Purpose To cross-validate skeletal muscle oxidative capacity measured by 31P-MRS with in vitro measurements of oxidative capacityin mitochondria isolated from muscle biopsies of the same muscle group in 18 healthy adults. Materials and Methods Oxidative capacity in vivo was determined from PCr recovery kinetics following a 30s maximal isometric knee extension. State 3 respiration was measured in isolated mitochondria using high-resolution respirometry. A second cohort of 10 individuals underwent two 31P-MRS testing sessions to assess the test-retest reproducibility of the method. Results Overall, the in vivo and in vitro methods were well-correlated (r = 0.66 –0.72) and showed good agreement by Bland Altman plots. Excellent reproducibility was observed for the PCr recovery rate constant (CV = 4.6%, ICC = 0.85) and calculated oxidative capacity (CV = 3.4%, ICC = 0.83). Conclusion These results indicate that 31P-MRS corresponds well with gold-standard in vitro measurements and is highly reproducible.

Aims Prior studies have reported that elevated concentrations of several plasma amino acids (AA) in plasma, particularly branched chain (BCAA) and aromatic AA predict the onset of type 2 diabetes. We sought to test the hypothesis that circulating BCAA, aromatic AA and related AA metabolites decline in response to the use of insulin sensitizing agents in overweight/obese adults with impaired fasting glucose or untreated diabetes. Methods We performed a secondary analysis of a randomized, double-blind, placebo, controlled study conducted in twenty five overweight/obese (BMI~30 kg/m2) adults with impaired fasting glucose or untreated diabetes. Participants were randomized to three months of pioglitazone (45 mg per day) plus metformin (1000 mg twice per day, N = 12 participants) or placebo (N = 13). We measured insulin sensitivity by the euglycemic-hyperinsulinemic clamp and fasting concentrations of AA and AA metabolites using ultra-pressure liquid chromatography tandem mass spectrometry before and after the three-month intervention. Results Insulin sensitizer therapy that significantly enhanced insulin sensitivity reduced 9 out of 33 AA and AA metabolites measured compared to placebo treatment. Moreover, insulin sensitizer therapy significantly reduced three functionally clustered AA and metabolite pairs: i) phenylalanine/tyrosine, ii) citrulline/arginine, and iii) lysine/α-aminoadipic acid. Conclusions Reductions in plasma concentrations of several AA and AA metabolites in response to three months of insulin sensitizer therapy support the concept that reduced insulin sensitivity alters AA and AA metabolites.

The presence of hypothyroidism at the first assessment of thyroid function after RAI administration is a strong predictor for adverse GO outcome. This risk is highest in patients with preexisting GO. We suggest that in order to prevent clinical hypothyroidism and the associated risk for GO, the optimal time for first measurement of fT4 is before 6 weeks after RAI therapy.

PABLO ALONSO-COELLO, MD 3SUMIT BHAGRA, MBBS 4 OBJECTIVE -We sought to systematically ascertain the quality of randomized controlled trials (RCTs) in diabetes.RESEARCH DESIGN AND METHODS -We identified the 10 most recently published trials as of 31 October 2003 in each of six general medical, five diabetes, and five metabolism and nutrition journals and further enriched our sample with 10 additional RCTs from each of five journals that published the most eligible RCTs in a year. We explored the association between trial characteristics and reporting quality using univariate analyses and a preplanned multivariate regression model. RESULTS-After excluding redundant reports of included trials and one trial that measured outcomes on the health system and not on patients, we included 199 RCTs: 119 assessed physiological and other laboratory outcomes, 42 assessed patient-important outcomes (e.g., morbidity and mortality, quality of life), and 38 assessed surrogate outcomes (e.g., disease progression or regression, HbA 1c , cholesterol). Fifty-three percent were of low methodological quality, as were one-third (36 -40%) of trials reporting patient-important or surrogate outcomes and two-thirds (64%) of laboratory investigations. Independent predictors of low quality were nonprofit funding source (odds ratio 3.1 [95% CI 1. CONCLUSIONS -There is ample room for improving the quality of diabetes trials. To enhance the practice of evidence-based diabetes care, trialists need to pay closer attention to the rigorous implementation and reporting of important methodological safeguards against bias in randomized trials. Diabetes Care 29:1833-1838, 2006A key principle of evidence-based practice is that one should seek to apply the best available evidence from clinical research (1,2). The expression "best available" suggests a hierarchy of evidence; one ought to draw stronger inferences from evidence that comes from high-quality studies with optimal safeguards to prevent random and systematic error (bias). Most hierarchies of evidence about interventions place high-quality randomized controlled trials (RCTs) at the top of the hierarchy (3). Following this principle, diabetes practitioners should pay particular attention to RCTs to guide their practice.Not all RCTs share the same quality; that is, not all RCTs yield unbiased results. In the laboratory clinical investigation tradition, "quality" has referred almost exclusively to the rigorousness and reproducibility of the experimental procedures performed on the volunteers as well as the precise and accurate nature of the laboratory determinations. In conducting systematic reviews of RCTs in diabetes (4 -6), we have noticed that investigators seem to pay little attention (as judged by the extent to which they report these methods) to methodological safeguards that limit the introduction of bias into RCTs. As a result, these potentially biased RCTs could mislead clinicians. Readers only have access to the methods as reported. When reports leave out critical information about methodol...

Dehydroepiandrosterone replacement increases bone mineral density in elderly subjects; however, the effect is relatively small compared with established therapies for osteoporosis. No additional benefits have been identified for long-term dehydroepiandrosterone replacement, when used in the elderly to prevent or delay ageing. Dehydroepiandrosterone replacement may improve some metabolic variables and measures of psychological well-being in adrenal deficiency, but these benefits are not consistently sustained in long-term therapy. Long-term studies are needed to confirm sustained benefits in adrenal deficiency and establish long-term safety.