The dose-response relationship between elevated plasma free fatty acid (FFA) levels and impaired insulin-mediated glucose disposal and insulin signaling was examined in 21 lean, healthy, normal glucose-tolerant subjects. Following a 4-h saline or Liposyn infusion at 30 (n ؍ 9), 60 (n ؍ 6), and 90 (n ؍ 6) ml/h, subjects received a 2-h euglycemic insulin (40 mU ⅐ m ؊2 ⅐ min ؊1 ) clamp. Basal plasma FFA concentration (ϳ440 mol/l) was increased to 695, 1,251, and 1,688 mol/l after 4 h of Liposyn infusion and resulted in a dose-dependent reduction in insulin-stimulated glucose disposal (R d ) by 22, 30, and 34%, respectively (all P < 0.05 vs. saline control). At the lowest lipid infusion rate (30 ml/h), insulin receptor and insulin receptor substrate (IRS)-1 tyrosine phosphorylation, phosphatidylinositol (PI) 3-kinase activity associated with IRS-1, and Akt serine phosphorylation were all significantly impaired (P < 0.05-0.01). The highest lipid infusion rate (90 ml/h) caused a further significant reduction in all insulin signaling events compared with the low-dose lipid infusion (P < 0.05-0.01) whereas the 60-ml/h lipid infusion caused an intermediate reduction in insulin signaling. However, about two-thirds of the maximal inhibition of insulin-stimulated glucose disposal already occurred at the rather modest increase in plasma FFA induced by the low-dose (30-ml/h) lipid infusion. Insulin-stimulated glucose disposal was inversely correlated with both the plasma FFA concentration after 4 h of lipid infusion (r ؍ ؊0.50, P ؍ 0.001) and the plasma FFA level during the last 30 min of the insulin clamp (r ؍ ؊0.54, P < 0.001). PI 3-kinase activity associated with IRS-1 correlated with insulin-stimulated glucose disposal (r ؍ 0.45, P < 0.01) and inversely with both the plasma FFA concentration after 4 h of lipid infusion (r ؍ ؊0.39, P ؍ 0.01) and during the last 30 min of the insulin clamp (r ؍ ؊0.43, P < 0.01). In summary, in skeletal muscle of lean, healthy subjects, a progressive increase in plasma FFA causes a dose-dependent inhibition of insulin-stimulated glucose disposal and insulin signaling. The inhibitory effect of plasma FFA was already significant following a rather modest increase in plasma FFA and develops at concentrations that are well within the physiological range (i.e., at plasma FFA levels observed in obesity and type 2 diabetes). Diabetes 54:1640 -1648, 2005
Purpose. Because parathyroid carcinoma is rare, clear consensus is not available regarding the optimal management of patients with this condition. Treatment strategies generally derive from clinical and anecdotal experiences. We report our experience with this entity.Methods. We included all patients with parathyroid carcinoma seen at The University of Texas M. D. Anderson Cancer Center since January 1, 1980. The medical records and pathology specimens were reviewed and verified in all cases.
Introduction: Falls are the leading cause of accidental death in older adults. Each year, 28.7% of US adults over 65 years experience a fall resulting in over 300,000 hip fractures and $50 billion in medical costs. Annual fall risk assessments have become part of the standard care plan for older adults. However, the effectiveness of these assessments in identifying at-risk individuals remains limited. This study characterizes the performance of a commercially available, automated method, for assessing fall risk using machine learning.Methods: Participants (N = 209) were recruited from eight senior living facilities and from adults living in the community (five local community centers in Houston, TX) to participate in a 12-month retrospective and a 12-month prospective cohort study. Upon enrollment, each participant stood for 60 s, with eyes open, on a commercial balance measurement platform which uses force-plate technology to capture center-of-pressure (60 Hz frequency). Linear and non-linear components of the center-of-pressure were analyzed using a machine-learning algorithm resulting in a postural stability (PS) score (range 1–10). A higher PS score indicated greater stability. Participants were contacted monthly for a year to track fall events and determine fall circumstances. Reliability among repeated trials, past and future fall prediction, as well as survival analyses, were assessed.Results: Measurement reliability was found to be high (ICC(2,1) [95% CI]=0.78 [0.76–0.81]). Individuals in the high-risk range (1-3) were three times more likely to fall within a year than those in low-risk (7–10). They were also an order of magnitude more likely (12/104 vs. 1/105) to suffer a spontaneous fall i.e., a fall where no cause was self-reported. Survival analyses suggests a fall event within 9 months (median) for high risk individuals.Conclusions: We demonstrate that an easy-to-use, automated method for assessing fall risk can reliably predict falls a year in advance. Objective identification of at-risk patients will aid clinicians in providing individualized fall prevention care.
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