Cognitive and Motor Development in 3- to 6-Year-Old Children Born to Mothers with Hyperglycaemia First Detected in Pregnancy in an Urban African Population.

OBJECTIVES: Hyperglycaemia first detected in pregnancy (HFDP), on the rise in urban sub-Saharan Africa (SSA), may negatively impact foetal neurodevelopment, with potential long-term cognitive consequences for the child. Data on this association from SSA is lacking, and we aimed to investigate the association in 3- to 6-year-old children in Soweto, South Africa. METHODS: In this comparative study, we compared cognitive skills measured with the Herbst Early Childhood Development Criteria test in 95 children born to mothers with HFDP and 99 participants unexposed to maternal HFDP. Fine and gross motor skills were secondary outcomes. Ordinal regression analysis with known confounders was performed for children born at-term. RESULTS: Of children exposed to HFDP born at-term, 24.3% scored 'high' and 25.7% scored 'low' in the cognitive subsection of the test, as opposed to 37.7% and 12.9% in the HFDP-unexposed group, respectively. In ordinal regression, exposed participants had a significantly lower odds of scoring in a higher cognitive category when adjusting for maternal confounders and socio-economic status (OR 0.33, 95% CI 0.15-0.74, p = 0.007). No difference was found in gross motor development between the two groups; differences in fine motor development were attenuated after adjustment for maternal pregnancy factors and household socioeconomic status (OR 0.62, 95% CI 0.28-1.37, p = 0.239). CONCLUSIONS FOR PRACTICE: Exposure to HFDP was negatively associated with cognitive development at preschool age. Optimising maternal (preconception) health and early childhood cognitive stimulation could help more children reach their developmental potential.

Sugar-sweetened beverage intake and relative weight gain among South African adults living in resource-poor communities: longitudinal data from the STOP-SA study.

OBJECTIVES: This study examines the prospective association between sugar-sweetened beverages (SSB) consumption and change in body weight over a 4-5-year period in a socio-economically disadvantaged South African population. METHODS: This is a longitudinal study involving 800 adults (212 men, 588 women); 247 from the original METS (Modelling the Epidemiological Transition Study) cohort (N = 504) and 553 of the original 949 members of the PURE (Prospective Urban and Rural Epidemiology) Study. Both cohorts were drawn from low-income, socio-economically disadvantaged communities. Mean follow-up duration and age were 4.5 (SD 0.45) and 50.0 (SD 11.8) years, respectively. Harmonised measurements included body mass index, self-reported moderate-to-vigorous physical activity, and intake of meat, snacks and 'take-aways', fruits and vegetables and SSB (in servings/week). Multivariate logistic regression models were developed to determine the extent to which SSB consumption predicted relative weight gain, after controlling for potential confounders and known predictors. RESULTS: Nearly a third (29%) of participants had a relative weight change ≥5.0%; higher in the non-obese compared to the obese group (32% vs. 25%; p = 0.026). The average SSB consumption was 9.9 servings/week and was higher in the food insecure compared to the food secure group (11.5 vs. 9.0 servings/week; p = 0.006); but there were no differences between women and men (10.3 vs. 9.1 servings/week; p = 0.054). Mean SSB consumption was higher in the group who gained ≥5% weight compared to those who did not (11.0 vs. 8.7; p = 0.004). After adjustment, SSB consumption of 10 or more servings/week was associated with a 50% greater odds of gaining at least 5% body weight (AOR: 1.50, 95% CI (1.05-2.18)). CONCLUSION: These results show that higher intake of SSB predicts weight gain in a sample of South Africans drawn from low-income settings. Comprehensive, population-wide interventions are needed to reduce SSB consumption in these settings.

Pregnancy outcome in patients with pregestational and gestational diabetes attending Groote Schuur Hospital, Cape Town, South Africa.

BACKGROUND: The burden of diabetes mellitus (DM) has increased dramatically worldwide. The association between poorly controlled DM and poor pregnancy outcomes has been well described. OBJECTIVES: To describe the pregnancy outcomes of patients with pregestational and gestational DM attending Groote Schuur Hospital, Cape Town, South Africa. METHODS: A retrospective audit was undertaken of all women with pregestational and gestational DM (GDM) who attended Groote Schuur Hospital obstetric care from 1 September 2010 to 31 August 2011. Information routinely collected at booking and during the rest of pregnancy was entered onto a data abstraction form. Patients diagnosed with GDM were further subdivided into two groups, GDM and impaired glucose tolerance (IGT), depending on the oral glucose tolerance test results. RESULTS: A total of 725 diabetic pregnancies were managed: 35 women had type 1 DM (T1DM), 194 had type 2 DM (T2DM), 192 had GDM and 304 had IGT. The median glycated haemoglobin (HbA1c) value at booking was highest for T1DM, followed by T2DM and lastly GDM. Overall, 10.7% of women had pre-existing hypertension and 9.8% developed pre-eclampsia (PET). The preterm delivery rate (before 38 weeks) was 68.8% for women with T1DM, 38.7% for those with T2DM, 34.9% for those with GDM and 22.4% for those with IGT. The caesarean section rate exceeded 50% in all groups. The overall perinatal mortality rate was 2.5% (25/1 000 births) for the study population, with T1DM and T2DM contributing most deaths (6.4% and 4.2%). The overall rate of congenital malformations was 2.4% (n=18 cases), but the rate was 5.7% for patients with T1DM and 4.6% for those with T2DM. CONCLUSION: The audit demonstrated outcomes similar to those in the developed world, with major congenital malformations, unexplained stillbirths and PET accounting for the majority of perinatal deaths. Stricter control with the aim of achieving lower or normal HbA1c levels before conception may be the only intervention that could bring about change.

High prevalence of "non-dipping" blood pressure and vascular stiffness in HIV-infected South Africans on antiretrovirals.

BACKGROUND: HIV-infected individuals are at increased risk of tissue inflammation and accelerated vascular aging ('inflamm-aging'). Abnormal diurnal blood pressure (BP) rhythms such as non-dipping may contribute to an increased risk of cardiovascular and cerebrovascular events in HIV infected individuals. However, little data exists on ambulatory blood pressure (ABP) and measures of vascular stiffness in the black African HIV infected population. METHODS: This is a cross-sectional analysis of otherwise well, HIV infected outpatients on ART for >5 years. Study assessments included: 24hr ABP monitoring, pulse wave velocity (PWV) and central aortic systolic pressure (CASP) using a AtCor Medical Sphygmocor device, fasting lipogram, oral glucose tolerance test, high-sensitivity C-reactive protein (hsCRP) and anthropometric data. Patients completed a questionnaire of autonomic symptoms. CD4+ counts and viral loads were obtained from the National Laboratory results system. RESULTS: Sixty seven black participants were included in the analysis of whom 91% (n = 61) were female with a mean age of 42.2 ± 8.6 years. The median duration on ART was 7.5 years (IQR = 6-10), 84% were virally supressed and the median CD4 count was 529.5cells/mm3 (IQR = 372.0-686.5). The majority (67%) were classified as overweight and 76% had an increased waist circumference, yet only 88% of participants were normotensive. A hsCRP level in the high cardiovascular risk category was found in 68% of participants. The prevalence of non-dipping BP was 65%. Interestingly, there was no association on multivariable analysis between dipping status and traditional risk factors for non-dipping BP, such as: obesity, autonomic dysfunction and older age. CONCLUSION: This relatively young cross-sectional sample of predominantly normotensive, but overweight black women on effective ART >5 years showed: a high prevalence of non-dipping BP, inflammation and vascular stiffness. Causality cannot be inferred but cardiovascular risk reduction should be emphasized in these patients.

Socioeconomic and modifiable predictors of blood pressure control for hypertension in primary care attenders in the Western Cape, South Africa.

BACKGROUND: Low socioeconomic status is associated with the risk of hypertension. There are few reports of the effect of socioeconomic and potentially modifiable factors on the control of hypertension in South Africa (SA). OBJECTIVES: To investigate associations between patients' socio-economic status and characteristics of primary healthcare facilities, and control and treatment of blood pressure in hypertensive patients. METHODS: We enrolled hypertensive patients attending 38 public sector primary care clinics in the Western Cape, SA, in 2011, and followed them up 14 months later as part of a randomised controlled trial. Blood pressure was measured and prescriptions for antihypertension medications were recorded at baseline and follow-up. Logistic regression models assessed associations between patients' socioeconomic status, characteristics of primary healthcare facilities, and control and treatment of blood pressure. RESULTS: Blood pressure was uncontrolled in 60% (1 917/3 220) of patients at baseline, which was less likely in patients with a higher level of education (p=0.001) and in English compared with Afrikaans respondents (p=0.033). Treatment was intensified in 48% (892/1 872) of patients with uncontrolled blood pressure at baseline, which was more likely in patients with higher blood pressure at baseline (p<0.001), concurrent diabetes (p=0.013), more education (p=0.020), and those who attended clinics offering off-site drug supply (p=0.009), with a doctor every day (p=0.004), or with more nurses (p<0.001). CONCLUSION: Patient and clinic factors influence blood pressure control and treatment in primary care clinics in SA. Potential modifiable factors include ensuring effective communication of health messages, providing convenient access to medications, and addressing staff shortages in primary care clinics.

Salivary Cortisol and Cortisone do not Appear to be Useful Biomarkers for Monitoring Hydrocortisone Replacement in Addison's Disease.

Salivary cortisol has been used to monitor hydrocortisone replacement in patients with Addison's disease (AD). Since salivary cortisol is metabolised to salivary cortisone, it may be an adjunctive analyte to assess adequacy of hydrocortisone replacement in patients with AD. We aimed to characterise the exposure of salivary cortisol and cortisone in patients and healthy controls. We measured salivary cortisol and cortisone by liquid chromatography-tandem mass spectrometry and constructed a day curve (08:00 until 24:00 h) with 16 time points in 25 AD patients taking their usual hydrocortisone dose and in 26 healthy controls. The median (interquartile range) area under the curve (AUC) for cortisol was not different for patients, compared with controls [55.63 (32.91-151.07) nmol*min*l-1 vs. 37.49 (27.41-52.00) nmol*min*l-1; p=0.098, respectively], whereas the peak cortisol Cmax was higher in patients [32.61 (5.75-146.19) nmol/l vs. 8.96 (6.96-12.23) nmol/l; p=0.013], compared with controls. The AUC for cortisone [23.65 (6.10-54.76) nmol*min*l-1 vs. 227.73 (200.10-280.52) nmol*min*l-1; p≤ 0.001, respectively], and peak cortisone Cmax was lower in patients than in controls [11.11 (2.91-35.85) nmol/l vs. 33.12 (25.97-39.95) nmol/l; p=0.002]. The AUC for salivary cortisol and salivary cortisone were not correlated with any measures of hydrocortisone dose. The time-course and AUC of salivary cortisol were similar between Addison's patients and healthy controls. Patients had substantially lower salivary cortisone AUC, compared to healthy controls. Salivary cortisol AUC and pharmacokinetics were not related to hydrocortisone dose and thus are not likely useful markers for the adequacy of hydrocortisone replacement.

The need for an integrated approach for chronic disease research and care in Africa.

With the changing distribution of infectious diseases, and an increase in the burden of non-communicable diseases, low- and middle-income countries, including those in Africa, will need to expand their health care capacities to effectively respond to these epidemiological transitions. The interrelated risk factors for chronic infectious and non-communicable diseases and the need for long-term disease management, argue for combined strategies to understand their underlying causes and to design strategies for effective prevention and long-term care. Through multidisciplinary research and implementation partnerships, we advocate an integrated approach for research and healthcare for chronic diseases in Africa.

H3Africa multi-centre study of the prevalence and environmental and genetic determinants of type 2 diabetes in sub-Saharan Africa: study protocol.

The burden and aetiology of type 2 diabetes (T2D) and its microvascular complications may be influenced by varying behavioural and lifestyle environments as well as by genetic susceptibility. These aspects of the epidemiology of T2D have not been reliably clarified in sub-Saharan Africa (SSA), highlighting the need for context-specific epidemiological studies with the statistical resolution to inform potential preventative and therapeutic strategies. Therefore, as part of the Human Heredity and Health in Africa (H3Africa) initiative, we designed a multi-site study comprising case collections and population-based surveys at 11 sites in eight countries across SSA. The goal is to recruit up to 6000 T2D participants and 6000 control participants. We will collect questionnaire data, biophysical measurements and biological samples for chronic disease traits, risk factors and genetic data on all study participants. Through integrating epidemiological and genomic techniques, the study provides a framework for assessing the burden, spectrum and environmental and genetic risk factors for T2D and its complications across SSA. With established mechanisms for fieldwork, data and sample collection and management, data-sharing and consent for re-approaching participants, the study will be a resource for future research studies, including longitudinal studies, prospective case ascertainment of incident disease and interventional studies.

Glucocorticoid receptor gene expression in adipose tissue and associated metabolic risk in black and white South African women.

BACKGROUND: Black women have lower visceral adipose tissue (VAT) but are less insulin sensitive than white women; the mechanisms responsible are unknown. OBJECTIVE: The study aimed to test the hypothesis that variation in subcutaneous adipose tissue (SAT) sensitivity to glucocorticoids might underlie these differences. METHODS: Body fatness (dual energy X-ray absorptiometry) and distribution (computerized tomography), insulin sensitivity (SI, intravenous and oral glucose tolerance tests), and expression of 11ß-hydroxysteroid dehydrogenase-1 (11HSD1), hexose-6-phosphate dehydrogenase and glucocorticoid receptor-α (GRα), as well as genes involved in adipogenesis and inflammation were measured in abdominal deep SAT, superficial SAT and gluteal SAT (GLUT) depots of 56 normal-weight or obese black and white premenopausal South African (SA) women. We used a combination of univariate and multivariate statistics to evaluate ethnic-specific patterns in adipose gene expression and related body composition and insulin sensitivity measures. RESULTS: Although 11HSD1 activity and mRNA did not differ by ethnicity, GRα mRNA levels were significantly lower in SAT of black compared with white women, particularly in the GLUT depot (0.52±0.21 vs 0.91±0.26 AU, respectively, P<0.01). In black women, lower SAT GRα mRNA levels were associated with increased inflammatory gene transcript levels and abdominal SAT area, and reduced adipogenic gene transcript levels, VAT/SAT ratio and SI. Abdominal SAT 11HSD1 activity associated with increased VAT area and decreased SI in white, but not in black women. CONCLUSIONS: In black SA women, downregulation of GRα mRNA levels with obesity and reduced insulin sensitivity, possibly via increased SAT inflammation, is associated with reduced VAT accumulation.

Male and female hypogonadism are highly prevalent in South Africans with Addison's disease.

Hypogonadism may complicate Addison's disease (primary hypoadrenalism), but prevalence and metabolic sequelae of hypogonadism in Addison's disease are poorly described. We recruited patients from the South African Addison's disease national registry who received stable replacement doses of hydrocortisone and had no acute illness. Male biochemical testosterone deficiency was defined as an early morning basal testosterone<9.9 nmol/l and premature ovarian failure (POF) when menopause occurred before 40 years of age. Cardiometabolic risk variables were measured in males only. Male hypogonadism prevalence was 33% (14/42), and 10 patients had newly diagnosed hypogonadism. Two untreated patients had elevated FSH or LH (>10 or 12 IU/l). Testosterone deficiency did not correlate with age, disease duration or hydrocortisone dose. Untreated male hypogonadal subjects had a higher (mean ± standard deviation) BMI compared to eugonadal subjects 29.2 ± 4.9 kg/m(2) vs. 24.7 ± 3.4 kg/m(2) (p=0.01) and a higher median (interquartile range) high-sensitive-CRP 6.4 (2.5-14.0) mg/l vs. 1.45 (0.6-2.8) mg/l (p=0.002). There were no differences between the 2 groups in lipids, lipoproteins and fasting glucose. The median (interquartile range) DHEAS was lower in the hypogonadal 0.31 (0.27-0.37) µmol/l, compared with the eugonadal group 0.75 (0.50-1.51) µmol/l (p=0.005). POF was documented in 11% of female patients. Male testosterone deficiency was highly prevalent in this cohort and was primarily due to secondary hypogonadism. Only BMI and hs-CRP were increased in untreated male hypogonadal subjects. Male and female hypogonadism appears to be a common complication of Addison's disease and may contribute to its morbidity.

Ethnic differences in microvascular function in apparently healthy South African men and women.

Microvascular dysfunction precedes the clinical manifestations of cardiovascular disease. Given the ethnic disparities in cardiovascular disease, we aimed to investigate ethnic differences in microvascular endothelial function in a group of young (18-33 years old), apparently healthy individuals (n = 33, nine Black African, 12 mixed ancestry and 12 Caucasian). Microvascular endothelium-dependent and -independent function was assessed by laser Doppler imagery and iontophoresis of ACh and sodium nitroprusside (SNP), respectively, adjusting for skin resistance. Microvascular reactivity was expressed as maximum absolute perfusion, percentage change from baseline and area under the curve (AUC). Skin resistance was significantly lower in the Caucasian group in response to ACh (Caucasian, mean 0.16 ± 0.03 Ω versus Black, 0.21 ± 0.04 Ω and mixed ancestry, 0.20 ± 0.02 Ω, P < 0.01) and SNP (Caucasian, 0.08 ± 0.01 Ω versus Black, 0.11 ± 0.02 Ω and mixed ancestry, 0.12 ± 0.01 Ω, P < 0.01). Microvascular function in response to ACh was significantly higher in the Caucasian group compared with the other two groups; however, after adjusting for skin resistance these differences were no longer significant. Conversely, the microvascular SNP response remained significantly higher in the Caucasian group, even after adjusting for skin resistance (P < 0.01). Diastolic blood pressure was inversely associated with the AUC of ACh (r = -0.4) and all SNP responses (r = -0.3 to -0.6). Skin resistance was inversely associated with AUC and maximum absolute ACh response (r = -0.59 and -0.64, respectively) and all SNP responses (r = -0.37 to -0.79). Ethnic differences in endothelium-independent microvascular function may contribute to ethnic disparities in cardiovascular disease. Moreover, skin resistance plays a significant role in the interpretation of the microvascular response to outcomes of iontophoresis in a multiethnic group.

Increased cardiovascular risk in South African patients with Addison's disease.

Patients with Addison's disease (AD) are believed to be at risk for cardiovascular disease (CVD). South Africa, like the rest of the developing world is experiencing an increase in CVD and patients with AD may be at double the risk of their peers. We wished to explore AD patients' CVD risk factors. A cross-sectional nationwide study in South Africa of patients with AD was conducted. A cohort of 147 patients with AD and 147 healthy control subjects were matched by age, gender, ethnicity, and BMI as far as was possible. Lipoproteins and highly-sensitive C-reactive-protein (hs-CRP) were the main outcome measures. AD patients had significantly higher triglycerides; (p=0.001), lower HDLC (p<0.001), higher hs-CRP (p<0.001), and more small dense LDL; (p=0.002) than controls. Nonesterified fatty acids were lower in patients (p<0.001). Approximately 65% [95% confidence interval (CI 55.6-72.4%)] had hypercholesterolaemia, 75% (CI 64.8-81.2%) had low HDLC, and 75% (CI 68.0-84.1%) had a higher LDLC. Thirteen percent of AD patients had diabetes mellitus, but none of the risk factors differed from the nondiabetics. Only HDLC correlated positively with daily hydrocortisone dose (r=0.32; p=0.005). In conclusion dyslipidaemia is common in South African AD patients; CVD risk assessment and intervention are probably warranted in the management of these patients.

Salivary cortisol day curves in Addison's disease in patients on hydrocortisone replacement.

Using salivary cortisol (SC) measurements, cortisol exposure in Addison's disease patients on hydrocortisone replacement was determined and compared with healthy controls. Cortisol pharmacokinetics was assessed in 31 patients with Addison's disease on replacement hydrocortisone doses (median daily dose 20 mg; range 5-50 mg) and 30 healthy control subjects. Saliva samples (n=16) were collected between 08:00 and 00:00 h in 1 day, using a passive drool technique. Cortisol exposure was evaluated by noncompartmental approach. In the patients, cortisol exposure was significantly higher than in controls: median inter-quartile range (IQR) peak cortisol (C(max)) 174.5 (59.3-837.0) vs. 6.50 (4.7-19.3) nmol/l, p=0.0001; area under the curve (AUC) 390.1 (177.1-928.9) vs. 21.4 (14.6-28.4) minutes*nmol/l, p=0.0001, trough cortisol level (C(min)) 0.49 (0.49-0.96) vs. 0.49 (0.49-0.49) nmol/l, p=0.02, occurring at 480.0 (0.1-660.0) vs. 405.0 (180.0-570.0) min, p=0.56. First peak cortisol was 174.5 (53.0-754.7) vs. 6.27 (3.90-8.47) nmol/l, p=0.0001 and second peak cortisol 18.90 (5.22-76.9) vs. 3.12 (1.76-4.79) nmol/l, p=0.0001. The time to first peak cortisol differed between the 2 groups, 30 (30-75) vs. 0.1 (0.1-30) minutes; p=0.0001. At doses studied, hydrocortisone replacement therapy results in cortisol pharmacokinetics being markedly different from endogenous cortisol profiles in healthy control subjects. Addison's disease patients had significantly higher SC levels compared to healthy control subjects.

Investigation of glucocorticoid receptor polymorphisms in relation to metabolic parameters in Addison's disease.

BACKGROUND: Uncertainty exists whether glucocorticoid receptor (GCR) polymorphisms play a role in steroid-related side effects in Addison's disease (AD) patients on hydrocortisone. The polymorphisms Bcll and N363S appear to increase sensitivity to cortisol, while the ER22/23EK polymorphism has been associated with resistance to cortisol. METHOD: One hundred and forty seven AD patients, and gender, and ethnicity-matched controls were recruited in South Africa. Three polymorphisms in the GCR were studied, using PCR followed by restriction fragment length analysis. Associations with BMI, lipids, glucose and inflammatory markers were investigated. RESULTS: In both patients and controls, the Bcll polymorphism occurred more frequently in whites than in other ethnic groups studied but was not associated with any of the metabolic parameters tested. The ER22/23EK polymorphism was associated with an increased BMI in both patients (29.4 vs 24.7  kg/m²) and control subjects (26.3 vs 24.2  kg/m²). The ER22/23EK polymorphism was also associated with lower LDL cholesterol in control subjects (3.46 vs 3.93  mmol/l) and in patients (3.52 vs 4.10  mmol/l). N363S was associated with increased BMI in controls 29.9  kg/m² vs wild type 24.8  kg/m². Median hydrocortisone doses were greater in patients heterozygous for either ER22/23EK 30.0  mg or N363S 25.0  mg polymorphisms than in wild type patients 20.0  mg (both comparisons). CONCLUSION: Alterations in lipids, BMI and hydrocortisone dose were associated with two polymorphisms. Further larger studies are warranted to corroborate these findings.

Site-specific differences in bone mineral density in black and white premenopausal South African women.

SUMMARY: We examined ethnic differences in bone mineral density (BMD) and the contribution of body composition, lifestyle and socioeconomic factors in South African women. Femoral neck and total hip BMD were higher, but lumbar spine BMD was lower in black women, with body composition, lifestyle and socioeconomic status (SES) factors contributing differently in ethnic groups. INTRODUCTION: There is a paucity of data on the relative contribution of body composition, lifestyle factors and SES, unique to different ethnic groups in South Africa, to BMD. We examined differences in femoral neck (FN), total hip (TH) and lumbar spine (LS) BMD between black and white premenopausal South African women and the associations between BMD and body composition, lifestyle factors and SES in these two ethnic groups. METHODS: BMD and body composition were measured in 240 black (27 ± 7; 18-45 years) and 187 white (31 ± 8; 18-45 years) women using dual-energy X-ray absorptiometry. Questionnaires were administered to examine SES, physical activity and dietary intake. RESULTS: After co-varying for age, FN and TH were higher in black than white women (FN 0.882 ± 0.128 vs. 0.827 ± 0.116 g/cm(2), P < 0.001; TH 0.970 ± 0.130 vs. 0.943 ± 0.124 g/cm(2), P = 0.018). When adjusting for ethnic differences in body composition, LS was higher in white than black women. In black women, fat-free soft tissue mass, SES and injectable contraceptive use explained 33-42% of the variance in BMD at the hip sites and 22% at the LS. In white women, fat-free soft tissue mass and leisure activity explained 24-30% of the variance in BMD at the hip sites, whereas fat mass, leisure activity and oral contraceptive use explained 11% of the variance at the LS. CONCLUSION: FN and TH BMD were higher, but LS BMD was lower in black than white South African women with body composition, lifestyle and SES factors contributing differently to BMD in these women.

Abnormal glucose metabolism in non-diabetic patients presenting with an acute stroke: prospective study and systematic review.

BACKGROUND: Non-diabetic patients presenting with an acute stroke often have hyperglycaemia. In most populations it is unknown whether the hyperglycaemia is transient and due to the acute stress response or whether it represents undiagnosed abnormal glucose metabolism. AIM: To evaluate the prevalence and predictors of persistent hyperglycaemia in non-diabetic patients with an acute stroke. DESIGN: Prospective observational study. METHODS: Non-diabetic patients over 40 years old with an acute stroke were enrolled over a 2-year period. On admission patients were evaluated with an HbA(1c) and a 75 g oral glucose tolerance test (OGTT). The OGTT was repeated 3 months later. A meta-analysis was performed to interpret our results in the context of published data. RESULTS: One hundred and seven patients were analysed. On admission 26 (24%) patients had diabetes, 39 (37%) had impaired glucose tolerance and 42 (39%) had normal glucose tolerance. Forty-four (68%) patients with hyperglycaemia on admission were re-investigated at least 3 months after discharge. Of these, 6 (14%) had diabetes, 12 (27%) had impaired glucose tolerance and 26 (59%) had normal glucose tolerance. A 2-h post-load glucose value >or=10 mmol/l predicted persistent hyperglycaemia with 72.2% sensitivity, 65.4% specificity and a positive predictive value and negative predictive value of 59.1 and 77.3%, respectively. A meta-analysis of prevalence data of impaired glucose metabolism in non-diabetic individuals 3 months after having had an acute stroke revealed a combined prevalence of 58% (95% confidence interval 25.4-90.5%). CONCLUSION: In this study hyperglycaemia in the setting of an acute stroke was transient in the majority of patients.

Hyperglycaemic crisis in the Eastern Cape province of South Africa: high mortality and association of hyperosmolar ketoacidosis with a new diagnosis of diabetes.

OBJECTIVES: To describe the frequencies, presenting characteristics (demographic, clinical and biochemical) and outcomes (duration of admission and mortality rates) for various types of hyperglycaemic crisis. METHODS: Retrospective review of medical records of patients with hyperglycaemic crisis admitted to Nelson Mandela Academic Hospital, Mthatha, E Cape, from 1 January 2008 to 31 December 2009. Outcome measures were duration of admission and mortality. RESULTS: Data were available for 269 admissions (response rate 81.0%), 169 females and 100 males. Admissions for hyperglycaemia (HG, N=119), and non-hyperosmolar diabetic ketoacidosis (NHDKA, N=97) were more frequent than those for hyperosmolar hyperglycaemic state (HHS, N=29) and hyperosmolar diabetic ketoacidosis (HDKA, N=24). Duration of admission was similar in all groups. Mortality was high in all groups, but was higher in patients with HDKA (37.5%, risk ratio (RR) 3.88, 95% confidence interval (CI) 1.41 - 10.67, p=0.009), HHS (31.0%, RR 2.91, 95% CI 1.09 - 7.75, p=0.033) and HG (19.5%, RR 1.56, 95% CI 0.75 - 3.21, p=0.236) than in those with NHDKA (13.4%). HDKA (62.5%) was associated with new-onset diabetes more often than NHDKA (27.8%), HHS (44.8%) or HG (17.6%) (p<0.0001). An altered level of consciousness was more frequent in HDKA than NHDKA admissions (RR 5.71, 95% CI 1.90 - 17.17, p=0.002). CONCLUSIONS: Duration of hospital stay was similar across groups. Mortality rates were high in all groups. New-onset diabetes, altered level of consciousness and mortality were more characteristically associated with HDKA than any of the other types of hyperglycaemic crisis. Optimal glycaemic control in known diabetic patients will reduce rates of hyperglycaemic crisis admissions.

Metabolic syndrome and alanine aminotransferase: a global perspective from the NAVIGATOR screening population.

AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with features of the metabolic syndrome (MetS) and may be an expression of the syndrome within the liver. Using screening data from the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study (n = 42 149), we examined whether alanine aminotransferase (ALT), a biomarker for NAFLD, clustered with features of MetS and whether the clusters differed across global geographic regions. METHODS: Exploratory factor analysis using principle components analysis was applied to data drawn from the NAVIGATOR screening population (n = 41 111). Demographic data, anthropomorphic measurements and blood pressure (BP) collected during the screening visit, as well as blood samples analysed for ALT, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and fasting and 2-h glucose measures after an oral glucose tolerance test were used for our analysis. RESULTS: Two factors, interpreted as lipid (Factor 1), and BP/obesity (Factor 2) were identified, explaining approximately 50% of the variance in the overall population. Similar patterns of aggregation were reproducible across all geographic regions except Asia, where fasting glucose loaded more consistently on Factor 1. ALT loaded with mean arterial pressure, fasting glucose and waist circumference except in Asia, where it loaded only with mean arterial pressure and waist circumference. CONCLUSIONS: ALT aggregated with components of MetS, and the pattern of aggregation of ALT with other features of MetS was similar across regions except Asia, possibly indicating a different pathophysiology for NAFLD in Asia. Predictive models of NAFLD may need to be adjusted for regional and ethnic differences.

Total daily energy expenditure in black and white, lean and obese South African women.

BACKGROUND/OBJECTIVES: In South Africa (SA), the prevalence of obesity in women is 56%, with black women being most at risk (62%). Studies in the United States have demonstrated ethnic differences in resting (REE) and total daily energy expenditure (TDEE) between African American (AA) and their white counterparts. We investigated whether differences in EE exist in black and white SA women, explaining, in part, the ethnic obesity prevalence differences. SUBJECTS/METHODS: We measured REE, TDEE and physical activity EE (PAEE) in lean (BMI <25 kg m(-2)) and obese (BMI >30 kg m(-2)) SA women (N=44, 30+/-6 year). REE, TDEE, PAEE and total awake EE were measured during a 21 h stay in a respiration chamber. RESULTS: Black and white subjects within obese and lean groups were not significantly different for age, mass, BMI and % body fat. However, fat-free mass (kg FFM) was consistently lower in the black women (P<0.01) in both weight groups. After adjusting EE measurements for differences in FFM, REE was not significantly different for either body weight or ethnicity, although 24 h TDEE (kJ) was significantly greater in the obese women (P<0.01) and white women (P<0.05). Total awake non-PAEE was not significantly different for either groups, while total awake time was only significantly lower for the lean groups (P<0.01). Total PAEE (kJ min(-1)) was significantly lower in the lean (P<0.001) and black groups (P<0.01). CONCLUSIONS: In this sample of matched, lean and obese, black and white SA women, differences in TDEE were largely explained by ethnic differences in PAEE, and were not as a result of ethnic differences in REE.

Diabetes in Africa: epidemiology, management and healthcare challenges.

Diabetes is an increasing problem in sub-Saharan Africa. Type 2 diabetes, the most common form, is becoming more prevalent owing to rising rates of obesity, physical inactivity and urbanisation. Type 1 diabetes exists in two major forms in the region: type 1A or autoimmune and type 1B or ketosis-prone type 2 diabetes. At present there are scanty epidemiological data on either. The current morbidity of diabetes is primarily due to the high rates of microvascular complications, while macrovascular complications, once rare, are becoming more common, particularly in the urban setting. Further, despite the HIV epidemic, the total number of people with diabetes in the region is expected to grow because of changing demography. A concerted multisectoral effort will be critical to ensuring improvement in healthcare delivery for people with diabetes in the region.