Lifestyle modification in the management of insulin resistance states in overweight/obesity: the role of exercise training

Physical inactivity is a major contributor to overweight/obesity and associated disorders including cardiovascular diseases (CVDs), diabetes, and insulin resistance (IR). Intensive lifestyle modification (ILM) is recommended as first-line treatment for obese individuals at risk for IR. Exercise is considered to be a critical component of ILM. This narrative review discusses the role of exercise in the management of IR in overweight/obesity. PubMed and Google Scholar were searched for articles published between January 1990 and January 2019 that examined mechanisms behind the effects of exercise on IR states associated with overweight/obesity. Studies examining and/comparing effects of exercise mode, volume and/intensity on IR were also retrieved. Medical Subject Headings (MeSH) used were ‘metabolic diseases’ OR ‘chronic diseases’ AND ‘exercise’ and their related terms. Text words used in conjunction with the MeSH terms were ‘aerobic training/exercise’ OR ‘resistance training/exercise’ OR ‘high intensity interval training/exercise’, OR ‘low volume training/exercise’. Reference lists of retrieved articles were also searched for appropriate studies. Aerobic exercise training (AET) and resistance exercise training (RET) appear to produce comparable effects on obesityinduced IR states. RET, however, appears to be associated with greater improvements in glucose disposal in skeletal muscle, which is usually the primary site for IR. This is partly attributed to greater increases in key proteins involved in the insulin signalling pathway including protein content of glucose transporter 4 (GLUT-4) following RET. A study on individuals with impaired glucose tolerance (IGT) showed that RET improved glucose disposal by 23%, primarily due to a 27% increase in non-oxidative glucose metabolism, suggesting that RET may delay the manifestation of diabetes in patients with IGT. Furthermore, studies reviewed here show that components of exercise including the mode, volume and intensity of exercise training are an integral element in exercise prescription and must be recommended in accordance with the desired outcome

Rickets mimicker: A report of two cases of primary hyperparathyroidism in adolescence

The presentation of primary hyperparathyroidism (PHPT) in most Western countries has evolved from the classic description of ‘stones, bones, and groans’ to becoming increasingly asymptomatic as a result of more frequent serum calcium screening. However, many developing countries are still reporting predominantly symptomatic PHPT with the classic complications of skeletal disease and nephrolithiasis still being quite common. Furthermore, the exact prevalence of PHPT in children is not known but it is thought to be uncommon and the clinical presentation and outcomes in this subgroup of patients are not well described in the literature. Two cases of PHPT occurring in adolescent boys are reported. Both cases initially presented with chronic bone pain involving the lower limbs and had a long delay before the diagnosis of PHPT was confirmed. They developed progressive deformities of the lower limbs, which resembled rickets clinically. Radiological features were also suggestive of rickets. However, biochemistry confirmed parathyroid hormone mediated hypercalcaemia in both cases and after parathyroid surgery a parathyroid adenoma was confirmed histologically as the aetiology of hypercalcaemia. Therefore, PHPT occurring in adolescence may have a clinical presentation almost identical to that of rickets. All patients presenting with skeletal deformities including a rickets phenotype must have serum calcium and phosphate levels measured as part of the diagnostic workup

Characteristics and outcome of surgically treated acromegaly patients attending an endocrinology clinic at a tertiary referral centre in Durban, South Africa over a period of 10 years

Background: The mode of presentation, clinical, radiologic and laboratory characteristics of patients with acromegaly and the outcome following various modalities of treatment are not well documented in South Africa.Aim: To evaluate treatment outcome and follow-up of patients with acromegaly over a period of 10 years.Methods: The study is a retrospective record review of patients with acromegaly attending Inkosi Albert Luthuli Central Hospital, Durban, 2003–2013.Results: The study included 27 patients (16 female and 11 male) with a mean age at diagnosis of 44.2 ± 14.0 years. The mean growth hormone (GH) at diagnosis was 51.8 ± 32.6 μg/l and mean IGF-1 956.8 ± 432.9 μg/l. In 25 patients (92.5%) pituitary macroadenoma was identified; microadenoma was present in 2 (7.4%) patients. Trans-sphenoidal surgery was employed in 26 (96.3%) as the initial therapy; only 1 patient was treated medically. Adjunctive medical therapy was used in 23 (88.5%) and radiotherapy in 6 (22.2%). After a mean follow-up of 4.4 ± 3.4 years, 9 (33.3%) subjects were cured (normal age-matched and gender-matched IGF-1 and random GH < 1.0 μg/l). No deaths were recorded and post-procedural hypopituitarism developed in 22 (84.6%) patients.Conclusions: Patients with acromegaly in KwaZulu-Natal present with advanced clinical features and large pituitary adenomata. The overall cure rate is lower than reported from developed countries.Keywords: acromegaly, diagnostic criteria, medical and radiotherapy, modes of treatment (surgery

Characteristics and outcome of patients with pheochromocytoma at a tertiary endocrinology clinic in Durban, South Africa over 14 years

Objectives: To evaluate the characteristics and outcomes of treatment of patients with pheochromocytoma at Inkosi Albert Luthuli Central Hospital (ILACH) in Durban, South Africa over 14 years.Design: Retrospective chart review.Setting and subjects: Patients with pheochromocytoma attending the endocrinology clinic at IALCH between 2012 and 2016 were studied.Outcome measures: Clinical, biochemical and radiological data were collected at presentation, on discharge, one year and five years after surgical intervention; tumour characteristics, histopathological features and surgical outcome were also assessed.Results: The analysis included 35 patients (mean age 33.2 ± 15.7 years; 60% female). Headache (68.6%), palpitation (60%) and sweating (57.6%) were the three most common presenting symptoms; hypertension was the predominant clinical finding (85.7%). Most pheochromocytomas were sporadic (82.9%), adrenal gland tumours (68.6%) and benign (77.1%); of eight patients with malignant tumours, two were familial. Adrenalectomy was undertaken in the majority (n = 34; 97.1%); 55.2% were large tumours. The use of adjunctive radiotherapy (n = 4; 11.4%) and chemotherapy (n = 1; 2.9%) was low. There was low overall mortality (5.7%), but 57.6% developed intraoperative hypotension. At one year postoperatively, 80% (n = 28) of patients were defined as cure, biochemically in 23 (82.1%) and with radiology in five (17.9%).Conclusions: Most patients presenting to IALCH had large intra-abdominal tumours with high cure rate, low mortality but a high rate of perioperative complications. Late presentation and large tumour size was a feature.Keywords: pheochromocytoma , South Africa, surgical outcom

Microvascular complications in South African patients with long duration diabetes mellitus

Objective. To determine the prevalence of microvascular complications in South African black and Indian patients with long-duration diabetes mellitus (DM).Design. A retrospective analysis was undertaken of clinical records of 219 OM patients (132 black, 87 Indian) with longduration OM (over 10 years) attending a diabetes clinic in Durban. Data recorded on each subject included demographic details (age, gender, ethnic group, type of diabetes, age of onset and duration of diabetes), presence of retinopathy, markers of nephropathy and biochemical variables. The prevalence of complications and the clinical and biochemical parameters were evaluated for type 1 and type 2 diabetes and for each ethnic group.Results. Of the 219 patients, 47 had type 1 OM (36 blacks, 11 Indians) and 172 were classified as type 2 OM (96 blacks, 76 Indians). The mean age of onset of OM wa later in blacks than Indians, both for type 1 (P < 0.05) and type 2 OM (P < 0.01). In patients with type 1 OM, the prevalence of retinopathy was 53.2% (blacks 55.6%, Indians 45.5%), persistent proteinuria was found in 23.4% (blacks 25%, Indians 18.2%) and hypertension in 34%. 0 ethnic difference was found except for the prevalence of hyperten ion which was higher in blacks than Indians (41.7% v. 9.1%, P < 0.5). Onset of retinopathy from time of diabetes diagno is occurred earlier in blacks than Indians (13.0 ± 4.6 yrs v. 18.0 ± 4.6 yrs, P < 0.05). For the type 2 DM group, retinopathy was found in 64.5% (black v. Indian 68.8 v. 59.2%) and per istent proteinuria in 25% (black v. Indian 30.2 v. 1 .4%). Hypertension wa observed in 68% and wa more prevalent in blacks (84.4 v. 47.,*%, P < 0.01) There was an earlier onset of retinopathy (P < 0,05) and hypertension (P < 0.01) from time of diabetes diagnosis in blacks than Indians. In the type 1 OM group retinopathy was a sociated with a ignificantly longer duration of diabetes (P < 0.05) and higher glycated haemoglobin (HbA1) (P < 0.05). For type 2 DM subjects there was a significant association between retinopathy and longer duration of diabetes (P < 0.05) and higher systolic blood pressure (P < 0.05).Conclusion. 1his study has shown that there is a high prevalence of microvascular complications in South African patients with long-duration diabetes mellitus

High prevalence of cardiovascular risk factors in Durban South African Indians: The Phoenix Lifestyle Project

Background. Previous studies show a high prevalence of cardiovascular (CV) risk factors in South African (SA) Asian Indians, with the emergence of premature coronary artery disease in young Indian subjects.Objective. To determine the prevalence of CV risk factors in this population.Methods. This was a cross-sectional study of randomly selected adults aged 15 - 64 years from the suburb of Phoenix in Durban, KwaZulu-Natal Province, SA. All participants had demographic, anthropometric and biochemical measurements using the modified World Health Organization (WHO) STEPwise survey methods. Hypertension, obesity, lipid abnormalities and diabetes mellitus (DM) were diagnosed using WHO criteria. Age-standardised frequencies for glycaemic indices were calculated according to the WHO standard world population distribution. Results. Of the 1 428 subjects who responded (response rate 72.1%), complete data for analysis were available on 1 378 (1 001 women). The mean age was 45.5 (standard deviation 13) years. There were high prevalences of hypertension (47.5%), DM (20.1%), total body obesity (raised body mass index) (32.4%) and increased waist circumference (73.1%). The ‘thin-fat’ Asian phenotype (isolated abdominal obesity) was found in only 4.8% of participants. High prevalences of total body obesity (32.1%), increased waist circumference (31.3%) and insulin resistance (28.2%) were documented in the youngest age group. Over half of the males and 14.6% of females were current smokers. Diabetic dyslipidaemia was found in 61 subjects (4.4%). In multivariate analysis, age, triglycerides and waist circumference measurement were significant independent risk factors associated with DM and, together with fasting glucose, also predicted hypertension. Conclusion. Compared with Asian Indian subjects with similar environmental exposure in previous studies, the magnitude of change in risk factor prevalence over the past two decades has been of epidemic proportions.

Genetic loci implicated in meta-analysis of body shape in Africans.

BACKGROUND AND AIMS: Obesity is one of the leading causes of non-communicable diseases (NCD). Thus, NCD risk varies in obese individuals based on the location of their fat depots; while subcutaneous adiposity is protective, visceral adiposity increases NCD risk. Although, previously anthropometric traits have been used to quantify body shape in low-income settings, there is no consensus on how it should be assessed. Hence, there is a growing interest to evaluate body shape derived from the principal component analysis (PCA) of anthropometric traits; however, this is yet to be explored in individuals of African ancestry whose body shape is different from those of Europeans. We set out to capture body shape in its multidimensional structure and examine the association between genetic variants and body shape in individuals of African ancestry. METHOD AND RESULTS: We performed a genome-wide association study (GWAS) for body shape derived from PCA analysis of anthropometric traits in the Ugandan General Population Cohort (GPC, n = 6407) and the South African Zulu Cohort (SZC, n = 2595), followed by a GWAS meta-analysis to assess the genetic variants associated with body shape. We identified variants in FGF12, GRM8, TLX1NB and TRAP1 to be associated with body shape. These genes were different from the genes been associated with BMI, height, weight, WC and waist-hip ration in continental Africans. Notably, we also observed that a standard deviation change in body shape was associated with an increase in blood pressure and blood lipids. CONCLUSION: Variants associated with body shape, as a composite variable might be different for those of individual anthropometric traits. Larger studies are required to further explore these phenomena

Comparative assessment of absolute cardiovascular disease risk characterization from non-laboratory-based risk assessment in South African populations

Background: All rigorous primary cardiovascular disease (CVD) prevention guidelines recommend absolute CVD risk scores to identify high- and low-risk patients, but laboratory testing can be impractical in low- and middle-income countries. The purpose of this study was to compare the ranking performance of a simple, non-laboratory-based risk score to laboratory-based scores in various South African populations. Methods: We calculated and compared 10-year CVD (or coronary heart disease (CHD)) risk for 14,772 adults from thirteen cross-sectional South African populations (data collected from 1987 to 2009). Risk characterization performance for the non-laboratory-based score was assessed by comparing rankings of risk with six laboratory-based scores (three versions of Framingham risk, SCORE for high- and low-risk countries, and CUORE) using Spearman rank correlation and percent of population equivalently characterized as ‘high’ or ‘low’ risk. Total 10-year non-laboratory-based risk of CVD death was also calculated for a representative cross-section from the 1998 South African Demographic Health Survey (DHS, n = 9,379) to estimate the national burden of CVD mortality risk. Results: Spearman correlation coefficients for the non-laboratory-based score with the laboratory-based scores ranged from 0.88 to 0.986. Using conventional thresholds for CVD risk (10% to 20% 10-year CVD risk), 90% to 92% of men and 94% to 97% of women were equivalently characterized as ‘high’ or ‘low’ risk using the non-laboratory-based and Framingham (2008) CVD risk score. These results were robust across the six risk scores evaluated and the thirteen cross-sectional datasets, with few exceptions (lower agreement between the non-laboratory-based and Framingham (1991) CHD risk scores). Approximately 18% of adults in the DHS population were characterized as ‘high CVD risk’ (10-year CVD death risk >20%) using the non-laboratory-based score. Conclusions: We found a high level of correlation between a simple, non-laboratory-based CVD risk score and commonly-used laboratory-based risk scores. The burden of CVD mortality risk was high for men and women in South Africa. The policy and clinical implications are that fast, low-cost screening tools can lead to similar risk assessment results compared to time- and resource-intensive approaches. Until setting-specific cohort studies can derive and validate country-specific risk scores, non-laboratory-based CVD risk assessment could be an effective and efficient primary CVD screening approach in South Africa