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.

Process evaluation of a brief messaging intervention to improve diabetes treatment adherence in sub-Saharan Africa.

BACKGROUND: The SMS text Adherence suppoRt for people with type 2 diabetes (StAR2D) intervention is a pragmatic randomised controlled trial, testing the effectiveness of brief text messaging for improving clinical outcomes and medication adherence. The intervention did not impact glycaemic control. We conducted a pre-and post-trial process evaluation alongside the StAR2D study in Malawi and South Africa, exploring the experiences and perceptions of patient participants, to better understand potential underlying reasons for the trial outcomes. METHODS: We employed a qualitative research design, including conducting semi structured in-depth interviews and focus groups at both trial sites. Purposive sampling was used to ensure representation of a wide range of patients with type 2 diabetes with regards to age, gender, ethnicity, language, and duration of diabetes. We interviewed the same participants at baseline and at the end of the trial. We used within-case and across-case thematic analysis to identify key themes. RESULTS: Brief messages delivered by text were acceptable and useful for addressing informational and support needs for participants. Some participants reported behaviour changes because of the text reminders and advice on a healthy lifestyle. Both participating in the trial and the messages were experienced as a source of support, caring, and motivation. Participants' ability to act on the messages was limited. A common theme was frustration over the lack of ability to effectively control one's blood glucose level. They reported a range of routinised, partial diabetes care adherence behaviours, shaped by complex and interacting individual, social, and health service factors. Participant responses and intervention impact were similar across sites, despite differences in health services. CONCLUSION: This process evaluation provided context and insight into the factors influencing participants' engagement with the text messaging intervention. The complex context in which patients take their diabetes medication, may explain in part, why brief text messaging may have been insufficient to bring about changes in health outcomes. The scale of need for self-management and health service support, suggests that health system strengthening, and other forms of self-management support should accompany digital communication interventions. (Current Controlled Trials ISRCTN70768808 , registered 03/08/2015.).

Digital messaging to support control for type 2 diabetes (StAR2D): a multicentre randomised controlled trial.

BACKGROUND: Failure to take medicines for diabetes as prescribed contributes to poor outcomes from the condition. Mobile phones are ubiquitous and short message service (SMS) texts have shown promise as a low-cost intervention. We tested the effectiveness of SMS-text messaging in improving outcomes in adults with type 2 diabetes. METHODS: StAR2D was a 12-month two-arm randomised trial of SMS-text messaging and usual care in Cape Town, South Africa and Lilongwe, Malawi. Messages used behaviour change theory and were developed with patients and staff. The intervention group received four messages each week. The primary outcome was change in HbA1c. Secondary outcomes were the proportion of patients who collected > 80% medication and changes in systolic blood pressure, lipids, cardiovascular risk, and the proportion of the participants reaching treatment goals. RESULTS: The trial took place between 1 October, 2016 and 1 October 2018, 1186 participants were randomised to intervention (593) and control (593) groups. 91% of participants completed follow-up. There was a reduction in HbA1c (DCCT) in both groups but not in mean change (95% CI) between groups (- 0.08% (- 0.31 to 0.16) (IFCC - 0.82 mmol/mol (- 3.44 to 1.79). There was a small but not significant increase in the proportions of participants likely to have collected 80% or more of medication (Relative risk 1.11 (0.84 to 1.47; P = 0.47). There was a significant difference between groups in change in systolic blood pressure from baseline of 3.46 mmHg (1.48 to 5.44, P = 0.001) in favour of the intervention group. The between group difference in change in 10-year risk of coronary heart disease was - 0.71% (- 1.46 to 0.04, P = 0.064). The proportion of participants meeting treatment goals in the intervention group was 36.0% and in the control group 26.8% (Relative risk 1.36 (1.13 to 1.63, P = 0.001). Participants reported many challenges to adherence despite finding messages acceptable and useful. CONCLUSIONS: Whilst SMS text messages do not lead to improved glycaemia in these low-resource settings there appeared to be an impact on blood pressure and achievement of treatment goals but the mechanisms for this are unclear. Text messages alone, may be unsuccessful unless accompanied by health system strengthening and other forms of self-management support for type 2 diabetes. TRIAL REGISTRATION: Trial registration: ISRCTN, ISRCTN70768808. Registered 1 July 2015, http://www.isrctn.com/I ISRCTN70768808.

A standard set of person-centred outcomes for diabetes mellitus: results of an international and unified approach.

AIMS: To select a core list of standard outcomes for diabetes to be routinely applied internationally, including patient-reported outcomes. METHODS: We conducted a structured systematic review of outcome measures, focusing on adults with either type 1 or type 2 diabetes. This process was followed by a consensus-driven modified Delphi panel, including a multidisciplinary group of academics, health professionals and people with diabetes. External feedback to validate the set of outcome measures was sought from people with diabetes and health professionals. RESULTS: The panel identified an essential set of clinical outcomes related to diabetes control, acute events, chronic complications, health service utilisation, and survival that can be measured using routine administrative data and/or clinical records. Three instruments were recommended for annual measurement of patient-reported outcome measures: the WHO Well-Being Index for psychological well-being; the depression module of the Patient Health Questionnaire for depression; and the Problem Areas in Diabetes scale for diabetes distress. A range of factors related to demographic, diagnostic profile, lifestyle, social support and treatment of diabetes were also identified for case-mix adjustment. CONCLUSIONS: We recommend the standard set identified in this study for use in routine practice to monitor, benchmark and improve diabetes care. The inclusion of patient-reported outcomes enables people living with diabetes to report directly on their condition in a structured way.

Multiple Sclerosis Performance Test: validation of self-administered neuroperformance modules.

BACKGROUND AND PURPOSE: The purpose was to determine the test-retest reliability, practice effects, convergent validity and sensitivity to multiple sclerosis (MS) disability of neuroperformance subtests from the patient self-administered Multiple Sclerosis Performance Test (MSPT) designed to assess low contrast vision (Contrast Sensitivity Test, CST), upper extremity motor function (Manual Dexterity Test, MDT) and lower extremity motor function (Walking Speed Test, WST) and to introduce the concept of regression-based norms to aid clinical interpretation of performance scores using the MSPT cognition test (Processing Speed Test, PST) as an example. METHODS: Substudy 1 assessed test-retest reliability, practice effects and convergent validity of the CST, MDT and WST in 30 MS patients and 30 healthy controls. Substudy 2 examined sensitivity to MS disability in over 600 MS patients as part of their routine clinic assessment. Substudy 3 compared performance on the PST in research volunteers and clinical samples. RESULTS: The CST, MDT and WST were shown to be reliable, valid and sensitive to MS outcomes. Performance was comparable to technician-administered testing. PST performance was poorer in the clinical sample compared with the research volunteer sample. CONCLUSIONS: The self-administered MSPT neuroperformance modules produce reliable, objective metrics that can be used in clinical practice and support outcomes research. Published studies which require patient voluntary consent may underestimate the rate of cognitive dysfunction observed in a clinical setting.

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.

Physical activity behaviours of persons living with HIV of low socioeconomic status: domain, intensity and sociodemographic correlates.

Physical activity (PA) is healthy for People Living with HIV and AIDS (PLWHA). This study examined the PA profile of 978 PLWHA based on PA domains and PA intensity. The study also sought to determine whether employment status and level of education can predict PA among PLWHA of low SES. PA and sociodemographic data of 978 PLWHA of mean age 35 (8.77) years were collected using the global physical activity questionnaire and a sociodemographic questionnaire. Results showed that, participants engaged more in work-related PA [160.11 (346.95) min/wk], followed by transport related PA [115.21(SD = 142.04) min/wk], and lastly in leisure related PA [40.84 (SD = 110.37) min/wk]. Participants also engaged more in moderate PA [265.86 (SD = 335.45) min/wk], than in vigorous PA [50.29 (SD = 205.30) min/wk]. Employment was a significant predictor of overall PA controlling for age, CD4 count and education level. The model explained 2.5% of the variance (R2 = 0.025) on overall PA and tested significant at a 0.01 alpha level (p < 0.01). PA interventions for this population should be domain- and intensity-specific. Researchers promoting healthy lifestyle behaviour change can benefit from determining the factors that facilitate domain-specific PA.

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.

Differential obesity indices identify the metabolic syndrome in Black men and women in Cape Town: the CRIBSA study.

AIMS: To determine the obesity indices, specifically waist circumference (WC), that identified ≥2 other metabolic syndrome (MS) components (2009 criteria) in 25- to 74-year-old Africans in Cape Town. METHODS: Data were collected from a cross-sectional sample by administered questionnaires, clinical measurements and biochemical analyses. The obesity cut points were estimated by the Youden Index. Logistic regression analyses determined whether obesity cut points identifying ≥2 MS components occurred at true inflection points. RESULTS: Among the 1099 participants, the calculated cut points and 95% confidence intervals (CI) were: men, WC 83.9 cm (81.6-86.2), waist-to-hip ratio (WHR) 0.89 (0.87-0.90), waist-to-height ratio (WHtR) 0.50 (0.48-0.52) and body mass index (BMI) 24.1 kg/m(2) (22.0-26.1); women, WC 94.0 cm (92.6-95.3), WHR 0.85 (0.83-0.87), WHtR 0.59 (0.57-0.60) and BMI 32.1 kg/m(2) (29.7-34.6). Raised WC was significantly associated with ≥2 MS components in men: WC 84.0-93.9 cm (odds ratio (OR): 3.19, 95% confidence interval (CI): 1.73-5.85) and WC ≥94.0 cm (OR: 8.50, 95% CI: 4.44-16.25) compared with WC <84.0 cm, and in women: WC 80.0-93.9 cm (OR: 2.93, 95% CI: 1.32-6.54) and WC ≥94.0 cm (OR: 5.33, 95% CI: 2.40-11.85) compared with WC <80.0 cm. In the logistic model with BMI for women, obesity (OR: 3.60, 95% CI: 1.82-7.10) but not overweight (P = 0.063) was significantly associated with ≥2 MS components. CONCLUSIONS: Obesity cut points for Africans should be re-evaluated and adjusted accordingly.

Differential associations of cardiovascular disease risk factors with relative wealth in urban-dwelling South Africans.

BACKGROUND: To examine the associations of cardiovascular disease risk factors (CVDRF) with wealth, defined by the asset index, in 25- to 74-year-old black Africans in Cape Town. METHODS: Assets, including consumer durable goods, and CVDRF were determined in a randomly selected cross-sectional sample. A principal component analysis of the pooled data, based on assets that defined wealth, was used to develop an asset index. Ordinal logistic regression analyses assessed the independent associations of CVDRF with wealth tertiles. RESULTS: Among the 1099 participants, the least poor compared with the poorest tertile had significantly higher prevalence of diabetes (16.3 versus 9.6%), hypercholesterolaemia (33.9 versus 21.4%), obesity (45.4 versus 26.3%) and fat intake ≥30% of diet (44.2 versus 29.3%). Daily smoking was highest in the poorest (35.8%) versus the least poor (26.4%). Psychosocial stress (low sense of coherence or locus of control) was significantly higher in poorer participants. In the regression analyses, wealth was associated with male gender [odds ratio (OR): 1.89, 95% confidence interval (CI): 1.37-2.60], urbanization (OR: 1.02, 95% CI: 1.01-1.02), high fat intake, obesity and hypercholesterolaemia. Daily smoking, problematic alcohol use (OR: 0.70, 95% CI: 0.52-0.94) and psychosocial stress were inversely related to wealth. CONCLUSIONS: Differential distribution of CVDRF by wealth mandates incorporating equity components when developing tailored interventions.

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.

Effectiveness of a group diabetes education programme in under-served communities in South Africa: a pragmatic cluster randomized controlled trial.

AIM: To evaluate the effectiveness of group education, led by health promoters using a guiding style, for people with type 2 diabetes in public sector community health centres in Cape Town. METHODS: This was a pragmatic clustered randomized controlled trial with 17 randomly selected intervention and 17 control sites. A total of 860 patients with type 2 diabetes, regardless of therapy used, were recruited from the control sites and 710 were recruited from the intervention sites. The control sites offered usual care, while the intervention sites offered a total of four monthly sessions of group diabetes education led by a health promoter. Participants were measured at baseline and 12 months later. Primary outcomes were diabetes self-care activities, 5% weight loss and a 1% reduction in HbA(1c) levels. Secondary outcomes were self-efficacy, locus of control, mean blood pressure, mean weight loss, mean waist circumference, mean HbA1c and mean total cholesterol levels and quality of life. RESULTS: A total of 422 (59.4%) participants in the intervention group did not attend any education sessions. No significant improvement was found in any of the primary or secondary outcomes, apart from a significant reduction in mean systolic (-4.65 mmHg, 95% CI 9.18 to -0.12; P = 0.04) and diastolic blood pressure (-3.30 mmHg, 95% CI -5.35 to -1.26; P = 0.002). Process evaluation suggested that there were problems with finding suitable space for group education in these under-resourced settings, with patient attendance and with full adoption of a guiding style by the health promoters. CONCLUSION: The reported effectiveness of group diabetes education offered by more highly trained professionals, in well-resourced settings, was not replicated in the present study, although the reduction in participants' mean blood pressure is likely to be of clinical significance.

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.

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.

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.

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.

Perspectives on gestational diabetes mellitus in South Africa.

The field of gestational diabetes mellitus has attracted increasing attention and research in South Africa (SA) over the past decade, creating a better understanding of the disease burden, risk factors, availability of specialised healthcare services, and importantly the far-reaching maternal and childhood consequences beyond the pregnancy. This article brings together all the local published literature in the field and outlines the implications of this condition, together with recommendations regarding particular areas that require attention in order to prevent and alleviate the disease burden in SA.

Estimating the changing burden of disease attributable to high fasting plasma glucose in South Africa for 2000, 2006 and 2012.

BACKGROUND: Worldwide, higher-than-optimal fasting plasma glucose (FPG) is among the leading modifiable risk factors associated with all- cause mortality and disability-adjusted life years (DALYs) due to the direct sequelae of diabetes and the increased risk for cardiovascular and chronic kidney disease. OBJECTIVES: To report deaths and DALYs of health outcomes attributable to high FPG by age and sex for South Africa (SA) for 2000, 2006 and 2012. METHODS: Comparative risk assessment methodology was used to estimate the burden attributable to high FPG. A meta-regression analysis was performed using data from national and small-area studies to estimate the population distribution of FPG and diabetes prevalence. Attributable fractions were calculated for selected health outcomes and applied to local burden estimates from the second South African National Burden of Disease Study (SANBD2). Age-standardised rates were calculated using World Health Organization world standard population weights. RESULTS: We estimated a 5% increase in mean FPG from 5.31 (95% confidence interval (CI) 5.18 - 5.43) mmol/L to 5.57 (95% CI 5.41 - 5.72) mmol/L and a 75% increase in diabetes prevalence from 7.3% (95% CI 6.7 - 8.3) to 12.8% (95% CI 11.9 - 14.0) between 2000 and 2012. The age-standardised attributable death rate increased from 153.7 (95% CI 126.9 - 192.7) per 100 000 population in 2000 to 203.5 (95% CI 172.2 - 240.8) per 100 000 population in 2012, i.e. a 32.4% increase. During the same period, age-standardised attributable DALY rates increased by 43.8%, from 3 000 (95% CI 2 564 - 3 602) per 100 000 population in 2000 to 4 312 (95% CI 3 798 - 4 916) per 100 000 population in 2012. In each year, females had similar attributable death rates to males but higher DALY rates. A notable exception was tuberculosis, with an age-standardised attributable death rate in males double that in females in 2000 (14.3 v. 7.0 per 100 000 population) and 2.2 times higher in 2012 (18.4 v. 8.5 per 100 000 population). Similarly, attributable DALY rates were higher in males, 1.7 times higher in 2000 (323 v. 186 per 100 000 population) and 1.6 times higher in 2012 (502 v. 321 per 100 000 population). Between 2000 and 2012, the age-standardised death rate for chronic kidney disease increased by 98.3% (from 11.7 to 23.1 per 100 000 population) and the DALY rate increased by 116.9% (from 266 to 578 per 100 000 population). CONCLUSION: High FPG is emerging as a public health crisis, with an attributable burden doubling between 2000 and 2012. The consequences are costly in terms of quality of life, ability to earn an income, and the economic and emotional burden on individuals and their families. Urgent action is needed to curb the increase and reduce the burden associated with this risk factor. National data on FPG distribution are scant, and efforts are warranted to ensure adequate monitoring of the effectiveness of the interventions.