We evaluated the metabolic, oxidative, and functional effects on the liver and blood vessels, both related to diabetes complications.MethodsHigh-fat diet (HFD), high-fructose beverages (HF) or both (HFHF) were compared to rats fed with normal diet (ND) for 8 months to induce T2D and its metabolic, oxidative, and functional complications. Metabolic control was determined by measuring body weight, fasting blood glucose, C-peptide, HOMA2-IR, leptin, and cholesterol; oxidative parameters were studied by lipid peroxidation and total antioxidant capacity in plasma and the use of ROS labelling on tissue. Histological analysis was performed on the liver and endothelial function was performed in main mesenteric artery using organ-baths.ResultsAfter 2 months, HFHF and HFD increased body weight, leptin, HOMA2-IR associated to steatosis, oxidative stress in plasma and tissues, whereas HF had only a transient increase of leptin and c-peptide. Only HFHF induced fasting hyperglycaemia after 6 months and persistent hyperinsulinaemia and fasting hyperglycaemia with complicated steatosis (inflammation and fibrosis) after 8 months. HFHF and HFD induced endothelial dysfunction at 8 months of diet.ConclusionsSix months, high fat and high carbohydrate induced T2D with widespread tissues effects. We demonstrated the role of oxidative stress in pathogenesis as well as in complications (hepatic and vascular), reinforcing interest in the use of antioxidants in the prevention and treatment of metabolic diseases, including T2D.

Graphical Abstract Highlights d T lymphocytes release exosomes containing specific microRNAs d T lymphocyte exosomes can transfer microRNAs to rodent and human pancreatic b cells d The transferred microRNAs trigger chemokine expression and apoptosis of b cells d Blockade of microRNAs transferred in b cells decreases diabetes incidence in NOD mice In Brief Guay et al. show that T cells release exosomes containing specific microRNAs that trigger chemokine expression and apoptosis in recipient pancreatic b cells in type 1 diabetes. Inactivation of miR-142-3p/-5p and miR-155 in b cells results in higher insulin levels, lower insulitis scores, and reduced inflammation and protects NOD mice from diabetes development.

Aims:To compare the efficacy and safety of once-daily prandial lixisenatide with placebo in type 2 diabetes mellitus (T2DM) insufficiently controlled by pioglitazone ± metformin. Methods:This randomized, double-blind study included a 24-week main treatment period and a ≥52-week variable extension period.Patients were randomized 2 : 1 to receive lixisenatide 20 μg once daily or placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) at week 24. Results:In total, 484 patients were randomized: 323 to lixisenatide; 161 to placebo. After 24 weeks, lixisenatide once daily significantly improved HbA1c (−0.56% vs. placebo; p < 0.0001) and increased the proportion of patients achieving HbA1c <7% compared with placebo (52.3% vs. 26.4%, respectively; p < 0.0001) and significantly improved fasting plasma glucose (−0.84 mmol/l vs. placebo; p < 0.0001). There was a small decrease in body weight with lixisenatide once daily and a small increase with placebo, with no statistically significant difference between the two groups. Overall, lixisenatide once daily was well tolerated, with a similar proportion of treatment-emergent adverse events (TEAEs) and serious TEAEs between groups (lixisenatide: 72.4% and 2.5%; placebo: 72.7% and 1.9%). Symptomatic hypoglycaemia rates were also relatively low in both groups (lixisenatide 3.4% and placebo 1.2%), with no severe episodes. Lixisenatide continued to be efficacious and well tolerated during the variable extension period. Conclusions:Lixisenatide once daily significantly improved glycaemic control with a low risk of hypoglycaemia, and was well tolerated over 24 weeks and during the long-term, double-blind extension period in patients with T2DM insufficiently controlled on pioglitazone ± metformin.

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