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BACKGROUND: West Africans and African Americans with substantial (∼80%) West African ancestry are characterized by low levels of triglycerides (TG) compared to East Africans and Europeans. The impact of these varying TG levels on other cardiometabolic risk factors is unclear. We compared the strength of association between TG with hypertension, blood pressure, BMI, waist circumference, type 2 diabetes (T2D), and fasting glucose across West African (WA), East African (EA), and European (EU) ancestry populations residing in three vastly different environmental settings: sub-Saharan Africa, United States, and Europe. METHODS: We analysed data from four cross-sectional studies that included WA in sub-Saharan Africa (n = 7201), the U.S. (n = 4390), and Europe (n = 6436), EA in sub-Saharan Africa (n = 781), and EU in the U.S. (n = 8670) and Europe (n = 4541). Linear regression analyses were used to test the association between TG and cardiometabolic risk factors. FINDINGS: Higher adjusted regression coefficients were observed in EU compared with WA ancestry for TG on hypertension (EU β [95% CI]: 0.179 [0.156, 0.203], WA β [95% CI]: 0.102 [0.086, 0.118]), BMI (EU β [95% CI]: 0.028 [0.027, 0.030], WA β [95% CI]: 0.015 [0.014, 0.016]), and waist circumference (EU β [95% CI]: 0.013 [0.013, 0.014], WA β [95% CI]: 0.009 [0.008, 0.009) (all ancestry × trait interaction P-values

Background: The glycosylated hemoglobin (HbA1c) test can be unreliable in the presence of hemoglobinopathies and remains cost-prohibited and impractical in many developing countries. The increasing burden of type 2 diabetes (T2D) in sub-Saharan Africa (SSA) where sickle cell anemia, the most common inherited hemoglobinopathy, is prevalent calls for alternative tests for the management of T2D. In the present study, we evaluated the utility of serum fructosamine (FRA) as a biomarker of glycemic control that is not affected by abnormal hemoglobin or red blood cell (RBC) turnover. Methods: The accuracy of FRA in monitoring and diagnosing T2D was evaluated using the Area under the Receiver Operating Characteristics (AUROC) and other measures in a training dataset of 618 Nigerians [155 (25·1%) carrying sickle cell trait (HbAS) and 463 (74·9%) without sickle cell trait (HbAA)]. The FRA’s diagnostic cut-off was validated in an independent cohort of 634 West Africans. Findings: FRA was similar between HbAS and HbAA participants (Median = 287 vs 275 umol/L, p=0·11) despite statistically different HbA1c median among the two groups. FRA was highly correlated with both HbA1c (r HbAA = 0·80, r HbAS =0·82, p

Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.

Background: Context-specific evidence of the spectrum of type 2 diabetes (T2D) burden is essential for setting priorities and designing interventions to reduce T2D morbidity and mortality. However, there are currently limited data on the burden of T2D complications and comorbidity in sub-Saharan Africa (SSA). Using a study of ~6,000 participants, we aimed to estimate the burden and risk factors for T2D complications and comorbidity in sub-Saharan Africans. Methods: Participants (2784 T2D, 3209 controls) were African men and women aged 18 years or older, enrolled from major academic medical centres and surrounding communities in Ghana, Nigeria and Kenya. T2D was defined according to the American Diabetes Association criteria. T2D complications and comorbidities evaluated included cardiometabolic, ocular, neurological and renal characteristics. Logistic regression models were used to identify risk factors and to adjust estimates of risk and prevalence for covariates. Results: T2D participants had a mean age of 56 [SD 11] years and a median duration of T2D of 5 (interquartile range 2-10) years. Among the T2D participants, notable associated complications/comorbidities included hypertension with a prevalence of 71% (95% CI 69-73), obesity 27% (25-29) and hyperlipidemia 34% (32-36). Diabetic retinopathy was found in 15% (13-17) and cataracts in 32% (30-35). About 13% (12-15) had impaired renal function as assessed by eGFR, representing 1 in 8 participants. Erectile dysfunction was a complication in 35% (32-38) of men. Age, duration of T2D and body mass index were significant risk factors for most complications/comorbidities. There was significant heterogeneity between sites in prevalence of most complications/comorbidities after adjusting for covariates. Population-attributable fraction ranged between 6 and 64 percent for most comorbidities. Conclusion: The burden of T2D complications and comorbidity is substantial among sub-Saharan Africans. Interventions to reduce T2D morbidity and mortality in SSA need to prioritise early detection, the maintenance of healthy blood pressure, weight and lipid levels, as well as strengthen health care system capacities to provide treatment and care for neurological and ophthalmological complications of T2D. Funding Statement: The study was supported in part by the Intramural Research Program of the National Institutes of Health in the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute (NHGRI), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the Center for Information Technology, and the Office of the Director at the National Institutes of Health (1ZIAHG200362). Support for participant recruitment and initial genetic studies of the AADM study was provided by NIH grant No. 3T37TW00041-03S2 from the Office of Research on Minority Health. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study received ethical approval from the Institutional Review Board at each study site, Howard University and the United States National Institutes of Health.

The metabolic syndrome (MetS) is a constellation of metabolic disorders that increase the risk of developing several diseases including type 2 diabetes and cardiovascular diseases. Although genome-wide association studies (GWAS) have successfully identified variants associated with individual traits comprising MetS, the genetic basis and pathophysiological mechanisms underlying the clustering of these traits remain unclear. We conducted GWAS of MetS in 1427 Africans from Ghana and Nigeria followed by replication testing and meta-analysis in another continental African sample from Kenya. Further replication testing was performed in an African American sample from the Atherosclerosis Risk in Communities (ARIC) study. We found two African-ancestry specific variants that were significantly associated with MetS: SNP rs73989312[A] near CA10 that conferred increased risk (P=3.86 × 10(-8), OR=6.80) and SNP rs77244975[C] in CTNNA3 that conferred protection against MetS (P=1.63 × 10(-8), OR=0.15). Given the exclusive expression of CA10 in the brain, our CA10 finding strengthens previously reported link between brain function and MetS. We also identified two variants that are not African specific: rs76822696[A] near RALYL associated with increased MetS risk (P=7.37 × 10(-9), OR=1.59) and rs7964157[T] near KSR2 associated with reduced MetS risk (P=4.52 × 10(-8), Pmeta=7.82 × 10(-9), OR=0.53). The KSR2 locus displayed pleiotropic associations with triglyceride and measures of blood pressure. Rare KSR2 mutations have been reported to be associated with early onset obesity and insulin resistance. Finally, we replicated the LPL and CETP loci previously found to be associated with MetS in Europeans. These findings provide novel insights into the genetics of MetS in Africans and demonstrate the utility of conducting trans-ethnic disease gene mapping studies for testing the cosmopolitan significance of GWAS signals of cardio-metabolic traits.

Background The stability of biomarkers in stored biomedical samples is crucial, especially when storage is for extended periods of time. High-sensitivity CRP (Hs-CRP) is a biomarker of low grade inflammation that is extensively used to identify and study cardiovascular and/or inflammatory processes in clinical care and large epidemiologic studies. Therefore, assessing Hs-CRP stability in archived samples at a given temperature is important to ensure precision of measurements over time and the validity of studies using archived samples. Methods We evaluated the stability of Hs-CRP in 30 randomly selected human serum samples by measuring Hs-CRP concentrations in freshly collected sample [Hs-CRP (0)] and in the same set of samples after 7–11 years of storage at − 80 °C [Hs-CRP (LT)]. Results Hs-CRP did not significantly change up to 11 years of storage at − 80 °C as shown by a negligible median difference between Hs-CRP (0) and Hs-CRP (LT), delta(Hs-CRP (0)–Hs-CRP (LT)) = − 0.01, p = 0.45. There was a good concordance and agreement between Hs-CRP (0) and Hs-CRP (LT) as measured respectively by Lin's coefficient of correlation (ρC = 0.98) and Bland–Altman analysis (mean difference = − 0.02, 95% CI [− 0.04–0.0045] p = 0.107). In addition, the data also suggest that the time elapsed between collection and Hs-CRP measurement does not affect Hs-CRP stability over time when samples are kept under the appropriate conditions. Conclusions Long-term storage at − 80 °C for up to 11 years did not significantly affect the stability of serum Hs-CRP. Given the cost and time for collecting fresh samples, this observation represents an important finding for biomedical research and clinical care.

There are scant data from African populations on the association between beta-cell function and response to treatment with oral hypoglycaemic agents in Type 2 diabetes mellitus (T2DM). Fasting plasma C-peptide (FCP) and glucagon-stimulated C-peptide (GSCP) levels were measured in 116 Nigerians with T2DM at a university teaching hospital. After 9 months of follow-up and treatment, they were categorized into three groups based on response to treatment: (A) good control but not on maximum sulphonylurea (SU) therapy, (B) inadequate control but not on maximum SU therapy and (C) on maximum SU therapy+/-insulin or biguanide. Logistic regression models were used to investigate how well C-peptide levels predicted the subjects belonging to Group C who are likely to require insulin. The mean FCP and mean GSCP levels of Group C were significantly lower than in the other groups (p=0.024; p=0.001 respectively). A GSCP cut-off value ofor =1.3 ng/mL predicted membership of Group C with 85% sensitivity and 89% specificity while a cut-off ofor =1.8 ng/mL was associated with 91% sensitivity and 66% specificity. In resource-poor settings where inadequate treatment are common, estimation of GSCP may be useful in predicting treatment response and should be weighed against the cost of inadequate therapy with higher morbidity and mortality.