The genetic legacy of the expansion of Bantu-speaking peoples in Africa.

The expansion of people speaking Bantu languages is the most dramatic demographic event in Late Holocene Africa and fundamentally reshaped the linguistic, cultural and biological landscape of the continent1-7. With a comprehensive genomic dataset, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we contribute insights into this expansion that started 6,000-4,000 years ago in western Africa. We genotyped 1,763 participants, including 1,526 Bantu speakers from 147 populations across 14 African countries, and generated whole-genome sequences from 12 Late Iron Age individuals8. We show that genetic diversity amongst Bantu-speaking populations declines with distance from western Africa, with current-day Zambia and the Democratic Republic of Congo as possible crossroads of interaction. Using spatially explicit methods9 and correlating genetic, linguistic and geographical data, we provide cross-disciplinary support for a serial-founder migration model. We further show that Bantu speakers received significant gene flow from local groups in regions they expanded into. Our genetic dataset provides an exhaustive modern-day African comparative dataset for ancient DNA studies10 and will be important to a wide range of disciplines from science and humanities, as well as to the medical sector studying human genetic variation and health in African and African-descendant populations.

Using Clinical Vignettes to Understand the Complexity of Diagnosing Type 1 Diabetes in Sub-Saharan Africa.

Lack of awareness, access to insulin and diabetes care can result in high levels of morbidity and mortality for children with type 1 diabetes (T1DM) in sub-Saharan Africa (SSA). Improvements in access to insulin and diabetes management have improved outcomes in some settings. However, many people still present in diabetic ketoacidosis (DKA) in parallel to misdiagnosis of children with T1DM in contexts with high rates of communicable diseases. The aim of this study was to highlight the complexity of diagnosing pediatric T1DM in a healthcare environment dominated by infectious diseases and lack of adequate health system resources. This was done by developing clinical vignettes and recreating the hypothetico-deductive process of a clinician confronted with DKA in the absence of identification of pathognomonic elements of diabetes and with limited diagnostic tools. A non-systematic literature search for T1DM and DKA in SSA was conducted and used to construct clinical vignettes for children presenting in DKA. A broad differential diagnosis of the main conditions present in SSA was made, then used to construct a clinician's medical reasoning, and anticipate the results of different actions on the diagnostic process. An examination of the use of the digital based Integrated Management of Childhood Illness diagnostic algorithm was done, and an analysis of the software's efficiency in adequately diagnosing DKA was assessed. The main obstacles to diagnosis were low specificity of non-pathognomonic DKA symptoms and lack of tools to measure blood or urine glucose. Avenues for improvement include awareness of T1DM symptomatology in communities and health systems, and greater availability of diagnostic tests. Through this work clinical vignettes are shown to be a useful tool in analyzing the obstacles to underdiagnosis of diabetes, a technique that could be used for other pathologies in limited settings, for clinical teaching, research, and advocacy.

Seroprevalence and associated risk factors of hepatitis C infection among diabetic patients in South-Kivu, Eastern Democratic Republic of the Congo: A cross-sectional study.

Background and Aims: Hepatitis C virus (HCV) infection and diabetes mellitus (DM) are two frequent diseases in the Democratic Republic of the Congo (DRC) and several studies seem to show a link between the two diseases worldwide. However, no study has evaluated this link in our country. The present study aimed at determining the seroprevalence of HCV in diabetic patients as well as associated risk factors. Methodology: A multicenter cross-sectional study allowed us to sample diabetic patients in two diabetic healthcare centers of Bukavu city in the eastern part of the DRC, from December 2020 to December 2022. A questionnaire was submitted to the diabetic patients to collect sociodemographic data, anamnestic data on risk factors for HCV infection, and clinical data on DM. These factors were analyzed based on anti-HCV serological results. Results: Among the 180 selected patients, 19 (10.6%) were tested positive for anti-HCV antibodies. After multivariate analysis, the identified factors influencing these outcomes were male sex (adjusted odds ratio [aOR]: 3.5, p = 0.027), dental extraction (aOR: 7.6, p = 0.001), and living in a privileged environment (aOR: 0.29, p = 0.03). The factors related to DM such as the type, the disease duration, or the usual type of treatment did not influence the serological results. Conclusion: This study shows that HCV seroprevalence in diabetic patients is very high compared with the general population. This suggests combined screening and management policies in this population.

Prevalence and influences of diabetes and prediabetes among adults living with HIV in Africa: a systematic review and meta-analysis.

INTRODUCTION: In people living with human immunodeficiency virus (PLHIV), traditional cardiovascular risk factors, exposure to HIV per se and antiretroviral therapy (ART) are assumed to contribute to cardiometabolic diseases. Nevertheless, controversy exists on the relationship of HIV and ART with diabetes. To clarify the relationship between HIV and type 2 diabetes, this review determined, in PLHIV in Africa, diabetes and prediabetes prevalence, and the extent to which their relationship was modified by socio-demographic characteristics, body mass index (BMI), diagnostic definitions used for diabetes and prediabetes, and HIV-related characteristics, including CD4 count, and use and duration of ART. METHODS: For this systematic review and meta-analysis (PROSPERO registration CRD42021231547), a comprehensive search of major databases (PubMed-MEDLINE, Scopus, Web of Science, Google Scholar and WHO Global Health Library) was conducted. Original research articles published between 2000 and 2021 in English and French were included, irrespective of study design, data collection techniques and diagnostic definitions used. Observational studies comprising at least 30 PLHIV and reporting on diabetes and/or prediabetes prevalence in Africa were included. Study-specific estimates were pooled using random effects models to generate the overall prevalence for each diagnostic definition. Data analyses used R statistical software and "meta" package. RESULTS: Of the 2614 records initially screened, 366 full-text articles were assessed for eligibility and 61 were selected. In the systematic review, all studies were cross-sectional by design and clinic-based, except for five population-based studies. Across studies included in the meta-analysis, the proportion of men was 16-84%. Mean/median age was 30-62 years. Among 86,412 and 7976 participants, diabetes and prediabetes prevalence rates were 5.1% (95% CI: 4.3-5.9) and 15.1% (9.7-21.5). Self-reported diabetes (3.5%) was lower than when combined with biochemical assessments (6.2%; 7.2%). DISCUSSION: While not statistically significant, diabetes and prediabetes were higher with greater BMI, in older participants, urban residents and more recent publications. Diabetes and prediabetes were not significantly different by HIV-related factors, including CD4 count and ART. CONCLUSIONS: Although HIV-related factors did not modify prevalence, the diabetes burden in African PLHIV was considerable with suboptimal detection, and likely influenced by traditional risk factors. Furthermore, high prediabetes prevalence foreshadows substantial increases in future diabetes in African PLHIV.

Association between severe acute malnutrition during childhood and blood pressure during adulthood in the eastern Democratic Republic of the Congo: the Lwiro cohort study.

INTRODUCTION: Little is known about the long-term outcomes of Severe Acute Malnutrition (SAM) during childhood. As such, this study aims to explore the association between childhood SAM and blood pressure (BP) in adulthood in a context without nutrition transition. METHODOLOGY: We identified 524 adults (Median age: 22 years) who were treated for SAM during childhood in Eastern DRC between 1988 and 2007. They were compared with 407 age-and-sex matched subjects with no history of SAM in the community. The variables examined for this study were the systolic (SBP), diastolic (DBP), mean (MBP) blood pressure (BP) and pulse pressure (PP), as well as high blood pressure (HBP) defined as BP ≥ 140/90 mmHg and/or use of BP-lowering drug(s) in adulthood. For comparison, linear and logistic regression models were used for analysing continuous and dichotomous variables, respectively. RESULTS: Of the 524 exposed located, 145 were selected according to age. A total of 97 unexposed were recruited. Compared to unexposed, exposed had slightly higher SBP and PP after adjusting for occupation, body mass index (BMI) and food consumption [SBP = 1.4 mmHg (- 2.2, 4.8) and PP = 2.6 mmHg (- 0.3, 6.0)]. However, their DBP was lower than that of the unexposed [- 1.6 mmHg (- 4.6, 1.5)]. MBP and creatinine levels were similar between the two groups. The prevalence of HBP adjusted for age was higher among exposed than unexposed (9.7% vs 5.3%). In addition, the odds of having HBP was higher among exposed than unexposed, however the observed difference was not statistically significant [Odds Ratio (OR) 1.9 (0.7, 5.6)]. Finally, using multiple regression analysis, although the effect was not significant, SAM was a major contributor to HBP [adjusted OR 3.1 (0.9,10.9), p = 0.064], while only male gender and higher BMI (overweight/obesity) emerged as independent predictors of HBP among this young study population. CONCLUSIONS: This study suggests that an episode of SAM in childhood has a weak impact on BP variability in young Congolese adults (from DRC) living in an environment without nutrition transition. However, people who experienced a period of SAM tended to have a higher prevalence of HBP and a much higher risk of developing HBP than unexposed. Additional multicentre studies involving a larger cohort would provide greater understanding of the impact of SAM on the overall risk of BP disorders during adulthood.

Atypical respiratory distress in eastern Democratic Republic of the Congo prior to the COVID-19 pandemic. A case report.

BACKGROUND: Predictions have been made that Africa would be the most vulnerable continent to the novel Coronavirus disease 2019 (COVID-19). Interestingly, the spread of the disease in Africa seems to have been delayed and initially slower than in many parts of the world. Here we report on two cases of respiratory distress in our region before the official declaration of the disease in December 2019, cases which in the present times would be suspect of COVID-19. CASE PRESENTATION: These two cases (one 55-year-old man and one 25-year-old woman) of acute respiratory distress secondary to atypical pneumonia were seen in Bukavu, in Eastern Democratic Republic of the Congo (DRC), between September and December 2019. One patient had returned from China and the other had close contacts with travellers from China in the 2 weeks prior to the onset of symptoms. In either case, the aetiology could not be accurately determined. However, the two cases presented a clinical picture (progressive dyspnoea, preceded by dry cough and fever) and laboratory changes (procalcitonin within the normal range, slight inflammation, and lymphopenia) compatible with a viral infection. The chest X-ray series of the first patient showed lesions (reticulations, ground glass, and nodules ≤6 mm) similar to those currently found in COVID-19 patients. In addition, unlike the 25-year-old female patient who had no comorbidity, the 55-year-old male patient who had hypertension as comorbidity, developed a more severe acute respiratory distress which progressed to death. CONCLUSION: These cases bring to the attention the fact that COVID-19-like syndromes may have already been present in the region months before the official beginning of the pandemic. This also brings to question whether a prior presence of the disease or infections with related virus may account for the delayed and less extensive development of the pandemic in the region.

Diabetes mellitus and laboratory medicine in sub-Saharan Africa: challenges and perspectives.

Diabetes mellitus is an increasing public health problem in sub-Saharan Africa with a substantial socioeconomic burden. Although laboratory medicine has been recognized as one of the six key public health functions, there are still gaps in strengthening of laboratory services in developing countries. In the last decades, a lot of progress has been made in the diagnostic field of infectious diseases, whereas the diagnosis of noncommunicable diseases is still insufficient and uneven. This article analyses the challenges encountered in diagnosing and monitoring of diabetes mellitus in sub-Saharan Africa and explores new alternative diagnostic tools.

Whole blood Fe isotopic signature in a sub-Saharan African population.

The Fe isotopic composition of an individual's whole blood has recently been shown to be an interesting clinical indicator of Fe status. The present study aimed to evaluate the influence of several endemic characteristics of a representative population of the South Kivu province, an Fe-rich volcanic African region, on the whole blood Fe isotopic composition. Both diabetes mellitus and the ferroportin Q248H mutation are very common in Africa and are strongly associated with impairments in Fe metabolism. Fe isotopic analysis of whole blood samples was carried out using multi-collector inductively coupled plasma-mass spectrometry (after chromatographic isolation of the target element). Forty-two male subjects (between 48 and 59 years old) living in Bukavu (South Kivu) were enrolled in this study. Among the selected population, wild-type subjects and subjects presenting the ferroportin Q248H mutation (heterozygotes and homozygotes) were included. Within each group, diabetic and non-diabetic patients were considered. The whole blood δ56Fe value ranged from -3.09‰ to -2.41‰. The δ56Fe value shows a significant negative correlation with the ferritin concentration. No correlation could be established between the whole blood δ56Fe value and the transferrin concentration, transferrin saturation or serum Fe concentration. The ferroportin Q248H mutation did not seem to have affected the whole blood Fe isotopic signature. The whole blood δ56Fe values were significantly higher in diabetic subjects than in non-diabetic subjects and showed a significant negative correlation with body mass index (BMI) values.

A simple colorimetric assay for measuring fructosamine 3 kinase activity.

BACKGROUND: Fructosamine 3 kinase (FN3K) is a deglycating enzyme, which may play a key role in reducing diabetes-induced organ damage by removing bound glucose from glycated proteins. We wanted to develop a simple colorimetric method for assaying FN3K activity in human body fluids. METHODS: Glycated bovine serum albumin (BSA) was obtained by glycation with a 10% glucose solution at 37 °C. After 72 h, glycated BSA was dialyzed against phosphate buffered saline (0.1 mol/L, pH 7.4). The dialyzed solution (containing ±1000 µmol/L fructosamine) was used as an FN3K substrate. In the assay, 300 µL of substrate was incubated with 50 µL of serum and 100 µL of MgCl2 (0.7 mmol/L)/ATP (3.2 mmol/L). The fructosamine concentration was determined at the start and after incubation (120 min, 25 °C). The decrease in fructosamine concentration over time is a measure for the FN3K activity (1 U corresponding to 1 µmol/min). Concomitantly, the FN3K SNP rs1056534 and the ferroportin SNP rs1156350 were genotyped. RESULTS: Within-assay CV was 6.0%. Reference values for FN3K activity in serum were 14.2±1.6 U/L (n=143). Reference values for FN3K were neither age- nor sex-dependent. The various FN3K SNP rs1056534 genotypes showed no significant differences in serum FN3K activity. In diabetics (n=191), values (14.0±2.2 U/L) were comparable to those of the controls. FN3K activity in erythrocytes was significantly higher (170.3±7.6 U/L). The intra-erythrocytic FN3K activity makes the results prone to hemolysis. FN3K activity depended on the ferroportin Q248H genotypes, with the highest value for the wild type genotype. Neither transferrin saturation nor ferritin were confounders for the FN3K activity. FN3K activity was significantly (p<0.0001) correlated with HbA1c values, although the correlation between FN3K and HbA1c was weak. CONCLUSIONS: The simple colorimetric method allows determining FN3K activity in human serum. The assay may be useful for studying the impact of deglycation processes in diabetes mellitus.

Glycation in human fingernail clippings using ATR-FTIR spectrometry, a new marker for the diagnosis and monitoring of diabetes mellitus.

OBJECTIVES: Although HbA1c is a good diagnostic tool for diabetes, the precarity of the health system and the costs limit the use of this biomarker in developing countries. Fingernail clippings contain ±85% of keratins, which are prone to glycation. Nail keratin glycation may reflect the average glycemia over the last months. We explored if attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) can be used as a non-invasive tool for assessing glycation in diabetes. DESIGN AND METHODS: Using ATR-FTIR spectroscopy, glycation and deglycation experiments with fructosamine 3-kinase allowed to identify the spectrum that corresponds with keratin glycation in fingernail clippings. Clippings of 105 healthy subjects and 127 diabetics were subjected to the standardized ATR-FTIR spectroscopy method. RESULTS: In vitro glycation resulted in an increased absorption at 1047cm-1. Following enzymatic deglycation, this peak diminished significantly, proving that the AUC between 970 and 1140cm-1 corresponded with glycated proteins. Within-run CV of the assay was 3%. Storage of nail clippings at 37°C for 2weeks did not significantly change results. In diabetics, glycated nail protein concentrations (median: 1.51µmol/g protein, IQR: 1.37-1.85µmol/g protein) were significantly higher than in the controls (median: 1.19µmol/g protein, IQR: 1.09-1.26µmol/g protein) (p<0.0001). ROC analysis yielded an AUC of 0.92 at a cut-off point of 1.28µmol/g nail (specificity: 82%; sensitivity: 90%). No correlation was observed between the glycated nail protein concentrations and HbA1c. CONCLUSIONS: Protein glycation analysis in fingernails with ATR-FTIR spectroscopy could be an alternative affordable technique for diagnosing and monitoring diabetes. As the test does not consume reagents, and the preanalytical phase is extremely robust, the test could be particularly useful in developing countries.

Obesity and diabetes mellitus association in rural community of Katana, South Kivu, in Eastern Democratic Republic of Congo: Bukavu Observ Cohort Study Results.

BACKGROUND: Factual data exploring the relationship between obesity and diabetes mellitus prevalence from rural areas of sub-Saharan Africa remain scattered and are unreliable. To address this scarceness, this work reports population study data describing the relationship between the obesity and the diabetes mellitus in the general population of the rural area of Katana (South Kivu in the Democratic Republic of the Congo). METHODS: A cohort of three thousand, nine hundred, and sixty-two (3962) adults (>15 years old) were followed between 2012 and 2015 (or 4105 person-years during the observation period), and data were collected using the locally adjusted World Health Organization's (WHO) STEPwise approach to Surveillance (STEPS) methodology. The hazard ratio for progression of obesity was calculated. The association between diabetes mellitus and obesity was analyzed with logistic regression. RESULTS: The diabetes mellitus prevalence was 2.8 % versus 3.5 % for obese participants and 7.2 % for those with metabolic syndrome, respectively. Within the diabetes group, 26.9 % had above-normal waist circumference and only 9.8 % were obese. During the median follow-up period of 2 years, the incidence of obesity was 535/100,000 person-years. During the follow-up, the prevalence of abdominal obesity significantly increased by 23 % (p <0.0001), whereas the increased prevalence of general obesity (7.8 %) was not significant (p = 0.53). Finally, diabetes mellitus was independently associated with age, waist circumference, and blood pressure but not body mass index. CONCLUSION: This study confirms an association between diabetes mellitus and abdominal obesity but not with general obesity. On the other hand, the rapid increase in abdominal obesity prevalence in this rural area population within the follow-up period calls for the urgent promoting of preventive lifestyle measures.

The association between fructosamine-3 kinase 900C/G polymorphism, transferrin polymorphism and human herpesvirus-8 infection in diabetics living in South Kivu.

Prevalences of human herpesvirus-8 (HHV-8) infection and diabetes mellitus are very common in certain parts of Africa, containing iron-rich soils. We hypothesized that some genetic factors could have a link with susceptibility to HHV-8 infection. We focused on ferroportin Q248H mutation (rs11568350), transferrin (TF) polymorphism and fructosamine-3 kinase (FN3K) 900C/G polymorphism (rs1056534). The study population consisted of 210 type 2 diabetic adults and 125 healthy controls recruited in Bukavu (South Kivu). In the whole study population (diabetics+healthy controls), ferroportin Q248H mutation was detected in 47 subjects (14.0%) with 43 heterozygotes and 4 homozygotes. TF phenotype frequencies were 88.1% (CC), 10.4% (CD) and 1.5% (BC). Genotype frequencies of FN3K 900C/G polymorphism were respectively 9,3% (CC), 43.3% (GC) and 47.4% (GG). Prevalence of HHV8-infection in the study population was 77.3%. HHV-8 infection rate and HHV-8 IgG antibody titer were significantly higher in diabetics then in controls (p<0.0001). Significant differences were observed in HHV-8 infection rate and in HHV-8 IgG antibody titer according to FN3K rs1056534 (p<0.05 and p<0.05, respectively) and TF polymorphism (p<0.05 and p=0.005, respectively). No significant differences in HHV-8 infection rate and in HHV-8 IgG antibody titer were observed in the ferroportin Q248H mutation carriers (rs11568350) in comparison with ferroportin wild type. In a multiple regression analysis, FN3K rs1056534, TF polymorphism and presence of diabetes mellitus were predictors for HHV-8 infection. In contrast to these findings, ferroportin Q248H mutation (rs11568350) did not influence the susceptibility for an HHV-8 infection in sub-Saharan Africans.

The presence of fructosamine in human aortic valves is associated with valve stiffness.

AIMS: Human heart valves are prone to glycation, a fundamental process of ageing. The aim of this study was to establish the relationship between fructosamine formation and the mechanical properties of human aortic valves. METHODS: 67 patients (age: 76±8 years) diagnosed with an aortic valve stenosis, who underwent an aortic valve replacement were enrolled. Fructosamine and calcium concentrations in aortic valves were determined. Using a transthoracic Doppler echocardiography, aortic valve orifice area and transvalvular pressure gradients were measured. In a subgroup of 32 patients, the aortic valve orifice area was sufficient to carry out mechanical testing on a LFPlus Universal material tester. An in vitro removal of fructosamine of the valve was initiated using ATP-dependent fructosamine 3-kinase (FN3K). RESULTS: A significant correlation was found between the aortic valve fructosamine concentration and the calculated aortic valve orifice area: Y (aortic valve orifice area, mm(2))=1.050-0.228X (aortic valve fructosamine concentration, µmol/g valve) (r=-0.38). A significantly higher calcium concentration was measured in the aortic valves of diabetics in comparison with those of non-diabetics. A multiple regression analysis revealed that the presence of diabetes mellitus and aortic valve fructosamine concentration were the main predictors of the extensibility of the aortic valves. In the in vitro deglycation study, a significant lower aortic valve fructosamine concentration was detected after treatment with FN3K. This resulted in an increased flexibility of the aortic valves. CONCLUSIONS: Although no direct causativeness is proven with the presented results, which just show an association between fructosamine, the effect of FN3K and aortic valve stiffness, the present study points for the first time towards a possible additional role of the Amadori products in the biomechanical properties of ageing aortic valves.

Glycated nail proteins as a new biomarker in management of the South Kivu Congolese diabetics.

INTRODUCTION: Diagnosis and monitoring of diabetes mellitus in sub-Saharan Africa, based on blood analyses, are hampered by infrastructural and cultural reasons. The first aim of this study was to evaluate the diagnostic accuracy of glycated nail proteins for diabetes mellitus. The second aim was to compare the course of short- and long-term glycemic biomarkers after 6 months of antidiabetic treatment. These objectives should support our hypothesis that glycated nail proteins could be used as an alternative glycemic biomarker. MATERIALS AND METHODS: This case-control study consisted of 163 black diabetics and 67 non-diabetics of the South Kivu (Democratic Republic of Congo). Diagnostic accuracy of glycated nail proteins was evaluated using ROC curve analysis. At the start of the study, glycated nail protein concentrations were compared between diabetics and non-diabetics, using a nitro blue tetrazolium (NBT) colorimetric method. In a subgroup of 30 diabetics, concentrations of glycated nail proteins, fasting glucose (Accu-Chek® Aviva), serum fructosamine (NBT) and HbA1c (DCA-2000+®) were measured at start and after 6 months. RESULTS: ROC analysis yielded an AUC of 0.71 (95% confidence interval (CI): 0.65-0.76) and a cut-off point of 3.83 µmol/g nail. Concentration of glycated nail proteins was significantly higher (P<0.001) in diabetics in comparison with non-diabetics. After 6 months of antidiabetic treatment, a significant drop in the fasting glucose concentration (P=0.017) and concentration of glycated nail proteins (P=0.008) was observed in contrast to serum fructosamine and HbA1c. CONCLUSIONS: Measurement of glycated nail proteins could be used to diagnose and monitor diabetes mellitus in sub-Saharan Africa.