[Show abstract][Hide abstract] ABSTRACT: The objective of this study is to compare lactate levels between users and non-users of diabetes medications under the hypothesis that the level of lactate is a marker of oxidative capacity.
The cross-sectional data of 493 participants aged 61-84 with type 2 diabetes who participated in the Atherosclerosis Risk in Communities Carotid MRI study were analyzed using survey weighted linear regression.
Median plasma lactate level was 8.58 (95% CI: 8.23, 8.87) mg/dl. Comparing users of diabetic medications with non-users, thiazolidinedione use was significantly associated with lower lactate level (7.57 (6.95-8.25) mg/dL vs. 8.78 (8.43-9.14) mg/dL), metformin use with a slightly higher lactate level (9.02 (8.51-9.58) mg/dL vs. 8.36 (7.96-8.77) mg/dL), and sulfonylurea and insulin use were not associated with lactate level. After adjustment for demographic and lifestyle factors, the plasma lactate level for thiazolidinedione users was 15.78% lower than that for non-users (p<0.001). Considering use of each medication separately and in combination did not change the results.
In conclusion, thiazolidinedione use was associated with lower plasma lactate level compared to non-use and metformin use was only marginally associated with a slightly higher lactate level. These results are consistent with the previously demonstrated effects of diabetes medications on oxidative metabolism. Further investigation of the role that diabetes medications play in improvement of oxidative metabolism is warranted.
PLoS ONE 12/2012; 7(12):e51237. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The availability of an adequate blood supply is a critical public health need. An influenza epidemic or another crisis affecting population mobility could create a critical donor shortage, which could profoundly impact blood availability. We developed a simulation model for the blood supply environment in the United States to assess the likely impact on blood availability of factors such as an epidemic. We developed a simulator of a multi-state model with transitions among states. Weekly numbers of blood units donated and needed were generated by negative binomial stochastic processes. The simulator allows exploration of the blood system under certain conditions of supply and demand rates, and can be used for planning purposes to prepare for sudden changes in the public's health. The simulator incorporates three donor groups (first-time, sporadic, and regular), immigration and emigration, deferral period, and adjustment factors for recruitment. We illustrate possible uses of the simulator by specifying input values for an 8-week flu epidemic, resulting in a moderate supply shock and demand spike (for example, from postponed elective surgeries), and different recruitment strategies. The input values are based in part on data from a regional blood center of the American Red Cross during 1996-2005. Our results from these scenarios suggest that the key to alleviating deficit effects of a system shock may be appropriate timing and duration of recruitment efforts, in turn depending critically on anticipating shocks and rapidly implementing recruitment efforts.
PLoS ONE 07/2011; 6(7):e21752. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Accumulating evidence implicates insufficient oxidative capacity in the development of type 2 diabetes. This notion has not been well tested in large, population-based studies.
To test this hypothesis, we assessed the cross-sectional association of plasma lactate, an indicator of the gap between oxidative capacity and energy expenditure, with type 2 diabetes in 1709 older adults not taking metformin, who were participants in the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study.
The prevalence of type 2 diabetes rose across lactate quartiles (11, 14, 20 and 30%; P for trend <0.0001). Following adjustment for demographic factors, physical activity, body mass index and waist circumference, the relative odds of type 2 diabetes across lactate quartiles were 0.98 [95% confidence interval (CI) 0.59-1.64], 1.64 (95% CI 1.03-2.64) and 2.23 (95% CI 1.38-3.59), respectively. Furthermore, lactate was associated with higher fasting glucose among non-diabetic adults.
Plasma lactate was strongly associated with type 2 diabetes in older adults. Plasma lactate deserves greater attention in studies of oxidative capacity and diabetes risk.
International Journal of Epidemiology 12/2010; 39(6):1647-55. · 9.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The mechanism linking obesity with its downstream complications is poorly understood. Accumulating evidence suggests that insufficient oxidative capacity plays a central role in the development of insulin resistance and, perhaps, hypertension.
To investigate this hypothesis, we measured lactate, a marker of the gap between energy expenditure and oxidative capacity, in 40 obese subjects with the metabolic syndrome (Ob-MS), 40 obese subjects without the metabolic syndrome (Ob), and 20 lean controls (LCs). The 40 Ob-MS participants were then entered into a 12-20 week very low-calorie diet (VLCD) intervention. The change in lactate and a number of other metabolic factors including blood pressure were subsequently assessed.
At baseline, median lactate levels were significantly higher in both the Ob (36.4 mg/dl) and Ob-MS (34.7 mg/dl) groups when compared to LCs (17.4 mg/dl; P < 0.001). After the VLCD intervention, Ob-MS subjects lost 14.7 kg on average, corresponding to a 5.0 kg/m(2) decrease in body mass index (BMI). Lactate levels fell from 41.3 to 28.7 mg/dl, a 31% reduction (P = 0.006). Even after adjustment for BMI change, change in lactate was strongly associated with change in diastolic blood pressure (DBP) (P = 0.007) and mean arterial pressure (P = 0.014), but not with systolic blood pressure (SBP) (P = 0.20) or other obesity-related traits.
Baseline and longitudinal associations between lactate and DBP suggest that insufficient oxidative capacity may play a role in obesity-related hypertension.
American Journal of Hypertension 10/2008; 21(12):1337-42. · 3.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Maintaining a stable blood supply is a critical goal of the American Red Cross Blood Services. Extensive Red Cross data provided the opportunity to assess both long-term and short-term trends in the variation of weekly blood donations.
Overall trends and week-to-week variation in donation rates were assessed in volunteer, whole-blood donations from 1995 to 2005 among three Red Cross donor regions: the Connecticut region, the Greater Chesapeake and Potomac (Maryland) region, and the Southern California region, adjusting for population change, calendar time, age, sex, and donor region.
Weekly donation rates varied widely by region, ranging from 3.5 donations per 10,000 persons in Southern California to 10.2 donations per 10,000 in Connecticut. Week-to-week variation in donation rates within each region was also quite high. Typical swings in weekly donation rates ranged from 38 percent in Connecticut to 56 percent in Southern California. Week-to-week variation was also 103 percent higher (95% confidence interval [CI], 87%-120%) among 18- to 24-year-old donors, compared to 25- to 44-year-olds, ranging from 32 to 49 percent. By comparison, week-to-week variation among adults 25 and older was more stable, ranging from 16 to 21 percent.
This study suggests that there is a great deal of variation in donation rates, particularly among the youngest donors. Improving recruitment and retention among these donors will be critical to maintaining an adequate blood supply as the donor population ages.
[Show abstract][Hide abstract] ABSTRACT: Magnetic resonance spectroscopy (MRS) measures hepatic fat and adenosine triphosphate (ATP), but magnetic resonance studies are challenging in obese subjects. We aimed to evaluate the inter- and intrarater reliability and stability of hepatic fat and ATP measurements in a cohort of overweight and obese adults.
We measured hepatic fat and ATP using proton MRS ((1)H MRS) and phosphorus MRS ((31)P MRS) at baseline in adults enrolled in the Action for Health in Diabetes (Look AHEAD) clinical trial at one site. Using logistic regression, we determined factors associated with successful MRS data acquisition. We calculated the intra- and inter-rater reliability for hepatic fat and ATP based on 20 scans analysed twice by two readers. We also calculated the stability of these measures three times on five healthy volunteers.
Of 244 participants recruited into our ancillary study, 185 agreed to MRS. We obtained usable hepatic fat data from 151 (82%) and ATP data from 105 (58%). Obesity was the strongest predictor of failed data acquisition; every unit increase in the body mass index reduced the likelihood of successful fat data by 11% and ATP data by 14%. The inter- and intrarater reliability were excellent for fat (intraclass correlation coefficient=0.99), but substantially more variable for ATP. Fat measures appeared relatively stable, but this was less true for ATP.
Obesity can hinder (1)H and (31)P MRS data acquisition and subsequent analysis. This impact was greater for hepatic ATP than hepatic fat.
Liver international: official journal of the International Association for the Study of the Liver 06/2008; 28(5):675-81. · 4.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Serum antibodies in 100 mothers of children with autistic disorder (MCAD) were compared to 100 age-matched mothers with unaffected children (MUC) using as antigenic substrates human and rodent fetal and adult brain tissues, GFAP, and MBP. MCAD had significantly more individuals with Western immunoblot bands at 36 kDa in human fetal and rodent embryonic brain tissue. The density of bands was greater in fetal brain at 61 kDa. MCAD plus developmental regression had greater reactivity against human fetal brain at 36 and 39 kDa. Data support a possible complex association between genetic/metabolic/environmental factors and the placental transfer of maternal antibodies in autism.
Journal of Neuroimmunology 03/2008; 194(1-2):165-72. · 2.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine five available software packages for the assessment of abdominal adipose tissue with magnetic resonance imaging, compare their features and assess the reliability of measurement results.Design:Feature evaluation and test-retest reliability of softwares (NIHImage, SliceOmatic, Analyze, HippoFat and EasyVision) used in manual, semi-automated or automated segmentation of abdominal adipose tissue.
A random sample of 15 obese adults with type 2 diabetes.
Axial T1-weighted spin echo images centered at vertebral bodies of L2-L3 were acquired at 1.5 T. Five software packages were evaluated (NIHImage, SliceOmatic, Analyze, HippoFat and EasyVision), comparing manual, semi-automated and automated segmentation approaches. Images were segmented into cross-sectional area (CSA), and the areas of visceral (VAT) and subcutaneous adipose tissue (SAT). Ease of learning and use and the design of the graphical user interface (GUI) were rated. Intra-observer accuracy and agreement between the software packages were calculated using intra-class correlation. Intra-class correlation coefficient was used to obtain test-retest reliability.
Three of the five evaluated programs offered a semi-automated technique to segment the images based on histogram values or a user-defined threshold. One software package allowed manual delineation only. One fully automated program demonstrated the drawbacks of uncritical automated processing. The semi-automated approaches reduced variability and measurement error, and improved reproducibility. There was no significant difference in the intra-observer agreement in SAT and CSA. The VAT measurements showed significantly lower test-retest reliability. There were some differences between the software packages in qualitative aspects, such as user friendliness.
Four out of five packages provided essentially the same results with respect to the inter- and intra-rater reproducibility. Our results using SliceOmatic, Analyze or NIHImage were comparable and could be used interchangeably. Newly developed fully automated approaches should be compared to one of the examined software packages.
International journal of obesity (2005) 02/2008; 32(1):100-11. · 5.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clinical case reports have suggested that the behaviors of children with autism spectrum disorders may improve with fever. The purpose of this study was to investigate the effect of illness on behaviors of children with autism spectrum disorders. Understanding the role of fever, if any, may be informative regarding causative mechanisms of and treatment opportunities for autism.
We conducted a prospective study of 30 children (aged 2-18 years) with autism spectrum disorders during and after an episode of fever. Parent responses to the Aberrant Behavior Checklist were collected during fever (body temperature > or = 38.0 degrees C/100.4 degrees F), when fever had abated and the child was asymptomatic, and when the child had been fever-free for 7 days. Data were compared with those collected from parents of 30 age-, gender-, and language skills-matched afebrile children with autism spectrum disorders during similar time intervals.
Fewer aberrant behaviors were recorded for febrile patients on the Aberrant Behavior Checklist subscales of irritability, hyperactivity, stereotypy, and inappropriate speech compared with control subjects. Per expectation, lethargy scores were greater during fevers, and all improvements were transient. Data from patients with fever were stratified on variables related to illness severity. In the majority of these subgroup comparisons, the data suggested that effects from fever persisted in the less sick patients as well as in those with more severe illness.
We documented behavior change among children with autism spectrum disorders during fever. The data suggest that these changes might not be solely the byproduct of general effects of sickness on behavior; however, more research is needed to prove conclusively fever-specific effects and elucidate their underlying biological mechanisms (possibly involving immunologic and neurobiological pathways, intracellular signaling, and synaptic plasticity).