SUNScholar - Browsing by Author "Zemlin, Annalise E."

Browsing by Author "Zemlin, Annalise E."

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The agreement between fasting glucose and markers of chronic glycaemic exposure in individuals with and without chronic kidney disease : a cross-sectional study
(BMC (part of Springer Nature), 2020-01-30) George, Cindy; Matsha, Tandi E.; Korf, Marizna; Zemlin, Annalise E.; Erasmus, Rajiv T.; Kengne, Andre P.
Background: To assess whether the agreement between fasting glucose and glycated proteins is affected by chronic kidney disease (CKD) in a community-based sample of 1621 mixed-ancestry South Africans. Methods: CKD was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m2. Fasting plasma glucose and haemoglobin A1c (HbA1c) concentrations were measured by enzymatic hexokinase method and highperformance liquid chromatography, respectively, with fructosamine and glycated albumin measured by immunoturbidimetry and enzymatic method, respectively. Results: Of those with CKD (n = 96), 79, 16 and 5% where in stages 3, 4 and 5, respectively. Those with CKD had higher levels of HbA1c (6.2 vs. 5.7%; p < 0.0001), glycated albumin (15.0 vs. 13.0%; p < 0.0001) and fructosamine levels (269.7 vs. 236.4 μmol/l; p < 0.0001), compared to those without CKD. Higher fasting glucose levels were associated with higher HbA1c, glycated albumin and fructosamine, independent of age, gender, and CKD. However, the association with HbA1c and glycated albumin differed by CKD status, at the upper concentrations of the respective markers (interaction term for both: p ≤ 0.095). Conclusion: Our results suggest that although HbA1c and glycated albumin perform acceptably under conditions of normoglycaemia, these markers correlate less well with blood glucose levels in people with CKD who are not on dialysis.
Assessment of the association of plant- based diets with cardiovascular disease risk profile in Africa: a systematic review and meta-analysis protocol
(BMJ Publishing, 2020-06) Lopes, Tatum; Zemlin, Annalise E.; Erasmus, Rajiv T.; Faber, Mieke; Kengne, Andre P.
Introduction Cardiovascular disease (CVD) is currently the leading cause of death worldwide. In Africa where infectious diseases are still the leading cause of death, the contribution of non-communicable diseases led by CVDs has significantly increased in recent years. The rise of CVDs in Africa is attributed at least in part to the adoption of sedentary behaviours and unhealthy eating habits, which are linked with urbanisation and westernisation of cultures. Dietary attributes associated with CVD risk have been less investigated in Africa. However, evidence from developed nations has reported a protective effect of healthy dietary patterns such as plant-based diets (PBDs) on cardiometabolic health. The current protocol is for a review aiming to assess existing evidence on the association of PBDs with CVD risk profile in African populations. Methods and analysis This protocol was developed following the 2015 guidelines of the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols. We will conduct a comprehensive search of the literature for published studies on PBDs in relation to CVD risk profile in African populations. Observational studies published between January 1990 and December 2019 will be screened. A search strategy using keywords and medical subject headings terms will be applied across multiple scientific databases including PubMed-Medline, Scopus and EBSCOhost and the African Journals Online platform. Manual searches of reference lists from relevant articles will be performed. Citations will be traced using the ISI Web of Science to further identify eligible studies. Grey literature will also be screened for relevant abstracts from conference proceedings, and experts in the field will be contacted where appropriate. Two investigators will independently screen all the titles and abstracts to determine which records are eligible for full-text review. Subsequently, two investigators will review the eligible full text using the selection criteria. A third investigator will be consulted to resolve any discrepancies. Data will be extracted from studies that are eligible for the review. Meta-analysis will be performed for studies with similar or comparable methods and reported outcome measures. This will be performed overall, and by major study-level characteristics. Heterogeneity in the estimates across studies will be assessed and quantified with the use of Cochrane Q and I2 statistics, respectively. Publication biases will be investigated through funnel plots and Egger test of bias. Relevant sensitivity analyses will be performed to confirm the robustness of the findings
An audit of 24-hour creatinine clearance measurements at Tygerberg Hospital and comparison with prediction equations
(Health and Medical Publishing Group (HMPG), 2007-10) Le Riche, Mia; Zemlin, Annalise E.; Erasmus, Rajiv T.; Davids, MR
BACKGROUND: Internationally, clinical guidelines recommend the use of creatinine-based equations to estimate glomerular filtration rate (GFR) for assessment and follow-up of kidney disease. The routine use of 24-hour creatinine clearances (CrCl) is no longer advocated. Objectives. To examine the indications for requesting CrCl at Tygerberg Hospital, identify problems associated with the procedure, and evaluate the utility of the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations with different levels of renal dysfunction in the ethnic groups of the Western Cape. Methods. A clinical audit of CrCl was performed. The estimated GFR as predicted by the modified CG and MDRD formulae was compared with CrCl in 252 patients, representing three local ethnic groups. MDRD formulae with and without the correction factor for black ethnic group (MDRD-B) were evaluated. Results. Problems with urine collection or data supplied were identified in one-third of CrCl requests, leading to unreliable results. The CG correlated best with CrCl in the group as a whole. The average absolute and percentage differences from CrCl in the different ethnic groups were as follows: coloured (mixed ethnicity) (N = 186) - CG 13.4 ml/min/1.73 m2 (18%), MDRD 16.8 ml/min/1.73 m2 (23%) and MDRD-B 27.9 ml/mim/1.73 m2 (37%); black (N = 21) - CG 14.8 ml/min/1.73 m2 (19%), MDRD 12.9 ml/min/1.73 m2 (17%) and MDRD-B 25.1 ml/min/1.73 m2 (33%); white (N = 45) CG 13.5 ml/min/1.73 m2 (19%), MDRD 15.3 ml/min/1.73 m2 (21%) and MDRD-B 24.8 ml/min/1.73 m2 (35%). Throughout the renal function levels (chronic kidney disease stages 1 - 5) CG correlated better with CrCl than MDRD. Conclusions. Possible reasons for poor correlations include a high prevalence of obesity, underweight and normal GFR in the study population. There is a need for further research, using a gold standard, into the accuracy of these prediction equations in our unique patient populations before firm recommendations can be made regarding their use. Until then CrCl will continue to be widely used. Greater efforts at patient and health care worker education are required to ensure proper collections.
Case report : an index of suspicion in hyponatraemia
(Hrvatsko društvo za medicinsku biokemiju, 2019) Barkhuizen, Marizna; Hoffmann, Mariza; Zöllner, Ekkehard W. A.; Erasmus, Rajiv T.; Zemlin, Annalise E.
Serum indices can give valuable information and should be interpreted as a result. Lipaemia can influence results through different mechanisms, an important one being the electrolyte exclusion effect. A case of pseudohyponatraemia due to this is reported. A 15-year-old female with type 2 diabetes was seen for follow-up. Her biochemistry results revealed severe hyponatraemia of 118 mmol/L. Her capillary glucose concentration was 13.7 mmol/L with a corrected sodium of 122 mmol/L. A lipaemic index of 3+ (absolute value 1320) was noted, which was not flagged by the laboratory information system, as it was below the critical lipaemia limit for sodium determination. Repeated analysis of the same sample using a direct ion selective electrode method, the serum sodium concentration was 134 mmol/L (sodium corrected for glucose = 138 mmol/L). A triglyceride concentration was requested, which was severely raised (100.1 mmol/L). The electrolyte exclusion effect is an analytical phenomenon that causes falsely low electrolyte concentrations in the presence of severe lipaemia or hyperproteinaemia when using indirect analytical methods. These methods are used on many modern-day automated chemistry analysers and should be considered in a patient with asymptomatic hyponatraemia.
Coronavirus disease 2019 (COVID-19) and the reninangiotensin system : a closer look at angiotensin-converting enzyme 2 (ACE2)
(Sage, 2020-05-01) Zemlin, Annalise E.; Wiese, Owen
ENGLISH ABSTRACT: Since the first cases of atypical pneumonia linked to the Huanan Seafood Wholesale Market in Wuhan, China were described in late December 2019, the global landscape has changed radically. In March 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic, and at the time of writing this review just over 3 million individuals have been infected with more than 200 000 deaths globally. Numerous countries are in “lockdown”, social distancing is the new norm, even the most advanced healthcare systems are under pressure, and a global economic recession seems inevitable. A novel coronavirus (SARS-CoV-2) was identified as the aetiological agent. From experience with previous coronavirus epidemics, namely the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in 2004 and 2012 respectively, it was postulated that the angiotensin-converting enzyme-2 (ACE2) receptor is a possible port of cell entry. ACE2 is part of the renin-angiotensin system (RAS), and is also associated with lung and cardiovascular disorders and inflammation. Recent studies have confirmed that ACE2 is the port of entry for SARS-CoV-2. Male sex, advanced age, and a number of associated comorbidities have been identified as risk factors for infection with COVID-19. Many high-risk COVID-19 patients with comorbidities are on ACE inhibitors and angiotensin receptor blockers, and this has sparked debate about whether to continue these treatment regimes. Attention has also shifted to ACE2 being a target for future therapies or vaccines against COVID-19. In this review, we discuss COVID-19 and its complex relationship with ACE2.
HbA1c as a screening tool for diabetes mellitus and its use with traditional and novel biochemical parameters to predict cardiovascular risk in a local urban community
(Stellenbosch : Stellenbosh University, 2016-12) Zemlin, Annalise E.; Erasmus, Rajiv T.; Matsha, Tandi E.; Kengne, Andre P.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology: Chemical Pathology.
ENGLISH SUMMARY: Introduction The global obesity pandemic has reached Africa and the diabetes mellitus (DM) prevalence is increasing in parallel. A high prevalence of DM and risk for cardiovascular disease (CVD) has been described in the South African mixed ancestry population. Recent guidelines advocate using HbA1c as a diagnostic tool for DM and prediabetes, which is more convenient. However, various studies have challenged these cut-offs. There is a paucity of studies validating these cut-offs in Africa. As DM is considered a CVD risk equivalent, emerging markers of CVD and adiposity also need evaluation. The adipokine adiponectin has anti-diabetic, anti-atherogenic and anti-inflammatory properties and levels decrease in obesity. E-selectin, a marker of endothelial cell dysfunction, is associated with subclinical atherosclerosis and hyperglycaemia. Carotid intima-media thickness (CIMT) is a noninvasive measure of subclinical atherosclerosis. The aim of this investigation was to verify recommended HbA1c cut-offs to diagnose DM and prediabetes and to examine the usefulness of emerging markers of subclinical CVD in our population. Methods This investigation consists of four substudies and was performed on participants of the Bellville South Africa Study. In the first, we challenged the recommended HbA1c cut-off of 6.5% to diagnose DM in 946 participants using oral glucose tolerance test (OGTT), fasting blood glucose (FBG), and receiver operator characteristic (ROC) curves. In the second, we derived an optimal HbA1c cut-off to detect prediabetes in 667 participants and validated this in two populations, using OGTT and ROC curves. In the third, we determined high molecular weight (hmw)-adiponectin levels in 101 participants, compared these in participants with and without hyperglycaemia and investigated their relationship with two polymorphisms (rs17300539 and rs266729) reported to affect adiponectin values. In the fourth, we determined E-selectin levels in 307 participants, compared these in participants with and without hyperglycaemia and assessed their effect on CIMT. Results The recommended HbA1c cut-off was not sensitive enough to detect DM. Using FBG, 117 (14%) participants were diagnosed with DM and 50% had an HbA1c of  6.5%; using OGTT 147 (18%) had DM and 46% had an HbA1c of  6.5%. Comparing HbA1c to FBG and OGTT, a cut-off of 6.1% gave a better sensitivity and specificity (area under curve (AUC) 0.85 and 0.82 respectively). Also, the recommended HbA1c cut-off to detect prediabetes was not appropriate and we determined that 5.75% was best. However, the low sensitivity and specificity (64.8% and 60.4% respectively for the derivation and first validation sample and 59.6% and 69.8% for the second validation sample), confirmed that HbA1c alone would miss a significant number of prediabetics. Hmw-adiponectin levels were not affected by glycaemia (median 11.6 g/mL in normoglycaemia vs. 10.5 g/mL in hyperglycaemia; p=0.3060) nor by two common polymorphisms. Using robust correlations, a significant correlation was found between hmw-adiponectin and high density lipoprotein cholesterol (HDL-c) (r=0.45; 95%CI: 0.27-0.59), which was similar in both normo-and hyperglycaemia (p>0.99). This association was attenuated in robust linear regressions adjusted for gender and adiposity. Eselectin levels were significantly higher in hyperglycaemia (median 139.8 g/L vs. 118.8 g/L in normoglycaemia; p=0.0007) but not associated with CIMT. Significant correlations were found between E-selectin and age, markers of glycaemia and inflammation, central obesity and lipid variables. Associations remained significant only with age, hyperglycaemia and C-reactive protein (CRP) in multivariable robust linear regression models. In similar regressions models, age and gender were the main predictors of CIMT, which was not associated with E-selectin. Conclusion The international HbA1c cut-offs recommended to detect DM and prediabetes were not appropriate in our population. Though a cut-off of 6.5% to diagnose DM is a good diagnostic tool with high specificity, the low sensitivity limits its screening use. Similarly, recommended HbA1c values to detect prediabetes may underestimate the true numbers. This emphasizes the importance of local evidence-based values being established. Additionally, hmw-adiponectin was not affected by glycaemia or polymorphisms, but correlated significantly with HDL-c which may explain its beneficial cardiovascular effect. Though Eselectin was influenced by glycaemia, possibly reflecting early endothelial damage, it did not correlate with CIMT, which was determined by age and male gender.
HbA1c of 6.5% to diagnose Diabetes Mellitus—Does it work for Us?—The Bellville South Africa study
(Public Library of Science (PLOS), 2011-08) Zemlin, Annalise E.; Matsha, Tandi E.; Hassan, Mogamat S.; Erasmus, Rajiv T.
Background: HbA1c has been the gold standard for glycaemic control follow-up for decades. In 2009, a level of 6.5% (48 mmol/mol) was proposed as diagnostic for diabetes. We test this cut-off in our community. Methods: Participants (946) from a community-based study were screened for diabetes using either a fasting blood glucose or oral glucose tolerance test (OFTT). The HbA1c cut-off of 6.5% was tested for each group. A receiver operator characteristic (ROC) curve for both groups was generated to establish an optimal cut-off. Results: Our study included 224 (23.7%) males and 722 (76.3%) females. Using fasting blood glucose alone, 117 (14%) were diagnosed with diabetes 250% had an HbA1c value of $6.5% (48 mmol/mol). Using an OGTT, 147 (18%) were diagnosed with diabetes 246% had an HbA1c value of $6.5% (48 mmol/mol). ROC curves found a level of 6.1% (43 mmol/mol) to be optimal in both groups (AUC 0.85 and 0.82 respectively). The sensitivities were 80% and 75% and the specificities 77% and 78% respectively. Conclusions: A cut off of 6.5% (48 mmol/mol) is a good diagnostic tool with its high specificity; however the low sensitivity limits its use. We found a level of 6.1% (43 mmol/mol) to be optimal. This emphasizes the need for evidenced based values to be established in various population groups.
High molecular weight adiponectin levels are neither influenced by adiponectin polymorphisms nor associated with insulin resistance in mixed-ancestry hyperglycemic subjects from South Africa
(De Gruyter Open, 2016) Zemlin, Annalise E.; Matsha, Tandi E.; Kengne, Andre P.; Hon, Gloudina; Erasmus, Rajiv T.
Background: High molecular weight (HMW) adiponectin has antiatherogenic, antiinflammatory and antidiabetic properties and these effects have been linked to its effect on high density lipoprotein cholesterol (HDL-c). Single nucleotide polymorphisms (SNPs) in the adiponectin gene influence adiponectin levels. We examined the relationship between HMW-adiponectin levels and cardiometabolic traits in normo- and hyperglycemic mixed ancestry South Africans and correlated these levels to two common polymorphisms. Methods: HMW-adiponectin was determined in 101 subjects from the Cape Town Bellville South community-based study on a mixed ancestry population. Comparisons were made between individuals with normo- and hyperglycemia. Two common SNPs, ADIPOQ SNPs rs17300539 and rs266729, known to affect adiponectin levels were also tested for. Levels of HMW-adiponectin were then correlated with cardiometabolic traits in all groups. Results: Levels of HMW-adiponectin were not significantly different in the normo- and hyperglycemic groups (median 11.6 vs. 10.5 μg/mL, p=0.3060) and in men and women (8.44 vs. 11.34 μg/mL, p=0.67). ADIPOQ SNPs rs17300539 and rs266729 did not influence levels of HMW-adiponectin. Robust correlation analyses revealed a significant positive correlation between HMW-adiponectin and HDL-c (r=0.45; 95%CI: 0.27–0.59), similarly in normo- and hyperglycemic participants (p>0.99). This association was substantially attenuated in robust linear regressions adjusted for age, gender and adiposity. Conclusions: Adiponectin levels in this population were not determined by the commonest SNPs of the adiponectin gene, were unaffected by glycemic status; but were significantly correlated with HDL-c levels. Previous studies have attributed some of the beneficial effects of adiponectin to its effect on HDL-c.
Molecules in pathogenesis: angiotensin converting enzyme 2 (ACE2)
(BMJ Publishing Group Ltd & Association of Clinical Pathologists, 2021-04) Wiese, Owen; Zemlin, Annalise E.; Pillay, Tahir S.
The renin–angiotensin system is mainly associated with the regulation of blood pressure, but recently many other functions of this system have been described. ACE2, an 805-amino acid monocarboxypeptidase type I transmembrane glycoprotein, was discovered in 2000 and has sequence similarity to two other proteins, namely ACE and collectrin. The ACE2 gene is located on Xp22 and is highly polymorphic. ACE2 is expressed in numerous tissues especially the lung alveolar epithelial cells, heart, kidney and gastrointestinal tract. Animal studies have found that ACE2 is central in diseases affecting almost all organ systems, among other cardiac, respiratory, renal and endocrine functions. ACE2 was identified as the cellular contact point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the global pandemic (COVID-19), and is a potential drug target. SARS-CoV-2 infection has several effects on the renin–angiotensin system and conversely, regulation of this receptor may affect the progress of infection. We describe the genetics and functions of ACE2, explore its various physiological functions in the renin–angiotensin system and discuss its role in the pathophysiology of disease. ACE2 opposes the vasopressor ACE pathway of the renin–angiotensin system by converting angiotensin (Ang) I to Ang (1–9) and Ang II to Ang (1–7) which initiates the vasodilatory pathway. ACE2 may have a protective effect in the lung and kidney as knockout mice display susceptibility to acute respiratory distress and hypertensive nephropathy. Binding of SARS-CoV-2 and the subsequent fusion and downregulation of this pathway during SARS-CoV-2 infection may explain some of the unusual sequelae seen in COVID-19. This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.
Potential for medical error : incorrectly completed request forms for thyroid function tests limit pathologists' advice to clinicians
(Health and Medical Publishing Group (HMPG), 2009) Zemlin, Annalise E.; Nutt, Louise; Burgess, Lesley J.; Eiman, Fredeline; Erasmus, Rajiv T.
Background. Various publications have highlighted the significance of laboratory errors in the pre- and post-analytical phases and their impact on results. Thyroid-stimulating hormone (TSH) is a first-line thyroid function test and, if abnormal, reflex thyroxine (T4) or tri-iodothyronine (T3) testing is requested, depending on clinical and medication data provided. Interpretative comments are added to all TFT results. Objectives. In view of the paucity of articles describing such errors, we audited laboratory request forms requesting thyroid function tests (TFT), received from primary care clinics and regional hospitals at our laboratory. Design. We assessed 482 laboratory request forms for TFT from primary health care clinics for specific parameters. Results. A total of 482 forms were analysed. Medication/s used by the patient (74.5%) and doctor's contact number (65.1%) were the most commonly incomplete parameters. Of the 123 patients with medication details, 62 (50.4%) were on thyroxine. Conclusions. There are few studies examining the frequency and impact of incomplete laboratory forms on laboratory errors, and even fewer studies examining interpretative comments accompanying clinical biochemistry results. We studied how pre-analytical errors in completing request forms may lead to incorrect interpretative comments and inappropriate reflex testing, and so influence the quality of the post-analytical phase.

Browsing by Author "Zemlin, Annalise E."

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