Mogamat S. Hassan

the 30-year cardiovascular risk profile of south africans with diagnosed diabetes, undiagnosed diabetes, pre-diabetes or normoglycaemia: the Bellville, south africa pilot study

Abstract The aim of this pilot study was to assess the 30-year risk for cardiovascular disease (CVD) in the South Africa population of mixed-ancestry in individuals with non-diabetic hyperglycaemia, and undiagnosed and self-reported diabetes. Participants were drawn from an urban community of the Bellville South suburb of Cape Town. In total, 583 subjects without a history of CVD were eligible for lifetime CVD risk estimation. Gender-specific prediction for CVD risk was calculated using the 30-year CVD interactive risk calculator. High CVD risk (> 20%) was evident in normoglycaemic and younger subjects (under 35 years). The significant predictors of CVD were sibling history of diabetes, and triglyceride, low-density lipoprotein cholesterol and glycated haemoglobin levels (p < 0.001). The high lifetime risk in normoglycaemic and younger subjects may be considered a warning that CVD might take on epidemic proportions in the near future in this country. We recommend the inclusion of education on CVD in school and university curricula.

HbA1c of 6.5% to Diagnose Diabetes Mellitus — Does It Work for Us? — The Bellville South Africa Study

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 −50% had an HbA1c value of ≥6.5% (48 mmol/mol). Using an OGTT, 147 (18%) were diagnosed with diabetes −46% 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.

Chronic kidney diseases in mixed ancestry south African populations: prevalence, determinants and concordance between kidney function estimators

BackgroundPopulation-based data on the burden of chronic kidney disease (CKD) in sub-Saharan Africa is still very limited. We assessed the prevalence and determinants of CKD, and evaluated the concordance of commonly advocated estimators of glomerular filtration rate (eGFR) in a mixed ancestry population from South Africa.MethodsParticipants were a population-based sample of adults selected from the Bellville-South community in the metropolitan city of Cape Town. eGFR was based on the Cockroft-Gault (CG), Modification of Diet in Kidney Disease (MDRD) and CKD Epidemiology Collaboration (CKD-EPI) equations (with and without adjustment for ethnicity). Kidney function staging used the Kidney Disease Outcome Quality Initiative (KDOQI) classification. Logistic regressions and kappa statistic were used to investigate determinants of CKD and assess the agreement between different estimators.ResultsThe crude prevalence of CKD stage 3–5 was 14.8% for Cockcroft-Gault, 7.6% and 23.9% respectively for the MDRD with and without ethnicity correction, and 7.4% and 17.3% for the CKD-EPI equations with and without ethnicity correction. The highest agreement between GFR estimators was between MDRD and CKD-EPI equations, both with ethnicity correction, Kappa 0.91 (95% CI: 0.86-0.95), correlation coefficient 0.95 (95% CI: 0.94-0.96). In multivariable logistic regression models, sex, age and known hypertension were consistently associated with CKD stage 3–5 across the 5 estimators.ConclusionsThe prevalence of CKD stages greater than 3 is the highest reported in Africa. This study provides evidence for support of the CKD-EPI equation for eGFR reporting and CKD classification.

The growing importance of PON1 in cardiovascular health: a review

The wide acceptance of the oxidation theory of atherogenesis has prompted attention to antioxidant mechanisms, particularly the prevention of lipid oxidation by high-density lipoprotein-associated proteins like paraoxonase 1 (PON1) enzyme. PON1 is a calcium-dependent enzyme that has interested toxicologists since its discovery as an organophosphate hydrolase. There is a growing interest in the enzymes importance in cardiovascular health prompted by evidence that it may have a role in lipid metabolism and the development of atherosclerosis via its antioxidant effects. PON1 is capable of hydrolyzing homocysteine thiolactone, a metabolite of homocysteine that can impair protein function leading to endothelial dysfunction and vascular damage. Although this lactonase activity has been suggested to be PON1s native activity, the enzymes specific physiological role and substrate remain unclear. In this review, we summarize developments in the field of PON1 research relating to cardiovascular health, and highlight those that perhaps warrant further research.

Immune cell membrane fatty acids and inflammatory marker, C-reactive protein, in patients with multiple sclerosis

Measurement of fatty acids in biological fluids and cell membranes including leucocytes from multiple sclerosis patients is inconsistent. The objective of the present study was to investigate the fatty acid composition within the different membrane phospholipid fractions in peripheral blood mononuclear cells in multiple sclerosis patients, and correlate with severity of neurological outcome as measured by the Kurtzke Expanded Disability Status Scale and Functional System Scores. The fatty acid composition of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin and phosphatidylinositol phospholipids in the peripheral blood mononuclear cells of twenty-six multiple sclerosis and twenty-five control subjects were measured by GC, and C-reactive protein was measured in all subjects. The elongation product of 20 : 4n-6, 22 : 4n-6, was significantly decreased in membrane phosphatidylethanolamine and phosphatidylserine in multiple sclerosis patients (P = 0.01 and P = 0.03 respectively), and correlated inversely with severity of disease and C-reactive protein. Also an inverse correlation was observed between the C-reactive protein and membrane phosphatidylcholine and phosphatidylserine 20 : 4n-6. Cultural and ethnic differences, as well as dietary variability, especially in a diseased state have been implicated in the differences observed in the fatty acid composition in peripheral blood mononuclear cell membranes of patients with multiple sclerosis. The present results suggest that the disease state may in part explain the reported inconsistencies in fatty acid levels in multiple sclerosis patients.

Bolus Administration of Intravenous Glucose in the Treatment of Hyperkalemia: A Randomized Controlled Trial

Background: Hyperkalemia is a common medical emergency that may result in serious cardiac arrhythmias. Standard therapy with insulin plus glucose reliably lowers the serum potassium concentration ([K+]) but carries the risk of hypoglycemia. This study examined whether an intravenous glucose-only bolus lowers serum [K+] in stable, nondiabetic, hyperkalemic patients and compared this intervention with insulin-plus-glucose therapy. Methods: A randomized, crossover study was conducted in 10 chronic hemodialysis patients who were prone to hyperkalemia. Administration of 10 units of insulin with 100 ml of 50% glucose (50 g) was compared with the administration of 100 ml of 50% glucose only. Serum [K+] was measured up to 60 min. Patients were monitored for hypoglycemia and EKG changes. Results: Baseline serum [K+] was 6.01 ± 0.87 and 6.23 ± 1.20 mmol/l in the insulin and glucose-only groups, respectively (p = 0.45). At 60 min, the glucose-only group had a fall in [K+] of 0.50 ± 0.31 mmol/l (p < 0.001). In the insulin group, there was a fall of 0.83 ± 0.53 mmol/l at 60 min (p < 0.001) and a lower serum [K+] at that time compared to the glucose-only group (5.18 ± 0.76 vs. 5.73 ± 1.12 mmol/l, respectively; p = 0.01). In the glucose-only group, the glucose area under the curve (AUC) was greater and the insulin AUC was smaller. Two patients in the insulin group developed hypoglycemia. Conclusion: Infusion of a glucose-only bolus caused a clinically significant decrease in serum [K+] without any episodes of hypoglycemia.

Optimal Waist-to-Height Ratio Values for Cardiometabolic Risk Screening in an Ethnically Diverse Sample of South African Urban and Rural School Boys and Girls

Background The proposed waist-to-height ratio (WHtR) cut-off of 0.5 is less optimal for cardiometabolic risk screening in children in many settings. The purpose of this study was to determine the optimal WHtR for children from South Africa, and investigate variations by gender, ethnicity and residence in the achieved value. Methods Metabolic syndrome (MetS) components were measured in 1272 randomly selected learners, aged 10–16 years, comprising of 446 black Africans, 696 mixed-ancestry and 130 Caucasians. The Youden’s index and the closest-top-left (CTL) point approaches were used to derive WHtR cut-offs for diagnosing any two MetS components, excluding the waist circumference. Results The two approaches yielded similar cut-off in girls, 0.465 (sensitivity 50.0, specificity 69.5), but two different values in boys, 0.455 (42.9, 88.4) and 0.425 (60.3, 67.7) based on the Youden’s index and the CTL point, respectively. Furthermore, WHtR cut-off values derived differed substantially amongst the regions and ethnic groups investigated, whereby the highest cut-off was observed in semi-rural and white children, respectively, Youden’s index0.505 (31.6, 87.1) and CTL point 0.475 (44.4, 75.9). Conclusion The WHtR cut-off of 0.5 is less accurate for screening cardiovascular risk in South African children. The optimal value in this setting is likely gender and ethnicity-specific and sensitive to urbanization.

Erythrocyte membrane fatty acids in patients with multiple sclerosis

Background Reports on fatty acids levels in multiple sclerosis remain inconclusive. Objective To determine the erythrocyte membrane fatty acid levels in multiple sclerosis patients and correlate with Kurtzke Expanded Disability Status Scale. Methods Fatty acid composition of 31 multiple sclerosis and 30 control individuals were measured by gas chromatography. Results The membrane phosphatidylcholine C20:4n – 6 concentration was lower in the multiple sclerosis patients when compared to that of the control group, P = 0.04 and it correlated inversely with the EDSS and FSS. Conclusion Decrease in C20:4n – 6 in the erythrocyte membrane could be an indication of depleted plasma stores, and a reflection of disease severity.

Three-year's changes in glucose tolerance status in the Bellville South cohort: rates and phenotypes associated with progression.

AIMS To determine the phenotypes associated with progression to type 2 diabetes or worsening in glucose tolerance during a 3-year follow-up of a community-based cohort in Cape Town, South Africa. METHODS A total of 198 eligible subjects (72.3% women) aged 55.2 years, from the Bellville-South community were followed-up between 2008 and 2011. Baseline and follow-up data collections included glucose tolerance status, anthropometric, blood pressure, lipids, insulin, γ-glutamyltransferase, cotinine, creatinine and HbA1c. Progression in glucose tolerance status at 3-year was the composite of new-onset diabetes and any worsening in glucose tolerance status. RESULTS The cumulative incidence of progression in glucose tolerance status was: 16.2% (32 participants including 11 with new-onset diabetes), and increased in a stepwise fashion with the number of components of metabolic syndrome (MetS). In age and sex-adjusted logistic regression analyses, MetS [odd ratio: 3.08 (95% CI: 1.34-7.10)], HbA1c [5.26 (1.94-14.24)], HDL-cholesterol [0.05 (0.01-0.33)], γ-glutamyltransferase [1.99 (1.07-3.67)], triglycerides [1.71 (1.13-2.58)] and total/HDL-cholesterol [1.45 (1.08-1.93)] were significant predictors of progression, while borderline effects were observed for baseline glucose and diastolic blood pressure. Markers of adiposity were mostly stable or improved among non-progressors during follow-up, but deteriorated significantly among progressors, resulting in significant statistical interactions. CONCLUSIONS High rates of deterioration of glucose status over time were found in our population, with nearly one-fifth of them acquiring a glucose tolerance worse status within a very short follow-up. Our study extends to this setting the well-known utility of phenotypes of MetS single or in combination, in predicting worsening in glucose tolerance status.

Gamma‐glutamyltransferase, insulin resistance and cardiometabolic risk profile in a middle‐aged African population

Background Mechanisms linking liver functions with cardiometabolic risk may involve insulin resistance (IR) and non‐alcoholic fatty liver disease. We assessed the associations of gamma‐glutamyltransferase (GGT) levels with IR and metabolic syndrome (MetS) in an adult South African urban cohort. Methods 1198 participants aged >15 years (297 men) were drawn from the Bellville‐South suburb (Cape Town). The homeostatic model assessment of insulin (HOMA‐IR), β‐cells function (HOMA‐B%), fasting insulin resistance index (FIRI) and the quantitative insulin‐sensitivity check index (QUICKI) were calculated, and MetS defined according to the Join Interim Statement 2009 criteria. Associations of GGT levels with covariates were assessed on a continuous scale and across sex‐specific quarters of GGT, with adjustment for confounders via generalized linear and logistic regressions. Results Indicators of IR (HOMA‐IR, FIRI and fasting insulin) increased, whereas those for insulin sensitivity (Sib and QUICKI) diminished significantly linearly and across increasing GGT quarters. In multivariable‐adjusted models, adjustment for sex, age, BMI, cigarette smoking and alcohol intake yielded the strongest, significant associations between GGT and all markers of IR/IS and glycemia excluding glucose insulin ratio. In a similar level of adjustments, with/without further adjustment for markers of IR/insulin sensitivity, the prevalence of MetS significantly increased across quarters of GGT. Conclusions GGT levels were independently associated with insulin sensitivity and MetS in this population. Unaccounted, chronic elevation of GGT may therefore be a cue to screen and monitor individuals for MetS and diabetes, and may warrant consideration as an indicator of high risk for the development of these metabolic disorders.