Pattern of dyslipidaemia in relation to statin use in patients with type 2 diabetes mellitus attending a tertiary care hospital

Introduction: Atherosclerotic cardiovascular disease is a major contributor to morbidity and mortality in diabetic patients. Strict goal-directed lipid control in patients with diabetes is associated with better cardiovascular outcomes.Aim: The main aim of this study is to describe the lipid profiles of a cohort of patients with type 2 diabetes mellitus in order to highlight the quality of lipid control by correlating the type and dose of lipid-modifying therapy used with lipid levels.Method: A retrospective analysis was performed on 200 type 2 diabetic patients who attended the Charlotte Maxeke Johannesburg Academic Hospital diabetic clinic. Their lipid profiles and the type and dose of lipid-modifying therapy prescribed was assessed.Results: Although the majority of participants (146 [73%]) were at the ideal level for total cholesterol, fewer (133 [66.5%]) were at the ideal level for triglycerides and 112 (56%) participants were at the ideal level for HDL cholesterol, only 53 (26.5%) participants were at target for LDL cholesterol, and very few, only 25 (12.5%), participants were at target for all four lipid parameters.Conclusion: Higher doses of statins or the use of more potent statins with or without the addition of other lipid modifying drugs is  recommended in order to achieve LDL cholesterol target in the majority of patients with type 2 diabetes

An unusual presentation of insulinoma and the serious consequences of delayed diagnosis

Insulinomas are rare functional neuroendocrine tumours. These tumours present with symptoms of hypoglycaemia, adrenergic and neuroglycopenic symptoms. Insulinomas are usually small in size, making them difficult to locate. Diagnosis is often delayed in these cases resulting in lasting neurological complications, often not reversible after surgical removal of the insulinoma. We report a case of a 33-year-old HIV-positive female with delayed presentation of an insulinoma. She presented with a long history of neurological symptoms with lasting neurological sequelae and poor functional status, during which time the diagnosis of insulinoma was repeatedly missed

Novel approaches to lipid-lowering therapy

Cardiovascular disease (CVD) remains a major cause of death worldwide, with dyslipidaemia playing a significant role in the disease process. It is clinically useful to demarcate hypercholesterolaemia from hypertriglyceridaemia, with an increased serum low-density lipoprotein (LDL) cholesterol being the most powerful predictor of CVD morbidity and mortality, and a significant elevation in triglyceride levels increasing the risk of acute pancreatitis. Statins (with or without ezetimibe) and fibrates are the current first-line therapy in the management of dyslipidaemia. Although these medications have shown effectiveness in reducing CVD complications, there are patients who require a greater modification in lipid profile or are intolerant of first-line therapy. Novel agents are on the horizon, which have shown to lead to a significant decrease in serum LDL cholesterol. These include the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (which have shown a reduction in CVD morbidity), mipomersen, cholesterol ester transfer protein (CETP) inhibitors and bempedoic acid. Further studies of the clinical benefit of these medications are ongoing. Drugs such as pemfibrate, angiopoietin-like protein 3 (ANGPTL3) inhibitors, apolipoprotein C3 (apo C3) inhibitors and diacylglycerol acyltransferase-1 (DGAT 1) inhibitors have shown promising results in the management of hypertriglyceridaemia. It is hoped that these exciting new technological advancements in the future management of dyslipidaemia will result in clinical benefit for patients

Frequencies of the T-455C and C-482T apoCIII gene polymorphisms in different South African population groups and their relationship to fasting serum triglyceride levels

Studies have demonstrated that serum triglyceride levels are higher in Indian and White than Black South African subjects. Polymorphisms in the apoCIII gene have been associated with raised triglyceride levels. This study investigated the prevalence of apoCIII polymorphisms and their effect on triglyceride levels in three South African population groups and in subjects with fasting hypertriglyceridaemia (HT). Two apoCIII polymorphic sites (T-455C and C-482T) were studied in 78 European, 24 Indian and 25 African subjects. Each ethnic group included HT and non-HT (control) patients. Although triglyceride levels were much higher in the HT subjects, no significant differences were noted between the groups for allele or genotype frequencies at either apoCIII locus. Furthermore, at neither locus was there an association between the genotype and serum triglyceride levels. The HT and control subjects were therefore combined and ethnic differences in allele frequencies were investigated. The African subjects had a higher frequency (0.79) of the unfavourable C allele at position 455 than both Indian (0.56; p‹0.05) and European (0.41; p‹0.0005) subjects. Furthermore, African subjects had a higher frequency (0.77) of the unfavourable T allele at locus 482 than Indian (0.44, p‹0.005) and European (0.36, p‹0.0005) subjects despite triglyceride levels being lower in the African (0.60 [1.60] mmol/l) than European (0.90 [0.40] mmol/l; p‹0.05) control subjects. These results suggest that the apoCIII polymorphisms studied do not contribute to the raised triglyceride levels in HT subjects and do not explain the ethnic differences observed in fasting serum triglyceride levels

Effects of diabetes mellitus on health-related quality of life at a tertiary hospital in South Africa: A cross-sectional study

Background. Diabetes mellitus (DM) is a chronic metabolic disease that potentially causes debilitating and life-threatening complications, demands a lifestyle change, and has important implications with regard to wellbeing and health-related quality of life (HRQOL).Objectives. To: (i) determine the HRQOL of a sample of patients with type 2 diabetes; (ii) describe the demographics (age, gender, and smoking and alcohol use) of the population studied; (iii) document the following parameters, which are important in determining the control and severity of type 2 diabetes: (a) glycosylated haemoglobin (HbA1c), (b) total amount of insulin required per day (if on insulin therapy), (c) body mass index (BMI), and (d) exercise compliance; (iv) determine whether there was an association between any or all of the above parameters and the HRQOL of these patients; and (v) determine whether coexisting diseases (hypertension (HT) and dyslipidaemia) were present, and compare HRQOL between diabetic patients with and without these diseases.Methods. This was a cross-sectional and descriptive study of 200 patients attending the diabetes clinic at Helen Joseph Hospital, Johannesburg, South Africa. HRQOL assessments were made using the Diabetes 39 (D-39) questionnaire, which patients filled in once consent had been obtained and if they fulfilled the inclusion criteria. Patients’ questionnaire forms were then analysed with regard to their demographics (age and gender), exercise regimen, smoking and alcohol history, employment status, living arrangements, age of diagnosis of DM, and concurrent use of antihypertensive and cholesterol-lowering drugs. The patients’ files were analysed and various clinical parameters were noted (HbA1c, lipogram, BMI, number of insulin units used per day, and whether any antihypertensive and/or lipidlowering drugs were used).Results. There was an association between HRQOL and HbA1c, and between HRQOL and HT and dyslipidaemia.Conclusions. No association was found between HRQOL and other clinical parameters, namely number of insulin units used per day, exercise, BMI, lipogram and the use of oral hypoglycaemic agents. Demographic parameters (age, gender, age at diagnosis, employment status and living arrangements) were also shown to have no impact on HRQOL. We found no association between HRQOL in patients who consumed alcohol and smoked cigarettes and in those who did not

Prevalence and pattern of dyslipidaemia in type 2 diabetes mellitus patients at a tertiary care hospital

Background: Diabetes mellitus (DM) is a common secondary cause of dyslipidaemia, particularly if glycaemic control is poor, which in turn is an important risk factor for atherosclerosis and coronary artery disease.Objectives: (1) To study the prevalence and pattern of dyslipidaemia in patients with type 2 DM. (2) To determine the relationship (if any) between HbA1C and the lipid profile in type 2 diabetic patients.Methods: This was a cross-sectional study done in 200 type 2 diabetic patients  attending the Diabetic Clinic at the Helen Joseph Hospital. Patients suffering from other known causes of secondary dyslipidaemia were excluded. Each patient’s  HbA1C and lipid profile results were recorded from their clinic files. The lipid profile included total cholesterol (TC), triglyceride (TG), high-density lipoprotein  cholesterol (HDL-C) and calculated low-density lipoprotein cholesterol (LDL-C). Patients with one or more of the above parameters outside the targets recommended by the 2012 South African Dyslipidaemia Guidelines were considered to have uncontrolled dyslipidaemia.Results: Of the 200 type 2 DM patients studied, 86 (43%) were male and 114 (57%) female. Despite all patients being treated with lipid-lowering therapy  (simvastatin at a mean daily dose of 20 mg), 187 patients (93.5%) did not achieve all their lipid targets. The most prevalent lipid parameter not at target was an LDL-C of ≥ 1.8 mmol/l in nearly 80% of patients. The most common pattern of  dyslipidaemia was a combined dyslipidaemia (any two abnormal lipid parameters) affecting a total of 82 out of the 187 patients (43.8%) not reaching recommended  targets. No significant relationship was found between HbA1C and any of the lipid parameters.Conclusion: The vast majority of the type 2 diabetic patients studied had  dyslipidaemia not meeting recommended targets, despite the use of lipid-lowering therapy in all patients. There is a need for more intensive lipid-lowering therapy, particularly statin therapy in patients with dyslipidaemia. Measures aimed at  combating obesity and other lifestyle-related risk factors are also vital and need to be implemented for effectively controlling dyslipidaemia and reducing the burden of CVD.Keywords: combined dyslipidaemia, LDL, lipid target

Case Studies: Unusual phaeochromocytomas in African families: the importance of genetic testing

No AbstractKeywords: phaeochromocytomas; genetic testing; Von Hippel-Lindau syndrome; familial cancer; genetic counsellin

Selected risk factors for coronary heart disease in male scholars from the major South African population groups

A num.ber of risk factors for coronary heart disease (CHD) in 7 groups of South African male scholars aged between 15 and 20 years were surveyed. Selection of the groups was based on socioeconomic status and comprised urban and rural blacks, Indians of higher and lower socio-economic status, coloureds of higher and lower socio-economic status, and middle-class whites. Both Indian groups, both coloured groups and the whites had a much greater prevalence and severity of CHD risk factors than the two black groups. This held for total cholesterol, low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), the HDLC/LDLC ratio, apolipoprotein B, apolipoprotein A-I, insulin, fibrinogen and mass. One exception was lipoprotein a, levels of which were higher in both black groups. In general the CHD risk factor profile was worse in the higher socio-economic groups, and it also tended to be worse in urban than in rural blacks. These findings stress the need to reduce CHD risk factors in our developed populations and to prevent their emergence in our developing peoples

Mipomersen, an Antisense Oligonucleotide to Apolipoprotein B-100, Reduces Lipoprotein(a) in Various Populations With Hypercholesterolemia : Results of 4 Phase III Trials

OBJECTIVE\u2014: Lp(a) is an independent, causal, genetic risk factor for cardiovascular disease and aortic stenosis. Current pharmacological lipid-lowering therapies do not optimally lower Lp(a), particularly in patients with familial hypercholesterolemia (FH).APPROACH AND RESULTS\u2014: In 4 phase III trials, 382 patients on maximally tolerated lipid-lowering therapy were randomized 2:1 to weekly subcutaneous mipomersen 200 mg (n=256) or placebo (n=126) for 26 weeks. Populations included homozygous FH, heterozygous FH with concomitant coronary artery disease (CAD), severe hypercholesterolemia, and hypercholesterolemia at high risk for CAD. Lp(a) was measured 8 7 between baseline and week 28 inclusive. Of the 382 patients, 57% and 44% had baseline Lp(a) levels >30 and >50 mg/dL, respectively. In the pooled analysis, the mean percent decrease (median, interquartile range in Lp(a) at 28 weeks was significantly greater in the mipomersen group compared with placebo ( 1226.4 [ 1242.8, 125.4] versus 120.0 [ 1210.7, 15.3]; P30 or >50 mg/dL, attainment of Lp(a) values 6430 or 6450 mg/dL was most frequent in homozygous FH and severe hypercholesterolemia patients. In the combined groups, modest correlations were present between percent change in apolipoprotein B-100 and Lp(a) (r=0.43; P<0.001) and low-density lipoprotein cholesterol and Lp(a) (r=0.36; P<0.001) plasma levels.CONCLUSIONS\u2014: Mipomersen consistently and effectively reduced Lp(a) levels in patients with a variety of lipid abnormalities and cardiovascular risk. Modest correlations were present between apolipoprotein B-100 and Lp(a) lowering but the mechanistic relevance mediating Lp(a) reduction is currently unknown