Longitudinal changes in vitamin D and its metabolites in pregnant South Africans.

BACKGROUND: Vitamin D deficiency (VDD) has been associated with adverse maternal and foetal outcomes and is determined by measuring 25 hydroxyvitamin D (25(OH)D). The 25(OH)D is catabolized to 24, 25-(OH) 2D and the ratio of 25(OH) D to 24, 25-(OH)2D, the vitamin D metabolite ratio (VMR), is thought to be a superior marker of VDD, being elevated in such states. The aims of this study were to assess the longitudinal vitamin D status of pregnant women by measuring cholecalciferol, 25(OH)D, 24, 25-(OH)2D and VMR at two time points and also to determine any association of vitamin D and metabolites with gestational age at birth, birth length and weight. METHODS: We recruited 400 pregnant black African women in their first trimester (V1) and measured weights and heights. Ultrasound scans were performed for gestational age. Blood was drawn at V1 and at about 26 weeks (V2) of gestation for cholecalciferol, 25(OH)D, 24, 25-(OH)2D, VMR and parathyroid hormone (PTH). An OGTT was performed at V2 where fasting glucose, insulin and 30-minute glucose were measured. At birth, we measured birth weight, length and gestational age. Maternal insulin, PTH and vitamin D binding protein (VDBP) were measured by immunoassay. Maternal albumin was measured colorimetrically. Maternal cholecalciferol, 25(OH)D and 24, 25-(OH)2D, were measured by mass spectrometry and free and bioavailable vitamin D were calculated. Initial gestation was determined by ultrasound. We compared analytes by visit as well as by 25(OH)D status. Vitamin D deficiency (<30 nmol/L) was defined according to the National Academy of Medicine guidelines. Linear regression analysis was used to determine associations of vitamin D molecules with maternal blood pressure, fasting and 30-minute insulin and blood glucose and neonatal parameters. RESULTS: Results are presented for participants for whom we had complete data (n = 330-346 depending on variable). The prevalence of vitamin D deficiency (VDD) was 35.8 % at V1 and 32.4 % at V2. Levels of 25(OH)D did not change significantly between visits. Levels of 24, 25(OH)2D dropped from the first to the second visit (17.64 ± 12.64 to 9.39 ± 9.07 nmol/L; p < 0.0001) while VMR increased ((3.15 (1.31; 7.67) to 7.90 (2.44; 25.98); p < 0.0001). The proportion of women with the lowest cholecalciferol concentrations increased at V2 compared to the V1 (36.1-42.8 %; p = 0.02). In multivariable regression models 25(OH)D was negatively associated with 30-minute glucose concentrations (p = 0.038) whilst 24, 25-(OH)2D was positively associated with fasting insulin (p = 0.017) and HOM A-I R (p = 0.023). There was no correlation of 25(OH)D or metabolites with infant birth weight, birth length or gestational age. CONCLUSIONS: Maternal VDD is common in pregnant black South African women. Decreased VMR suggest that catabolism of 25(OH)D is reduced in pregnancy to maintain adequate free vitamin D levels.

Menopausal symptoms, menopausal stage and cognitive functioning in black urban African women.

Objective: Studies, conducted largely in North America and Europe, demonstrate that menopausal symptoms and menopausal stage influence cognitive function. Here, we evaluate these associations in a large cohort of sub-Saharan African women, a population where these associations are understudied. We hypothesized that premenopausal women would show better cognitive performance than women later in the transition, and that menopausal symptoms would be inversely related to cognition.Methods: This cross-sectional study included 702 black urban South African women between the ages of 40 and 60 years from the Study of Women Entering and in Endocrine Transition. Participants completed the Symbol Digit Modalities Test, a measure of processing speed and incidental recall. Menopausal stage was ascertained using the Stages of Reproductive Aging Workshop+ 10 criteria and symptoms using the Menopause Rating Scale. Multivariable linear regression analyses were used to examine adjusted associations between menopausal stage and menopausal symptoms on cognitive performance.Results: In adjusted analyses, menopausal stage was not associated with processing speed (p = 0.35) or incidental recall (p = 0.64). However, more severe symptoms of hot flushes and anxiety were associated with slower processing speed (all p < 0.05), and more severe mood symptoms were associated with worse incidental recall (p = 0.008).Conclusion: Menopausal symptoms, but not menopausal stage, were associated with cognitive function in this cross-sectional study of sub-Saharan African women.

Identification of a subgroup of black South Africans with type 1 diabetes who are older at diagnosis but have lower levels of glutamic acid decarboxylase and islet antigen 2 autoantibodies.

AIMS: To compare the age at diagnosis and prevalence of islet autoantibody [glutamic acid decarboxylase (65 kDa) 65 and islet antigen 2] positivity in black and white participants with type 1 diabetes in South Africa, and to analyse the relationship between age at diagnosis and the presence of autoantibodies. METHODS: Participants were recruited from diabetes outpatient departments and autoantibodies to glutamic acid decarboxylase (65 kDa) and islet antigen 2 were measured by enzyme-linked immunosorbent assay. RESULTS: We recruited 472 (353 black and 119 white) participants with type 1 diabetes. Age at diagnosis of diabetes was later in black (19.7 ± 10.5) than in white participants (12.7 ± 10.8 years; P < 0.001) with a median (interquartile range) disease duration of 5.0 (2.0-10.0) and 8.5 (4.0-20.0) years (P < 0.001), respectively. An older age at diagnosis (≥ 21 years) was more frequent in black (152 of 340, 45%) than in white participants (24 of 116, 21%; P < 0.001). The prevalence of islet antigen 2 autoantibodies was 19% (66/352) in black and 41% in white participants (48/118; P < 0.001). There was no significant difference in glutamic acid decarboxylase (65 kDa) autoantibody positivity between black (212/353, 60%) and white participants (77/117, 66%; P = 0.269). In black, but not white, participants the prevalence of both glutamic acid decarboxylase (65 kDa) and islet antigen 2 autoantibody positivity was significantly lower in participants diagnosed at age ≥ 21 years (P < 0.001 for both comparisons). CONCLUSIONS: The older age at diagnosis, lower prevalence of islet antigen 2 autoantibodies and a distinct subgroup of participants with type 1 diabetes with age at diagnosis of > 20 years in the black compared to white population suggest a difference in the immunological aetiology of type 1 diabetes in these two population groups.

Deriving an optimal threshold of waist circumference for detecting cardiometabolic risk in sub-Saharan Africa.

BACKGROUND: Waist circumference (WC) thresholds derived from western populations continue to be used in sub-Saharan Africa (SSA) despite increasing evidence of ethnic variation in the association between adiposity and cardiometabolic disease and availability of data from African populations. We aimed to derive a SSA-specific optimal WC cut-point for identifying individuals at increased cardiometabolic risk. METHODS: We used individual level cross-sectional data on 24 181 participants aged ⩾15 years from 17 studies conducted between 1990 and 2014 in eight countries in SSA. Receiver operating characteristic curves were used to derive optimal WC cut-points for detecting the presence of at least two components of metabolic syndrome (MS), excluding WC. RESULTS: The optimal WC cut-point was 81.2 cm (95% CI 78.5-83.8 cm) and 81.0 cm (95% CI 79.2-82.8 cm) for men and women, respectively, with comparable accuracy in men and women. Sensitivity was higher in women (64%, 95% CI 63-65) than in men (53%, 95% CI 51-55), and increased with the prevalence of obesity. Having WC above the derived cut-point was associated with a twofold probability of having at least two components of MS (age-adjusted odds ratio 2.6, 95% CI 2.4-2.9, for men and 2.2, 95% CI 2.0-2.3, for women). CONCLUSION: The optimal WC cut-point for identifying men at increased cardiometabolic risk is lower (⩾81.2 cm) than current guidelines (⩾94.0 cm) recommend, and similar to that in women in SSA. Prospective studies are needed to confirm these cut-points based on cardiometabolic outcomes.International Journal of Obesity advance online publication, 31 October 2017; doi:10.1038/ijo.2017.240.

Diabetes and abnormal glucose tolerance in subjects with tuberculosis in a South African urban center.

SETTING: Primary health care clinics. OBJECTIVES: To determine the prevalence of diabetes mellitus (DM) in tuberculosis (TB) patients using glycated haemoglobin (HbA1c), and to compare the performance of laboratory and point-of-care (POC) HbA1c measurement. METHODS: This was a cross-sectional study of 325 patients. Screening was at POC using laboratory HbA1c methods; DM was confirmed by the oral glucose tolerance test (OGTT). Multivariate regression analysis was performed to determine predictors of HbA1c. RESULTS: Mean laboratory-derived HbA1c was significantly higher than mean POC HbA1c (P = 0.007). Of 83 subjects who underwent OGTT, 2 (2.4%) were diagnosed with DM, 3 (3.60%) with impaired fasting glucose and 15 (18.1%) with impaired glucose tolerance. Twelve (14.5%) had an HbA1c of 6.50% using POC HbA1c and 21 (25.3%) using laboratory HbA1c. In multivariate regression analysis, age and weight were positively associated with both laboratory and POC HBA1c, while duration of anti-tuberculosis treatment was negatively associated with both. CONCLUSION: Glucose and HbA1c levels fell with increased duration of anti-tuberculosis treatment, suggesting that the optimal time for DM screening in this population was at least 5 months after TB was first diagnosed. Our data suggest that the use of HbA1c is inappropriate for testing glycaemia in patients with TB.

Visceral adiposity is a predictor of parathyroid hormone levels in healthy adults.

PURPOSE: Parathyroid hormone (PTH) has been shown to correlate positively with fat mass, however there are no studies that have investigated whether this association is a result of, or is modified by, body fat distribution. The aim of this study was to investigate the association of PTH with several body composition indices, namely visceral (VAT) and subcutaneous adiposity (SCAT) as well as with lean mass and with serum leptin, which has been reported to increase PTH. METHODS: This was a cross-sectional study in which PTH was measured by chemiluminescent assay; body fat and lean mass by dual-energy X-ray absorptiometry (DXA) and abdominal fat by ultrasonography in 714 healthy adults aged 18-65 years. Serum leptin was measured by ELISA. RESULTS: In a multivariate linear regression model that included height, age, gender, ethnicity, serum 25 hydroxyvitamin D, leptin levels, calcium, magnesium and phosphate concentrations, glomerular filtration rate, smoking status, and calcium and vitamin D supplementation as independent variables and PTH as the dependent variable, VAT (ß = 0.094, p = 0.035) correlated significantly with PTH levels but SCAT (ß = -0.045, p = 0.386) and body fat mass (ß = 0.098, p = 0.126) did not. Leptin did not correlate with PTH (ß = 0.013, p = 0.832) in this regression model. CONCLUSIONS: Plasma PTH is significantly associated with VAT in healthy adults. In view of the association of PTH with increased cardiovascular mortality, it is important to investigate this association further.

H3Africa AWI-Gen Collaborative Centre: a resource to study the interplay between genomic and environmental risk factors for cardiometabolic diseases in four sub-Saharan African countries.

Africa is experiencing a rapid increase in adult obesity and associated cardiometabolic diseases (CMDs). The H3Africa AWI-Gen Collaborative Centre was established to examine genomic and environmental factors that influence body composition, body fat distribution and CMD risk, with the aim to provide insights towards effective treatment and intervention strategies. It provides a research platform of over 10 500 participants, 40-60 years old, from Burkina Faso, Ghana, Kenya and South Africa. Following a process that involved community engagement, training of project staff and participant informed consent, participants were administered detailed questionnaires, anthropometric measurements were taken and biospecimens collected. This generated a wealth of demographic, health history, environmental, behavioural and biomarker data. The H3Africa SNP array will be used for genome-wide association studies. AWI-Gen is building capacity to perform large epidemiological, genomic and epigenomic studies across several African counties and strives to become a valuable resource for research collaborations in Africa.

Exploring genetic markers of adult obesity risk in black adolescent South Africans-the Birth to Twenty Cohort.

To date more than 90 loci that show an association with body mass index (BMI) and other obesity-related traits, have been discovered through genome-wide association studies. These findings have been widely replicated, mostly in European and Asian populations, but systematic investigation in African cohorts is still lacking. Therefore, the aim of our study was to replicate the association of six single-nucleotide polymorphisms (SNPs) previously linked to BMI, in a South African black adolescent cohort. The SNPs were in or near GNPDA2 (rs10938397), MTCH2 (rs10838738), NEGR1 (rs2568958), SH2B1 (rs7498665), STK33 (rs10769908) and TMEM18 (rs6548238). The SNPs were genotyped in 990 adolescents from the Birth to Twenty study, using an Illumina VeraCode assay, and association with BMI statistically assesed by using PLINK. Three of the SNPs tested were associated with BMI in this African cohort, and showed a consistent (albeit smaller) directional effect to that observed in non-African cohorts. We identified significant association between BMI and rs10938397 (effect allele-G) near GNPDA2 (Padj=0.003), rs7498665 (effect allele-G) in SH2B1 (Padj=0.014) and rs6548238 (effect allele-C) near TMEM18 (Padj=0.030). This data suggests that common genetic variants potentially contributes to obesity risk in diverse population groups.

The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups.

CONTEXT AND OBJECTIVE: There are few data on the contribution of body composition to bone mineral density (BMD) in non-Caucasian populations. We therefore studied the contribution of body composition, and possible confounding of 25-hydroxyvitamin D and PTH, to BMD at various skeletal sites in black African (BA) and Asian Indian (AI) subjects. DESIGN AND SETTING: This was a cross-sectional study in Johannesburg, South Africa. PARTICIPANTS: BMD, body fat, and lean mass were measured using dual x-ray absorptiometry and abdominal fat distribution by ultrasound in 714 healthy subjects, aged 18-65 years. RESULTS: Whole-body (subtotal), hip, femoral neck, and lumbar spine (lumbar) BMD were significantly higher in BA than AI subjects (P < .001 for all). Whole-body lean mass positively associated with BMD at all sites in both ethnic groups (P < .001 for all) and partially explained the higher BMD in BA females compared with AI females. Whole-body fat mass correlated positively with lumbar BMD in BA (P = .001) and inversely with subtotal BMD in AI subjects (P < .0001). Visceral adiposity correlated inversely with subtotal BMD in the BA (P = .037) and with lumbar BMD in the AI group (P = .005). No association was found between serum 25-hydroxyvitamin D and BMD. PTH was inversely associated with hip BMD in the BA group (P = .01) and with subtotal (P = .002), hip (P = .001), and femoral BMD (P < .0001) in the AI group. CONCLUSIONS: Significant differences in whole-body and site-specific BMD between the BA and AI groups were observed, with lean mass the major contributor to BMD at all sites in both groups. The contribution of other components of body composition differed by site and ethnic group.

A randomized clinical trial comparing metabolic parameters after 48 weeks of standard- and low-dose stavudine therapy and tenofovir disoproxil fumarate therapy in HIV-infected South African patients.

OBJECTIVES: Low-dose stavudine therapy may have a lower toxicity profile compared with standard dose. A randomized controlled trial comparing these two doses of stavudine with tenofovir disoproxil fumarate (tenofovir DF) was performed to assess the effects on anthropometry, markers of inflammation, and lipid and glucose metabolism in Black South African patients. METHODS: Sixty patients were randomized 1:1:1 to either standard-dose (30-40 mg) or low-dose (20-30 mg) stavudine or tenofovir DF (300 mg), each combined with lamivudine and efavirenz, for 48 weeks. Anthropometry, markers of inflammation, and lipid and glucose metabolism were assessed using standard techniques. RESULTS: In all three treatment arms, there was a significant increase in lipid levels over the study period. At 48 weeks, fasting glucose level (P < 0.005) and homeostasis model assessment (HOMA) score (P < 0.05) increased significantly in the standard-dose stavudine arm, as did insulin and C-peptide levels in both the standard- and low-dose stavudine arms. At week 48, a significant decrease (P < 0.05) in adiponectin was noted in the standard-dose stavudine arm, but there was an increase (P < 0.005) in the tenofovir DF arm. In both the stavudine arms, significant increases in anthropometric measures occurred at 24 weeks but these decreased by week 48. Mitochondrial toxicities occurred in both the stavudine arms. Immunological and virological outcomes were similar for all three arms. CONCLUSIONS: This study highlights the occurrence of metabolic abnormalities with both stavudine and tenofovir DF treatment. Awareness of the potential increased cardiovascular risk should be of concern with the use of both these therapies.

The early effects of stavudine compared with tenofovir on adipocyte gene expression, mitochondrial DNA copy number and metabolic parameters in South African HIV-infected patients: a randomized trial.

OBJECTIVES: Stavudine is being phased out because of its mitochondrial toxicity and tenofovir (TDF) is recommended as part of first-line highly active antiretroviral therapy (HAART) in South Africa. A prospective, open-label, randomized controlled trial comparing standard- and low-dose stavudine with TDF was performed to assess early differences in adipocyte mtDNA copy number, gene expression and metabolic parameters in Black South African HIV-infected patients. METHODS: Sixty patients were randomized 1:1:1 to either standard-dose (30-40 mg) or low-dose (20-30 mg) stavudine or TDF (300 mg) each combined with lamivudine and efavirenz. Subcutaneous fat biopsies were obtained at weeks 0 and 4. Adipocyte mtDNA copies/cell and gene expression were measured using quantitative polymerase chain reaction (qPCR). Markers of inflammation and lipid and glucose metabolism were also assessed. RESULTS: A 29% and 32% decrease in the mean mtDNA copies/cell was noted in the standard-dose (P < 0.05) and low-dose stavudine (P < 0.005) arms, respectively, when compared with TDF at 4 weeks. Nuclear respiratory factor-1 (NRF1) and mitochondrial cytochrome B (MTCYB) gene expression levels were affected by stavudine, with a significantly (P < 0.05) greater fall in expression observed with the standard, but not the low dose compared with TDF. No significant differences were observed in markers of inflammation and lipid and glucose metabolism. CONCLUSIONS: These results demonstrate early mitochondrial depletion among Black South African patients receiving low and standard doses of stavudine, with preservation of gene expression levels, except for NRF1 and MTCYB, when compared with patients on TDF.

The interrelationship between bone and fat: from cellular see-saw to endocrine reciprocity.

The number of mature osteoblasts and marrow adipocytes in bone is influenced by the differentiation of the common mesenchymal progenitor cell towards one phenotype and away from the other. Consequently, factors which promote adipogenesis not only lead to fatty marrow but also inhibit osteoblastogenesis, resulting in decreased osteoblast numbers, diminished bone formation and, potentially, inadequate bone mass and osteoporosis. In addition to osteoblast and bone adipocyte numbers being influenced by this skewing of progenitor cell differentiation towards one phenotype, mature osteoblasts and adipocytes secrete factors which may evoke changes in the cell fate and function of each other. This review examines the endogenous factors, such as PPAR-γ2, Wnt, IGF-1, GH, FGF-2, oestrogen, the GP130 signalling cytokines, vitamin D and glucocorticoids, which regulate the selection between osteoblastogenesis and adipogenesis and the interrelationship between fat and bone. The role of adipokines on bone, such as adiponectin and leptin, as well as adipose-derived oestrogen, is reviewed and the role of bone as an energy regulating endocrine organ is discussed.

Adipokine serum concentrations, anthropometric measurements and socio-economic status in two ethnic groups with different prevalence levels for cardiovascular diseases and type 2 diabetes.

Obesity is more common in African than Asian-Indian populations and yet type 2 diabetes and cardiovascular diseases are more common in the latter populations. The main purpose of the current study was therefore to determine whether ethnic differences in body fat distribution, adipokine levels, and socio-economic status may explain population differences in the prevalence of these metabolic disorders. Leptin, IL-6, CRP, visceral fat, education level, and socio-economic status were measured in 50 African and the same number of Indian women residing in Johannesburg, South Africa. Serum leptin levels were significantly higher in Indian than African subjects (41.3±2.0 and 34.2±2.9 ng/ml, respectively; p<0.05). TNF-α levels were significantly higher in the African group, (5.22±0.86 vs. 2.54±0.52 pg/ml; p<0.05), whilst visceral fat levels were significantly lower (56.1±5.5 vs. 77.9±6.5 cm(2); p<0.05). The CRP and IL-6 levels were not different between groups. Education levels (p<0.005) and socio-economic status (p<0.0001) were both lower in the African subjects, however, adjusting for these variables in ANCOVA did not attenuate differences in adipokine or visceral fat levels. We hypothesise that one of the reasons for the higher prevalence of obesity in the African than Indian population may be related to lower leptin levels, whilst ethnic differences in the prevalence of metabolic disorders cannot be explained by differences in adipokine levels, but maybe related to higher visceral adiposity in the Indian group.

Once fat was fat and that was that: our changing perspectives on adipose tissue.

Past civilisations saw excess body fat as a symbol of wealth and prosperity as the general population struggled with food shortages and famine. Nowadays it is recognised that obesity is associated with co-morbidities such as cardiovascular disease and diabetes. Our views on the roll of adipose tissue have also changed, from being solely a passive energy store, to an important endocrine organ that modulates metabolism, immunity and satiety. The relationship between increased visceral adiposity and obesity-related co-morbidities has lead to the recognition that variation in fat distribution contributes to ethnic differences in the prevalence of obesity-related diseases. Our current negative view of adipose tissue may change with the use of pluripotent adipose-derived stromal cells, which may lead to future autologous stem cell therapies for bone, muscle, cardiac and cartilage disorders. Here, we briefly review the concepts that adipose tissue is an endocrine organ, that differences in body fat distribution underline the aetiology of obesity-related co-morbidities, and the use of adipose-derived stem cells for future therapies.

Insulin resistance in the control of body fat distribution: a new hypothesis.

Obesity causes insulin resistance, which is a prime etiological factor for type 2 diabetes, dyslipidemia, and cardiovascular disease. However, insulin resistance may be a normal physiological response to obesity that limits further fat deposition and which only has pathological effects at high levels. The current hypothesis suggests that in obesity the initial deposition of triglycerides occurs in subcutaneous adipose tissue and as this increases in size insulin resistance will rise and limit further subcutaneous lipid accumulation. Triglycerides will then be diverted to the visceral fat depot as well as to ectopic sites. This leads to a substantial rise in insulin resistance and the prevalence of its associated disorders. Evidence supporting this hypothesis includes studies showing that in lean subjects the prime determinant of insulin resistance is BMI, that is, subcutaneous fat whilst in overweight and obese subjects it is waist circumference and visceral adiposity. It has also been shown that the metabolic syndrome suddenly increases in prevalence at high levels of insulin resistance and we suggest that this is due to the diversion of lipids from the subcutaneous to the visceral depot. This system may have functioned in our evolutionary past to limit excessive adiposity by causing lipid deposition to occur at a site that has maximal effects on insulin resistance but involves minimal weight gain.

Depot-specific differences in the insulin response of adipose-derived stromal cells.

Visceral adiposity is more strongly linked to insulin resistance than subcutaneous adiposity. High insulin levels can be mitogenic or adipogenic to adipocytes, but little is known regarding these effects of insulin on stromal cells from visceral and subcutaneous fat depots. Consequently, we measured adipogenesis and mitosis in response to elevated insulin levels in rat adipose-derived stromal cells (ADSCs) from visceral (perirenal) and subcutaneous depots. Insulin alone, at 10 microM, did not stimulate adipogenesis in naïve perirenal visceral (pvADSCs) or subcutaneous ADSCs (scADSCs), although a significant increase in proliferation occurred in both. Adipogenesis, induced using adipocyte differentiation medium (AM), resulted in greater lipid accumulation in pvADSCs, but the associated decrease in proliferation was less than in scADSCs. Omission of insulin from AM significantly reduced lipid accumulation in pvADSCs, but had little effect in scADSC, whilst proliferation was inhibited more in scADSCs than pvADSCs. Consequently, insulin is more lipogenic and less mitogenic in differentiating pvADSCs compared to scADSCs.

The effect of poly-L-lysine/alginate bead membrane characteristics on the absorption of heparin.

During extracorporeal procedures like hemodialysis, heparin is administered to patients to prevent clotting. Unfractionated heparin has side effects such as excessive bleeding. It would be advantageous if the blood could be deheparinased before it returns to the patient. Previous work has indicated that poly-L-lysine/alginate beads can efficiently remove heparin from saline solutions 1. Heparin is irreversibly absorbed onto the beads. This article explores ways of optimizing the absorption process by performing in vitro rate experiments with varying physical parameters of the beads. Fetal calf serum and blood are also used in experiments to investigate the possibility of designing a safe and efficient reactor to absorb heparin. All the experiments were performed to obtain the required parameters for optimal reactor design. The results indicate that the absorption could be optimized by controlling the membrane thickness of the beads. The beads also showed efficient removal of heparin from whole blood.

Efficiency of polymer beads in the removal of heparin: toward the development of a novel reactor.

Administration of heparin during extracorporeal procedures increases the risk of haemorrhage. Various reactor designs, including the use of heparinase and poly-L-lysine. HBr hollow fiber, have been investigated for the removal of heparin prior to the blood being returned to the patient; however, none of them have been implemented clinically. In this paper it is proposed that beads made from poly-L-lysine/alginate can be used to remove the heparin. The aim of this work is to perform the necessary experiments in order to get the information required to design a heparin removal reactor that uses these beads. The experiments are aimed at measuring the removal rates of heparin by the beads, testing the efficiency of the beads to remove heparin, determining repeatability and identifying factors that could influence the removal rate. Batch rate experiments using poly-L-lysine/alginate beads in saline solutions were performed to investigate the removal rate of heparin. The results, which indicate that heparin is efficiently removed, may lead to improved bioreactor designs.

The effect of abdominal obesity on insulin sensitivity and serum lipid and cytokine concentrations in African women.

OBJECTIVES: Studies have shown clear associations of abdominal obesity with lipid and glucose metabolism and cytokine levels in a number of different population groups. However, no such studies have been performed in an African population in which visceral adipose tissue levels have been shown to be lower than in European subjects. DESIGN AND PATIENTS: Cross-sectional analysis in 124 African women. MEASUREMENTS: Fasting serum samples were taken from all subjects and anthropometric measurements obtained. Blood levels of glucose, insulin, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglyceride, interleukin (IL)-6, IL-8 and IL-18 were measured. Subjects were separated into normal and abnormal glucose tolerant groups and into tertiles according to waist circumference (WC). Insulin resistance was assessed using the homeostasis model assessment (HOMA). RESULTS: Abnormal glucose-tolerant subjects had higher WC, glucose and HOMA levels than the normal glucose-tolerant group. Increased WC was associated with higher triglyceride, insulin and HOMA levels and lower HDL levels. Multiple regression analyses showed that WC associated positively with HOMA and serum triglyceride levels and negatively with HDL levels. IL18 was a positive but weak determinant of the HOMA level and BMI correlated positively with serum IL-6 concentrations. CONCLUSIONS: Although previous studies have shown that African subjects have a lower visceral adipose depot size than European subjects, abdominal obesity is still associated with insulin resistance and dyslipidaemia. The association between abdominal obesity and metabolic dysfunction within this population is not dependent upon IL-6, IL-8 or IL-18.