Naomi Sharlene Levitt

Differential Effects of Abdominal Adipose Tissue Distribution on Insulin Sensitivity in Black and White South African Women

Black South African women are more insulin resistant than BMI‐matched white women. The objective of the study was to characterize the determinants of insulin sensitivity in black and white South African women matched for BMI. A total of 57 normal‐weight (BMI 18–25 kg/m2) and obese (BMI > 30 kg/m2) black and white premenopausal South African women underwent the following measurements: body composition (dual‐energy X‐ray absorptiometry), body fat distribution (computerized tomography (CT)), insulin sensitivity (SI, frequently sampled intravenous glucose tolerance test), dietary intake (food frequency questionnaire), physical activity (Global Physical Activity Questionnaire), and socioeconomic status (SES, demographic questionnaire). Black women were less insulin sensitive (4.4 ± 0.8 vs. 9.5 ± 0.8 and 3.0 ± 0.8 vs. 6.0 ± 0.8 × 10−5/min/(pmol/l), for normal‐weight and obese women, respectively, P < 0.001), but had less visceral adipose tissue (VAT) (P = 0.051), more abdominal superficial subcutaneous adipose tissue (SAT) (P = 0.003), lower SES (P < 0.001), and higher dietary fat intake (P = 0.001) than white women matched for BMI. SI correlated with deep and superficial SAT in both black (R = −0.594, P = 0.002 and R = 0.495, P = 0.012) and white women (R = −0.554, P = 0.005 and R = −0.546, P = 0.004), but with VAT in white women only (R = −0.534, P = 0.005). In conclusion, body fat distribution is differentially associated with insulin sensitivity in black and white women. Therefore, the different abdominal fat depots may have varying metabolic consequences in women of different ethnic origins.

Glucocorticoid metabolism within superficial subcutaneous rather than visceral adipose tissue is associated with features of the metabolic syndrome in South African women.

Objectiveu2002 Glucocorticoid hyperactivity in adipose tissue, due to up‐regulation of local glucocorticoid reactivation by 11β‐hydroxysteroid dehydrogenase‐1 (11HSD1) or of glucocorticoid receptors (GR), may underpin susceptibility to the metabolic syndrome. This hypothesis has been tested extensively in subcutaneous adipose tissue (SAT) but inadequately in visceral adipose tissue (VAT). The aim of the study was therefore to examine expression of 11HSD1, GRα and hexose‐6‐phosphate dehydrogenase (H6PDH), which supplies cofactor for 11HSD1, in abdominal adipose tissue compartments and to characterize their relation to metabolic syndrome parameters.

A High Burden of Hypertension in the Urban Black Population of Cape Town: The Cardiovascular Risk in Black South Africans (CRIBSA) Study

Objective To determine the prevalence, associations and management of hypertension in the 25–74-year-old urban black population of Cape Town and examine the change between 1990 and 2008/09 in 25–64-year-olds. Methods In 2008/09, a representative cross-sectional sample, stratified for age and sex, was randomly selected from the same townships sampled in 1990. Cardiovascular disease risk factors were determined by administered questionnaires, clinical measurements and fasting biochemical analyses. Logistic regression models evaluated the associations with hypertension. Results There were 1099 participants, 392 men and 707 women (response rate 86%) in 2008/09. Age-standardised hypertension prevalence was 38.9% (95% confidence interval (CI): 35.6–42.3) with similar rates in men and women. Among 25–64-year-olds, hypertension prevalence was significantly higher in 2008/09 (35.6%, 95% CI: 32.3–39.0) than in 1990 (21.6%, 95% CI: 18.6–24.9). In 2008/09, hypertension odds increased with older age, family history of hypertension, higher body mass index, problematic alcohol intake, physical inactivity and urbanisation. Among hypertensive participants, significantly more women than men were detected (69.5% vs. 32.7%), treated (55.7% vs. 21.9%) and controlled (32.4% vs. 10.4%) in 2008/09. There were minimal changes from 1990 except for improved control in 25–64-year-old women (1990∶14.1% vs. 2008/09∶31.5%). Conclusions The high and rising hypertension burden in this population, its association with modifiable risk factors and the sub-optimal care provided highlight the urgent need to prioritise hypertension management. Innovative solutions with efficient and cost-effective healthcare delivery as well as population-based strategies are required.

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

SummaryWe 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.IntroductionThere 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.MethodsBMD and body composition were measured in 240 black (27u2009±u20097; 18–45xa0years) and 187 white (31u2009±u20098; 18–45xa0years) women using dual-energy X-ray absorptiometry. Questionnaires were administered to examine SES, physical activity and dietary intake.ResultsAfter co-varying for age, FN and TH were higher in black than white women (FN 0.882u2009±u20090.128 vs. 0.827u2009±u20090.116xa0g/cm2, Pu2009<u20090.001; TH 0.970u2009±u20090.130 vs. 0.943u2009±u20090.124xa0g/cm2, Pu2009=u20090.018). 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.ConclusionFN 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.

Adult BMI and fat distribution but not height amplify the effect of low birthweight on insulin resistance and increased blood pressure in 20-year-old South Africans

Aims/hypothesisWe examined whether associations between low birthweight and adult chronic cardio-metabolic disease were dependent upon birthweight alone, or on interactions with BMI, fat accumulation either generally or abdominally, or attained height in young South African adults.MethodsBlood pressure (BP), lipids, glucose tolerance, insulin sensitivity and secretion (homeostasis model) were measured in 20-year-olds (n=132) born at full term and with birthweights on or below the tenth centile (underweight for gestational age [UFA]) or between the 25th and 75th centiles for gestational age (appropriate weight for gestational age, [AFA]). Sex-specific median measurements of BMI, waist circumference, percentage body fat and height defined current anthropometric status, providing four groups for each measure: UFA-low or UFA-high and AFA-low or AFA-high.ResultsThe UFA-high BMI group was more insulin-resistant than both low BMI groups (p<0.04), but not the AFA-high BMI group. In contrast, plasma triglycerides and systolic BP were higher in the UFA-high than in all other groups (all p<0.04). When characterised by body fatness, both high percentage (%) body fat groups had higher fasting [insulin] than low percentage (%) body fat groups (p<0.03), and higher [total cholesterol] and [LDL cholesterol] than the UFA-low percentage (%) body fat group (p<0.05). The UFA-high group had higher systolic and diastolic BP than all other groups (all at least p<0.03). A similar pattern was observed when groups were characterised by waist circumference; however, current height status had no effect.Conclusions/interpretationThese data indicate that the “fetal origins” expression of the chronic disease phenotype is not dependent on birthweight alone, but on its interaction with subsequent fat accumulation, though not on attained height, in this cohort of young adults.

Effects of a lipase inhibitor (Orlistat) on cholecystokinin and appetite in response to a high-fat meal

OBJECTIVE: To examine the short-term effects of a lipase inhibitor (Orlistat) on physiological and behavioural measures of appetite in response to a high-fat meal.DESIGN: Randomised, single blind, placebo-controlled, crossover trial.SUBJECTS: A total of 19 healthy nonobese male subjects.PROCEDURES: After an overnight fast, subjects ingested a test meal of 2940u2009kJ (60% fat, 30% CHO, 10% protein) with Orlistat (120u2009mg) or a placebo, separated by 2 weeks. Appetite, as assessed by a standard line scale, and plasma cholecystokinin (CCK) concentrations were measured prior to and every hour after the test meal for 4u2009h. Thereafter, subjects ingested a quantified, but self-selected portion of a standardised lunch (15% protein, 37% fat and 45% CHO), before completing a final line scale questionnaire.RESULTS: The CCK response to the test meal was negatively correlated with BMI in both the Orlistat and placebo trials (R=−0.69 and −0.65, P<0.01). Orlistat administration did not significantly alter the CCK response to the test meal (6.30±3.27 vs 7.36±3.94u2009pMu2009min, for Orlistat and placebo, P=0.193). Similarly, the line scale measures of appetite and subsequent intake (520±205 vs 554±197u2009g, P=0.48) were not different between the trials.CONCLUSION: Orlistat administration did not alter short-term physiological or behavioural measures of satiety in response to a high-fat meal in healthy, nonobese subjects. The CCK response to a test meal may be partly determined by BMI.

Quality of life in individuals living with HIV/AIDS attending a public sector antiretroviral service in Cape Town, South Africa

BackgroundHealth related quality of life (HRQoL) is an important outcome helping to understand the impact of antiretroviral therapy (ART). We examined and compared the HRQoL in relation to ART status among HIV-infected patients in a public sector service in Cape Town, South Africa. In addition, we aimed to examine the relationship between ART status and HRQoL according to CD4 count strata.MethodsA cross sectional study sample of 903 HIV-infected patients who were categorized as not receiving ART (ART-naïve) or receiving first-line ART foru2009>u20096xa0months (ART). HRQoL outcomes were compared in the two groups. HRQoL was assessed using the EQ-5D (five domains) and Visual Analogue Scale (EQ-5D VAS).ResultsOf the total sample, 435 were categorised as ART naïve (76% women) and 468 were on ART (78% women). There were no significant associations between groups for most of the EQ-5D domains, however ART-naïve experienced a significantly greater problem with mobility than the ART group. Being ART-naïve (adjusted odds ratio (aOR) 3.08 95% confidence interval (CI) 1.63- 7.89) and obese 2.78 (95% CI 1.24- 6.22) were identified as predictors for increased mobility problems in multivariate analysis. In addition, receiving ART (5.61 difference; 95% CI 2.50 - 8.72) and having some source of income (4.76; 95% CI 1.63 -7.89) were identified as predictors for a higher EQ-5D VAS score. When grouped according to CD4 count strata, there were no significant difference between groups for most of the EQ-5D domains, however the ART-naïve group indicated having significantly greater problems under the CD4 count of >500 cells/μL in the anxiety/depression domain (22.4% vs 8.8%, pu2009=u20090.018) and significantly lower EQ-5D VAS scores under the CD4 counts of ≤200 cells/μL (median 80 (IQR 60–90) vs 90 (IQR 80–100), pu2009=u20090.0003) and 201–350 cells/μL (median 80 (IQR 70–90) vs 90 (80–100), pu2009=u20090.0004) compared to ART group.ConclusionsHRQoL (self-rated health state) was improved with ART use, including those with immunocompromised status, which may be relevant to the public sector ART program in South Africa.

Risk Factors for Incident Diabetes in a Cohort Taking First-Line Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy

AbstractEfavirenz is the preferred nonnucleoside reverse transcriptase inhibitor (NNRTI) in first-line antiretroviral therapy (ART) regimens in low- and middle-income countries, where the prevalence of diabetes is increasing. Randomized control trials have shown mild increases in plasma glucose in participants in the efavirenz arms, but no association has been reported with overt diabetes. We explored the association between efavirenz exposure and incident diabetes in a large Southern African cohort commencing NNRTI-based first-line ART.Our cohort included HIV-infected adults starting NNRTI-based ART in a private sector HIV disease management program from January 2002 to December 2011. Incident diabetes was identified by the initiation of diabetes treatment. Patients with prevalent diabetes were excluded.We included 56,298 patients with 113,297 patient-years of follow-up (PYFU) on first-line ART. The crude incidence of diabetes was 13.24 per 1000 PYFU. Treatment with efavirenz rather than nevirapine was associated with increased risk of developing diabetes (hazard ratio 1.27 (95% confidence interval (CI): 1.10–1.46)) in a multivariate analysis adjusting for age, sex, body mass index, baseline CD4 count, viral load, NRTI backbone, and exposure to other diabetogenic medicines. Zidovudine and stavudine exposure were also associated with an increased risk of developing diabetes.We found that treatment with efavirenz, as well as stavudine and zidovudine, increased the risk of incident diabetes. Interventions to detect and prevent diabetes should be implemented in ART programs, and use of antiretrovirals with lower risk of metabolic complications should be encouraged.

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 <25u2009kgu2009m−2) and obese (BMI >30u2009kgu2009m−2) SA women (N=44, 30±6 year). REE, TDEE, PAEE and total awake EE were measured during a 21u2009h 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 24u2009h 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 (kJu2009min−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.

Amiodarone-induced thyroid dysfunction

Background. Little is known about the frequency of thyroid dysfunction (TD) associated with amiodarone therapy in southern Africa. Objectives. To determine the incidence of TD in a cohort of patients initiated on amiodarone therapy at a cardiac clinic in Cape Town, South Africa, believed to be an iodine-replete area. Patients. Pharmacy records were used to obtain the names of patients who received amiodarone between November 1999 and December 2002. Results. The sample size was 194, but data analysis was limited to the 163 patients for whom there were complete data. The mean age ± standard deviation (SD) was 59.0 ± 15.0 years (range 22–89 years). There were 67 female and 96 male patients. The indications for amiodarone therapy were supraventricular tachycardias (N = 102, 62.6%), ventricular tachycardia (N = 55, 33.7%), and prophylaxis against tachycardias (N = 3, 1.8%). The indication was uncertain in 3 patients (1.8%). The median duration of amiodarone treatment was 679.0 days (quartile deviation (QD) 1 172 days, range 3–6 425 days) in the whole cohort. The median duration of amiodarone therapy until new TD was 943 days (QD 1 185 days), significantly longer than in patients who remained euthyroid (547 days, QD 1 135 days) (P = 0.05). There were 45 new TD cases (27.6%): 11 patients (6.7%) were thyrotoxic, 1(0.6%) transient thyrotoxicosis, 1 (0.6%) subclinical hyperthyroidism, 13 (8.0%) had subclinical hypothyroidism, 12 (7.4%) hypothyroidism and 7 (4.3%) had minor changes in thyroid function. Conclusions. We found a high incidence of new-onset TD, similar to the highest rates reported internationally. Local factors responsible for this need to be investigated.