Search

Objectives Monitoring quality indicators (QIs) is an important part of laboratory quality assurance (QA). Here, the Canadian Society of Clinical Chemists (CSCC) Point of Care Testing (POCT) and QI Special Interest Groups describe a process for establishing and monitoring QIs for POCT glucose testing. Methods Key, error prone steps in the POCT glucose testing process were collaboratively mapped out, followed by risk assessment for each step. Steps with the highest risk and ability to detect a non-conformance were chosen for follow-up. These were positive patient identification (PPID) and repeat of critically high glucose measurements. Participating sites were asked to submit aggregate data for these indicators from their site(s) for a one-month period. The PPID QI was also included as part of a national QI monitoring program for which fifty-seven sites submitted data. Results The percentage of POCT glucose tests performed without valid PPID ranged from 0–87%. Sites without Admission-Discharge-Transfer (ADT) connectivity to POCT meters were among those with the highest percentage of POCT glucose tests performed without valid PPID. The percentage repeated critically high glucose measurements ranged from 0–50%, indicating low compliance with this recommendation. A high rate of discordance was also noted when critically high POCT glucose measurements were repeated, demonstrating the importance of repeat testing prior to insulin administration. Conclusions Here, a process for establishing these QIs is described, with preliminary data for two QIs chosen from this process. The findings demonstrate the importance of QIs for identification and comparative performance monitoring of non-conformances to improve POCT quality.

In a CODE-MI sub-study, six troponin assays were evaluated over 12 months using 3-samples (normal, female and male 99th-percentile levels; n=2,142 results from 67 instruments). Mean differences varied per assay with maximum values being ±4, ±8 and ±9 ng/L at the normal and sex-specific 99th-percentiles, respectively. A pragmatic approach, combining all assays, established maximum differences of ±3 ng/L or ±30%.

Introduction The type of blood collection tube used when obtaining samples for therapeutic drug monitoring (TDM) has important implications on the accuracy of results. Serum tubes without a gel separator are currently considered best practice. We sought to evaluate the performance of of Barricor™, a novel plasma tube that utilizes an inert mechanical separator, as well as a gel-based tube (PST™) for testing acetaminophen, digoxin, gentamicin, methotrexate, phenobarbital, phenytoin, salicylate, vancomycin, valproic acid, carbamazepine, and theophylline on a Roche Cobas® 8000 platform. Methods Paired patient samples were collected from individuals taking at least one of the medications evaluated. These were supplemented with spiked specimens to ensure a minimum of 40 paired samples per drug. All drugs were measured within two hours of collection on Roche e602 or c502 instruments. Deming regression was used to assess bias between Barricor™ vs serum and PST™ vs serum. Seven-day refrigerated stability was also assessed in Barricor™, PST™, and serum tubes in a subset of samples (n=10) for each drug. Results Drug concentrations in Barricor™ were similar to serum for each drug assessed. In contrast, a negative bias was observed in PST™ compared to serum tubes for carbamazepine (-7.6%) and phenytoin (-6.8%) although this did not surpass our total allowable error goal of 10%. All drugs recovered within ±10% of baseline value when samples were stored refrigerated for 7 days except for carbamazepine, phenytoin, and phenobarbital where significant analyte loss was observed within the first day in PST™ tubes. Conclusion Barricor™ tubes are a suitable alternative to serum for TDM on the Roche Cobas® 8000 platform.

Point of Care Testing (POCT) refers to clinical laboratory testing performed outside the central laboratory, nearer to the patient and sometimes at the patient bedside. The testing is usually performed by clinical staff, such as physicians or nurses, who are not laboratory trained. This document was developed by the POCT Interest group of the Canadian Society of Clinical Chemists (CSCC) as practical guidance for quality assurance practices related to POCT performed in hospital and outside hospital environments. The aspects of quality assurance addressed in this document include: (1) device selection, (2) initial device verification, (3) ongoing device verification, (4) ongoing quality assurance including reagent and quality control (QC) lot changes, and (5) quality management including operator and document management.

Since recreational legalization of cannabis in Canada in 2018, self-reported use in New Brunswick (NB) has increased from 15.1% to 20.3%, the largest increase of any province. Current literature on the impact of recreational cannabis legislation in other jurisdictions is conflicting, though retail availability has often been delayed on enactment. Given the immediate availability of cannabis in NB after legalization, we sought to establish the effect this had on post-mortem cannabinoid detection. Furthermore, we wanted to investigate the impact that age, sex, and manner of death had on cannabis use. We also established if there were any increases in commonly detected drugs over the study period.A retrospective chart review was conducted on all adult Coroner's cases with toxicology analysis in NB between January 2014 and May 2020 (n = 3060). Differences in the proportion of cannabinoid-positive samples pre- versus post-legalization in the overall cohort as well as within each demographic parameter were assessed using chi-square tests. The effects of demographic parameters on cannabis presence were further assessed by logistic regression. Lastly, chi-square tests for trend were performed to identify increasing trends in cannabis detection, as well as cocaine, ethanol, opiates/opioids, benzodiazepines, and amphetamines over the study period.After controlling for age, sex, and manner of death, participants that died after recreational legalization had higher odds of having cannabis present post-mortem than those that died pre-legalization. In addition, demographic sub-analysis identified a greater proportion of cannabinoid-positive samples post-legalization in 25- to 44-year-olds and in deaths classified as either suicide or accidental compared to pre-legalization. We also observed a significant increase in the presence of cocaine and amphetamines in post-mortem samples over the study period.This study demonstrates that cannabis use has increased post-legalization in NB, particularly within young adults and those dying by suicide or accidental means. It also highlights the need for future research into the impact that legalization has on cannabis use in other jurisdictions.

Barricor™ Vacutainers® are a novel non-gel separator blood collection tube. These tubes enable faster pre-analytical processing which could reduce turnaround time and be beneficial in an acute care setting. We sought to evaluate the bias, stability, and integrity of plasma generated from these tubes compared to Plasma Separator Tubes™ (PST) for 50 routine chemistry analytes on a Roche Cobas® 8000 analyzer.Paired samples were collected from 150 patients originating in the emergency department and outpatient collections at the Saint John Regional Hospital. Barricor™ vacutainers were centrifuged for 3 min at 4000g and PST™ vacutainers for 10 min at 1300 g within two hours of collection. Plasma samples (n = 126) were then analyzed for 50 chemistry analytes and bias determined between tubes. Ten-day stability of AST, glucose, potassium, phosphate, and LDH was also assessed in a subset of paired samples (n = 4). Lastly, the quality of plasma (n = 20) was assessed through measurement of cell counts on a DxH Hematology Analyzer.All 50 analytes demonstrated comparable results across a broad concentration range between Barricor™ and PST™ vacutainers (average percent bias -1.5% to 6.1%; Deming linear regression slopes 0.933-1.041; correlation coefficients ≥ 0.9144). AST, potassium, glucose and LDH were stable for 10 days in Barricor™ vacutainers (change from baseline 10%) but5 days in PST™ vacutainers while phosphate was stable for 4 days in Barricor™ vs 2 days in PST™ vacutainers. Platelet counts were statistically lower in Barricor™ compared to PST™ vacutainers.Our data suggest that Barricor™ vacutainers are an acceptable alternative to PST™ vacutainers while offering the added benefit of decreased pre-analytical processing time, increased stability of certain analytes, and possibly less cellular contamination.

Adverse Cardiometabolic Outcomes in Obese Patients Correlates Strongly with Defective Branched-Chain Amino Acid Catabolism

HbA1c is used in forensic toxicology to identify undiagnosed diabetes mellitus (DM) and those with poor glycemic control prior to death. HbA1c is typically measured in whole blood collected in tubes containing ethylenediaminetetraacetic acid (EDTA). The effect of other additives, including sodium fluoride (NaF), is unclear. Furthermore, the assessment of short- and long-term stability of HbA1c has produced conflicting results. In this study, we collected paired postmortem blood samples in EDTA and NaF tubes (n = 142) to assess their comparability for HbA1c measurement. Stability was assessed by measuring HbA1c at baseline, 2, 3, and 4 weeks postcollection (stored at 4°C) and at 2, 4, 6, and 12 months postcollection (stored at -20°C). We found no significant difference in HbA1c between the two preservatives at any of the time points indicating NaF is a suitable preservative for HbA1c measurement. We also determined that DM status, postmortem interval, and decomposition had no effect on stability.

Background Lysophosphatidic acid (LPA) receptor signaling has been implicated in cardiovascular and obesity-related metabolic disease. However, the distribution and regulation of LPA receptors in the myocardium and adipose tissue remain unclear. Objectives This study aimed to characterize the mRNA expression of LPA receptors (LPA1-6) in the murine and human myocardium and adipose tissue, and its regulation in response to obesity. Methods LPA receptor mRNA levels were determined by qPCR in i) heart ventricles, isolated cardiomyocytes, and perigonadal adipose tissue from chow or high fat-high sucrose (HFHS)-fed male C57BL/6 mice, ii) 3T3-L1 adipocytes and HL-1 cardiomyocytes under conditions mimicking gluco/lipotoxicity, and iii) human atrial and subcutaneous adipose tissue from non-obese, pre-obese, and obese cardiac surgery patients. Results LPA1-6 were expressed in myocardium and white adipose tissue from mice and humans, except for LPA3, which was undetectable in murine adipocytes and human adipose tissue. Obesity was associated with increased LPA4, LPA5 and/or LPA6 levels in mice ventricles and cardiomyocytes, HL-1 cells exposed to high palmitate, and human atrial tissue. LPA4 and LPA5 mRNA levels in human atrial tissue correlated with measures of obesity. LPA5 mRNA levels were increased in HFHS-fed mice and insulin resistant adipocytes, yet were reduced in adipose tissue from obese patients. LPA4, LPA5, and LPA6 mRNA levels in human adipose tissue were negatively associated with measures of obesity and cardiac surgery outcomes. This study suggests that obesity leads to marked changes in LPA receptor expression in the murine and human heart and white adipose tissue that may alter LPA receptor signaling during obesity.

BACKGROUND Pediatric endocrinopathies are commonly diagnosed and monitored by measuring hormones of the hypothalamic-pituitary-gonadal axis. Because growth and development can markedly influence normal circulating concentrations of fertility hormones, accurate reference intervals established on the basis of a healthy, nonhospitalized pediatric population and that reflect age-, gender-, and pubertal stage–specific changes are essential for test result interpretation. METHODS Healthy children and adolescents (n = 1234) were recruited from a multiethnic population as part of the CALIPER study. After written informed parental consent was obtained, participants filled out a questionnaire including demographic and pubertal development information (assessed by self-reported Tanner stage) and provided a blood sample. We measured 7 fertility hormones including estradiol, testosterone (second generation), progesterone, sex hormone–binding globulin, prolactin, follicle-stimulating hormone, and luteinizing hormone by use of the Abbott Architect i2000 analyzer. We then used these data to calculate age-, gender-, and Tanner stage–specific reference intervals according to Clinical Laboratory Standards Institute C28-A3 guidelines. RESULTS We observed a complex pattern of change in each analyte concentration from the neonatal period to adolescence. Consequently, many age and sex partitions were required to cover the changes in most fertility hormones over this period. An exception to this was prolactin, for which no sex partition and only 3 age partitions were necessary. CONCLUSIONS This comprehensive database of pediatric reference intervals for fertility hormones will be of global benefit and should lead to improved diagnosis of pediatric endocrinopathies. The new database will need to be validated in local populations and for other immunoassay platforms as recommended by the Clinical Laboratory Standards Institute.

Introduction: Laboratory turnaround times (TAT) influence length of stay for emergency department (ED) patients. We studied biochemistry TATs around the implementation of a plasma separating tube (PST) that omitted a 20-minute clotting step in processing when compared to the standard serum separating tubes (SST). Methods: We compared laboratory TATs using PST vs SST in a prospective before-and-after study with a washout period. TATs for creatinine, urea, electrolytes, troponin, and N-terminal pro b-type natriuretic peptide (NT-proBNP), as well as hemolysis rates, were collected for all ED patients. Results were excluded if the TAT was four minutes or less (data entry error). We recorded the 90th percentile response times (TAT90; the time for 90% of the tests to be completed). Statistical analysis used survival analyses, Mann-Whitney U tests, and Chi-square tests of independence. Results: SST and PST groups were matched for days of the week, critical values, or hemolysis. There was a statistically significant reduction in median TAT and proportion completed by 60 minutes. However, the effect size was only two to four minutes in the In-Lab-TAT90 with the PST tubes for all tests, except B-type natriuretic peptide (BNP). Conclusions: Reducing the machine processing time for stat blood work with PST tubes did not produce a clinically meaningful reduction of TAT. Clinically important improvement for Lab TAT requires process analysis and intervention that is inclusive of the entire system. Fractile response times at a 90th percentile for TAT within 60 minutes may be an accurate benchmark for analysis.

Studies have demonstrated improved analytical performance of the Nova StatStrip glucose meter, but limited data is available on its clinical performance in critically ill neonates in the neonatal intensive care unit (NICU).A retrospective charge review was conducted on 651 neonates admitted to the NICU over 2 years. Demographics, sample collection information, and clinical details were recorded. Glucose measurements were performed at the bedside using either the Nova StraStrip or LifeScan SureStep Flexx meters as well as corresponding measurements of laboratory venous plasma glucose. Performance was analyzed by receiver operator characteristic (ROC) curves for detecting hypoglycemia and critical glucose levels.Linear regression analysis comparing StatStrip and laboratory venous plasma glucose samples demonstrated significantly tighter agreement (r(2)=0.7994) and accuracy (mean bias=0.13mmol/L) than SureStep (r(2)=0.6845 and mean bias=0.53mmol/L). StatStrip also showed improved sensitivity for detecting critical low glucose values ≤3.0mmol/L (80.9 vs 68.9%, p0.05). ROC curve analysis further demonstrated excellent performance of StatStrip at this cutoff with an AUC of 0.98. Overall, neonates were also tested significantly less frequently with the StatStrip meter by 24% compared to SureStep.Implementation of StatStrip led to better agreement with venous plasma glucose, improved detection of critical low glucose results, and more efficient test utilization. This study demonstrates the importance of accurate and sensitive glucose monitoring in the NICU.

Nearly 25% of normal weight individuals display abnormal metabolic profiles associated with obesity. As a wide range in body fat percentage (%BF) exists for BMI-defined normal weight individuals, we investigated whether elevated %BF (determined using DXA) was associated with cardiometabolic dysregulation among 977 normal weight subjects (192 men, 785 women) from the Canadian province of Newfoundland and Labrador.BMI and %BF were measured after a 12-h fasting period. Cardiometabolic abnormalities considered included elevated triglyceride, glucose and hsCRP levels, decreased HDL cholesterol, insulin resistance, and hypertension. Subjects were classified as metabolically healthy (0 or 1 cardiometabolic abnormality) or abnormal (≥2 cardiometabolic abnormalities) and divided into sex-specific %BF tertiles as follows: low (≤15.2% men, ≤29.7% women), medium (15.3-20.7%% men, 29.8-34.9%% women) and high (≥20.8% men, ≥35.0% women). The prevalence of the metabolically abnormal phenotype was higher among medium and high %BF subjects (12.0% and 19.5%, respectively) compared to the low group (7.4%; p 0.05). Furthermore, the odds of being metabolically abnormal were 1.61 (95% CI 0.94-2.77) for medium %BF subjects compared to the low group and nearly tripled for high %BF subjects (OR 2.73, 95% CI 1.63-4.86). ORs remained significant after further adjustment for waist circumference.Our findings indicate that those with elevated %BF are at increased risk of developing cardiometabolic disease despite having a normal BMI. Future development of adequate screening tools to identify these individuals is crucial to the prevention of obesity-associated disease.

The prevalence of obesity is increasing at an alarming rate and with it the occurrence of a number of comorbidities, including cardiovascular disease, type 2 diabetes, stroke, and certain types of cancer. Approximately one third of adults in the US population are currently classified as obese. Globally, >400 × 106 adults are classified as obese, a number that is expected to double by 2015. Consequently, obesity and its associated health problems are placing a large burden on an already overwhelmed healthcare system. The worldwide costs attributable to this disease are estimated to be between 0.7% and 2.8% of total healthcare expenditures. Furthermore, medical costs for obese individuals are substantially higher than for nonobese people. Obesity is a multifactorial disease caused by a chronic energy surplus in which energy intake exceeds energy expenditure, leading to the accumulation of excess adipose tissue. Regulation of energy homeostasis is a complex process, and that fact imparts a considerable challenge in trying to elucidate the pathogenesis of obesity. Although poor lifestyle choices, including inappropriate diets and lack of physical activity, undoubtedly play a large role, genetic susceptibility also puts an individual at increased risk. The majority of obesity therapies have been aimed at behavior modification and pharmacologic intervention, although to date these therapies have led to only modest weight loss. Although less common, bariatric surgery has led to substantial long-term weight loss in morbidly obese patients; this type of treatment, however, is both invasive and costly. Given the growing trend of obesity in both developed and developing countries, considerable importance has been placed on increasing awareness of the problem. In this article, 4 leaders in the field of obesity provide their opinions on obesity and discuss the latest advancements in pathogenesis, therapy, prevention, and the use of novel biomarkers to identify those at risk …

Nearly one-third of obese (OB) people are reported to be metabolically healthy based on BMI criteria. It is unknown whether this holds true when more accurate adiposity measurements are applied such as dual-energy X-ray absorptiometry (DXA). We compared differences in the prevalence of cardiometabolic abnormalities among adiposity groups classified using BMI vs. DXA criteria. A total of 1,907 adult volunteers from Newfoundland and Labrador participated. BMI and body fat percentage (%BF; measured using DXA) were measured following a 12-h fasting period. Subjects were categorized as normal weight (NW), overweight (OW), or OB based on BMI and %BF criteria. Cardiometabolic abnormalities considered included elevated triglyceride, glucose, and high-sensitivity C-reactive protein (hsCRP) levels, decreased high-density lipoprotein (HDL) cholesterol levels, insulin resistance, and hypertension. Subjects were classified as metabolically healthy (0 or 1 cardiometabolic abnormality) or abnormal (≥2 cardiometabolic abnormalities). We found low agreement in the prevalence of cardiometabolic abnormalities between BMI and %BF classifications (κ = 0.373, P < 0.001). Among NW and OW subjects, the prevalence of metabolically healthy individuals was similar between BMI and %BF (77.6 vs. 75.7% and 58.8 vs. 62.5%, respectively) however, there was a pronounced difference among OB subjects (34.0 vs. 47.7%, P < 0.05). Similar trends were evident using three additional definitions to characterize metabolically healthy individuals. Our findings indicate that approximately one-half of OB people are metabolically healthy when classified using %BF criteria which is significantly higher than previously reported using BMI. Caution should therefore be taken when making inferences about the metabolic health of an OB population depending on the method used to measure adiposity.

Testosterone, the most abundant androgen in men, is a steroid hormone that is synthesized predominantly by the testes. In women, minor amounts are synthesized in the ovaries. Androgen precursors are also produced and secreted from the adrenal glands in both sexes, where they undergo peripheral conversion to testosterone. Circulating concentrations are approximately 15-25 times higher in adult men compared to women. Maintenance of these levels is necessary for development and maintenance of secondary sexual characteristics, libido, growth, prevention of osteoporosis, and most importantly in men, spermatogenesis. Most testosterone circulates tightly bound to sex hormone-binding globulin (SHBG) or weakly bound to albumin. A minor amount circulates as free testosterone, and it is believed that this is the metabolically active fraction. Measurement of free testosterone is important in the diagnosis of many diseases, most importantly disorders of androgen deficiency in men (i.e., hypogonadism) and androgen excess in women (i.e., polycystic ovary syndrome and hirsutism). Many methodologies are available for free testosterone measurement including the reference methods (equilibrium dialysis and ultrafiltration), analog immunoassay, and calculated free testosterone based on measurement of total testosterone, SHBG, and albumin. Moreover, measurement of bioavailable testosterone, a combination of albumin-bound and free testosterone, also has clinical utility and can be measured by selective protein precipitation or calculation. In this review, the advantages and limitations of each of these methods will be discussed in the context of clinical utility and implementation into a routine hospital laboratory. Furthermore, up and coming methodologies for free testosterone measurement, including liquid chromatography-tandem mass spectrometry, will also be discussed.

Testosterone, the most abundant androgen in men, is a steroid hormone that is synthesized predominantly by the testes. In women, minor amounts are synthesized in the ovaries. Androgen precursors are also produced and secreted from the adrenal glands in both sexes, where they undergo peripheral conversion to testosterone. Circulating concentrations are approximately 15-25 times higher in adult men compared to women. Maintenance of these levels is necessary for development and maintenance of secondary sexual characteristics, libido, growth, prevention of osteoporosis, and most importantly in men, spermatogenesis. Most testosterone circulates tightly bound to sex hormone-binding globulin (SHBG) or weakly bound to albumin. A minor amount circulates as free testosterone, and it is believed that this is the metabolically active fraction. Measurement of free testosterone is important in the diagnosis of many diseases, most importantly disorders of androgen deficiency in men (i.e., hypogonadism) and androgen excess in women (i.e., polycystic ovary syndrome and hirsutism). Many methodologies are available for free testosterone measurement including the reference methods (equilibrium dialysis and ultrafiltration), analog immunoassay, and calculated free testosterone based on measurement of total testosterone, SHBG, and albumin. Moreover, measurement of bioavailable testosterone, a combination of albumin-bound and free testosterone, also has clinical utility and can be measured by selective protein precipitation or calculation. In this review, the advantages and limitations of each of these methods will be discussed in the context of clinical utility and implementation into a routine hospital laboratory. Furthermore, up and coming methodologies for free testosterone measurement, including liquid chromatography-tandem mass spectrometry, will also be discussed.

Prenatal screening for chromosomal aneuploidies is a fundamental part of routine obstetric care in most countries. Typically, maternal age, weight, ethnicity, serum biomarkers (including pregnancy-associated plasma protein A, human chorionic gonadotropin, α-fetoprotein, inhibin A, and estriol), and sonographic features (i.e., nuchal translucency) are included in a risk algorithm to determine the probability of the fetus being affected. Pregnant women identified as at high risk according to the prenatal screen can then undergo invasive procedures, such as amniocentesis and chorionic villus sampling, to confirm the diagnosis. Current prenatal-screening methods are able to identify approximately 90% of pregnancies affected by trisomy 21 (Down syndrome) at a false-positive rate of approximately 5%. Given that the prevalence of chromosomal aneuploidies is generally quite low, a false-positive rate of 5% means that a large number of women with unaffected pregnancies undergo invasive procedures, putting the fetus at an unnecessary risk for miscarriage. The discovery of fetal cell-free DNA in the plasma of pregnant women 14 years ago opened up the possibility of identifying chromosomal abnormalities noninvasively, through a single blood sample. Approximately 10% of cell-free DNA in the maternal circulation is of fetal origin, and this property was initially exploited to determine rhesus D status and the sex of the unborn fetus. The advent of next-generation DNA sequencing, however, has allowed prenatal detection of chromosomal aneuploidies, including trisomy 21, from maternal blood. In brief, the proportion of chromosome 21 DNA molecules in maternal plasma is measured directly; an increase above a predetermined threshold is indicative of trisomy 21. The clinical performance of this noninvasive prenatal test has been promising, with recent clinical studies having shown a diagnostic sensitivity of 100% and a diagnostic specificity of 98%–99%, compared with full karyotyping by invasive means. When used as a second-tier screening procedure, this technology also has the …

Levamisole is an anthelminthic that was first used as a de-worming agent in humans and animals. It has also been used to treat inflammatory conditions as well as certain types of cancer. Levamisole was discontinued for human use in the early 21st century due to toxic side effects including agranulocytosis and vasculitis. Recently, levamisole was discovered as a cocaine adulterant after reports emerged of drug users with the above disorders. As the prevalence of cocaine usage has grown in the last 15 years, measurement of levamisole in human samples has become increasingly important. This review focuses on the various bioanalytical methods available for the determination of levamisole in human plasma and urine. Earlier methods employed gas chromatography coupled with nitrogen-selective thermionic specific detection and nitrogen-phosphorus detection, as well as high performance liquid chromatography coupled with ultraviolet detection. In addition, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) have also been described. Currently, GC-MS appears to be the method of choice however recent developments in the area of LC-MS/MS make this technology an attractive alternative. The merits of both GC-MS and LC-MS/MS for the determination of levamisole are evaluated on the basis of sample preparation, chromatographic separation conditions, run time, and analytical performance. In addition, emerging methods in this area are also reviewed.

Background Peptide YY (PYY), a gut hormone that inhibits appetite, has been linked to the development of obesity. Objective This study investigated the nutritional regulation of PYY after 7 d of overfeeding (70% above normal energy requirements) in normal-weight, overweight, and obese men. Design Sixty-nine men (aged 19-29 y) participated in the study. We analyzed the relation between fasting serum PYY before and after a 7-d overfeeding challenge in normal-weight, overweight, and obese men. In addition, we analyzed PYY with obesity-related phenotypes including weight, percentage body fat (measured by dual-energy X-ray absorptiometry), body mass index (BMI), total cholesterol, HDL, LDL, glucose, insulin, insulin resistance, and β cell function evaluated by the homeostasis model assessment of insulin resistance (HOMA-IR) and β cell function (HOMA-β) at baseline and in response to the energy surplus. Results Fasting serum PYY concentrations at baseline were not significantly different between the normal-weight, overweight, and obese subjects on the basis of dual-energy X-ray absorptiometry or BMI. Although the PYY concentration significantly increased due to overfeeding, no differences were observed between adiposity statuses. In addition, basal PYY was negatively correlated with the changes of total cholesterol, HDL, and LDL in normal weight. In addition, the increase in PYY after overfeeding was positively correlated with HDL cholesterol and glucose in normal-weight subjects. Conclusions Our findings suggest that fasting PYY concentrations are not associated with adiposity status. Moreover, the 7-d overfeeding challenge significantly increased fasting PYY, which is likely a protective response to the positive energy balance.

Retinol-binding protein 4 (RBP4) is a novel adipokine that likely contributes to systemic insulin resistance and dyslipidemia. The role of genetic variations in RBP4 on phenotypes of glucose and lipid metabolism is not clear in humans. The purpose of this study was to examine five single-nucleotide polymorphisms (SNPs) in the RBP4 gene to determine their relationship with markers of insulin resistance and serum lipids in the CODING Study. The CODING Study consists of 1,836 subjects recruited from the genetically homogeneous population of Newfoundland and Labrador (NL), Canada. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA(IR)), HOMA for beta cell function (HOMA(beta)), total cholesterol (Chol), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides were determined after a 12-h fast. Five SNPs within RBP4 (rs3758539, G/A 5' flanking region; rs61461737, A/G intron; rs10882280, C/A intron; rs11187545, A/G intron; and rs12265684, C/G intron) were genotyped using TaqMan validated or functionally tested SNP genotyping assays. After correcting for multiple testing, we observed a significant association between the minor allele of two noncoding SNPs (rs10882280 and rs11187545) and higher serum HDL-C (P = 0.043 and 0.042, respectively). No significant associations were observed with any other parameter related to lipid metabolism. We also found no significant association between any variant sites and markers of insulin resistance. Our results suggest that genetic variations in RBP4 may play a role in the differences in serum HDL-C levels in the NL population.

Although BMI is the most widely used measure of obesity, debate still exists on how accurately BMI defines obesity. In this study, adiposity status defined by BMI and dual-energy X-ray absorptiometry (DXA) was compared in a large population to evaluate the accuracy of BMI. A total of 1,691 adult volunteers from Newfoundland and Labrador participated in the study. BMI and body fat percentage (%BF) were measured for all subjects following a 12-h fasting period. Subjects were categorized as underweight (UW), normal weight (NW), overweight (OW), or obese (OB) based on BMI and %BF criteria. Differences between the two methods were compared within gender and by age-groups. According to BMI criteria, 1.2% of women were classified as UW, 44.2% as NW, 34.2% as OW, and 20.3% as OB. When women were classified according to %BF criteria, 2.2% were UW, 29.6% were NW, 30.9% were OW, and 37.1% were OB. The overall discrepancy between the two methods for women was substantial at 34.7% (14.6% for NW and 16.8% for OB, P < 0.001). In men, the overall discrepancy was 35.2% between BMI and DXA (17.6% for OW and 13.5% for OB, P < 0.001). Misclassification by BMI was dependent on age, gender, and adiposity status. In conclusion, BMI misclassified adiposity status in approximately one-third of women and men compared with DXA. Caution should be taken when BMI is used in clinical and scientific research as well as clinical practice.

Background: Retinol-binding protein 4 (RBP4) is a novel adipokine that induces insulin resistance in mice. Studies in humans have shown a correlation between serum RBP4 and insulin resistance in obese subjects and in subjects with type 2 diabetes. Few data are available regarding the nutritional regulation of RBP4. Objective: The study investigated the relation of RBP4 with phenotypes of glucose and lipid metabolism at baseline and in response to a 7-d overfeeding protocol in young men. Design: Sixty-five men participated in the study. Subjects were classified on the basis of body mass index (BMI; kg/m 2 ) as normal-weight (≤24.9) or as overweight or obese (≥25.0). Serum RBP4, interleukin-6, visfatin, glucose, insulin, total cholesterol, HDL cholesterol, and LDL cholesterol (calculated), and triacylglycerols were measured. Insulin resistance and (3 cell function were assessed by using the homeostasis model. Percentage body fat was measured by using dual-energy X-ray absorptiometry. Results: No significant differences were found in serum RBP4 between the 2 groups at baseline. Likewise, no significant differences were observed in fasting serum RBP4 in response to overfeeding. Baseline RBP4 was negatively correlated with the change in insulin resistance in normal-weight subjects, independent of age and BMI. No significant correlation was found between serum RBP4 and visfatin, interleukin-6, or any other variables measured. Conclusions: Short-term overfeeding did not induce significant changes in RBP4. Baseline RBP4 concentrations may predict insulin resistance when exposed to a positive energy challenge in normal-weight men.

As an essential nutrient, Selenium (Se) is involved in many metabolic activities including mimicking insulin function. Data on Se in various biological samples and insulin resistance are contradictory, moreover there is no large study available regarding the relationship of dietary Se intake with insulin resistance in the general population. To investigate the association between dietary Se intake and variation of insulin resistance in a large population based study, a total of 2420 subjects without diabetes from the CODING (Complex Diseases in the Newfoundland Population: Environment and Genetics) study were assessed. Dietary Se intake was evaluated from the Willett Food Frequency questionnaire. Fasting blood samples were used for the measurement of glucose and insulin. Insulin resistance was determined with the homeostasis model assessment (HOMA-IR). Body composition was measured using dual energy X-ray absorptiometry. Analysis of covariance showed that high HOMA-IR groups in both males and females had the lowest dietary Se intake (μg/kg/day) (p < 0.01), being 18% and 11% lower than low HOMA-IR groups respectively. Insulin resistance decreased with the increase of dietary Se intake in females but not in males after controlling for age, total calorie intake, physical activity level, serum calcium, serum magnesium, and body fat percentage (p < 0.01). Partial correlation analysis showed that dietary Se intake was negatively correlated with HOMA-IR after adjusting for the Se confounding factors in subjects whose dietary Se intake was below 1.6 μg/kg/day (r = -0.121 for males and -0.153 for females, p < 0.05). However, the negative correlation was no longer significant when dietary Se intake was above 1.6 μg/kg/day. Our findings suggest that higher dietary Se intake is beneficially correlated with lower insulin resistance when total dietary Se intake was below 1.6 μg/kg/day. Above this cutoff, this beneficial effect disappears.

Objective Visfatin is a novel adipokine initially reported to exhibit insulin-mimetic effects that increase insulin sensitivity. Further studies indicate it may also be associated with obesity, serum lipids, and systemic inflammation. At the current time, the role of genetic variation in the visfatin gene (NAMPT) on these parameters is not clear. In the present study, we examined the association between 10 SNPs in NAMPT and insulin resistance, obesity, serum lipids and hsCRP levels. Research design and methods A total of 1838 subjects (413 men, 1425 women) were recruited from the ongoing CODING Study. All subjects were from the genetically homogenous population of Newfoundland and Labrador, Canada. BMI, waist circumference, waist-to-hip ratio, and body fat percentage (determined using DXA) were measured for all subjects. Serum glucose, insulin, HOMAIR, HOMAβ, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and hsCRP were also determined after a 12-hour fast. Ten SNPs in NAMPT were genotyped using TaqMan validated or functionally tested SNP genotyping assays including rs7789066 (A > G 5′ flanking region), rs3801266 (A > G intron), rs6963243 (G > C intron), rs2058539 (A > C intron), rs6947766 (C > T intron), rs4730153 (G > A intron), rs10808150 (G > A intron), rs2098291 (C > T intron), rs10953502 (T > C intron), and rs10953501 (A > G 3′ UTR). Results We observed no significant associations between any of the variants sites and any parameter of insulin resistance, body composition, serum lipids or hsCRP under an additive model with age and gender included as covariates. This was also true when both dominant and recessive models were applied. Conclusions Our results do not support a significant role for variations in NAMPT with differences in the measured variables in the Newfoundland population.