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

[摘要] ENGLISH SUMMARY: IntroductionThe global obesity pandemic has reached Africa and the diabetes mellitus (DM) prevalence isincreasing in parallel. A high prevalence of DM and risk for cardiovascular disease (CVD)has been described in the South African mixed ancestry population. Recent guidelinesadvocate using HbA1c as a diagnostic tool for DM and prediabetes, which is moreconvenient. However, various studies have challenged these cut-offs. There is a paucity ofstudies 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 hasanti-diabetic, anti-atherogenic and anti-inflammatory properties and levels decrease inobesity. E-selectin, a marker of endothelial cell dysfunction, is associated with subclinicalatherosclerosis and hyperglycaemia. Carotid intima-media thickness (CIMT) is a noninvasivemeasure of subclinical atherosclerosis. The aim of this investigation was to verifyrecommended HbA1c cut-offs to diagnose DM and prediabetes and to examine the usefulnessof emerging markers of subclinical CVD in our population.MethodsThis investigation consists of four substudies and was performed on participants of theBellville South Africa Study. In the first, we challenged the recommended HbA1c cut-off of6.5% to diagnose DM in 946 participants using oral glucose tolerance test (OGTT), fastingblood glucose (FBG), and receiver operator characteristic (ROC) curves. In the second, wederived an optimal HbA1c cut-off to detect prediabetes in 667 participants and validated thisin two populations, using OGTT and ROC curves. In the third, we determined high molecularweight (hmw)-adiponectin levels in 101 participants, compared these in participants with andwithout hyperglycaemia and investigated their relationship with two polymorphisms(rs17300539 and rs266729) reported to affect adiponectin values. In the fourth, wedetermined E-selectin levels in 307 participants, compared these in participants with andwithout hyperglycaemia and assessed their effect on CIMT.ResultsThe 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 andOGTT, 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 wasnot appropriate and we determined that 5.75% was best. However, the low sensitivity andspecificity (64.8% and 60.4% respectively for the derivation and first validation sample and59.6% and 69.8% for the second validation sample), confirmed that HbA1c alone would missa 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) norby two common polymorphisms. Using robust correlations, a significant correlation wasfound 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). Thisassociation was attenuated in robust linear regressions adjusted for gender and adiposity. Eselectinlevels 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 correlationswere found between E-selectin and age, markers of glycaemia and inflammation, centralobesity and lipid variables. Associations remained significant only with age, hyperglycaemiaand C-reactive protein (CRP) in multivariable robust linear regression models. In similarregressions models, age and gender were the main predictors of CIMT, which was notassociated with E-selectin.ConclusionThe international HbA1c cut-offs recommended to detect DM and prediabetes were notappropriate in our population. Though a cut-off of 6.5% to diagnose DM is a good diagnostictool with high specificity, the low sensitivity limits its screening use. Similarly,recommended HbA1c values to detect prediabetes may underestimate the true numbers. Thisemphasizes the importance of local evidence-based values being established. Additionally,hmw-adiponectin was not affected by glycaemia or polymorphisms, but correlatedsignificantly with HDL-c which may explain its beneficial cardiovascular effect. Though Eselectinwas influenced by glycaemia, possibly reflecting early endothelial damage, it did notcorrelate with CIMT, which was determined by age and male gender.

[发布机构] Stellenbosch University