The MicroRNA Landscape of Acute Beta Cell Destruction in Type 1 Diabetic Recipients of Intraportal Islet Grafts.

Ongoing beta cell death in type 1 diabetes (T1D) can be detected using biomarkers selectively discharged by dying beta cells into plasma. microRNA-375 (miR-375) ranks among the top biomarkers based on studies in animal models and human islet transplantation. Our objective was to identify additional microRNAs that are co-released with miR-375 proportionate to the amount of beta cell destruction.

Metabolic effects of exposure to pesticides during gestation in female Wistar rats and their offspring: a risk factor for diabetes?

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.

Cell Mass Increase Associated with Formation of Glucose-Controlling β-Cell Mass in Device-Encapsulated Implants of hiPS-Derived Pancreatic Endoderm.

Device-encapsulated human stem cell-derived pancreatic endoderm (PE) can generate functional β-cell implants in the subcutis of mice, which has led to the start of clinical studies in type 1 diabetes. Assessment of the formed functional β-cell mass (FBM) and its correlation with in vivo metabolic markers can guide clinical translation. We recently reported ex vivo characteristics of device-encapsulated human embryonic stem cell-derived (hES)-PE implants in mice that had established a metabolically adequate FBM during 50-week follow-up.

Gestational Exposure to Pesticides Induces Oxidative Stress and Lipid Peroxidation in Offspring that Persist at Adult Age in an Animal Model.

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.

Relative adrenal insufficiency in adults with sickle cell disease.

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.

Human herpesvirus 8 infection DNA positivity is associated with low insulin secretion: A case-control study in a sub-Saharan African population with diabetes.

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.

An analytical comparison of three immunoassay platforms for subpicomolar detection of protein biomarker GAD65.

A disproportional increase of circulating GAD65 within hours from an intraportal islet allotransplantation has been validated as biomarker of beta cell loss and poor functional outcome. More sensitive assays are, however, needed to allow detection of episodes of subtle beta cell loss during late-stage graft rejection or in the peri-onset period of type 1 diabetes. We applied the same sandwich monoclonal antibody couple reactive towards the C- and N-terminus of GAD65 on three advanced immunoassay platforms-the Cytometric Bead Array (CBA, Becton, Dickinson and Company), ElectroChemiLuminescence ImmunoAssay (ECLIA, Meso Scale Discovery) and digital ELISA technology (Single Molecule Array-SIMOA, Quanterix.

Functional Beta Cell Mass from Device-Encapsulated hESC-Derived Pancreatic Endoderm Achieving Metabolic Control.

Human stem cells represent a potential source for implants that replace the depleted functional beta cell mass (FBM) in diabetes patients. Human embryonic stem cell-derived pancreatic endoderm (hES-PE) can generate implants with glucose-responsive beta cells capable of reducing hyperglycemia in mice. This study with device-encapsulated hES-PE (4 × 10 cells/mouse) determines the biologic characteristics at which implants establish metabolic control during a 50-week follow-up.

Heterogeneity in the Beta-Cell Population: a Guided Search Into Its Significance in Pancreas and in Implants.

Purpose Of Review: Intercellular differences in function have since long been noticed in the pancreatic beta-cell population. Heterogeneity in cellular glucose responsiveness is considered of physiological and pathological relevance. The present review updates evidence for the physiologic significance of beta-cell heterogeneity in the pancreas.

Trends in pediatric echocardiography and the yield for congenital heart disease in a major cardiac referral hospital in Cameroon.

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.

Prediction of Impending Type 1 Diabetes through Automated Dual-Label Measurement of Proinsulin:C-Peptide Ratio.

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).

Immunogenicity of human embryonic stem cell-derived beta cells.

Aims/hypothesis: To overcome the donor shortage in the treatment of advanced type 1 diabetes by islet transplantation, human embryonic stem cells (hESCs) show great potential as an unlimited alternative source of beta cells. hESCs may have immune privileged properties and it is important to determine whether these properties are preserved in hESC-derived cells.

Methods: We comprehensively investigated interactions of both innate and adaptive auto- and allo-immunity with hESC-derived pancreatic progenitor cells and hESC-derived endocrine cells, retrieved after in-vivo differentiation in capsules in the subcutis of mice.

Ketosis-prone atypical diabetes in Cameroonian people with hyperglycaemic crisis: frequency, clinical and metabolic phenotypes.

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 Yaoundé Central Hospital, Cameroon.

Direct effect of glucocorticoids on glucose-activated adult rat β-cells increases their cell number and their functional mass for transplantation.

Compounds that increase β-cell number can serve as β-cell replacement therapies in diabetes. In vitro studies have identified several agents that can activate DNA synthesis in primary β-cells but only in small percentages of cells and without demonstration of increases in cell number. We used whole well multiparameter imaging to first screen a library of 1,280 compounds for their ability to recruit adult rat β-cells into DNA synthesis and then assessed influences of stimulatory agents on the number of living cells.

Concise Review: Markers for Assessing Human Stem Cell-Derived Implants as β-Cell Replacement in Type 1 Diabetes.

Unlabelled: : A depleted β-cell mass causes diabetes complications that cannot be avoided by insulin administration. β-Cell replacement can stop their development when restoring insulin's homeostatic role. This requires a sufficient number and an adequate functional state of the β cells, together defined as "functional β-cell mass.

Performance of three glomerular filtration rate estimation equations in a population of sub-Saharan Africans with Type 2 diabetes.

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 of two consecutive 24-h urine samples. Results were adjusted for body surface area using the Dubois formula.

Stroke mortality and its determinants in a resource-limited setting: A prospective cohort study in Yaounde, Cameroon.

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).

Species-Related Differences in the Proteome of Rat and Human Pancreatic Beta Cells.

The core proteomes of human and rat pancreatic beta cells were compared by label-free LC-MS/MS: this resulted in quantification of relative molar abundances of 707 proteins belonging to functional pathways of intermediary metabolism, protein synthesis, and cytoskeleton. Relative molar abundances were conserved both within and between pathways enabling the selection of a housekeeping network for geometric normalization and the analysis of potentially relevant differential expressions. Human beta cells differed from rat beta cells in their lower level of enzymes involved in glucose sensing (MDH1, PC, and ACLY) and upregulation of lysosomal enzymes.

Fructosamine measurement for diabetes mellitus diagnosis and monitoring: a systematic review and meta-analysis protocol.

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.

Plasma GAD65, a Marker for Early β-Cell Loss After Intraportal Islet Cell Transplantation in Diabetic Patients.

Context And Objective: Intraportal islet transplantation can restore insulin production in type 1 diabetes patients, but its effect is subject to several interfering processes. To assess the influence of β-cell loss before and during engraftment, we searched for a real-time marker of β-cell destruction. Previous studies showed that 65-kDa isoform of glutamate decarboxylase (GAD65) is discharged by chemically damaged rat β-cells.

Study of the effect of altitude on the measurement of glycated haemoglobin using point-of-care instruments.

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.

The Cocreation of Crazy Patchworks: Becoming Rhizomatic in Systemic Therapy.

In the field of systemic therapy, there has been much discussion recently about the narrative self. This concept refers to the idea that the self is narratively constructed in and through the stories which someone tells about him/herself. The story is thereby not only viewed as a metaphor for selfhood: Selfhood is not compared to a story, it is a story.

Association of HLA class II markers with autoantibody-negative ketosis-prone atypical diabetes compared to type 2 diabetes in a population of sub-Saharan African patients.

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.

Hyperglycemic clamp and oral glucose tolerance test for 3-year prediction of clinical onset in persistently autoantibody-positive offspring and siblings of type 1 diabetic patients.

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.

Osteoprotegerin is not a determinant of metabolic syndrome in sub-Saharan Africans after age adjustment.

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.