Resveratrol as Add-on Therapy in Subjects With Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial

Item does not contain fulltextOBJECTIVE: To determine whether resveratrol supplementation can improve insulin sensitivity and promote overall metabolic health on top of standard diabetes care. RESEARCH DESIGN AND METHODS: Seventeen subjects with well-controlled type 2 diabetes (T2D) were treated with placebo and 150 mg/day resveratrol (resVida) in a randomized double-blind crossover study for 30 days. The main outcome measure was insulin sensitivity by the hyperinsulinemic-euglycemic clamp technique. RESULTS: Hepatic and peripheral insulin sensitivity were not affected by resveratrol treatment. Intrahepatic lipid content also remained unaffected by resveratrol; however, the change in intrahepatic lipid content correlated negatively with plasma resveratrol levels (R = -0.68, P = 0.03). Intramyocellular lipid content increased in type 2 muscle fibers (P = 0.03), and systolic blood pressure tended to decrease (P = 0.09) upon resveratrol treatment. In addition, resveratrol significantly improved ex vivo mitochondrial function (state 3 and state U respiration upon malate with octanoyl-carnitine, P < 0.005). Intriguingly, a correlation was found between plasma levels of a metabolite of resveratrol (dihydroresveratrol) and the metformin dose used by the patients (R = 0.66, P = 0.005), suggesting an interaction between metformin and resveratrol. It could be speculated that the lack of a resveratrol-induced insulin-sensitizing effect is caused by this interaction. CONCLUSIONS: Resveratrol supplementation does not improve hepatic or peripheral insulin sensitivity. Our results question the generalized value of resveratrol as an add-on therapy in the treatment of T2D and emphasize the need to perform studies in drug-naive patients with T2D or subjects with prediabetes.1 december 201

Cardiac lipid content is unresponsive to a physical activity training intervention in type 2 diabetic patients, despite improved ejection fraction

Background: Increased cardiac lipid content has been associated with diabetic cardiomyopathy. We recently showed that cardiac lipid content is reduced after 12 weeks of physical activity training in healthy overweight subjects. The beneficial effect of exercise training on cardiovascular risk is well established and the decrease in cardiac lipid content with exercise training in healthy overweight subjects was accompanied by improved ejection fraction. It is yet unclear whether diabetic patients respond similarly to physical activity training and whether a lowered lipid content in the heart is necessary for improvements in cardiac function. Here, we investigated whether exercise training is able to lower cardiac lipid content and improve cardiac function in type 2 diabetic patients. Methods: Eleven overweight-to-obese male patients with type 2 diabetes mellitus (age: 58.4 +/- 0.9 years, BMI: 29.9 +/- 0.01 kg/m(2)) followed a 12-week training program (combination endurance/strength training, three sessions/week). Before and after training, maximal whole body oxygen uptake (VO2max) and insulin sensitivity (by hyperinsulinemic, euglycemic clamp) was determined. Systolic function was determined under resting conditions by CINE-MRI and cardiac lipid content in the septum of the heart by Proton Magnetic Resonance Spectroscopy. Results: VO2max increased (from 27.1 +/- 1.5 to 30.1 +/- 1.6 ml/min/kg, p = 0.001) and insulin sensitivity improved upon training (insulin stimulated glucose disposal (delta Rd of glucose) improved from 5.8 +/- 1.9 to 10.3 +/- 2.0 mu mol/kg/min, p = 0.02. Left-ventricular ejection fraction improved after training (from 50.5 +/- 2.0 to 55.6 +/- 1.5%, p = 0.01) as well as cardiac index and cardiac output. Unexpectedly, cardiac lipid content in the septum remained unchanged (from 0.80 +/- 0.22% to 0.95 +/- 0.21%, p = 0.15). Conclusions: Twelve weeks of progressive endurance/strength training was effective in improving VO(2)max, insulin sensitivity and cardiac function in patients with type 2 diabetes mellitus. However, cardiac lipid content remained unchanged. These data suggest that a decrease in cardiac lipid content in type 2 diabetic patients is not a prerequisite for improvements in cardiac function.Cardiovascular Aspects of Radiolog

Evidence for a direct effect of the NAD+ precursor acipimox on muscle mitochondrial function in humans.

Recent preclinical studies showed the potential of nicotinamide adenine dinucleotide (NAD(+)) precursors to increase oxidative phosphorylation and improve metabolic health, but human data are lacking. We hypothesize that the nicotinic acid derivative acipimox, an NAD(+) precursor, would directly affect mitochondrial function independent of reductions in nonesterified fatty acid (NEFA) concentrations. In a multicenter randomized crossover trial, 21 patients with type 2 diabetes (age 57.7 +/- 1.1 years, BMI 33.4 +/- 0.8 kg/m(2)) received either placebo or acipimox 250 mg three times daily dosage for 2 weeks. Acipimox treatment increased plasma NEFA levels (759 +/- 44 vs. 1,135 +/- 97 mumol/L for placebo vs. acipimox, P < 0.01) owing to a previously described rebound effect. As a result, skeletal muscle lipid content increased and insulin sensitivity decreased. Despite the elevated plasma NEFA levels, ex vivo mitochondrial respiration in skeletal muscle increased. Subsequently, we showed that acipimox treatment resulted in a robust elevation in expression of nuclear-encoded mitochondrial gene sets and a mitonuclear protein imbalance, which may indicate activation of the mitochondrial unfolded protein response. Further studies in C2C12 myotubes confirmed a direct effect of acipimox on NAD(+) levels, mitonuclear protein imbalance, and mitochondrial oxidative capacity. To the best of our knowledge, this study is the first to demonstrate that NAD(+) boosters can also directly affect skeletal muscle mitochondrial function in humans

Cardiac metabolic imaging: current imaging modalities and future perspectives

Cardiovascular Aspects of Radiolog

Imaging of osteomyelitis with FDG PET-MR

Osteomyelitis is an inflammatory process accompanied by bone destruction, and is caused by microorganism infection. The infection can be limited to a single portion of the bone or can involve several compartments such as marrow, cortex, periosteum and the surrounding soft tissue. Osteomyelitis can be (1) spread locally from a focal source of infection, (2) secondary to vascular insufficiency, or (3) caused by hematogenous spread of the microorganism from a different source. For osteomyelitis in the extremities, the most common pathogen is Staphylococcus aureus. In skull-base osteomyelitis (SBO) it is Pseudomonas aeruginosa (50–90% of cases) [1]. Osteomyelitis of the skull base most often occurs as a complication of otitis externa, and can be categorized within the first category of focal infections. However, it is perceived as a special case due to the severe complications that can arise, given the location. The bacterial infection causes bone erosions, and uses fascial planes and venous sinuses for distant tissue invasion. It then can progress and spread to the surrounding osseous and soft tissues via the skull base

Imaging of osteomyelitis with FDG PET-MR

Osteomyelitis is an inflammatory process accompanied by bone destruction, and is caused by microorganism infection. The infection can be limited to a single portion of the bone or can involve several compartments such as marrow, cortex, periosteum and the surrounding soft tissue. Osteomyelitis can be (1) spread locally from a focal source of infection, (2) secondary to vascular insufficiency, or (3) caused by hematogenous spread of the microorganism from a different source. For osteomyelitis in the extremities, the most common pathogen is Staphylococcus aureus. In skull-base osteomyelitis (SBO) it is Pseudomonas aeruginosa (50–90% of cases) [1]. Osteomyelitis of the skull base most often occurs as a complication of otitis externa, and can be categorized within the first category of focal infections. However, it is perceived as a special case due to the severe complications that can arise, given the location. The bacterial infection causes bone erosions, and uses fascial planes and venous sinuses for distant tissue invasion. It then can progress and spread to the surrounding osseous and soft tissues via the skull base

Pericardial fat and its influence on cardiac diastolic function

Background Pericardial fat (PF) has been suggested to directly act on cardiomyocytes, leading to diastolic dysfunction. The aim of this study was to investigate whether a higher PF volume is associated with a lower diastolic function in healthy subjects. Methods 254 adults (40-70 years, BMI 18-35 kg/m(2), normal left ventricular ejection fraction), with (a)typical chest pain (otherwise healthy) from the cardiology outpatient clinic were retrospectively included in this study. All patients underwent a coronary computed tomographic angiography for the measurement of pericardial fat volume, as well as a transthoracic echocardiography for the assessment of diastolic function parameters. To assess the independent association of PF and diastolic function parameters, multivariable linear regression analysis was performed. To maximize differences in PF volume, the group was divided in low (lowest quartile of both sexes) and high (highest quartile of both sexes) PF volume. Multivariable binary logistic analysis was used to study the associations within the groups between PF and diastolic function, adjusted for age, BMI, and sex. Results Significant associations for all four diastolic parameters with the PF volume were found after adjusting for BMI, age, and sex. In addition, subjects with high pericardial fat had a reduced left atrial volume index (p = 0.02), lower E/e (p &lt;0.01) and E/A (p = 0.01), reduced e ' lateral (p &lt;0.01), reduced e ' septal p = 0.03), compared to subjects with low pericardial fat. Conclusion These findings confirm that pericardial fat volume, even in healthy subjects with normal cardiac function, is associated with diastolic function. Our results suggest that the mechanical effects of PF may limit the distensibility of the heart and thereby directly contribute to diastolic dysfunction. Trial registrationNCT01671930</p

Predicted relationships from stepwise linear regression analyses; on the x-axis you can find the values predicted by the models by the different parameters in the model, on the y-axis you can find the actual value as measured in the study.

<p>The results were plotted for the following models: (<b>A</b>) Model 1, relationship between actual metabolic flexibility (ΔRER) and the metabolic flexibility predicted by Model 1 (by plasma NEFA and WGD during insulin stimulation), (<b>B</b>) Model 2; relationship between actual basal respiratory exchange ratio (basal RER) and the basal RER predicted by Model 2 (by plasma PCr-recovery half-time, BMI and age), (<b>C</b>) Model 3; relationship between insulin-stimulated respiratory exchange ratio (ins. stim. RER) and the insulin-stimulated RER predicted by Model 3 (by WGD during insulin stimulation), (<b>D</b>) Model 4; relationship between actual PCr-recovery half-time and PCr-recovery half-time predicted by Model 4 (by basal RER and VO2max).</p