Search

Recent evidence suggests that omega-3 polyunsaturated fatty acids [n-3 PUFAs: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)], improve insulin sensitivity in humans. In a double-blind, placebo-controlled, randomized, crossover study, we investigated the effects of EPA/DHA on paraoxonase-1 activity as well as fasting and postprandial levels of circulating adiponectin and leptin in 34 subjects with type 2 diabetes mellitus who received daily for 6 weeks either 2 g purified EPA/DHA or olive oil (placebo), separated by a 6 weeks washout. At the end of each treatment, measurements were performed in fasting state and 2, 4, and 6 h following a standardized high-fat meal (600 kcal). No significant differences in fasting and postprandial circulating adiponectin, leptin, and paraoxonase-1 activity were seen between n-3 PUFAs and placebo. Our data do not support an insulin sensitizing effect of n-3 PUFAs by means of influencing circulating adipocytokines in this population. Clinical Trial Register Number: NCT00328536., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Recent evidence indicates that heat-enhanced food advanced glycation end products (AGEs) adversely affect vascular function. The aim of this study was to examine the acute effects of an oral load of heat-treated, AGE-modified β-lactoglobulins (AGE-BLG) compared with heat-treated, nonglycated BLG (C-BLG) on vascular function in patients with type 2 diabetes mellitus (T2DM)., Research Design and Methods: In a double-blind, controlled, randomized, crossover study, 19 patients with T2DM received, on two different occasions, beverages containing either AGE-BLG or C-BLG. We measured macrovascular [brachial ultrasound of flow-mediated dilatation (FMD)] and microvascular (laser-Doppler measurements of reactive hyperemia in the hand) functions at baseline (T0), 90 (T90), and 180 (T180) min., Results: Following the AGE-BLG, FMD decreased at T90 by 80% from baseline and remained decreased by 42% at T180 (P < 0.05 vs. baseline, P < 0.05 vs. C-BLG at T90). By comparison, following C-BLG, FMD decreased by 27% at T90 and 51% at T180 (P < 0.05 vs. baseline at T180). A significant decrease in nitrite (T180) and nitrate (T90 and T180), as well as a significant increase in N(ε)-carboxymethyllisine, accompanied intake of AGE-BLG. There was no change in microvascular function caused by either beverage., Conclusions: In patients with T2DM, acute oral administration of a single AGE-modified protein class significantly though transiently impaired macrovascular function in concert with decreased nitric oxide bioavailability. These AGE-related changes were independent of heat treatment.

Background and Aim: Despite improvements in surgical revascularisation, limitations like anatomical factors or atherosclerosis limit the success of revascularisation in diabetic patients with critical limb ischaemia. Stem cells were shown to improve microcirculation in published studies. The aim of this study was to evaluate safety, feasibility and efficacy of transplantation of bone marrow derived cellular products regarding improvement in microcirculation and lowering of amputation rate., Methods: Bone marrow mononuclear cells (BMCs) in comparison with expanded bone marrow cells enriched in CD90+ cells ('tissue repair cells', TRCs) were used in the treatment of diabetic ulcers to induce revascularisation. Diabetic foot patients with critical limb ischaemia without option for surgical or interventional revascularisation were eligible. Parameters examined were ABI, TcPO(2) , reactive hyperaemia and angiographic imaging before and after therapy., Results: Of 30 patients included in this trial, 24 were randomised to receive either BMCs or TRCs. The high number of drop-outs in the control group (4 of 6) led to exclusion from evaluation. A total of 22 patients entered treatment; one patient in the TRC group and two in the BMC group did not show wound healing during follow up, one patient in each treatment group died before reaching the end of the study; one after having achieved wound healing (BMC group), the other one without having achieved wound healing (TRC group). Thus, 18 patients showed wound healing after 45 weeks. The total number of applicated cells was 3.8 times lower in the TRC group, but TRC patients received significantly higher amounts of CD90+ cells. Improvement in microvascularisation was detected in some, but not all patients by angiography, TcPO(2) improved significantly compared with baseline in both therapy groups., Conclusion: The transplantation of BMCs as well as TRCs proved to be safe and feasible. Improvements of microcirculation and complete wound healing were observed in the transplant groups., (© 2012 Blackwell Publishing Ltd.)

Background: Recent evidence supports the protective effects of n-3 (omega-3) fatty acids (n-3 FAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on vascular function., Objective: We investigated the effects of EPA and DHA on postprandial vascular function in subjects with type 2 diabetes mellitus., Design: In a double-blind, placebo-controlled, randomized, crossover manner, 34 subjects with type 2 diabetes mellitus received daily either 2 g purified EPA/DHA (termed n-3 FAs) or olive oil (placebo) for 6 wk. At the end of this period, we measured macrovascular (brachial ultrasound of flow-mediated dilatation; FMD) and microvascular [laser-Doppler measurements of reactive hyperemia (RH) of the hand] function at fasting and 2, 4, and 6 h after a high-fat meal (600 kcal, 21 g protein, 41 g carbohydrates, 40 g fat)., Results: Fasting vascular function remained unchanged after n-3 FAs and placebo. Postprandial FMD decreased from fasting after placebo, with a maximum decrease (38%) at 4 h-an effect that was significantly reduced (P = 0.03 for time x treatment interaction) by n-3 FA supplementation (maximum decrease in FMD was at 4 h: 13%). RH remained unchanged after placebo, whereas it improved significantly (P = 0.04 for time x treatment interaction) after n-3 FA supplementation (maximum increase was at 2 h: 27%)., Conclusions: In subjects with type 2 diabetes mellitus, 6 wk of supplementation with n-3 FAs reduced the postprandial decrease in macrovascular function relative to placebo. Moreover, n-3 FA supplementation improved postprandial microvascular function. These observations suggest a protective vascular effect of n-3 FAs.

Leptin modulates satiety and increases in obesity and type 2 diabetes mellitus in parallel with leptin resistance. Postprandial leptin regulation has been previously postulated to depend on meal composition, but data are controversial. The hypothesis of our study was that in people with type 2 diabetes mellitus, a postprandial leptin regulation exists that can be regulated not only by meal composition but also by the cooking method. In 20 inpatients with type 2 diabetes (mean age: 55.9 years), the acute effects of 2 meals, a high-heat-processed meal HHPM or a low-heat-processed meal LHPM, on leptin levels were studied on 2 different days in a randomized, crossover design. Both test meals had similar ingredients and differed only in the cooking method used. Parameters were measured after an overnight fast and at 2, 4, and 6 h postprandially. The HHPM induced a marked decrease in leptin levels, from 8 717+/-2 079 pg/ml at baseline to 6 788+/-1 598 pg/ml at 2 h postprandially (-1 929 pg/ml, -22%*), an effect significantly reduced by the LHPM, where values were 8 563+/-1 900 pg/ml at baseline and 7 425+/-1 591 pg/ml at 2 h postprandially (-1 138 pg/ml, -13%* (double dagger)) (*p<0.05 vs. baseline, (double dagger)p<0.05 vs. HHPM). Parameters of oxidative stress and blood AGEs increased only following the HHPM, while postprandial glucose, triglycerides, and insulin excursions were similar between meals. Postprandial leptin decreases following a HHPM meal in people with T2DM, an effect reduced by the cooking method.

Advanced glycation endproducts (AGEs) and oxidative stress (OS) contribute to the development and progression of diabetic complications. We have reported that dietary AGEs and OS induce acute endothelial dysfunction in vivo, but little is known about their effects on adipokines. Twenty inpatients with type 2 diabetes mellitus (mean age: 55.9; range: 32-71 years), received a standard diabetes diet for 6 days. On days 4 and 6, the acute effects of a high-AGE (HAGE) or a low-AGE (LAGE) meal (15.100 vs. 2.750 kU AGE) were studied in a randomized, cross-over, investigator-blinded design. Measurements were performed after an overnight fast, at baseline (B) and at 2, 4, and 6 h after the HAGE or LAGE meals. Both meals had the same ingredients and differed only by the cooking method. Two h following HAGE, a significant decrease from baseline occurred in adiponectin (-10%*double dagger vs. +0%) and leptin (-22%*double dagger vs. -13%*), and a significant increase occurred in vascular cell adhesion molecule 1 (+19%*double dagger vs. -5%) and thiobarbituric acid reactive substances (+23%*double dagger vs. +6%). These changes did not occur, or occurred to a lesser extent, following LAGE. At 4 h following HAGE, an increase in methylglyoxal (+20%double dagger vs. -5%) and E-selectin (+54%*double dagger vs. -3%) occurred. Urinary AGEs increased only after HAGE (+51%*double dagger vs. -2%; values presented as HAGE vs. LAGE; *P < 0.05 vs. baseline, double daggerP < 0.05 vs. LAGE). The postprandial excursions in glucose, insulin, and triglycerides were similar between both meals. A meal rich in AGEs induces acute endothelial and adipocyte dysfunction. These effects were prevented by changing the cooking method.

Background: An advanced glycation endproducts (AGEs)-rich diet induces significant increases in inflammatory and endothelial dysfunction markers in type 2 diabetes mellitus (T2DM)., Objective: The aim was to investigate the acute effects of dietary AGEs on vascular function in T2DM patients., Design: Twenty inpatients with T2DM [x (+/-SEM) age: 55.4 +/- 2.2 y; glycated hemoglobin: 8.8 +/- 0.5%] were investigated. In a randomized crossover design, the effects of a low-AGE (LAGE) and high-AGE (HAGE) meal on macrovascular [by flow-mediated dilatation (FMD)] and microvascular (by Laser-Doppler flowmetry) function, serum markers of endothelial dysfunction (E-selectin, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1), oxidative stress, and serum AGE were assessed. The meals had identical ingredients but different AGE amounts (15.100 compared with 2.750 kU AGE for the HAGE and LAGE meals, respectively), which were obtained by varying the cooking temperature and time. The measurements were performed at baseline and 2, 4, and 6 h after each meal., Results: After the HAGE meal, FMD decreased by 36.2%, from 5.77 +/- 0.65% (baseline) to 3.93 +/- 0.48 (2 h), 3.70 +/- 0.42 (4 h), and 4.42 +/- 0.54% (6 h) (P<0.01 for all compared with baseline). After the LAGE meal, FMD decreased by 20.9%, from 6.04 +/- 0.68% (baseline) to 4.75 +/- 0.48% (2 h), 4.69 +/- 0.51% (4 h), and 5.62 +/- 0.63% (6 h), respectively (P<0.01 for all compared with baseline; P<0.001 for all compared with the HAGE meal). This impairment of macrovascular function after the HAGE meal was paralleled by an impairment of microvascular function (-67.2%) and increased concentrations of serum AGE and markers of endothelial dysfunction and oxidative stress., Conclusions: In patients with T2DM, a HAGE meal induces a more pronounced acute impairment of vascular function than does an otherwise identical LAGE meal. Therefore, chemical modifications of food by means of cooking play a major role in influencing the extent of postprandial vascular dysfunction.

Objective: Diabetes is characterized by marked postprandial endothelial dysfunction induced by hyperglycemia, hypertriglyceridemia, advanced glycation end products (AGEs), and dicarbonyls (e.g., methylglyoxal [MG]). In vitro hyperglycemia-induced MG formation and endothelial dysfunction could be blocked by benfotiamine, but in vivo effects of benfotiamine on postprandial endothelial dysfunction and MG synthesis have not been investigated in humans until now., Research Design and Methods: Thirteen people with type 2 diabetes were given a heat-processed test meal with a high AGE content (HAGE; 15.100 AGE kU, 580 kcal, 54 g protein, 17 g lipids, and 48 g carbohydrates) before and after a 3-day therapy with benfotiamine (1,050 mg/day). Macrovascular flow-mediated dilatation (FMD) and microvascular reactive hyperemia, along with serum markers of endothelial disfunction (E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1), oxidative stress, AGE, and MG were measured during both test meal days after an overnight fast and then at 2, 4, and 6 h postprandially., Results: The HAGE induced a maximum reactive hyperemia decrease of -60.0% after 2 h and a maximum FMD impairment of -35.1% after 4 h, without affecting endothelium-independent vasodilatation. The effects of HAGE on both FMD and reactive hyperemia were completely prevented by benfotiamine. Serum markers of endothelial dysfunction and oxidative stress, as well as AGE, increased after HAGE. These effects were significantly reduced by benfotiamine., Conclusions: Our study confirms micro- and macrovascular endothelial dysfunction accompanied by increased oxidative stress following a real-life, heat-processed, AGE-rich meal in individuals with type 2 diabetes and suggests benfotiamine as a potential treatment.