Browsing by Author "Motala, Ayesha Ahmed."
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Item Effects of high or moderate intensity training on inflammation and endothelial function in insulin resistance.(2019) Thaane, Tshidi.; McKune, Andrew James.; Motala, Ayesha Ahmed.Exercise training improves insulin resistance (IR) via numerous mechanisms including improved endothelial function and reduced systemic inflammation. However, it is unclear whether high intensity interval training (HIIT) offers superior benefit when compared with continuous moderate intensity training (CMIT) in a clinical population. This thesis reports findings from a clinical trial designed to determine the effects of short-term high or moderate intensity training on inflammation and endothelial function in overweight/obese adults with IR. Furthermore, the thesis provides a report on factors associated with IR in this population. Clinical examinations (body composition), blood tests [serum insulin and serum C-reactive protein (CRP), plasma glucose] and physiological tests (microvascular function and aerobic fitness tests) were undertaken on consenting individuals who volunteered to participate in the study. Study participants were stratified into IR and insulin sensitive (IS) groups based on their homeostatic model assessment (HOMA-IR) scores. The IR and IS groups were each further randomized into control (CNT), HIIT or CMIT sub-groups. The HIIT and CMIT sub-groups underwent baseline measures and exercise training for 10 consecutive days, followed by a repeat of baseline measures. The CNT sub-group was tested at baseline and post follow-up without taking part in the exercise intervention. When compared with CMIT, HIIT produced a greater improvement in markers of IR [(HOMA-IR); 32% vs. 9% by CMIT] and endothelial function [(PORHmax and MV); 37.59% and 27.45%, respectively, vs. 8.24% and -25.71%, respectively, by CMIT]. These improvements occurred without changes in body fat or aerobic fitness. Cohen’s (d) effect sizes indicated that the improvements produced by HIIT were large, while those of CMIT were unclear, suggesting that HIIT may be the ideal mode of training when the primary goal is to improve IR and endothelial function in overweight/obese adults. Cross-sectional analysis of baseline data indicated that the acute-phase inflammatory protein, CRP, was strongly associated with IR in black Africans. However, this association was only significant in males. Suggesting that CRP has potential clinical application as a maker of systemic inflammation in this population. The gender of the patient, however, must be taken into consideration.Item Impaired glucose tolerance (IGT) : a study in South African Indians in Durban.(1990) Motala, Ayesha Ahmed.No abstract available.Item Metabolic complications of antiretroviral therapy (ART) in a South African black population..(2014) Magula, Nombulelo Princess.; Lalloo, Umesh Gangaram.; Motala, Ayesha Ahmed.Aims To determine the prevalence and incidence of lipodystrophy (fat distribution [lipoatrophy and lipohypertrophy] and metabolic complications [insulin resistance-dysglycaemia and dyslipidemia]) in HIV-1 infected adult subjects of second generation Zulu descent at baseline and during 24 months of follow-up on antiretroviral therapy (ART). Methods The total study group included three groups: HIV infected ART naive patients eligible for ART (HIV-ART, n=150), age, gender and ethnically matched HIV infected not eligible for ART (HIV-no ART, n=88) and HIV negative (control, n=88) subjects. All participants had demographic, anthropometric, biochemical and radiological assessments at baseline; in addition, the HIV-ART group had follow-up assessments for 24 months on ART (tenofovir, lamivudine and nevirapine or efavirenz). Fat distribution was assessed using FRAM questionnaires, computerized tomography (CT) scans and dual energy absorptiometry X-ray (DXA). Disorders of glycaemia (diabetes mellitus (DM), impaired glucose tolerance and impaired fasting glucose) were defined using WHO criteria. Total, LDL, HDL cholesterol and triglycerides were measured for each group; CD4 cell count and HIV RNA for group 2 and 3, at baseline, 3, 6, 12, 18 and 24 months. Poisson approximations estimated incidence of disorders of glycaemia. Results At baseline, when compared with the control group, the mean BMI (kg/m2) was significantly lower in the HIV-ART and HIV-no ART subjects (26.4 vs. 28.6 vs. 29.1; p =0.01). Prevalence of lipoatrophy as measured by participant and physician examination questionnaires was similar in the three groups. Visceral and subcutaneous fat area by CT scan were similar between the groups but limb and trunk fat mass by DXA scan was significantly lower in the HIV-ART compared to control subjects. In the HIV-ART group, at the 24 month follow-up, there was a significant mean reduction in HIV RNA (p<0.0001) and increase in CD4 cell count (p<0.0001). The mean BMI increased to 29.4 kg/m2 and no lipoatrophy developed; DXA scan showed a 33.6% increase in trunk fat mass (mean difference 4.2 kg, p <0.0001) and 30.8% increase in total fat mass (mean difference 9.4 kg, p < 0.0001); visceral (p 0.005) and subcutaneous (p 0.0002) fat area also increased. At baseline, the prevalence of DM was 0% in HIV-ART and HIV-no ART and 4.9% in control subjects (p 0.005); the prevalence of “any dysglycaemia” was 3.7% in HIV-ART and HIV-no ART compared to 8.6% in control subjects. When compared with group 1, mean values in group 3 were lower for the following serum lipids: total cholesterol (p<0.0001), LDL (p=0.0007) and HDL (p<0.0001). There was no difference in mean total triglycerides in the three groups (p=0.3). During follow-up, in the HIV-ART group, using glucose-based WHO criteria, the incidence of diabetes mellitus was 2.3 per 100 person year follow-up (PYFU) and of “any dysglycaemia” 7.6 per 100 PYFU. The only independent predictor of DM was visceral: subcutaneous fat ratio measured by CT scan (HR 2.95 [95% CI 1.25-6.98], p 0.01). Significant predictors for development of “any dysglycaemia” included systolic blood pressure (HR 1.04 [95%CI 1.02-1.07], p=0.0006), serum albumin (HR 0.85 [95% CI 0.76-0.94], p=0.002), CD4 cell count (HR 0.988 [95%CI 0.978-0.997], p=0.01) and efavirenz (HR 6.27 [95%CI 1.65-23.80], p=0.01) Serum total (p<0.0001), LDL (p<0.0001) and HDL-cholesterol (p<0.0001) increased significantly during follow-up. Conclusion: In this cohort of South Africans with HIV-1 infection, at baseline (prior to ART) there was no significant fat redistribution or lipoatrophy and an absent to low prevalence of dysglycaemia. In the follow-up study, ART use was not associated with lipoatrophy although there was significant increase in BMI and in limb and trunk fat mass by DXA scan. ART was associated with increased incidence of dysglycaemia. These findings underscore the importance of clinical monitoring on ART. The association of efavirenz with dysglycaemia warrants further evaluation.Item Myotonic dystrophy : clinical and molecular spectrum in KwaZulu-Natal.(2006) Motala, Ayesha Ahmed.; Bill, Pierre Louis Alfred.Myotonic dystrophy is the commonest form of adult muscular dystrophy. Myotonic dystrophy 1 and 2 (DM 1 and DM 2) are autosomal dominant inherited disorders with unusual multisystem clinical features characterized by myotonia, progressive muscle weakness and wasting, cataracts, hypogonadism, frontal balding, cardiac conduction defects and diabetes. Severity varies from asymptomatic to severely affected phenotypes. DM1 presents with predominantly distal weakness whereas DM2 have predominantly proximal weakness.98% of patients identified worldwide present with DM1. DM 1 is caused by the expansion of an unstable CTG trinucleotide repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene on chromosome 19ql3.3. DM 2 is linked to the long arm of chromosome 3q21. It is caused by a tranucleotide, CCTG expansion in intron 1 of the zinc finger protein 9(ZNF9) gene that interferes with processing of a variety of RNAs. All DM mutations can be detected using a combination of the Southern Blot and Polymerase Chain reaction (PCR) techniques. Aim: This study aims to characterize the clinical spectrum and molecular features of myotonic dystrophy patients in KwaZulu - Natal between 1989 and 2005. Methodology: Patients included in this study were obtained from the database of patients diagnosed with Myotonic Dystrophy at the Department of Neurology in KwaZulu-Natal from 1989 to 2005. Patients were subjected to clinical, radiological and neurophysiological assessment. Molecular testing was performed using PCR and Southern blot. Results: Thirty-seven patients with Myotonic Dystrophy were identified. Twenty patients consented and were included into the study. Eighty-five percent of patients were of Indian descent and the remaining fifteen percent were White. No African patients were identified. Sixty-five percent were male and thirty-five percent female. Myotonia was clinically present in all patients. Ninety-five percent of patients presented with predominantly distal weakness of which 40% demonstrated mild weakness, 35% moderate weakness and 25 % severe weakness. No patients were identified with predominantly proximal wasting or weakness. Southern blotting demonstrated expanded CTG repeats (DM1) in all 20 samples analysed. The PCR analysis was unable to demonstrate expanded alleles. Conclusion: This study identified patients presenting with Myotonic dystrophy to the Department of Neurology in KwaZulu-Natal and demonstrated that Myotonic Dystrophy Type 1 remains the commonest clinical and molecular presentation. In addition it substantiated previous research findings wherein no South African of African descent was found to be affected by the disease. There have been no reported cases of Myotonic Dystrophy in African Black patients presenting to the Department of Neurology in Durban, no African Black patients have been diagnosed with Myotonic Dystrophy over the past 20 years. However ,the predominance of Indians in this study is more likely a reflection of referral bias than differing incidence amongst sections of the population. PCR analysis cannot detect trinucleotide repeat expansions beyond 200 repeats and as a result Southern Blotting remains the gold standard in obtaining a molecular diagnosis. A clinical diagnosis is sufficient and molecular confirmation is not an absolute requirement.Item Prevalence of low serum testosterone levels among men with type 2 diabetes mellitus attending two outpatient diabetes clinics in Durban, South Africa.(2017) Paruk, Imran Mahomed.; Motala, Ayesha Ahmed.; Pirie, Fraser James.Background: Studies showing a high prevalence of low serum testosterone in men with type 2 diabetes mellitus (T2DM) are well documented but evidence from sub-Saharan Africa is scanty. Aim: To determine the prevalence and associated risk factors of low serum testosterone and the prevalence of androgen deficiency symptoms in South African men with T2DM. Methods: A cross-sectional observational study was performed among men with T2DM attending two outpatient adult diabetes clinics in KwaZulu-Natal. Androgen deficiency symptoms were assessed using the Ageing Male’s Symptom Scale (AMS) questionnaire and direct enquiry. Serum total testosterone (TT), sex-hormone binding globulin (SHBG), luteinising hormone (LH), HbA1c, fructosamine, serum lipids were measured and free-testosterone (FT) was calculated. TT, SHBG and FT levels were measured in control subjects with no history of diabetes. Results: The study included 148 men with T2DM (Study Group) and 50 control subjects (Control Group). The mean age of the control group was 43.9 ± 10.7 years and the mean BMI was 27.11 ± 4.2 kg/m2. In the study group, the majority were African (Black) (58.7%); Indians (39.2%) and Whites (2.1%) constituted the remainder. Mean age was 57.5 ± 11.2 years; mean duration of diabetes 11.4 ± 8.9 years; mean HbA1c was 8.6 ± 1.9%. Metabolic syndrome was found in 86.4% (n:127) of the Study group. Mean TT, SHBG, FT and median LH (IQR) in the Study group were within normal range (14.5 ± 5.8 nmol/l, 40.7 ± 20.3 nmol/l, 265.9 ± 90.4 pmol/l and 5.3 [3.8-7.3] IU/l, respectively). However, mean serum TT and FT was lower in the Study group than Control subjects (14.5 ± 5.8 vs. 18.8 ± 7.2 nmol/l, p <0.001 and 265.9 ± 90.4 vs. 351.7 ± 127.3 pmol/l, p<0.001). The prevalence of LSTT and LSFT was 35.8% and 16.2%, respectively. Prevalence of LSFT increased with age and higher body mass index (BMI) categories with the highest rate noted in >40 kg/m2 BMI category (50%). In multivariate analysis, LSFT was significantly associated with age [OR 1.05 (95% CI 1.02-1.218), p=0.043] and waist circumference (WC) [OR 1.033 (95% CI 0.999- 1.068), p=0.059]. LSTT was associated with BMI only [OR 1.138 (95%CI 1.063- 1.218), p<0.0001]. TT correlated inversely with BMI, WC and the number of metabolic syndrome criteria. FT correlated inversely with BMI, WC and WHR. For both FT and TT, no significant correlation was observed with HbA1c. The prevalence of androgen deficiency symptoms using AMS score was 74.5%. The prevalence of any androgen deficiency symptom on direct enquiry was 68.9%. The AMS score correlated poorly with LSTT or LSFT and was not superior to direct enquiry. Conclusion: In this group of predominantly African and Indian men with T2DM from KwaZulu-Natal, there was a high prevalence of LSTT and LSFT. Serum TT and FT was lower in men with T2DM compared to control subjects. Waist circumference was a significant risk factor associated with LSFT while LSTT was associated with higher BMI and older age. There was a high prevalence of androgen deficiency symptoms using both the AMS score and on direct enquiry. The AMS score was a poor predictor of low testosterone and was not superior to direct enquiry. More research is required locally and from other sub-Saharan African countries before routine screening can be recommended.Item Radioactive iodine in the management of thyrotoxicosis.(2011) Narsai, Neil Yeshwant.; Motala, Ayesha Ahmed.Objective : An audit of the use and outcomes of Radioactive Iodine (RAI) therapy in the definitive management of thyrotoxicosis at Inkosi Albert Luthuli Central Hospital (IALCH), KwaZulu-Natal, South Africa. Methods : The clinical records of all new patients with thyrotoxicosis, referred in a 4 year period between 01/01/2003 and 31/12/2006, were analysed. Response to RAI was monitored using biochemical parameters (namely, Thyroid Stimulating Hormone and Free T4 levels). Rates of euthyroidism (cure), hypothyroidism and hyperthyroidism (treatment failure) were correlated to dose of RAI. Patients were followed-up for at least 2 years or until the onset of hypothyroidism. The follow-up period was until 31/12/2007. Results : One hundred and fourteen patients (37.7%), of a cohort of 302 new thyrotoxic patients treated with RAI, met the inclusion criteria. Ninety-six patients (84.2%) had Graves Disease (GD) whilst 18 had Toxic Nodular Disease (TND). At 2 year follow-up, 91 patients (79.8%) were hypothyroid, 10 (8.8%) were euthyroid and 13 (11.4%) were hyperthyroid. The average dose of RAI to achieve euthyroidism was 10mCi and hypothyroidism, 9.7mCi. The average time to achieve euthyroidism was 5.9 months and 10.1 months to become hypothyroid. Thirty-one patients (27.2%) remained persistently hyperthyroid after one dose of RAI. Patients with GD (88.5%) were more likely to become hypothyroid (p < 0.001) whilst 38.9% of TND patients remained hyperthyroid (p = .001). Baseline TFT values were significant in terms of outcomes correlated with the prescribed RAI dose i.e Low Dose (<8mCi) vs. Intermediate Dose (8-9mCi) vs. High Dose (>9mCi)(TSH p = 0.05; FT4 p = 0.003; FT3 p = 0.001). Conclusion : The majority of patients became hypothyroid over time, in keeping with reported data. In the public health sector, where early access to RAI (in terms of waiting times for appointments for RAI) and follow-up are major problems, early cure is essential to minimize the morbidity of thyrotoxicosis and this may be achieved with an initial high dose of RAI.