Experimental determination of oxidation rate, phosphorylation rate and ADP/ATP concentrations.

<p>Our experimental set-up was composed of an oxygraph, a spectrophotometer and a luminometer. An optic fiber, connected to the spectrophotometer, was inserted in the oxygraphic vessel (picture on the top-left hand corner). Mitochondrial oxidation rate was determined using the Clark electrode of the oxygraph. Phosphorylation rate was assessed, with the help of the optic fiber, by the continuous monitoring of NADPH production in the oxygraphic vessel. Samplings were performed at the onset and the end of the recording to assess both ADP and ATP concentrations using a bioluminescence-based assay with the help of a luminometer (picture on the top-right hand corner). For clarity, all parameters that were measured during each experiment are highlighted by colored circles. HK: hexokinase, G6PDH: glucose 6 phosphate dehydrogenase, G6P: glucose 6 phosphate, OM: outer membrane, IM: inner membrane.</p

Changes in the P/O ratio as a function of ADP concentration in liver and muscle mitochondria.

<p>P/O ratio was determined by calculating the phosphorylation to oxidation rates ratio. Data for liver (n = 4) and muscle (n = 5) are presented as mean ± SD. Differences were tested using an unpaired bilateral student's t-test. ** p<0.01 between liver and muscle.</p

Typical recording of oxidation rate, phosphorylation rate and ADP/ATP concentrations.

<p>Oxidation and phosphorylation rates were recorded simultaneously in liver and muscle mitochondria oxidizing glutamate+malate+succinate as substrates. Mitochondrial protein concentration in the oxygraphic vessel was 25 µg.ml⁻¹. Steady states of oxygen consumption and phosphorylation rates were obtained using the coupled enzymatic system composed of Glucose (5 mM) - Hexokinase (2.5 U.ml⁻¹, Sigma-Aldrich, H4502) - Glucose-6-phosphotate dehydrogenase (2.5 U.ml⁻¹, Sigma-Aldrich, G6378) - NADP⁺ (1.6 mM). Dashed arrows correspond to the sampling of measurement medium taken from the oxygraphic vessel during each recording for determination of ADP and ATP concentrations.</p

Dependence of oxidation and phosphorylation rates on ADP concentration in liver and muscle mitochondria.

<p>Oxidation and phosphorylation rates were recorded simultaneously in liver (n = 4) and muscle (n = 5) mitochondria oxidizing glutamate+malate+succinate as substrates. True steady state of oxidation and phosphorylation rates were obtained using coupled enzymatic system composed of Glucose (5 mM) - Hexokinase (2.5 U.ml⁻¹, Sigma-Aldrich, H4502) - Glucose-6-phosphotate dehydrogenase (2.5 U.ml⁻¹, Sigma-Aldrich, G6378) - NADP⁺ (1.6 mM). Data presented in panels A and B correspond to absolute oxidation and phosphorylation rates, respectively. Maximal oxidation and phosphorylation rates obtained for muscle and liver mitochondria were 408.0±42.5 vs. 85.2±5.5 nmolO₂.min⁻¹.mg⁻¹ and 1672.8±134.1 vs. 361.3±33.41 nmolATP.min⁻¹.mg⁻¹, respectively. Panels C and D show normalized oxidation and phosphorylation rates, respectively. Data were fitted using the Michaelis-Menten equation presented in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0020709#s2" target="_blank">materials and methods</a> section. Data are presented as mean ± SD. Differences were tested using an unpaired bilateral student's t-test. ** p<0.01 between liver and muscle, # p<0.01 vs. KmVox.</p

Association between sarcopenia and diabetes: A systematic review and meta-analysis of observational studies

Purpose: Sarcopenia and diabetes are two common conditions in older people. Some recent literature has proposed that these two conditions can be associated. However, to date, no attempt has been made to collate this literature. Therefore, we aimed to summarize the prevalence of sarcopenia in diabetes (and vice versa) and the prevalence of sarcopenia in people with diabetes complications, through a systematic review and meta-analysis. Methods: Two authors searched major electronic databases from inception until March 2019 for case control/cross-sectional/longitudinal studies investigating sarcopenia and diabetes. The strength of the reciprocal associations between sarcopenia and diabetes was assessed through odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for potential confounders, where possible. Results: From 953 potential eligible articles, 20 were included in the systematic review, with 17 providing data for meta-analysis. Overall, 54,676 participants were included (mean age= 65.4 years). Diabetic participants had an increased prevalence of sarcopenia compared to controls (n=10; OR=1.635; 95%CI: 1.204-2.220; p=0.002; I2=67%), whilst, after adjusting for potential confounders, sarcopenia was associated with an increased odds of having diabetes (OR=2.067; 95%CI: 1.396-3.624; p<0.0001; I2=0%). In 1,868 diabetic participants with a complication, there was an increased prevalence of sarcopenia (OR=2.446; 95%CI: 1.839-3.254; p<0.0001; I2=0%), as compared with those with no complication. Very limited data existed regarding studies with a longitudinal design. Conclusions: Our study suggests a bi-directional association between diabetes and sarcopenia, particularly when diabetic complications are present

ROC curves of predictive score among derivative population (A) and validation population (B) and respective calibration plots (C and D).

<p>Vertical bars correspond to 95%.</p

Flow chart of patients included in derivative cohort based on screening for participation in randomized controlled study and in validation cohort.

<p>Flow chart of patients included in derivative cohort based on screening for participation in randomized controlled study and in validation cohort.</p

Two-year mortality and other outcomes.

<p>Two-year mortality and other outcomes.</p

Main baseline characteristics of participants in the trial.

<p>ECOG PS: Eastern Cooperative Oncology Group performance status.</p><p>Main baseline characteristics of participants in the trial.</p

Two-year mortality according to groups UC and UC+NI. N = 336.

<p>Comparisons were performed with Cox model adjusted on recruiting centres.</p