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INTRODUCTION: Legionnaires' disease (LD) is a recognised cause of community-acquired pneumonia. However, Legionella is an overlooked pathogen in hospital-acquired pneumonia. The European Surveillance System 2008-2017 found 23% of the Belgian LD reported cases being healthcare-related, with a higher death-rate than in community-acquired patients. This study aims to describe patients admitted for community-acquired LD or affected by hospital-acquired LD and investigate discriminants associated with lethality. METHODS: Medical records were retrospectively reviewed at three Belgian University Hospitals, between 1 January 2016 up to 31 January 2019. Hospital-acquired LD was defined as symptom onset at 10 days or more after admission, according to the Centres for Disease Control and prevention. Community-acquired LD was defined as diagnosis at admission or within 10 days after admission. RESULTS: Fifty patients were included in the study, among them 26% were diagnosed with hospital-acquired LD. The case-fatality rate was 22%, with eight of the eleven deceased patients (73%) being in the hospital-acquired LD group. Medical history of asthma or chronic obstructive pulmonary disease and higher sequential organ failure assessment (SOFA) score at diagnosis were more frequently observed in the hospital-acquired LD group. Furthermore, significantly lower SOFA score at diagnosis of LD and higher rates of treatment with levofloxacin or moxifloxacin were observed in survivors. CONCLUSION: In the current cohort, LD death-rate was mainly driven by hospital-acquired LD patients. Hospital-acquired LD might especially affect patients with chronic respiratory disease. Respiratory fluoroquinolones treatment and lower SOFA score at diagnosis may be associated with favourable outcomes.

Background In the midst of the COVID-19 pandemic, to palliate to the lockdown and cover academic programs, the faculty of medicine and pharmaceutical sciences (FMPS) of the university of Dschang (UDs) in Cameroon has implemented e-learning using WhatsApp®. Aim Describe the opinion of students and lecturers after its implementation of e-learning at the FMPS of UDs. Methods We designed a uniform teaching scheme using WhatsApp® during the university lockdown. Students and members of the teaching staff of the FMPS of UDs were enrolled after receiving clear information on the study implementation. At the end of the online-teaching period of two and a half months, we surveyed our students and teaching staff. Sociodemographic characteristics and opinions about e-learning were collected using a standard questionnaire. Results We enrolled 229 students and 40 lecturers of the FMPS. Students reported a decremented quality of internet connection (p p p > 0.05). While lecturers were mainly more comfortable conveying the contents of their lectures, students tended to be less prone to actively participate. The motivation and satisfaction of the latter group toward e-learning were modest compared to classroom-based lectures while their feedback about the organization was positive. Conclusions E-learning using WhatsApp® could be an effective alternative to conventional classroom-based lessons in the context of COVID-19 pandemic. The use of a blended-learning program including classroom-based sessions could help improve its limitations.

Pesticide exposure may induce biochemical alterations including oxidative stress and lipid peroxidation. However, in the context of developmental origin of health and disease, putative trans-generational effect of exposure to pesticides are insufficiently studied. We therefore aimed to evaluate the biochemical effect of gestational exposure to four pesticides on female Wistar rats and their offspring at adult age. We studied 30 female nulliparous Wistar rats divided into 5 equal groups. Group 1 served as the control group and received distilled water while group 2, 3, 4 and 5 received orally pesticide 1 (imidacloprid), pesticide 2 (chlorpyrifos), pesticide 3 (imidacloprid + lambda cyhalothrin) and pesticide 4 (oxamyl) respectively once daily throughout gestation at a dose equivalent to 1/10 lethal dose 50. The mothers were followed up until one month post gestation. The offspring were followed up from birth until adult age (12 weeks). In all animals at each time point we evaluated malondialdehyde (MDA), oxidative stress and liver function enzymes. There was similar variation of total body weight in all the groups during and after gestation. However, Female Wistar rats of the exposed groups had significant alterations in liver SOD (−30.8% to +64.1%), catalase (−38.8% to −85.7%) and GSH (−29.2% to −86.5%) and; kidney catalase (> 100%), GSH (> 100%). Moreover, MDA, alanine transaminase (ALT) and aspartate transaminase (AST) levels were significantly higher in pesticide exposed rats compared to the control group. Similar alterations in antioxidant enzymes, MDA and liver function enzymes were observed in offspring of treated rats evidenced at weaning and persisting until adult age. Exposure to pesticides causes oxidative stress and lipid peroxidation in exposed female Wistar rats and their offspring. The persistence in offspring at adult age suggests transgenerational adverse effects.

Background: In the midst of the COVID-19 pandemic, to palliate to the lockdown and cover academic programs, the Faculty of Medicine and Pharmaceutical Sciences of the University of Dschang (FMPS-UDs) in Cameroon has implemented e-learning using WhatsApp®. We aimed to describe the opinion of students and lecturers about it after its implementation at the FMPS-UDs.Methods: We designed a uniform scheme to teach using WhatsApp® during the university lock-down, and both the students and the teaching staff of the FMPS-UDs received clear information on the implementation. At the end of the online-teaching period of two and a half months prior to the reopening of the university, we surveyed our students and teaching staff. Sociodemographic characteristics and opinions about e-learning were collected using a standard questionnaire. Results: We enrolled 229 students and 40 lecturers of the FMPS-UDs. Students reported a poorer internet connection (p0.05). While lecturers were mainly [n(%)=16(40%)] more comfortable conveying the contents of their lectures, students tended to be less prone to actively participate [n(%)=137(59.8%)]. The motivation and satisfaction of the latter group toward e-learning were modest compared to classroom-based lectures while their feedback about the organization was positive. Conclusion: E-learning using WhatsApp® could be an effective alternative to conventional classroom-based lessons in SSA. The use of a blended-learning program including classroom-based sessions could help improve its limitations.

Despite some cases of severe or critical manifestations of the coronavirus disease 2019 (COVID-19) described among children, the prevalence of this infection in the pediatric population is quite low worldwide, particularly in sub-Saharan Africa. Current data suggest indeed that, independent of the population considered overall, severe and critical cases of COVID-19 are rare among children. This observation prompted us to discuss the possible hypotheses which could explain the low prevalence of COVID-19 among children; amongst others, we discuss (1) immunomodulation by the Bacillus Calmette–Guerin vaccine or by some parasitic infections such as malaria, schistosomiasis, and helminthiasis and (2) cross immunization with other coronaviruses commonly found in the sub-Saharan African setting.

To the editors of the Pan African Medical Journal The current outbreak of the new coronavirus disease (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), initially originating from Wuhan, in China, has nowadays spread to all the continents. This pandemic leads to great challenges and sets a major burden on health systems. One of these challenges is the development of effective treatments, particularly for severely ill patients with COVID-19. Sanders et al. described several potential treatment targets, based on the current understanding of the pathophysiology of this disease [1]. Among the drugs targeting these processes, some have been rather disappointing. The association lopinavir-ritonavir has not shown any benefit in severe COVID-19 so far [2]. The initial worldwide enthusiasm for the use of hydroxychloroquine (associated or not with azithromycin) [3] seems to give way in the light of the latest evidence to an increase in the risk of ventricular arrhythmia [4]. Current data on tocilizumab and remdesivir, from case series and randomized controlled trials, show interesting results in severe and critical COVID-19 [5-7]. Tocilizumab is a recombinant humanized monoclonal antibody that binds to the interleukin 6 (IL-6) receptor. The use of this treatment option relies on the pathophysiology of severe COVID-19 which is closely linked to a cytokine storm in which IL-6 plays a major role. In a recent report, Xu et al. describe a series of severely and critically ill patients with COVID-19 treated with tocilizumab in two reference hospitals of China [7]. Disease severity was assessed using high respiratory rate (≥30 breaths/minute), decreased capillary oxygen saturation at room air (SpO2 ≤ 93%) and compliance with criteria of acute respiratory distress syndrome based on PaO2/FiO2 ≤ 300 mm Hg. Critical cases were reported as such when respiratory failure required ventilation support and/or in the presence of features of shock with or without failure of other organs that needed admission to the intensive care unit. The use of tocilizumab in severely or critically ill COVID-19 patients led to a reduction of invasive ventilation needs as well as oxygen support, decline in C-reactive protein values, increase in the percentage of lymphocytes in peripheral blood and improvement in radiological images by day five of treatment. Interestingly, there were no adverse effects accounted for, by the treatment [7]. Despite these promising results, as acknowledged by the authors, one needs to mention the limited sample size and the need for confirmatory results from an independent study population and further exploration in randomized controlled trials. While looking at the panel of currently investigated therapies, we can´t refrain from having concerns for countries of sub-Saharan Africa (SSA) once effective treatment options will be confirmed and recommended. Indeed, healthcare systems in SSA settings are poorly prepared for the COVID-19 pandemic. The lack of sufficiently equipped critical care units, in addition to the absence of universal health coverage, increase patients´ vulnerability [8]. As a result, more than in other contexts, these health systems are and will be facing more difficulties in the management of patients with COVID-19. On the one hand, the expected high cost of both supportive and disease-specific treatments represents an additional challenge to the accessibility to the latter. On the other hand, the populations are already facing the burden of other communicable as well as non-communicable diseases, with rather limited resources. There is therefore an urgent need to anticipate finding solutions to cover expenditures related to the management of COVID-19 in SSA. Some solutions that could be developed to allow the availability of these drugs might include a partial waiver of the medications´ cost by pharmaceutical companies. Moreover, the out-of-pocket expenditure for patients could be reduced by governmental subsidies. The development of biosimilars would be an interesting alternative with costs reduced by around 30% [9]. However, the implementation of these tentative solutions will require concertation between various stakeholders including health care providers, patients´ associations, insurance companies, governments´ representatives, charity organizations, and pharmaceutical companies. The use of convalescent plasma could be a rescue solution using the existing blood bank facilities, where available, under strict regulation [10]. Well-conducted clinical trials on their efficacy and safety are however still warranted. Local solutions to identify alternative treatment options from traditional pharmacopeia should also be considered. However, one could not emphasize enough that all the stages of drug development -except in the context of drug repurposing- and marketing authorization should be completed before their use for COVID-19. Conclusion The COVID-19 pandemic has generated various attempts to identify successful treatments specifically for severe cases. Current data suggest promising results using IL-6 receptor targeting therapy. However, questions on the accessibility of this treatment option, and others, in resource-limited settings including SSA should be anticipated. Addressing this concern will require the implication of various stakeholders in designing a sound health policy. Accessibility to medical supplies and attempts to lower treatment costs could help to overcome the pitfalls related to the management of severely ill patients. Competing interests The author declares no competing interests.

Some pesticides increase the risk of type 2 diabetes, but whether fetal exposure carries transgenerational risk remains unknown. We evaluated the metabolic effects of gestational exposure to chlorpyrifos and imidacloprid in female Wistar rats and their offspring. We studied female nulliparous Wistar rats, including six exposed to imidacloprid (IMI) and six to chlorpyrifos (CPF) once daily throughout gestation at 1/10 lethal dose 50, while six (control group) received distilled water. These were explored 1 month after the birth of the offspring, while their offspring were explored at weaning (4 weeks) and adult age (12 weeks). Blood glucose, insulin and lipid profile were determined at each stage, while glucose transporter 4 (GLUT4) and nuclear factor kappa beta (NFkβ) protein expression was measured in skeletal muscle at the end of follow up. Exposure to pesticides was associated with significantly higher fasting glucose (+25.4 to 30.9%) and insulin (> 100%) levels, with > 100% increased insulin resistance (HOMA-IR), − 18.3 to − 21.1% reduced HDL-cholesterol and + 60.9 to + 102.6% increased LDL-cholesterol in mothers. GLUT4 expression was reduced by 28.9–42.3% while NFkβ expression increased by 32.8–35.4% in mothers. In offspring, similar abnormalities were observed at weaning (+ 18.4 to 67.4% fasting glucose, + 57.1 to 72.2% LDL-cholesterol, + 72.3 to 78.2% fasting insulin), persisting at adult age with decreased expression of GLUT4 (− 52.8 to 54.5%) and increased expression of NFkβ (+ 30.5 to 30.7%). Gestational exposure to imidacloprid and chlorpyrifos induces hyperglycemia, insulin resistance and dyslipidemia in female Wistar rats and their offspring. The effects on offspring persist until adult age, suggesting intergenerational adverse effects.

Summary Background The burden of dyslipidaemia in Africa remains inadequately characterised. We aimed to estimate the prevalence of dyslipidaemia in African adults from hospital-based and community-based studies. Methods In this systematic review and meta-analysis, we searched MEDLINE via PubMed, Embase, African Journals Online, and African Index Medicus for studies published between Jan 1, 1980, and July 31, 2017, without language restriction. We assessed methodological quality of all cross-sectional studies reporting on the prevalence of elevated concentrations of total cholesterol, LDL cholesterol, or triglycerides, or low concentrations of HDL cholesterol in adults residing in African countries. We excluded reports on Africans living outside Africa, studies of individuals selected on the basis of existing dyslipidaemia or those including children and adolescents, and case series with a small sample size. The most frequently used cutoffs in the included studies were chosen for the subgroup analysis. We used random-effect model meta-analysis to derive the pooled prevalence of elevated total cholesterol, low HDL cholesterol, elevated LDL cholesterol, and elevated triglyceride concentrations. This study is registered with PROSPERO, number CRD42014015376. Findings 177 studies (294 063 participants) were included in the meta-analysis. The pooled prevalence of dyslipidaemia in the general population from population-based studies was 25·5% (95% CI 20·0–31·4) for elevated concentrations of total cholesterol with a cutoff of at least 5·2 mmol/L, 37·4% (29·4–45·7) for low concentrations of HDL cholesterol with a cutoff of less than 1·0 mmol/L, 28·6% (15·8–43·5) for elevated concentrations of LDL cholesterol with a cutoff of at least 3·3 mmol/L, and 17·0% (11·9–22·7) for elevated concentrations of triglycerides with a cutoff of at least 1·7 mmol/L. Interpretation The prevalence of dyslipidaemia is high in the general adult population in Africa. Ongoing efforts to reduce cardiovascular diseases in Africa should integrate effective detection and treatment of dyslipidaemia. Funding None.

Aims: Insulin autoantibodies (IAA) are often the first marker of autoimmunity detected in children in the preclinical phase of type 1 diabetes (T1D). Currently, the vast majority of laboratories adopt the radiobinding micro-assay (RBA) for measuring IAA. Our aim was to replace RBA with a novel non-radioactive IAA Luciferase Immuno Precipitation System (LIPS) assay with improved performance. Methods: We developed (pro)insulin antigens with alternative placements of a NanoLuc™ luciferase reporter (NLuc). Performance in LIPS was evaluated by testing sera from new onset T1D (n = 80), blood donors (n = 123), schoolchildren (n = 186), first-degree relatives (FDRs) from the Bart’s Oxford family study (n = 53) and from the Belgian Diabetes Registry (n = 136), coded sera from the Islet Autoantibody Standardization Program (IASP) (T1D n = 50, blood donors n = 90). Results: IAA LIPS based on B chain-NLuc proinsulin or B chain-NLuc insulin, in which NLuc was fused at the C-terminus of the insulin B chain, required only 2 μL of serum and a short incubation time, showed high concordance with RBA (Spearman r = 0.866 and 0.833, respectively), high assay performance (B chain-NLuc proinsulin ROC-AUC = 0.894 and B chain-NLuc insulin ROC-AUC = 0.916), and an adjusted sensitivity at 95% specificity ranking on par with the best assays submitted to the two most recent IASP workshops. In FDRs, the IAA LIPS showed improved discrimination of progressors to T1D compared to RBA. Conclusions: We established a novel high-performance non-radioactive IAA LIPS that might replace the current gold standard RBA and find wide application in the study of the IAA response in T1D.

Aim It is unclear whether ketosis-prone diabetes is a specific type or a subtype of Type 2 diabetes. We aimed to describe the clinical and metabolic features of ketosis-prone diabetes in a sub-Saharan population. Methods We consecutively enrolled and characterized 173 people with non-autoimmune diabetes admitted for hyperglycaemic crisis at the Yaounde Central Hospital, Cameroon. Blood samples were collected for fasting glucose, HbA1c, lipid profile and C-peptide assays with insulin resistance and secretion estimation by homeostasis model assessment. People were classified as having Type 2 diabetes (n = 124) or ketosis-prone diabetes (n = 49). Ketosis-prone diabetes was sub-classified as new-onset ketotic phase (n = 34) or non-ketotic phase (n = 15). Results Ketosis-prone diabetes was found in 28.3% of the hyperglycaemic crises. Age at diabetes diagnosis was comparable in Type 2 and ketosis-prone diabetes [48 ± 14 vs 47 ± 11 years; P = 0.13] with a similar sex distribution. Overall BMI was 27.7 ± 13.4 kg/m2 and was ≥ 25 kg/m2 in 55.8% of those taking part, however, 73.5% of those with ketosis-prone diabetes reported weight loss of > 5% at diagnosisBlood pressure and lipid profile were comparable in both types. Ketosis-prone diabetes in the ketotic phase was characterized by lower insulin secretion and higher serum triglycerides compared with non-ketotic ketosis prone and Type 2 diabetes. Type 2 and ketosis prone diabetes in the non-ketotic phase were comparable in terms of lipid profile, blood pressure, waist-to-hip ratio, BMI and fat mass, insulin secretion and insulin resistance indices. Conclusions Ketosis-prone diabetes is likely to be a subtype of Type 2 diabetes with the potential to develop acute insulinopenic episodes. This article is protected by copyright. All rights reserved.

Background Type 2 diabetes (T2D) is growing faster in Africa than anywhere else, driven by the dual effects of genetic and environmental factors. We conducted a systematic review and meta-analyses of published studies on genetic markers of T2D in populations within Africa. Methods Multiple databases were searched for studies of genetic variants associated with T2D in populations living in Africa. Studies reporting on the association of a genetic marker with T2D or indicators of glycaemia were included. Data were extracted on study design and characteristics, genetic determinants, effect estimates of associations with T2D. Findings Overall, 100 polymorphisms in 57 genes have been investigated in relation with T2D in populations within Africa, in 60 studies. Almost all studies used the candidate gene approach, with >88% published during 2006–2014 and 70% (42/60) originating from Tunisia and Egypt. Polymorphisms in ACE, AGRP , eNOS , GSTP1, HSP70-2, MC4R , MTHFR , PHLPP , POL1, TCF7L2, and TNF-α gene were found to be associated with T2D, with overlapping effect on various cardiometabolic traits. The polymorphisms investigated in multiple studies mostly had consistent effects across studies, with only modest or no statistical heterogeneity. Effect sizes were modestly significant [e.g., odd ratio 1.49 (95%CI 1.33–1.66) for TCF7L2 ( rs7903146)]. Underpowered genome-wide studies revealed no diabetes risk loci specific to African populations. Interpretation Current evidence on the genetic markers of T2D in African populations mostly originate from North African countries, is overall scanty and largely insufficient to reliably inform the genetic architecture of T2D across Africa.

Background Viruses have been considered potential triggers for the development of diabetes. This study assessed insulin secretion and insulin sensitivity in human herpesvirus 8 (HHV8)-infected and uninfected sub-Saharan African people with diabetes. Methods In all, 173 people with non-autoimmune diabetes were enrolled consecutively: 124 with type 2 diabetes mellitus (T2DM) and 49 with ketosis-prone diabetes (KPD) admitted in hyperglycemic crisis. Those with KPD were further subdivided into those with new-onset ketotic-phase KPD (n = 34) or non-ketotic phase KPD (n = 15). All participants were screened for HHV8-specific antibodies and genomic DNA. Blood samples were collected for analysis of fasting glucose, HbA1c, lipid profile, and C-peptide, with insulin resistance and secretion estimated by homeostasis model assessment. Results Among the 173 diabetic participants, 88 (50.9%) were positive for HHV8 antibodies (Ac-HHV8+), including 15 (8.7%) positive for HHV8 DNA (DNA-HHV8+). The seroprevalence of HHV8 was similar between T2DM (55.6%) and KPD (61.2%) subjects. Of those with and without ketotic-phase KPD, 35.3% and 46.7% were Ac-HHV8+, respectively. Body mass index was significantly in lower DNA-HHV8+ than DNA-HHV8- subjects. Low-density lipoprotein and total cholesterol were significantly higher, but C-peptide and homeostatic model assessment of β-cell function (HOMA-β) were significantly lower in DNA-HHV8+ than DNA-HHV8- participants. After excluding DNA-HHV8+ participants, triglyceride concentrations were significantly higher in Ac-HHV8+ (n = 73) than Ac-HHV8- (n = 85) subjects. In contrast, HOMA-β was significantly higher among Ac-HHV8+ than Ac-HHV8- participants. Conclusions In the present study, HHV8 DNA positivity was associated with low insulin secretion in this sub-Saharan African diabetes population.

In a systematic review, the authors explored genetic association studies of essential hypertension in African populations. Studies reporting on the association of polymorphism(s) with hypertension in African populations were included. Appropriate studies were pooled using random effects model meta-analysis, under six potential inheritance models. In all, 46 polymorphisms in 33 genes were investigated for their association with hypertension or blood pressure levels. Meta-analysis was possible for three single nucleotide polymorphisms: rs4340, rs699, and rs5186. An association was found between rs5186, rs699, and hypertension under allele contrast and homozygous codominant models (odds ratio, 1.63 [95% confidence interval, 1.04–2.54] and 4.01 [95% confidence interval, 1.17–13.80] for rs5186, respectively; and 1.80 [95% confidence interval, 1.13–2.87] for rs699). Findings were mostly robust in sensitivity analyses. According to the systematic review, there is currently insufficient evidence on the specific polymorphisms that pose the risk of hypertension in African populations. Large-scale genetic studies are warranted to better understand susceptibility polymorphisms that may be specific to African populations.

Viruses have been considered potential triggers for the development of diabetes. This study assessed insulin secretion and insulin sensitivity in human herpesvirus 8 (HHV8)-infected and uninfected sub-Saharan African people with diabetes.In all, 173 people with non-autoimmune diabetes were enrolled consecutively: 124 with type 2 diabetes mellitus (T2DM) and 49 with ketosis-prone diabetes (KPD) admitted in hyperglycemic crisis. Those with KPD were further subdivided into those with new-onset ketotic-phase KPD (n = 34) or non-ketotic phase KPD (n = 15). All participants were screened for HHV8-specific antibodies and genomic DNA. Blood samples were collected for analysis of fasting glucose, HbA1c, lipid profile, and C-peptide, with insulin resistance and secretion estimated by homeostasis model assessment.Among the 173 diabetic participants, 88 (50.9%) were positive for HHV8 antibodies (Ac-HHV8+), including 15 (8.7%) positive for HHV8 DNA (DNA-HHV8+). The seroprevalence of HHV8 was similar between T2DM (55.6%) and KPD (61.2%) subjects. Of those with and without ketotic-phase KPD, 35.3% and 46.7% were Ac-HHV8+, respectively. Body mass index was significantly in lower DNA-HHV8+ than DNA-HHV8- subjects. Low-density lipoprotein and total cholesterol were significantly higher, but C-peptide and homeostatic model assessment of β-cell function (HOMA-β) were significantly lower in DNA-HHV8+ than DNA-HHV8- participants. After excluding DNA-HHV8+ participants, triglyceride concentrations were significantly higher in Ac-HHV8+ (n = 73) than Ac-HHV8- (n = 85) subjects. In contrast, HOMA-β was significantly higher among Ac-HHV8+ than Ac-HHV8- participants.In the present study, HHV8 DNA positivity was associated with low insulin secretion in this sub-Saharan African diabetes population.

AIM: Several biomarkers have been proposed to detect pancreatic β cell destruction in vivo but so far have not been compared for sensitivity and significance. METHODS: We used islet transplantation as a model to compare plasma concentrations of miR-375, 65-kDa subunit of glutamate decarboxylase (GAD65), and unmethylated insulin DNA, measured at subpicomolar sensitivity, and study their discharge kinetics, power for outcome prediction, and detection of graft loss during follow-up. RESULTS: At 60 minutes after transplantation, GAD65 and miR-375 consistently showed near-equimolar and correlated increases proportional to the number of implanted β cells. GAD65 and miR-375 showed comparable power to predict poor graft outcome at 2 months, with areas under the curve of 0.833 and 0.771, respectively (P = 0.53). Using receiver operating characteristic analysis, we defined likelihood ratios (LRs) for rationally selected result intervals. In GADA-negative recipients (n = 28), GAD65 12.2 pmol/L (LR = ∞) predicted good and poor outcomes, respectively. miR-375 could be used in all recipients irrespective of GAD65 autoantibody status (n = 46), with levels 7.6 pmol/L (LR = 9.53) as dual thresholds. The posttransplant surge of unmethylated insulin DNA was inconsistent and unrelated to outcome. Combined measurement of these three biomarkers was also tested as liquid biopsy for β cell death during 2-month follow-up; incidental surges of GAD65, miR-375, and (un)methylated insulin DNA, alone or combined, were confidently detected but could not be related to outcome. CONCLUSIONS: GAD65 and miR-375 performed equally well in quantifying early graft destruction and predicting graft outcome, outperforming unmethylated insulin DNA.

Background About three quarters of stroke deaths occur in developing countries including those in sub-Saharan African. Short and long-term stroke fatality data are needed for health service and policy formulation. Methods We prospectively followed up from stroke onset, 254 patients recruited from the largest reference hospitals in Yaounde (Cameroon). Mortality and determinants were investigated using the accelerated failure time regression analysis. Results Stroke mortality rates at one-, six- and 12 months were respectively 23.2% (Ischemic strokes: 20.4%, hemorrhagic strokes: 26.1%, and undetermined strokes: 34.8, p = 0.219), 31.5% (ischemic strokes: 31.5%, hemorrhagic strokes: 30.4%, and undetermined strokes: 34.8%, p = 0.927), and 32.7% (ischemic strokes: 32.1%, hemorrhagic strokes: 30.4%, undetermined strokes: 43.5%, p = 0.496). Fever, swallowing difficulties, and admission NIHSS independently predicted mortality at one month, six and 12 months. Elevated systolic blood pressure (BP) predicted mortality at one month. Elevated diastolic blood pressure was a predictor of mortality at one month in participants with hemorrhagic stroke. Low hemoglobin level on admission only predicted long term mortality. Conclusion In this resource-limited setting, post-stroke mortality was high with 1 out of 5 deaths occurring at one month and up to 30% deaths at six and twelve months after the index event. Fever, stroke severity, elevated BP and anemia increased the risk of death. Our findings add to the body of evidence for the poor outcome after stroke in resource limited environments.

We examined whether measures of glycaemic variability (GV), assessed by continuous glucose monitoring (CGM) and self-monitoring of blood glucose (SMBG), can complement or replace measures of beta cell function and insulin action in detecting the progression of preclinical disease to type 1 diabetes. Twenty-two autoantibody-positive (autoAb+) first-degree relatives (FDRs) of patients with type 1 diabetes who were themselves at high 5-year risk (50%) for type 1 diabetes underwent CGM, a hyperglycaemic clamp test and OGTT, and were followed for up to 31 months. Clamp variables were used to estimate beta cell function (first-phase [AUC5–10 min] and second-phase [AUC120–150 min] C-peptide release) combined with insulin resistance (glucose disposal rate; M 120–150 min). Age-matched healthy volunteers (n = 20) and individuals with recent-onset type 1 diabetes (n = 9) served as control groups. In autoAb+ FDRs, M 120–150 min below the 10th percentile (P10) of controls achieved 86% diagnostic efficiency in discriminating between normoglycaemic FDRs and individuals with (impending) dysglycaemia. M 120–150 min outperformed AUC5–10 min and AUC120–150 min C-peptide below P10 of controls, which were only 59–68% effective. Among GV variables, CGM above the reference range was better at detecting (impending) dysglycaemia than elevated SMBG (77–82% vs 73% efficiency). Combined CGM measures were equally efficient as M 120–150 min (86%). Daytime GV variables were inversely correlated with clamp variables, and more strongly with M 120–150 min than with AUC5–10 min or AUC120–150 min C-peptide. CGM-derived GV and the glucose disposal rate, reflecting both insulin secretion and action, outperformed SMBG and first- or second-phase AUC C-peptide in identifying FDRs with (impending) dysglycaemia or diabetes. Our results indicate the feasibility of developing minimally invasive CGM-based criteria for close metabolic monitoring and as outcome measures in trials.

Obesity is increasing in Africa, but the underlying genetic background largely remains unknown. We assessed existing evidence on genetic determinants of obesity among populations within Africa. MEDLINE and EMBASE were searched and the bibliographies of retrieved articles were examined. Included studies had to report on the association of a genetic marker with obesity indices and the presence/occurrence of obesity/obesity trait. Data were extracted on study design and characteristics, genetic determinants and effect estimates of associations with obesity indices. According to this data, over 300 polymorphisms in 42 genes have been studied in various population groups within Africa mostly through the candidate gene approach. Polymorphisms in genes such as ACE, ADIPOQ, ADRB2, AGRP, AR, CAPN10, CD36, C7orf31, DRD4, FTO, MC3R, MC4R, SGIP1 and LEP were found to be associated with various measures of obesity. Of the 36 polymorphisms previously validated by genome-wide association studies (GWAS) elsewhere, only FTO and MC4R polymorphisms showed significant associations with obesity in black South Africans, Nigerians and Ghanaians. However, these data are insufficient to establish the true nature of genetic susceptibility to obesity in populations within Africa. There has been recent progress in describing the genetic architecture of obesity among populations within Africa. This effort needs to be sustained via GWAS studies.

Context and Objective: In preparation of future prevention trials, we aimed to identify predictors of 3-year diabetes onset among oral glucose tolerance test (OGTT)- and hyperglycemic clamp-derived metabolic markers in persistently islet autoantibody positive (autoAb+) offspring and siblings of patients with type 1 diabetes (T1D). Design: The design is a registry-based study. Setting: Functional tests were performed in a hospital setting. Participants: Persistently autoAb+ first-degree relatives of patients with T1D (n = 81; age 5–39 years). Main Outcome Measures: We assessed 3-year predictive ability of OGTT- and clamp-derived markers using receiver operating characteristics (ROC) and Cox regression analysis. Area under the curve of clamp-derived first-phase C-peptide release (AUC5–10min; min 5–10) was determined in all relatives and second-phase release (AUC120–150min; min 120–150) in those aged 12–39 years (n = 62). Results: Overall, the predictive ability of AUC5–10min was better than that of peak C-peptide, the best predictor among OGTT-derived parameters (ROC-AUC [95%CI]: 0.89 [0.80–0.98] vs 0.81 [0.70–0.93]). Fasting blood glucose (FBG) and AUC5–10min provided the best combination of markers for prediction of diabetes within 3 years; (ROC-AUC [95%CI]: 0.92 [0.84–1.00]). In multivariate Cox regression analysis, AUC5–10min (P = .001) was the strongest independent predictor and interacted significantly with all tested OGTT-derived parameters. AUC5–10min below percentile 10 of controls was associated with 50–70% progression to T1D regardless of age. Similar results were obtained for AUC120–150min. Conclusions: Clamp-derived first-phase C-peptide release can be used as an efficient and simple screening strategy in persistently autoAb+ offspring and siblings of T1D patients to predict impending diabetes.

OBJECTIVE Immune intervention trials in recent-onset type 1 diabetes would benefit from biomarkers associated with good therapeutic response. In the previously reported randomized placebo-controlled anti-CD3 study (otelixizumab; GlaxoSmithKline), we tested the hypothesis that specific diabetes autoantibodies might serve this purpose. RESEARCH DESIGN AND METHODS In the included patients (n = 40 otelixizumab, n = 40 placebo), β-cell function was assessed as area under the curve (AUC) C-peptide release during a hyperglycemic glucose clamp at baseline (median duration of insulin treatment: 6 days) and every 6 months until 18 months after randomization. (Auto)antibodies against insulin (I[A]A), GAD (GADA), IA-2 (IA-2A), and ZnT8 (ZnT8A) were determined on stored sera by liquid-phase radiobinding assay. RESULTS At baseline, only better preserved AUC C-peptide release and higher levels of IAA were associated with better preservation of β-cell function and lower insulin needs under anti-CD3 treatment. In multivariate analysis, IAA (P = 0.022) or the interaction of IAA and C-peptide (P = 0.013) independently predicted outcome together with treatment. During follow-up, good responders to anti-CD3 treatment (i.e., IAA+ participants with relatively preserved β-cell function [≥25% of healthy control subjects]) experienced a less pronounced insulin-induced rise in I(A)A and lower insulin needs. GADA, IA-2A, and ZnT8A levels were not influenced by anti-CD3 treatment, and their changes showed no relation to functional outcome. CONCLUSIONS There is important specificity of IAA among other diabetes autoantibodies to predict good therapeutic response of recent-onset type 1 diabetic patients to anti-CD3 treatment. If confirmed, future immune intervention trials in type 1 diabetes should consider both relatively preserved functional β-cell mass and presence of IAA as inclusion criteria.

We investigated the effect of HLA class I risk alleles on disease progression in various phases of subclinical islet autoimmunity in first-degree relatives of patients with type 1 diabetes.A registry-based group of siblings/offspring (aged 0-39 years) was monitored from single- to multiple-autoantibody positivity (Unlike

OBJECTIVE We investigated whether islet autoantibody profile, HLA-DQ genotype, and age influenced a 20-year progression to diabetes from first autoantibody positivity (autoAb+) in first-degree relatives of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Persistently islet autoAb+ siblings and offspring (n = 462) under 40 years of age were followed by the Belgian Diabetes Registry. AutoAbs against insulin (IAA), GAD (GADA), IA-2 antigen (IA-2A), and zinc transporter 8 (ZnT8A) were determined by radiobinding assay. RESULTS The 20-year progression rate of multiple-autoAb+ relatives (n = 194) was higher than that for single-autoAb+ participants (n = 268) (88% vs. 54%; P < 0.001). Relatives positive for IAA and GADA (n = 54) progressed more slowly than double-autoAb+ individuals carrying IA-2A and/or ZnT8A (n = 38; P = 0.001). In multiple-autoAb+ relatives, Cox regression analysis identified the presence of IA-2A or ZnT8A as the only independent predictors of more rapid progression to diabetes (P < 0.001); in single-autoAb+ relatives, it identified younger age (P < 0.001), HLA-DQ2/DQ8 genotype (P < 0.001), and IAA (P = 0.028) as independent predictors of seroconversion to multiple positivity for autoAbs. In time-dependent Cox regression, younger age (P = 0.042), HLA-DQ2/DQ8 genotype (P = 0.009), and the development of additional autoAbs (P = 0.012) were associated with more rapid progression to diabetes. CONCLUSIONS In single-autoAb+ relatives, the time to multiple-autoAb positivity increases with age and the absence of IAA and HLA-DQ2/DQ8 genotype. The majority of multiple-autoAb+ individuals progress to diabetes within 20 years; this occurs more rapidly in the presence of IA-2A or ZnT8A, regardless of age, HLA-DQ genotype, and number of autoAbs. These data may help to refine the risk stratification of presymptomatic type 1 diabetes.

Background: Congenital heart disease (CHD) is a common condition in children in Sub-Saharan Africa (SSA), where it is associated with poor outcomes. Diagnosis of CHD in SSA depends essentially on echocardiography, which is available only in few urban referral centers. Our aim was to assess time changes in the pattern of referral for pediatric echocardiography and the subsequent diagnosis of structural CHD in a major SSA city. Methods: All pediatric echocardiography performed between 2004 and 2013 at the echocardiography laboratory of the Yaounde General Hospital were reviewed. The primary indication of the study and the presence of structural CHD were recorded. Results: Between 2004 and 2013, 9,390 echocardiograms were performed and 834 (8.9%) children aged 1 day to 15 years underwent echocardiography at the center, and 227 (27.2%) cases of definite structural CHD were diagnosed, with 123 (54.2%) in boys. The most frequent indications for echocardiography were heart murmurs (40%) and the suspicion of CHD (37.4%). The commonest CHD was ventricular septal defect (VSD) (30%) with tetralogy of Fallot being the most frequent cyanotic heart lesion (5.3%). The proportion of pediatric echocardiography decreased from 13.3% in 2004–2005 to 6.1% in 2012–2013 (P=0.001) but not in a linear fashion (P=0.072 for linear trend).The diagnosis of structural CHD increased from 25.1% in 2004–2005 to 27.1% in 2012–2013. This increase however was non-significant (P=0.523) and did not follow a linear trend (P=0.230). Conclusions: The pattern of referral for pediatric echocardiography at this center has changed over time, but diagnosis of structural CHD has remained the same. Improving access to this diagnostic procedure and subsequent treatment of diagnosed CHD will help improving the outcome of the disease in this setting.

[This corrects the article DOI: 10.1371/journal.pone.0166702.].

Objectives Osteoprotegerin (OPG), a soluble member of tumor necrosis factor receptor superfamily that inhibits bone resorption, has been suggested as a cardiovascular risk factor in humans. In this study, we aim to investigate the potential relationship between OPG and MetS (MetS) in a sub-Saharan African population. Methods Four hundred and eleven volunteers (152 men, 259 women) aged ≥ 18 years recruited from the general population in Douala and Edea, Cameroon participated in this study. Anthropometric parameters measured and blood samples were collected for glucose, serum lipids and OPG concentrations measurements. Mean differences of the variables in different groups were compared using Students’ t test. We performed logistic regressions to analyze the impact of independent factors on the relation between OPG and MetS outcome. MetS was defined using the Joint Interim Statement 2009. Results OPG levels did not vary significantly between both men and women with and without MetS (both P > 0.05). However, with high fasting blood glucose (≥ 5.6 mmol/L) had a significantly higher OPG level than those with lower glucose level ( P = 0.014). In multiple logistic regression analysis, MetS did not show any significant association with serum OPG levels in men and women after adjusting for age, physical activity, alcohol consumption and menopausal status in women ( P = 0.720 and P = 0.930 respectively). Conclusion This study failed to demonstrate any relationship between OPG and MetS. Nevertheless, the positive association between blood glucose and OPG levels reveals that OPG might be involved in cardiovascular risk development in this sub-Saharan African population.

We measured the glycated haemoglobin (HbA1c) levels of a total of 24 non-diabetic volunteers and diabetic patients using a point-of-care (POC) analyser in three Cameroonian cities at different altitudes. Although 12 to 25% of duplicates had more than 0.5% (8 mmol/mol) difference across the sites, HbA1c values correlated significantly (r = 0.89-0.96). Further calibration studies against gold-standard measures are warranted.

Background In the absence of existing data, the present review intends to determine the incidence, prevalence and/or genetic determinants of neonatal diabetes mellitus (NDM), with expected contribution to disease characterization. Methods We will include cross-sectional, cohort or case-control studies which have reported the incidence, prevalence and/or genetic determinants of NDM between January 01, 2000 and May 31, 2016, published in English or French languages and without any geographical limitation. PubMed and EMBASE will be extensively screened to identify potentially eligible studies, completed by manual search. Two authors will independently screen, select studies, extract data, and assess the risk of bias; disagreements will be resolved by consensus. Clinical heterogeneity will be investigated by examining the design and setting (including geographic region), procedure used for genetic testing, calculation of incidence or prevalence, and outcomes in each study. Studies found to be clinically homogeneous will be pooled together through a random effects meta-analysis. Statistical heterogeneity will be assessed using the chi-square test of homogeneity and quantified using the I 2 statistic. In case of substantial heterogeneity, subgroup analyses will be undertaken. Publication bias will be assessed with funnel plots, complemented with the use of Egger’s test of bias. Discussion This systematic review and meta-analysis is expected to draw a clear picture of phenotypic and genotypic presentations of NDM in order to better understand the condition and adequately address challenges in respect with its management. Systematic review registration PROSPERO CRD42016039765 Electronic supplementary material The online version of this article (doi:10.1186/s13643-016-0369-3) contains supplementary material, which is available to authorized users.

We investigated whether islet autoantibody profile,Persistently islet autoAbThe 20-year progression rate of multiple-autoAbIn single-autoAb

AIM: We evaluated the performance of the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockcroft-Gault (CG) equations against creatinine clearance (CrCl) to estimate glomerular filtration rate (GFR) in 51 patients with Type 2 diabetes. METHODS: The CrCl value was obtained from the average from two consecutive 24-h urine samples. Results were adjusted for body surface area using the Dubois formula. Serum creatinine was measured using the kinetic Jaffe method and was calibrated to standardized levels. Bland-Altman analysis and kappa statistic were used to examine agreement between measured and estimated GFR. RESULTS: Estimates of GFR from the CrCl, MDRD, CKD-EPI and CG equations were similar (overall P = 0.298), and MDRD (r = 0.58; 95% CI: 0.36-0.74), CKD-EPI (r = 0.55; 95% CI: 0.33-0.72) and CG (r = 0.61; 95% CI: 0.39-0.75) showed modest correlation with CrCl (all P < 0.001). Bias was -0.3 for MDRD, 1.7 for CKD-EPI and -5.4 for CG. All three equations showed fair-to-moderate agreement with CrCl (kappa: 0.38-0.51). The c-statistic for all three equations ranged between 0.75 and 0.77 with no significant difference (P = 0.639 for c-statistic comparison). CONCLUSIONS: The MDRD equation seems to have a modest advantage over CKD-EPI and CG in estimating GFR and detecting impaired renal function in sub-Saharan African patients with Type 2 diabetes. The overall relatively modest correlation with CrCl, however, suggests the need for context-specific estimators of GFR or context adaptation of existing estimators. This article is protected by copyright. All rights reserved.

INTRODUCTION: Glycated haemoglobin (HbA1c) is the best surrogate of average blood glucose control in diabetic patients, and lowering HbA1c significantly reduces diabetes complications. Moreover, immediate feedback of HbA1c measurement to patients may improve control. However, HbA1c is unavailable in most parts of Africa, a continent with one of the highest burden of diabetes. To translate these evidences, we are conducting a multicentric project in 10 health care facilities in Guinea and Cameroon to evaluate the feasibility and one-year benefit of affordable HbA1c measurement with immediate feedback to patients on diabetes control and related outcomes. PARTICIPANTS: we consecutively enrolled patients with diabetes mellitus independently of the type of disease. We hypothesised an average 1%-decrease in HbA1c in a 1000-patient study population, with a 20% increase in the number of patients reaching treatment goals within 12 months of intervention and follow-up. FINDINGS TO DATE: a total of 1, 349 diabetic patients aged 56.2±12.6 years were enrolled (813 in Cameroon and 536 in Guinea) of whom 59.8% are women. The mean duration of diabetes was 7.4±6.3 years and baseline HbA1c was 9.7±2.6% in Guinea and 8.6±2.5% in Cameroon. FUTURE PLANS: to investigate whether the introduction of routine HbA1c measurement with immediate feedback to patients and provision of relevant education would improve diabetes control after one year. The impact of the intervention on diabetes associated-complications and mortality warrant further assessment in the long term.

BACKGROUND: The hyperglycemic clamp test, the gold standard of beta cell function, predicts impending type 1 diabetes in islet autoantibody-positive individuals, but the latter may benefit from less invasive function tests such as the proinsulin:C-peptide ratio (PI:C). The present study aims to optimize precision of PI:C measurements by automating a dual-label trefoil-type time-resolved fluorescence immunoassay (TT-TRFIA), and to compare its diagnostic performance for predicting type 1 diabetes with that of clamp-derived C-peptide release. METHODS: Between-day imprecision (n = 20) and split-sample analysis (n = 95) were used to compare TT-TRFIA (AutoDelfia, Perkin-Elmer) with separate methods for proinsulin (in-house TRFIA) and C-peptide (Elecsys, Roche). High-risk multiple autoantibody-positive first-degree relatives (n = 49; age 5-39) were tested for fasting PI:C, HOMA2-IR and hyperglycemic clamp and followed for 20-57 months (interquartile range). RESULTS: TT-TRFIA values for proinsulin, C-peptide and PI:C correlated significantly (r2 = 0.96-0.99; P

Background Diabetes is a growing health concern in developing countries, with Cameroon population having an estimated 6% affected. Of note, hospital attendees appear to be increasing all over the country, with fluctuating numbers throughout the annual calendar. The aim of the study was to investigate the relationship between diabete hospitalization admission rates and climate variations in Yaounde. Methods A retrospectively designed study was conducted in four health facilities of Yaounde (Central Hospital, University teaching hospital, Biyem-Assi and Djoungolo District Hospitals), using medical records from 2000 to 2008. A relationship between diabetes (newly diagnosed diabetes patients or decompensated diabetics) hospitalization admissions and climate variations was determined using the “2000–2008” national meteorological database (precipitation and temperature). Results The monthly medians of precipitation and temperature were 154mm and 25 °C, respectively. The month of October received 239mm of precipitation. The monthly medians of diabetic admissions rates (newly diagnosed or decompensated diabetes patients) were 262 and 72 respectively. October received 366 newly diagnosed diabetics and 99 decompensated diabetics. Interestingly, diabetic hospitalization admissions rates were higher during the rainy (51 %, 1633/3232) than the dry season, though the difference was non-significant. The wettest month (October) reported the highest cases (10 %, 336/3232) corresponding to the month with the highest precipitation level (239mm). Diabetes hospitalization admissions rates varied across health facilities [from 6 % (189/3232) in 2000 to 15 % (474/3232) in 2008]. Conclusion Diabetes is an important epidemiological disease in the city of Yaounde. The variation in the prevalence of diabetes is almost superimposed to that of precipitation; and the prevalence seems increasing during raining seasons in Yaoundé.

Haemodialysis improves uraemia-induced insulin sensitivity and is therefore likely to induce significant changes in circulating glucose concentrations in end-stage renal disease (ESRD). We aimed to assess clinically relevant circulating glucose changes in patients undergoing chronic maintenance haemodialysis using continuous interstitial monitoring. We investigated 14 non-diabetic ESRD subjects aged 40.6 ± 2.4 years. Participants were examined 24-h day pre-dialysis, during the index dialysis session and 24-h post-dialysis with simultaneous measurement of capillary blood glucose and continuous interstitial glucose (CGMS). Participants performed five capillary blood glucose measurements the day before dialysis, and 10 during and after dialysis. Mean capillary blood glucose was 128 ± 20 mg/dl the day before, 93 ± 8 mg/dl during haemodialysis, and 105 ± 13 mg/dl after haemodialysis. There was a significant trend towards lower blood glucose during the session from 105 ± 16 mg/dl to a 3rd hour nadir of 83 ± 15 mg/dl (Anova F = 2.89, p = 0.029). No hypoglycaemia was recorded. Interstitial glucose profile was comparable to capillary glucose profile. Glucose concentrations varied significantly from 126 ± 13 mg/dl before to 112 ± 12 mg/dl after haemodialysis respectively (p = 0.006). This study provides evidence for the use of CGMS in ESRD and haemodialysis, and demonstrates significant changes in glucose concentrations during and after haemodialysis that would guide treatment monitoring and adjustments.

Reason for Withdrawal This protocol was withdrawn because finishing the project within adequate deadlines could not be achieved To view the published versions of this article, please click the 'Other versions' tab.

The aim of this study is to examine the association between cardiovascular risk profile, diabetes-specific factors, and prevalent retinopathy in sub-Saharan Africans with type 2 diabetes. We enrolled 213 (41 % women) diabetic adults from the Cameroon National Obesity Center in 2008. Prevalent retinopathy was based on history and digital mydriatic retinal photography. Cardiovascular risk profile was assessed, and global absolute coronary risk was estimated with the UK Prospective Diabetes Study (UKPDS) and Framingham coronary risk equations. Logistic regressions were used to relate risk factors to prevalent retinopathy and discrimination and calibration assessed. Fifty-four patients (25.4 %) had prevalent of retinopathy. Patients with retinopathy had more often hypertension (88 vs 43 %, p = 0.003), and age at diagnosis, known duration of diabetes, blood glucose, and systolic blood pressure were associated with retinopathy. Estimated 10-year coronary risks by the Framingham and UKPDS had low discrimination for retinopathy, with C-statistic (95 % confidence interval) of 0.593 (0.504–0.682) and 0.603 (0.518–0.688), respectively. New equations developed from this sample had better discrimination and calibration, with a maximum C-statistic of 0.881 (0.828–0.933). Cardiovascular risk profile was poorly correlated with prevalent retinopathy in this population. Strategies based upon routinely assessed diabetes-related factors can improve the selection of patients at high risk of retinopathy for costly confirmatory investigations.

INTRODUCTION: Fructosamine is a marker of glucose control reflecting the average glycaemic level over the preceding 2-3 weeks. Fructosamine has not gained as much popularity as glycated haemoglobin (HbA1c) for diabetes mellitus (DM) control monitoring, and the related underlying reasons remain unclear. We aim to search for and summarise available evidence on the accuracy of fructosamine measurements to diagnose and monitor DM. METHODS AND ANALYSIS: This systematic review will include randomised control trials, controlled before-and-after studies, time series designs, cohort studies, case-control studies and cross-sectional surveys reporting the diagnosis and/or monitoring of DM (type 1 DM, type 2 DM and gestational DM) with fructosamine compared with other measures of glycaemia (fasting glucose, oral glucose tolerance test, random glucose, HbA1c), without any language restriction. We will perform electronic searches in PubMed, Scopus and other databases, supplemented with manual searches. Articles published from 1 January 1980 to 30 June 2015 will be eligible for inclusion in this review. Two authors will independently screen, select studies, extract data and assess the risk of bias with discrepancies resolved by consensus. We will assess clinical heterogeneity by examining the types of interventions and outcomes in each study, and pool studies judged to be clinically homogeneous. We will also assess statistical heterogeneity using the χ(2) test of homogeneity and quantify it using the I(2) statistic. Absolute accuracy measures (sensitivity, specificity) will be pooled in a bivariate random-effects model, allowing for intersetting variability. Negative and positive predictive values will be computed for fructosamine, compared with another measure of glycaemia from the pooled estimates of sensitivity and specificity, using Bayes' theorem. ETHICS AND DISSEMINATION: This systematic review will use data from published studies and does not require ethics approval. Findings will be published in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: PROSPERO (ID=CRD42015015930).

Aim We investigated the association of HLA DRB1 and DQB1 alleles, haplotypes and genotypes with unprovoked antibody-negative ketosis-prone atypical diabetes (A − KPD) in comparison to type 2 diabetes (T2D). Methods A − KPD and T2D sub-Saharan African patients aged 19–63 years were consecutively recruited. Patients positive for cytoplasmic islet cell, insulin, glutamic acid decarboxylase or islet antigen-2 autoantibodies were excluded. Odds ratios were obtained via logistic regression after considering alleles with a minimum frequency of 5% in the study population. Bonferroni correction was used in the case of multiple comparisons. Results Among the 130 participants, 35 (27%) were women and 57 (44%) were A − KPD. DRB1 and DQB1 allele frequencies were similar for both A − KPD and T2D patients; they did not confer any substantial risk even after considering type 1 diabetes susceptibility and resistance alleles. We found no association between A − KPD and the derived DRB1*07-DQB1*02:02 (OR: 0.55 [95%CI: 0.17–1.85], P = 0.336); DRB1*11-DQB1*03:01 (OR: 2.42 [95%CI: 0.79–7.42], P = 0.123); DRB1*15-DQB1*06:02 (OR: 0.87 [95%CI: 0.39–1.95], P = 0.731) and DRB1*03:01-DQB1*02:01 (OR: 1.48 [95%CI: 0.55–3.96], P = 0.437) haplotypes. Overall, we did not find any evidence of susceptibility to ketosis associated with DRB1 and DQB1 genotypes (all P > 0.05) in A − KPD compared to T2D. Similar results were obtained after adjusting the analysis for age and sex. Conclusion Factors other than DRB1 and DQB1 genotype could explain the propensity to ketosis in A − KPD. These results need to be confirmed in a larger population with the perspective of improving the classification and understanding of the pathophysiology of A − KPD.

The growing burden of diabetes mellitus has raised interest in uncovering disease susceptibility factors, in order to contain further increases in the burden (1). It is currently admitted that both genetic and environmental factors play a critical role in the disease occurrence and progression. Besides the traditional diabetes risk factors such as unhealthy lifestyles, obesity, and family history of diabetes, interest for emerging factors such as ambient air pollutants, has significantly increased in recent years. This is reflected in a number of studies recently summarized by our group and other investigators (2-4). While existing studies suggest a modest effect of exposure to ambient air pollutants on diabetes risk, the underlying mechanisms largely remain elusive. With regard to type 2 diabetes, the progression to clinically overt disease is determined by the interplay between insulin resistance and alteration of beta-cell secretory capacity (5). It has been suggested that air pollutants could possibly interfere with these pathophysiological derangements either directly or via multiple pathways including endothelial dysfunction, systemic inflammation, dysregulation of visceral adipose tissue, mitochondrial dysfunction, non-alcoholic steatohepatosis, among others (6).

Rheological modifications observed in sickle cell anemia are associated with ischemic complications that can cause target organ functional impairment. The objective was to investigate adrenal function of adult patients with sickle cell disease. In this cross-sectional study conducted in a tertiary referral hospital of the capital city of Cameroon, we enrolled ten crisis-free adult patients with sickle cell disease (SCD) and ten age- and sex-matched healthy individuals. We assessed adrenal function by testing basal cortisol levels and 60 min after tetracosactide (Synacthen®) injection using immuno-chemiluminescence method. Post-stimulatory cortisol was defined as primary endpoint and secondary endpoints include basal cortisol levels, post-stimulatory cortisol increments and the fold increase of cortisol one hour after stimulation. Sickle cell patients had an impairment of adrenal function despite no significant difference between patients' and controls' for basal or post-stimulatory cortisol levels. In fact, one patient in two failed to achieve a two-fold increase in cortisol levels after stimulation (5/10) as opposed to 1 in 10 in the control population (1/10), P = 0.070. The percent increment of cortisol after stimulation was lower in patients versus controls (133 vs 207, P = 0.047). Relative adrenal insufficiency is frequent in sub-Saharan adult patients with sickle cell disease despite normal basal cortisol levels. Our results suggest that adrenal function require further investigation during SCD crises as these represent an important stress and may worsen the prognosis.

We measured the glycated haemoglobin (HbA1c) levels of a total of 24 non-diabetic volunteers and diabetic patients using a point-of-care (POC) analyser in three Cameroonian cities at different altitudes. Although 12 to 25% of duplicates had more than 0.5% (8 mmol/mol) difference across the sites, HbA1c values correlated significantly (r = 0.89–0.96). Further calibration studies against gold-standard measures are warranted.

Aim Whether exposure to relatively high levels of air pollution is associated with diabetes occurrence remains unclear. We sought to assess and quantify the association between exposure to major air pollutants and risk of type 2 diabetes. Methods PubMed and EMBASE databases (through September 2013) were searched using a combination of terms related to exposure to gaseous (NO 2 and NO x ) or particulate matter pollutants (PM 2.5 , PM 10 and PM 10–2.5 ) and type 2 diabetes. Descriptive and quantitative information were extracted from selected studies. We used random-effects models meta-analysis to derive overall risk estimates per type of pollutant. Results We included ten studies (five cross-sectional and five prospective), assessing the effects of air pollutants on the occurrence of diabetes. In prospective investigations, the overall effect on diabetes occurrence was significant for both NO 2 (adjusted hazard ratio [HR], 1.13; 95% confidence interval [95%CI], 1.01–1.22; p I 2 = 36.4%, p heterogeneity = 0.208) and PM 2.5 (HR, 1.11; 95%CI, 1.03–1.20; p I 2 = 0.0%, p heterogeneity = 0.827). Odds ratios were reported by two cross-sectional studies which revealed similar associations between both NO 2 and PM 2.5 with type 2 diabetes. Across studies, risk estimates were generally adjusted for age, gender, body mass index and cigarette smoking. Conclusions Available evidence supports a prospective association of main air pollutants with an increased risk for type 2 diabetes. This finding may have implications for population-based strategies to reduce diabetes risk.

In Figure 3A, "no-MetS" month 36 should show n=2. In Figure 3B, "All patients" month 24 should show n=16, and "All patients" month 36 should show n=16. Please see the corrected Figure 3 here: http://plosone.org/corrections/pone.0060117.g003.cn.tif

Background and purposeDeterminants of post-acute stroke outcomes in Africa have been less investigated. We assessed the association of metabolic syndrome (MetS) and insulin resistance with post-stroke mortality in patients with first-ever-in-lifetime stroke in the capital city of Cameroon (sub-Saharan Africa).MethodsPatients with an acute first-stroke event (n = 57) were recruited between May and October 2006, and followed for 5 years for mortality outcome. MetS definition was based on the Joint Interim Statement 2009, insulin sensitivity/resistance assessed via glucose-to-insulin ratio, quantitative insulin sensitivity check index and homeostatic model assessment.ResultsOverall, 24 (42%) patients deceased during follow-up. The prevalence of MetS was higher in patients who died after 28 days, 1 year and 5 years from any cause or cardiovascular-related causes (all p≤0.040). MetS was associated with an increased overall mortality both after 1 year (39% vs. 9%) and 5 years of follow-up (55% vs. 26%, p = 0.022). Similarly, fatal events due to cardiovascular-related conditions were more frequent in the presence of MetS both 1 year (37% vs. 9%) and 5 years after the first-ever-in-lifetime stroke (43% vs. 13%, p = 0.017). Unlike biochemical measures of insulin sensitivity and resistance (non-significant), in age- and sex-adjusted Cox models, MetS was associated with hazard ratio (95% CI) of 2.63 (1.03-6.73) and 3.54 (1.00-12.56) respectively for all-cause and cardiovascular mortality 5 years after stroke onset.ConclusionThe Joint Interim Statement 2009 definition of MetS may aid the identification of a subgroup of black African stroke patients who may benefit from intensification of risk factor management.

Summary In first-degree relatives of type 1 diabetic patients, we investigated whether diabetes risk assessment solely based on insulinoma antigen 2 (IA-2) and zinc transporter 8 (ZnT8) antibody status (IA-2A, respectively, ZnT8A) is as effective as screening for three or four autoantibodies [antibodies against insulin (IAA), glutamate decarboxylase 65 kDa (GAD) glutamate decarboxylase autoantibodies (GADA) and IA-2A with or without ZnT8A] in identifying children, adolescents and adults who progress rapidly to diabetes (within 5 years). Antibodies were determined by radiobinding assays during follow-up of 6444 siblings and offspring aged 0–39 years at inclusion and recruited consecutively by the Belgian Diabetes Registry. We identified 394 persistently IAA+, GADA+, IA-2A+ and/or ZnT8A+ relatives (6·1%). After a median follow-up time of 52 months, 132 relatives developed type 1 diabetes. In each age category tested (0–9, 10–19 and 20–39 years) progression to diabetes was significantly quicker in the presence of IA-2A and/or ZnT8A than in their joint absence (P

Cochrane review protocol.