Sub-Optimal Management of Type 2 Diabetes Mellitus – A Local Audit

Background: Despite increased awareness of risk factors for coronary artery disease and randomized trial data supporting comprehensive diabetic care, these risk factors continue to be largely ignored in patients with type 2 diabetes mellitus. Objective: Cross-sectional study to determine the level of control in patients with type 2 diabetes in tertiary diabetes clinics. Methods: Patient demographic, diabetes and cardiovascular disease related (CVD) data was collected from 150 (F:M; 98:52) randomly selected patients with type 2 diabetes mellitus attending the diabetes clinics at the three academic teaching hospitals served by the University of the Witwatersrand. Blood pressure, height, weight, body mass index and waist circumference were measured. Glycated haemoglobin and fasting serum lipid levels were obtained from patient records. Black patients contributed 68%, White 12, 7%, Indian 10, 7% and Coloured 8, 7%. Results: Mean HbA1c for the whole cohort was 8, 7%. Obesity was present in 37, 3%, hypercholesterolaemia in 29, 3% and hypertriglyceridaemia in 45, 3%. Waist circumference was ≥ 80 cm in 98% of the females and ≥ 94 cm in 69% of the males. 127 patients out of 150 (85%) were hypertensive and 74% of these had a systolic blood pressure ≥ 130 mmHg and 84% a diastolic blood pressure ≥ 80 mmHg. 43% of the patients did minimal exercise, 6% smoked and only 51% were on aspirin. Conclusion: Comprehensive diabetic care is still largely lacking despite clinical trial data documenting improved outcomes associated not only with glycaemic control but also with use of antihypertensive, lipid lowering and anti-platelet therapy

Analysis of mutations causing familial hypercholesterolaemia in black South African patients of different ancestry

Background. Familial hypercholesterolaemia (FH) is usually caused by mutations in three genes (LDLR, APOB and PCSK9).Objective. To identify the spectrum of FH-causing mutations in black South African (SA) patients.Methods. DNA samples of 16 unrelated South African FH patients with elevated low-density lipoprotein cholesterol levels, tendon xanthomas and corneal arcus (3 clinically homozygous FH and 13 heterozygous FH) of ethnic African origin were screened for mutations in the LDLR (coding region, promoter and intron/exon boundaries), APOB (part of exon 26) and PCSK9 genes (exon 7), using high-resolution melting.Results. Eight LDLR mutations were identified, for an overall detection rate of 8/19 predicted FH-causing alleles (42.1%). The previously reported six base pair deletion p.(D47_G48del) was found in two patients, and two novel variants (c.1187-25T>C and c.1664T>G p.(L555R)) were found, both predicted to be pathogenic using in silico web-based predictive algorithms. No pathogenic variants in APOB or PCSK9 were found.Conclusions. These findings contribute to the knowledge of allelic heterogeneity in the spectrum of FH-causing mutations in black SA patients, signifying their ancestral diversity. The relatively low overall detection rate may reflect locus heterogeneity of the FH phenotype in black SA FH patients

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 lipid-lowering 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

Functional foods with added plant sterols for treatment of hypercholesterolaemia and prevention of ischaemic heart disease

Background. A spread with added plant sterols, Pro-activ, is marketed in South Africa as an adjunct to low-fat diets for lowering of total and low-density lipoprotein (LDL) cholesterol concentrations and to decrease risk of ischaemic heart disease (IHD). Objectives. The need for this functional food in South Africa, its efficacy, safety and target market, are evaluated in this review. Results. The high, and probably increasing incidence of hypercholesterolaemia and cardiovascular disease in South Africa motivates the need for appropriate functional foods. There is convincing evidence in the literature that an average daily intake of about 2 g plant sterols in about 20 g of spread significantly lowers total and LDL cholesterol concentrations by approximately 10 - 15%, without influencing high-density lipoprotein (HDL) cholesterol and triglyceride concentrations. There is some concern about the effects on absorption of lipid-soluble vitamins and pro-vitamins, but safety tests lasting for up to 3 years found no serious adverse effects. Conclusions. The target market for this spread should be nonpregnant, non-lactating adults with hypercholesterolaemia and/or increased risk of IHD. If it is considered for use in hypercholesterolaemic children, fat-soluble vitamin status should be monitored. It is recommended that post-marketing surveillance should be established to determine long-term effects and safety

Effect of Alirocumab on Lipoprotein(a) Over ≥1.5 Years (from the Phase 3 ODYSSEY Program)

Elevated lipoprotein(a) [Lp(a)] is independently associated with increased cardiovascular risk. However, treatment options for elevated Lp(a) are limited. Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, reduced low-density lipoprotein cholesterol (LDL-C) by up to 62% from baseline in phase 3 studies, with adverse event rates similar between alirocumab and controls. We evaluated the effect of alirocumab on serum Lp(a) using pooled data from the phase 3 ODYSSEY program: 4,915 patients with hypercholesterolemia from 10 phase 3 studies were included. Eight studies evaluated alirocumab 75 mg every 2 weeks (Q2W), with possible increase to 150 mg Q2W at week 12 depending on LDL-C at week 8 (75/150 mg Q2W); the other 2 studies evaluated alirocumab 150-mg Q2W from the outset. Comparators were placebo or ezetimibe. Eight studies were conducted on a background of statins, and 2 studies were carried out with no statins. Alirocumab was associated with significant reductions in Lp(a), regardless of starting dose and use of concomitant statins. At week 24, reductions from baseline were 23% to 27% with alirocumab 75/150-mg Q2W and 29% with alirocumab 150-mg Q2W (all comparisons p <0.0001 vs controls). Reductions were sustained over 78 to 104 weeks. Lp(a) reductions with alirocumab were independent of race, gender, presence of familial hypercholesterolemia, baseline Lp(a), and LDL-C concentrations, or use of statins. In conclusion, in addition to marked reduction in LDL-C, alirocumab leads to a significant and sustained lowering of Lp(a)

Lower levels of high-density lipoprotein cholesterol in urban Africans presenting with communicable versus non-communicable forms of heart disease: the 'Heart of Soweto' hospital registry study

Objectives: To investigate if urban Africans displayed lower levels of atheroprotective high-density lipoprotein cholesterol (HDLC) when presenting with communicable versus non-communicable forms of heart disease (HD) as both acute infection and chronic inflammation reduce HDLC levels. Design: Hospital registry of 5328 de novo cases of HD over a 3-year period. Setting: Cardiology Unit, Baragwanath Hospital in Soweto, South Africa. Participants: A total of 1199 patients of African descent (59% women; 57.0±13.4 years) had fasting blood lipid levels (total cholesterol (TC), triglyceride, HDLC and low-density lipoprotein cholesterol (LDLC)) documented on admission. Serum inflammatory marker C reactive protein (CRP) was measured in a subset of 367 patients (31% of cases). Main Outcome Measures: Lipid profiles were compared according to prespecified classification of non-communicable (eg, hypertensive HD) versus communicable (eg, rheumatic HD) HD. Low HDLC was defined as <1.0 mmol/L for men and <1.2 mmol/L for women, according to applicable South African Clinical Guidelines. Results: Overall 694 (58%) of those presenting with HD had low HDLC levels; 344 of 678 (51%) and 350 of 521 (67%) for non-communicable and communicable, respectively (p<0.001). Comparatively, overall prevalence of high TC was 32% and high LDLC was 37%. On an adjusted basis, those with non-communicable HD were more likely to record a low HDLC relative to non-communicable presentations (odds ratio (OR) 1.91, 95% CI 1.42 to 2.57; p<0.001). There was a strong relationship between low HDLC and higher levels of CRP, but only in women. Conclusions: Despite largely favourable lipid profiles, there are clear differences according to aetiology of underlying HD in urban Africans, with younger patients with communicable HD having particularly low levels of HDLC. Appropriate prospective evidence is needed to determine if persistent low levels of HDLC expose patients to increased, long-term risk of atherosclerotic forms of HD. The women-only inverse association between HDLC and CRP warrants further investigation.Jasmine G Lyons, Karen Sliwa, Melinda J Carrington, Frederick Raal, Sandra Pretorius, Friedrich Thienemann, Simon Stewar