Doctoral Degrees (Chemical Pathology)

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Browsing Doctoral Degrees (Chemical Pathology) by Subject "Biochemical markers"

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    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.