Endocytosis of the CdtA subunit from the Haemophilus ducreyi cytolethal distending toxin.

Many Gram-negative pathogens produce a cytolethal distending toxin (CDT) with two cell-binding subunits (CdtA + CdtC) and a catalytic CdtB subunit. After adhesion to the plasma membrane of a target cell, CDT moves by retrograde transport to endoplasmic reticulum. CdtB then enters the nucleus where it generates DNA breaks that lead to cell cycle arrest and apoptosis or senescence. CdtA anchors the CDT holotoxin to the plasma membrane and is thought to remain on the cell surface after endocytosis of the CdtB/CdtC heterodimer. Here, we re-examined the potential endocytosis and intracellular transport of CdtA from the Haemophilus ducreyi CDT. We recorded the endocytosis of holotoxin-associated CdtA with a cell-based enzyme-linked immunoabsorbent assay (CELISA) and visualised its presence in the early endosomes by confocal microscopy 10 min after CDT binding to the cell surface. Western blot analysis documented the rapid degradation of internalised CdtA. Most of internalised CdtB and CdtC were degraded as well. The rapid rate of CDT internalisation and turnover, which could explain why CdtA endocytosis was not detected in previous studies, suggests only a minor pool of cell-associated CdtB reaches the nucleus. Our work demonstrates that CDT is internalised as an intact holotoxin and identifies the endosomes as the site of CdtA dissociation from CdtB/CdtC. TAKE AWAYS: During the endocytosis of CDT, CdtA is thought to remain at the cell surface. A cell-based ELISA documented the rapid endocytosis of CdtA. CdtA was visualised in the early endosomes by confocal microscopy. Intracellular CdtA was rapidly degraded, along with most of CdtB and CdtC.

Teenager With Abdominal Pain and Decreased Appetite.

A 16-year-old girl presented to her primary care physician with a one-month history of decreased appetite and abdominal pain. She had normal bowel movements and no vomiting, but her periumbilical pain limited her ability to finish most meals. She had gradual weight loss over the previous 2 years, and during the previous 4 years, she intermittently received counseling for depression after the loss of her mother. Her initial physical examination and laboratory evaluation were unremarkable. She was referred to a nutritionist, adolescent medicine, and pediatric gastroenterology. Her presentation evolved over time, which ultimately led to a definitive diagnosis.

Association between mindfulness and interoceptive accuracy in patients with diabetes: Preliminary evidence from blood glucose estimates.

OBJECTIVE: Mindfulness-based interventions, which increase dispositional mindfulness, may be useful adjunctive therapies for patients with chronic diseases, including diabetes. One way that mindfulness may benefit patients with diabetes is by fostering more accurate interoception, particularly in the form of blood glucose estimate accuracy. Many people with diabetes regulate their behavior based on estimates of their blood glucose levels from interoception, but they vary in estimate accuracy. Therefore, our objective was to conduct a preliminary test of the hypothesis that, in a sample of patients with diabetes, more mindful individuals would demonstrate greater blood glucose estimate accuracy. METHODS: In a cross-sectional study, patients (N=28) with type 2 diabetes estimated their blood glucose levels immediately before their actual levels were assessed. Participants also completed two measures of mindfulness: one assessing general dispositional mindfulness and another assessing mindfulness specifically in the face of difficulty. RESULTS: Although general dispositional mindfulness was unrelated to blood glucose estimate accuracy, individuals who reported more mindfulness during difficulties were approximately four times more likely to meet established accuracy criteria. CONCLUSIONS: Mindfulness specifically during difficulties might play a role in disease-relevant interoception for patients with diabetes. Future research should aim to replicate this finding in larger and different samples, and to examine the potential role of mindfulness during difficulties in mindfulness-based interventions for patients with diabetes.

Characterization of mitochondrial injury after cardiac arrest (COMICA).

INTRODUCTION: Mitochondrial injury post-cardiac arrest has been described in pre-clinical settings but the extent to which this injury occurs in humans remains largely unknown. We hypothesized that increased levels of mitochondrial biomarkers would be associated with mortality and neurological morbidity in post-cardiac arrest subjects. METHODS: We performed a prospective multicenter study of post-cardiac arrest subjects. Inclusion criteria were comatose adults who suffered an out-of-hospital cardiac arrest. Mitochondrial biomarkers were measured at 0, 12, 24, 36 and 48h after return of spontaneous circulation as well as in healthy controls. RESULTS: Out of 111 subjects enrolled, 102 had evaluable samples at 0h. Cardiac arrest subjects had higher baseline cytochrome c levels compared to controls (2.18ng/mL [0.74, 7.74] vs. 0.16ng/mL [0.03, 0.91], p<0.001), and subjects who died had higher 0h cytochrome c levels compared to survivors (3.66ng/mL [1.40, 14.9] vs. 1.27ng/mL [0.16, 2.37], p<0.001). There were significantly higher Ribonuclease P (RNaseP) (3.3 [1.2, 5.7] vs. 1.2 [0.8, 1.2], p<0.001) and Beta-2microglobulin (B2M) (12.0 [1.0, 22.9], vs. 0.6 [0.6, 1.3], p<0.001) levels in cardiac arrest subjects at baseline compared to the control subjects. There were no differences between survivors and non-survivors for mitochondrial DNA, nuclear DNA, or cell free DNA. CONCLUSIONS: Cytochrome c was increased in post- cardiac arrest subjects compared to controls, and in post-cardiac arrest non-survivors compared to survivors. Nuclear DNA and cell free DNA was increased in plasma of post-cardiac arrest subjects. There were no differences in mitochondrial DNA, nuclear DNA, or cell free DNA between survivors and non-survivors. Mitochondrial injury markers showed mixed results in the post-cardiac arrest period. Future research needs to investigate these differences.

Inflammatory markers following resuscitation from out-of-hospital cardiac arrest-A prospective multicenter observational study.

AIM: The post-cardiac arrest syndrome is a complex set of pathophysiological processes including a systemic inflammatory response. The goal of the current investigation was to test the hypothesis that early inflammatory markers are independently associated with in-hospital mortality and poor neurological outcome in patients initially resuscitated from out-of-hospital cardiac arrest. METHODS: This was a preplanned analysis of data collected from a prospective observational multicenter study in adult out-of-hospital cardiac arrest patients. Blood was drawn at baseline, 12 and 24h after return of spontaneous circulation and plasma levels of interleukin (IL)-1ß, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α were measured. The primary outcome measure was survival to hospital discharge. We utilized a mixed linear model to compare the levels of cytokines in survivors and non-survivors over time. We used multivariable logistic regression to assess the association between IL-6 levels and mortality. RESULTS: A total of 102 patients were analyzed. Non-survivors and patients with poor functional outcome had statistical significant higher IL-1Ra, IL-6, IL-8, and IL-10 levels (all p<0.001) at all time points (0, 12 and 24h) compared to survivors. Baseline IL-6 levels were a good predictor of mortality (AUC=0.83 [95%CI: 0.75-0.92]). Baseline IL-6 levels were strongly associated with mortality in multivariable analysis (OR: 2.58 [95%CI: 1.93-3.45], p<0.001) but were not associated with neurological outcome in multivariable analysis (OR: 1.33 [95%CI: 0.62-2.86], p=0.47). CONCLUSION: Early inflammatory markers, especially IL-6, are higher in patients with a poor outcome after OHCA. IL-6 remained associated with mortality, but not functional outcome, in multivariable analysis adjusting for patient and event characteristics.

Impact of HbA1c measurement on hospital readmission rates: analysis of 70,000 clinical database patient records.

Management of hyperglycemia in hospitalized patients has a significant bearing on outcome, in terms of both morbidity and mortality. However, there are few national assessments of diabetes care during hospitalization which could serve as a baseline for change. This analysis of a large clinical database (74 million unique encounters corresponding to 17 million unique patients) was undertaken to provide such an assessment and to find future directions which might lead to improvements in patient safety. Almost 70,000 inpatient diabetes encounters were identified with sufficient detail for analysis. Multivariable logistic regression was used to fit the relationship between the measurement of HbA1c and early readmission while controlling for covariates such as demographics, severity and type of the disease, and type of admission. Results show that the measurement of HbA1c was performed infrequently (18.4%) in the inpatient setting. The statistical model suggests that the relationship between the probability of readmission and the HbA1c measurement depends on the primary diagnosis. The data suggest further that the greater attention to diabetes reflected in HbA1c determination may improve patient outcomes and lower cost of inpatient care.

Initial lactate and lactate change in post-cardiac arrest: a multicenter validation study.

OBJECTIVE: Rate of lactate change is associated with in-hospital mortality in post-cardiac arrest patients. This association has not been validated in a prospective multicenter study. The objective of the current study was to determine the association between percent lactate change and outcomes in post-cardiac arrest patients. DESIGN: Four-center prospective observational study conducted from June 2011 to March 2012. SETTING: The National Post-Arrest Research Consortium is a clinical research network conducting research in post-cardiac arrest care. The network consists of four urban tertiary care teaching hospitals. PATIENTS: Inclusion criteria consisted of adult out-of-hospital non-traumatic cardiac arrest patients who were comatose after return of spontaneous circulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was survival to hospital discharge, and secondary outcome was good neurologic outcome. We compared the absolute lactate levels and the differences in the percent lactate change over 24 hours between survivors and nonsurvivors and between subjects with good and bad neurologic outcomes. One hundred patients were analyzed. The median age was 63 years (interquartile range, 50-75) and 40% were female. Ninety-seven percent received therapeutic hypothermia, and overall survival was 46%. Survivors and patients with good neurologic outcome had lower lactate levels at 0, 12, and 24 hours (p< 0.01). In adjusted models, percent lactate decrease at 12 hours was greater in survivors (odds ratio, 2.2; 95% CI, 1.1-6.2) and in those with good neurologic outcome (odds ratio, 2.2; 95% CI, 1.1-4.4). CONCLUSION: Lower lactate levels at 0, 12, and 24 hours and greater percent decrease in lactate over the first 12 hours post cardiac arrest are associated with survival and good neurologic outcome.

Reorganizing the General Clinical Research Center to improve the clinical and translational research enterprise.

In 2010, Virginia Commonwealth University (VCU) was granted a Clinical and Translational Science Award which prompted reorganization and expansion of their clinical research infrastructure. A case study approach is used to describe the implementation of a business and cost recovery model for clinical and translational research and the transformation of VCU's General Clinical Research Center and Clinical Trials Office to a combined Clinical Research Services entity. We outline the use of a Plan, Do, Study, Act cycle that facilitated a thoughtful transition process, which included the identification of required changes and cost recovery processes for implementation. Through this process, the VCU Center for Clinical and Translational Research improved efficiency, increased revenue recovered, reduced costs, and brought a high level of fiscal responsibility through financial reporting.

A new system for comparative functional genomics of Saccharomyces yeasts.

Whole-genome sequencing, particularly in fungi, has progressed at a tremendous rate. More difficult, however, is experimental testing of the inferences about gene function that can be drawn from comparative sequence analysis alone. We present a genome-wide functional characterization of a sequenced but experimentally understudied budding yeast, Saccharomyces bayanus var. uvarum (henceforth referred to as S. bayanus), allowing us to map changes over the 20 million years that separate this organism from S. cerevisiae. We first created a suite of genetic tools to facilitate work in S. bayanus. Next, we measured the gene-expression response of S. bayanus to a diverse set of perturbations optimized using a computational approach to cover a diverse array of functionally relevant biological responses. The resulting data set reveals that gene-expression patterns are largely conserved, but significant changes may exist in regulatory networks such as carbohydrate utilization and meiosis. In addition to regulatory changes, our approach identified gene functions that have diverged. The functions of genes in core pathways are highly conserved, but we observed many changes in which genes are involved in osmotic stress, peroxisome biogenesis, and autophagy. A surprising number of genes specific to S. bayanus respond to oxidative stress, suggesting the organism may have evolved under different selection pressures than S. cerevisiae. This work expands the scope of genome-scale evolutionary studies from sequence-based analysis to rapid experimental characterization and could be adopted for functional mapping in any lineage of interest. Furthermore, our detailed characterization of S. bayanus provides a valuable resource for comparative functional genomics studies in yeast.

Continuous neuromuscular blockade is associated with decreased mortality in post-cardiac arrest patients.

AIM: Neuromuscular blockade may improve outcomes in patients with acute respiratory distress syndrome. In post-cardiac arrest patients receiving therapeutic hypothermia, neuromuscular blockade is often used to prevent shivering. Our objective was to determine whether neuromuscular blockade is associated with improved outcomes after out-of-hospital cardiac arrest. METHODS: A post hoc analysis of a prospective observational study of comatose adult (>18 years) out-of-hospital cardiac arrest at 4 tertiary cardiac arrest centers. The primary exposure of interest was neuromuscular blockade for 24h following return of spontaneous circulation and primary outcomes were in-hospital survival and functional status at hospital discharge. Secondary outcomes were evolution of oxygenation (PaO2:FiO2), and change in lactate. We tested the primary outcomes of in-hospital survival and neurologically intact survival with multivariable logistic regression. Secondary outcomes were tested with multivariable linear mixed-models. RESULTS: A total of 111 patients were analyzed. In patients with 24h of sustained neuromuscular blockade, the crude survival rate was 14/18 (78%) compared to 38/93 (41%) in patients without sustained neuromuscular blockade (p=0.004). After multivariable adjustment, neuromuscular blockade was associated with survival (adjusted OR: 7.23, 95% CI: 1.56-33.38). There was a trend toward improved functional outcome with neuromuscular blockade (50% versus 28%; p=0.07). Sustained neuromuscular blockade was associated with improved lactate clearance (adjusted p=0.01). CONCLUSIONS: We found that early neuromuscular blockade for a 24-h period is associated with an increased probability of survival. Secondarily, we found that early, sustained neuromuscular blockade is associated with improved lactate clearance.

Total and high-molecular weight adiponectin in women with the polycystic ovary syndrome.

Adiponectin, an adipokine with antidiabetic properties, forms multimers; and the high-molecular weight (HMW) form most closely correlates with insulin sensitivity (S(i)). Therefore, we hypothesize that HMW adiponectin levels are decreased in women with polycystic ovary syndrome (PCOS), a condition characterized by insulin resistance, compared with healthy controls and that HMW adiponectin correlates with testosterone and S(i). A cross-sectional study involving 13 women with PCOS and 13 age- and body mass index-matched healthy controls was performed. Waist-to-hip ratios (WHRs), glucose, insulin, sex hormone-binding globulin, total testosterone, and total and HMW adiponectin levels were measured after an overnight fast. Free testosterone was calculated from sex hormone-binding globulin and total testosterone, and S(i) was determined using a frequently sampled intravenous glucose tolerance test. The study's primary outcomes were differences in total and HMW adiponectin between women with PCOS and healthy control women. Total adiponectin (P < .01), HMW adiponectin (P < .01), and the ratio of HMW to total adiponectin (P = .03) were lower in women with PCOS compared with healthy women. Total and HMW adiponectin levels correlated inversely with WHR (P < .01) and free testosterone (P < .01) and positively with S(i) (P < .001). Using forward stepwise multivariate analysis, HMW adiponectin and WHR, but not PCOS status, were independent predictors of S(i). Women with PCOS have lower total and HMW adiponectin levels compared with healthy women. High-molecular weight adiponectin also comprises a smaller proportion of total circulating adiponectin in women with PCOS. Alterations in HMW adiponectin levels in women with PCOS may contribute to the insulin resistance intrinsic to the syndrome.

Relationship between alcohol use disorders, cortisol concentrations, and cytokine levels in patients with sepsis.

INTRODUCTION: Patients with alcohol use disorders (AUD) are at increased risk of developing sepsis and have higher mortality. AUD are associated with higher cortisol and anti-inflammatory cytokine profile. Higher cortisol increases risk of death in septic patients. The relationship between AUD and cortisol in septic patients is unknown. We aimed to study this relationship and postulated that AUD would be associated with higher cortisol and anti-inflammatory cytokine profile. METHODS: This was a prospective cohort study of 40 medical intensive care unit (ICU) patients admitted with sepsis. Cortisol, anti-inflammatory interleukin (IL) 10, and pro-inflammatory IL1ß, IL6, tumor necrosis factor (TNF) α were measured. RESULTS: Thirteen (32%) out of 40 patients had AUD. AUD patients had higher cortisol by univariate (39 microg/dl versus 24, P = 0.04) and multivariable analyses (44 microg/dl versus 23, P = 0.004). By univariate analyses, AUD patients had higher IL10 (198 picog/dl versus 47, P = 0.02) and IL6 (527 picog/ml versus 156, P = 0.048), but similar IL1ß and TNFα. By multivariable analyses, AUD patients had higher IL10 (182 picog/dl versus 23, P = 0.049) but similar IL1ß, IL6, and TNFα. AUD patients had lower IL1ß/IL10 (univariate 0.01 versus 0.10, P = 0.04; multivariable 0.01 versus 0.03, P = 0.04), lower TNFα/IL10 (univariate 0.15 versus 0.52, P = 0.03; multivariable 0.11 versus 0.63, P = 0.01), but similar IL6/IL10. CONCLUSIONS: AUD are common diagnoses among medical ICU patients with sepsis. Patients with AUD have higher cortisol concentrations and have differences in cytokine expression. Future studies should seek to determine if these differences may explain the higher severity of illness seen in patients with sepsis and AUD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00615862.

Health information seeking, receipt, and use in diabetes self-management.

PURPOSE: Diabetes self-management is essential for diabetes control, yet little is known about patient preferences for sources of health information or about the extent to which information is sought directly or received passively through various media sources. The aim of this qualitative study was to identify how individuals with diabetes seek and use health care information. METHODS: Using a health information model to guide our research, we conducted 9 focus groups with 46 adults with a diagnosis of diabetes and then analyzed the transcripts and notes from these focus groups. RESULTS: Five themes emerged: (1) passive receipt of health information about diabetes is an important aspect of health information behavior; (2) patients weave their own information web depending on their disease trajectory; (3) patients' personal relationships help them understand and use this information; (4) a relationship with a health care professional is needed to cope with complicated and sometimes conflicting information; and (5) health literacy makes a difference in patients' ability to understand and use information. CONCLUSIONS: Patients make decisions about diabetes self-management depending on their current needs, seeking and incorporating diverse information sources not traditionally viewed as providing health information. Based on our findings, we have developed a new health information model that reflects both the nonlinear nature of health information-seeking behavior and the interplay of both active information seeking and passive receipt of information.

Analysis of factors associated with durable remission of diabetes after Roux-en-Y gastric bypass.

BACKGROUND: Data on the durability of remission of type 2 diabetes mellitus (T2DM) after gastric bypass are limited. Our purpose was to identify the rate of long-term remission of T2DM and the factors associated with durable remission. METHODS: A total of 177 patients with T2DM who had undergone Roux-en-Y gastric bypass from 1993 to 2003 had 5-year follow-up data available. T2DM status was determined by interview and evaluation of the diabetic medications. Patients with complete remission or recurrence of T2DM were identified. RESULTS: Follow-up ranged from 5 to 16 years. Of the 177 patients, 157 (89%) had complete remission of T2DM with a decrease in their mean body mass index from baseline (50.2 +/- 8.2 kg/m(2)) to 31.3 +/- 7.2 kg/m(2) postoperatively (mean percentage of excess weight loss 70.0% +/- 18.6%). However, 20 patients (11.3%) did not have T2DM remission despite a mean percentage of excess weight loss of 58.2% +/- 12.3% (P <.0009). Of the 157 patients with initial remission of their T2DM, 68 (43%) subsequently developed T2DM recurrence. Remission of T2DM was durable in 56.9%. Durable (>5-year) resolution of T2DM was greatest in the patients who originally had either controlled their T2DM with diet (76%) or oral hypoglycemic agents (66%). The rate of T2DM remission was more likely to be durable in men (P = .00381). Weight regain was a statistically significant, but weak predictor, of T2DM recurrence. CONCLUSION: Early remission of T2DM occurred in 89% of patients after Roux-en-Y gastric bypass. T2DM recurred in 43.1%. Durable remission correlated most closely with an early disease stage at gastric bypass.

Glucocorticoid-induced hyperglycemia.

OBJECTIVE: To review the current literature on glucocorticoid-induced hyperglycemia and provide a strategy for its treatment. METHODS: We undertook an electronic (MEDLINE) and a library review of the existing pertinent literature published from 1950 to March 2009. RESULTS: Glucocorticoid-induced hyperglycemia is common in patients with and without diabetes. The odds ratio for new-onset diabetes mellitus in patients treated with glucocorticoids ranges from approximately 1.5 to 2.5. Total glucocorticoid dose and duration of therapy are strong predictors of diabetes induction. Other risk factors include age and body mass index. Failure to treat glucocorticoid-induced hyperglycemia is related to the presumed short duration of administration of glucocorticoid treatment and the emphasis on fasting plasma glucose only. Understanding the pharmacodynamics of glucocorticoids can lead to increased recognition and improved treatment of the condition. Recent demonstrations that even shortterm elevations in blood glucose level may be associated with adverse sequelae argue for greater attention to the condition. CONCLUSION: Glucocorticoid-induced hyperglycemia is an important clinical finding that, if recognized, can be effectively treated. We propose a relatively simple schema for the proactive management of corticosteroid-induced hyperglycemia that has been effective and easily adaptable to both the inpatient and the outpatient setting.

Prevalence of the metabolic syndrome among obese adolescents enrolled in a multidisciplinary weight management program: clinical correlates and response to treatment.

OBJECTIVE: The aim of this study was to determine the prevalence of the metabolic syndrome at baseline and after 6 months of lifestyle modification among obese adolescents referred to a multidisciplinary weight management program. METHODS: A total of 165 obese adolescents were evaluated at baseline, and measurements were repeated in 57 subjects who completed 6 months of the program. Metabolic syndrome was defined as having three or more of the following: a body mass index (BMI) >97(th) percentile, hypertension, low high-density lipoprotein cholesterol (HDL-C), hypertriglyceridemia, and impaired fasting glucose (IFG). RESULTS: The prevalence of a BMI >97(th) percentile, hypertension, hypertriglyceridemia, low HDL-C, and IFG was 92.7, 54.5, 29.1, 26.7, and 2.4%, respectively. The prevalence of the metabolic syndrome at baseline was 30.3%. After 6 months of lifestyle modification, BMI z scores, percent body fat, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) decreased significantly from baseline; however, there was no significant change in the number of subjects demonstrating >or=three criteria of the metabolic syndrome. CONCLUSIONS: Approximately one third of the study subjects met the criteria of the metabolic syndrome, emphasizing the growing concern for the future development of premature cardiovascular disease in this high-risk population. Our data suggest that new strategies for lifestyle modification may be needed to improve cardiovascular risk factors significantly among adolescents with obesity.

Computationally driven, quantitative experiments discover genes required for mitochondrial biogenesis.

Mitochondria are central to many cellular processes including respiration, ion homeostasis, and apoptosis. Using computational predictions combined with traditional quantitative experiments, we have identified 100 proteins whose deficiency alters mitochondrial biogenesis and inheritance in Saccharomyces cerevisiae. In addition, we used computational predictions to perform targeted double-mutant analysis detecting another nine genes with synthetic defects in mitochondrial biogenesis. This represents an increase of about 25% over previously known participants. Nearly half of these newly characterized proteins are conserved in mammals, including several orthologs known to be involved in human disease. Mutations in many of these genes demonstrate statistically significant mitochondrial transmission phenotypes more subtle than could be detected by traditional genetic screens or high-throughput techniques, and 47 have not been previously localized to mitochondria. We further characterized a subset of these genes using growth profiling and dual immunofluorescence, which identified genes specifically required for aerobic respiration and an uncharacterized cytoplasmic protein required for normal mitochondrial motility. Our results demonstrate that by leveraging computational analysis to direct quantitative experimental assays, we have characterized mutants with subtle mitochondrial defects whose phenotypes were undetected by high-throughput methods.

Glucose uptake after resistance training of different intensities but of equal work volume.

High-intensity (HI) resistance exercise augments postexercise glucose uptake to a greater degree than low-intensity (LO) resistance exercise; however, few studies have equated the work volumes between intensity levels. The purpose of this study was to compare the effect of acute HI and LO resistance exercise of equal work volume on glucose uptake in resistant-trained men. Fifteen healthy male (22.9 +/- 3.8 years old), resistance-trained (6.7 +/- 3.9 years) subjects completed three treatment sessions: CON (no-exercise control), HI (3 x 8, 85% 10-RM), and LO (3 x 15, 45% 10-RM). HI and LO sessions consisted of eight exercises. Glucose uptake was measured the following morning by using the hyperinsulinemic euglycemic clamp technique. Glucose disposal was measured by analyzing the glucose infusion rate during the final 30 minutes of steady-state blood glucose concentrations. Insulin sensitivity was calculated by dividing the glucose infusion rate by the average insulin infusion. Results indicate that fasting blood glucose levels were not significantly different among treatment sessions (CON = 80.5 +/- 5.3 versus HI = 77.0 +/- 4.9 versus LO = 77.1 +/- 6.0 mg.dL). Glucose uptake was not significantly different among treatment sessions (CON = 11.3 +/- 3.0 versus HI = 11.7 +/- 2.7 versus LO = 11.4 +/- 2.8 mg.kg FFM.min). Insulin sensitivity did not change among treatment sessions (CON = 0.26 +/- 0.09 versus HI = 0.28 +/- 0.07 versus LO = 0.27 +/- 0.06 (mg.kg FFM.min)/(uU.mL)). The data indicate that the resistance training sessions did not modify acute insulin sensitivity. This may have been because of the high levels of fitness of the subjects, which allowed for the cellular adaptations for enhanced insulin sensitivity and glucose uptake that are unaffected by this volume of acute exercise.

Aerobic exercise alters postprandial lipemia in African American versus White women.

PURPOSE: To determine whether ethnicity influences postprandial lipemia after a bout of aerobic exercise. METHODS: Randomized crossover design. Healthy White (W; n=6) and African American (AA; n=6) women (age, W 27.0+/-3.3 yr, AA 21.6+/-1.4 yr; body-mass index, W 25.0+/-0.93 kg/m2, AA 25.8+/-0.79 kg/m2) participated in 2 treatments (control and exercise), each conducted over 2 d. On d 1, participants rested (control) or walked at 60% of maximal oxygen uptake for 90 min (exercise) and then consumed a meal. On d 2, after a 12-hr overnight fast, participants consumed an oral fat-tolerance test (OFTT) meal of 1.7 g fat, 1.65 g carbohydrate, and 0.25 g protein per kg fat-free mass. Blood was collected pre-meal and at 0.5, 1, 2, 3, 4, 5, and 6 hr post-OFTT and analyzed for triacylglycerol (TAG), glucose, and insulin. Areas under the curve (AUCs) were calculated for each blood variable. RESULTS: A significantly lower TAG AUC was observed for AA (0.86+/-0.24 mmol x L(-1) x 6 hr(-1)) after exercise than for W (2.25+/- .50 mmol x L(-1) x 6 hr(-1)). Insulin AUC was significantly higher for AA after exercise (366.2+/-19.9 mmol x L(-1) x 6 hr(-1)) than for the control (248.1+/-29.2 mmol x L(-1) x 6 hr(-1)). CONCLUSIONS: The data indicate that exercise performed approximately 13 hr before an OFTT significantly reduces postprandial lipemia in AA compared with W. It appears that AA women have an increased ability to dispose of TAG after exercise and a high-fat meal.

Which basal insulin should be used in patients with type 2 diabetes mellitus?

The initiation of insulin therapy is a significant event for patients with diabetes and the physicians who care for them. Reluctance to begin insulin is multifactorial, with major stumbling blocks being the perceived complexity of insulin and fear of hypoglycemia. Recent guidelines supporting earlier introduction of insulin to achieve glycemic goals in patients with type 2 diabetes mellitus will require that traditional approaches to insulin therapy be altered and a new paradigm be introduced into clinical practice. In particular, an understanding of the role of basal insulin in the regulation of glucose and the development of strategies to implement basal insulin therapy can provide a transition that is rational and highly effective in most patients. The strategy also offers a unique approach to diabetes education that permits a focused and patient-specific correction to glucose abnormalities.