Metabolic Profile of Individuals with and without Type 2 Diabetes from Sub-Saharan Africa.

Epidemiological data predicts that sub-Saharan Africa will have the largest increase in type 2 diabetes (T2D) prevalence over the next two decades. Metabolomics studies have identified biomarkers that could improve T2D diagnosis and follow-up. However, no studies have characterized the metabolome of people from sub-Saharan Africa. Plasma samples from Senegalese individuals with T2D (n = 31) or without T2D (n = 34) were compared using measures of oxidative stress damage and plasma antioxidant enzyme activity and mass-spectrometry-based metabolomics analyses. Results showed that glucose, lactate, and tricarboxylic acid metabolites (fumarate, malate, and succinate) were increased in the T2D group, suggesting alterations in glycolysis and mitochondrial dysfunction. Several amino acids (leucine, isoleucine, valine, and tryptophan) and long-to-very-long-chain fatty acids were higher in the T2D group. Finally, elevated levels of ketone bodies and acylcarnitines were observed along with increased levels of oxidative stress damage and antioxidant activity. In conclusion, the T2D group exhibited modifications in metabolites previously shown to be associated with T2D risk in populations from other areas of the world. Future studies should seek to test whether these metabolites could be used as predictors for T2D-related complications in people from sub-Saharan Africa.

Health system capacity to manage diabetic ketoacidosis in nine low-income and lower-middle income countries: A cross-sectional analysis of nationally representative survey data.

Background: There has been increasing awareness about the importance of type 1 diabetes (T1D) globally. Diabetic ketoacidosis (DKA) is a life-threatening complication of T1D in low-income settings. Little is known about health system capacity to manage DKA in low- and lower-middle income countries (LLMICs). As such, we describe health system capacity to diagnose and manage DKA across nine LLMICs using data from Service Provision Assessments. Methods: In this cross-sectional study, we used data from Service Provision Assessment (SPA) surveys, which are part of the Demographic and Health Survey (DHS) Program. We defined an item set to diagnose and manage DKA in higher-level (tertiary or secondary) facilities, and a set to assess and refer patients presenting to lower-level (primary) facilities. We quantified each item's availability by service level in Bangladesh (Survey 1: May 22 2014-Jul 20 2014; Survey 2: Jul 2017-Oct 2017), the Democratic Republic of the Congo (DRC) (Oct 16 2017-Nov 24 2017 in Kinshasha; Aug 08 2018-Apr 20 2018 in rest of country), Haiti (Survey 1: Mar 05 2013-Jul 2013; Survey 2: Dec 16 2017-May 09 2018), Ethiopia (Feb 06 2014-Mar 09 2014), Malawi (Phase 1: Jun 11 2013-Aug 20 2013; Phase 2: Nov 13 2013-Feb 7 2014), Nepal (Phase 1: Apr 20 2015-Apr 25 2015; Phase 2: Jun 04 2015-Nov 05 2015), Senegal (Survey 1: Jan 2014-Oct 2014; Survey 2: Feb 09 2015-Nov 10 2015; Survey 3: Feb 2016-Nov 2016; Survey 4: Mar 13 2017-Dec 15 2017; Survey 5: Apr 15 2018-Dec 31 2018; Survey 6: Apr 15 2019-Feb 28 2020), Tanzania (Oct 20 2014-Feb 21 2015), and Afghanistan (Nov 1 2018-Jan 20 2019). Variation in secondary facilities' capacity and trends over time were also explored. Findings: We examined data from 2028 higher-level and 7534 lower-level facilities. Of these, 1874 higher-level and 6636 lower-level facilities' data were eligible for analysis. Availability of all item sets were low at higher-level facilities, where less than 50% had the minimal set of supplies, less than 20% had the full minimal set, and less than 15% had the ideal set needed to diagnose and manage DKA. Across countries in lower-level facilities, less than 14% had the minimal set of supplies and less than 9% the full set of supplies for diagnosis and transfer of DKA patients. No country had more than 20% of facilities with the minimal set of items needed to assess or manage DKA. Where data were available for more than one survey (Bangladesh, Senegal, and Haiti), changes in availability of the minimal set and ideal set of items did not exceed 15%. Tertiary facilities performed best in Haiti, Ethiopia, Malawi, Nepal, Senegal, Tanzania, and Afghanistan. Secondary facilities that were rural, public, and had fewer staff had lower capacity. Interpretation: Health system capacity to manage DKA was low across these nine LLMICs. Although efforts are underway to strengthen health systems, a specific focus on DKA management is still needed. Funding: Leona M. and Harry B. Helmsley Charitable Trust, and Juvenile Diabetes Research Foundation Ltd.

Estimating the total incidence of type 1 diabetes in children and adolescents aged 0-19 years from 1990 to 2050: a global simulation-based analysis.

BACKGROUND: Previous studies of type 1 diabetes in childhood and adolescence have found large variations in reported incidence around the world. However, it is unclear whether these reported incidence levels are impacted by differences in country health systems and possible underdiagnosis and if so, to what degree. The aim of this study was to estimate both the total and diagnosed incidence of type 1 diabetes globally and to project childhood type 1 diabetes incidence indicators from 1990 to 2050 for each country. METHODS: We developed the type 1 diabetes global microsimulation model to simulate the natural history and diagnosis of type 1 diabetes for children and adolescents (aged 0-19 years) in 200 countries and territories, accounting for variability in underlying incidence and health system performance. The model follows an open population of children and adolescents in monthly intervals and simulates type 1 diabetes incidence and progression, as well as health system factors which influence diagnosis. We calibrated the model to published data on type 1 diabetes incidence, autoantibody profiles, and proportion of cases diagnosed with diabetic ketoacidosis from 1990 to 2020 and assessed the predictive accuracy using a randomly sampled test set of data withheld from calibration. FINDINGS: We estimate that in 2021 there were 355 900 (95% UI 334 200-377 300) total new cases of type 1 diabetes globally among children and adolescents, of which 56% (200 400 cases, 95% UI 180 600-219 500) were diagnosed. Estimated underdiagnosis varies substantially by region, with over 95% of new cases diagnosed in Australia and New Zealand, western and northern Europe, and North America, but less than 35% of new cases diagnosed in west Africa, south and southeastern Asia, and Melanesia. The total number of incident childhood cases of type 1 diabetes is projected to increase to 476 700 (95% UI 449 500-504 300) in 2050. INTERPRETATION: Our research indicates that the total global incidence of childhood and adolescent type 1 diabetes is larger than previously estimated, with nearly one-in-two children currently undiagnosed. Policymakers should plan for adequate diagnostic and medical capacity to improve timely type 1 diabetes detection and treatment, particularly as incidence is projected to increase worldwide, with highest numbers of new cases in Africa. FUNDING: Novo Nordisk.

African Cuisine-Centered Insulin Therapy: Expert Opinion on the Management of Hyperglycaemia in Adult Patients with Type 2 Diabetes Mellitus.

The prevalence of diabetes in sub-Saharan Africa (SSA) is growing rapidly, and a steadily increasing number of adults are estimated to be living with type 2 diabetes mellitus (T2DM). Insulin therapy is the treatment of choice in patients who present with severe hyperglycaemia and in most of those who do not achieve target goals on oral hypoglycaemic agents. Initiating treatment with the appropriate type of insulin based on the meal patterns and lifestyle of the individual patient is a strategy that is more likely than others to improve glycaemic control and adherence. African cuisine typically has a high carbohydrate load. Given these predominantly carbohydrate-rich food habits, it is essential to modify this dietary pattern whilst at the same time ensuring that insulin therapy is initiated, titrated and maintained in a timely manner, as needed to suit the patient's habits. To date, there are no published clinical guidelines to guide practitioners and patients on tailoring insulin to match the high carbohydrate content in African cuisine. To address this gap, we have reviewed current insulin therapy practices and propose a patient-centric guide to insulin therapy based on African cuisine. A literature search was conducted for studies published in English up to November 2019 that focused on the choice of insulin and its dosing in relation to African foods. All articles extracted were reviewed by an expert group. The recommendation of the expert group was that basal-bolus and premix insulin regimens are best suited to manage post-meal glycaemia in African cuisine. The timing and constituents of the meal, portion sizes, glycaemic load and glycaemic index of meals should be considered when choosing the type of insulin and insulin regimen. Assessment of individual preferences and comorbidities should be prioritised and form an integral part of diabetes management.

[A no scarring persistent skin lesion for 3 years pyoderma gangrenosum]. / Une lesion cutanée persistante non cicatricielle depuis 3 ans pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a rare non-infectious neutrophilic dermatosis often unknowed. It usually presents with inflammatory skin ulcer, very painful, with rapid evolution. It is commonly found in a context of malignancy, inflammatory bowel disease, rheumatic and/or haematological disease. Its diagnosis is very often late after multiple therapeutic failures. We report a case of pyoderma gangrenosum whose diagnosis was not obvious. A patient was admitted to our department for a persistent dermatological lesion and adverse evolution despite debridements and the administration of antibiotics. He was followed for prostate cancer, high blood pressure and asthma. Due to observed biological abnormalities such as neutrophil leukocytosis with myelocyte and metamyelocyte myeloma, without blood blastosis and normochromic normocytic anemia, chronic myelogenous leukemia was suspected. It was later overturned by the various inconclusive supplementary examinations. This is how the diagnosis of PG was evoked and confirmed by anatomopathological examination showing a histopathological appearance of granulation tissue consistent with pyoderma gangrenosum and no sign of malignancy. The institution of a corticotherapy treatment resulted in the cure.

Increased Prevalence of Type 2 Diabetes-Related Complications in Combined Type 2 Diabetes and Sickle Cell Trait.

OBJECTIVE: The prevalence of type 2 diabetes (T2D) is rapidly increasing in sub-Saharan Africa, where sickle cell trait (SCT) is also frequent. Although SCT is generally considered a benign condition, evidence suggests that SCT could exaggerate vascular dysfunction in T2D. However, it remains unclear whether SCT could increase the risk of the development of T2D complications. Therefore, this study was conducted to determine whether T2D complications were more prevalent among Senegalese individuals with SCT and T2D than among those with T2D only. RESEARCH DESIGN AND METHODS: Rates of hypertension, retinopathy, peripheral neuropathy, peripheral artery disease, and impaired renal function as well as arterial stiffness, blood rheology, and concentrations of plasma advanced glycation end products (AGEs) and cytokines were compared between groups of Senegalese individuals with combined SCT and T2D (T2D-SCT) (n = 60), T2D (n = 52), SCT (n = 53), and neither T2D nor SCT (control) (n = 56). Human aortic endothelial cell (HAEC) expression of inflammatory and adhesion factors was measured after treatment with tumor necrosis factor-α and subjects' plasma. Effects of AGE inhibition or tiron on HAEC expression of E-selectin were measured. RESULTS: Retinopathy, hypertension, and reduced renal function were more prevalent, and arterial stiffness, blood viscosity at high shear rates, and thixotropic index were higher, in the SCT group compared with the other groups. Multivariable analysis showed that plasma AGE concentration was significantly associated with arterial stiffness. E-selectin expression was elevated in HAECs treated with T2D-SCT plasma compared with the other groups, but AGE inhibition reversed this. CONCLUSIONS: SCT could potentially augment the risk of the development of T2D-related complications, including retinopathy, nephropathy, and hypertension.

Sickle Cell Trait Worsens Oxidative Stress, Abnormal Blood Rheology, and Vascular Dysfunction in Type 2 Diabetes.

OBJECTIVE: It is predicted that Africa will have the greatest increase in the number of patients with type 2 diabetes mellitus (T2DM) within the next decade. T2DM patients are at risk for cardiovascular disorders. In Sub-Saharan African countries, sickle cell trait (SCT) is frequent. Despite the presence of modest abnormalities in hemorheology and oxidative stress, SCT is generally considered a benign condition. Little is known about vascular function in SCT, although recent studies demonstrated an increased risk of cardiovascular disorders, including venous thromboembolism, stroke, and chronic kidney disease. We hypothesized that SCT could accentuate the vascular dysfunction observed in T2DM. RESEARCH DESIGN AND METHODS: The current study, conducted in Senegal, compared vascular function, hemorheological profile, and biomarkers of oxidative stress, inflammation, and nitric oxide metabolism in healthy individuals (CONT), subjects with T2DM or SCT, and patients with both T2DM and SCT (T2DM-SCT). RESULTS: Flow-mediated dilation was blunted in individuals with T2DM, SCT, and T2DM-SCT compared with CONT, with vascular dysfunction being most pronounced in the latter group. Carotid-femoral pulse wave velocity measurements demonstrated increased arterial stiffness in T2DM-SCT. Oxidative stress, advanced glycation end products, and inflammation (interleukin-1ß) were greater in patients with T2DM-SCT compared with the other groups. Blood viscosity was higher in individuals with TD2M, SCT carriers, and individuals with T2DM-SCT, and the values were further increased in the latter group. CONCLUSIONS: Our results demonstrate severe biological abnormalities and marked vascular dysfunction in patients with both T2DM and SCT. SCT should be viewed as a risk factor for further cardiovascular disorders in individuals with T2DM.

Dyslipidemia, obesity and other cardiovascular risk factors in the adult population in Senegal.

INTRODUCTION: According to the WHO, 50% of deaths worldwide (40.1% in developing countries) are due to chronic non-communicable diseases (NCDs). Of these chronic NCDs, cardiovascular diseases remain the leading cause of death and disability in developed countries. The Framingham study has shown the importance of hypercholesterolemia as a primary risk factor. In Senegal, the epidemiology of dyslipidemia and obesity are still poorly understood due to the lack of comprehensive studies on their impact on the general population. This motivated this study to look into the key epidemiologic and socio-demographic determinants of these risk factors. METHODS: It was a cross-sectional descriptive epidemiological survey which included 1037 individuals selected by cluster sampling. Data were collected using a questionnaire following the WHO STEPwise approach. Socio-demographic, health and biomedical variables were collected. P value <0.05 was considered to be statistically significant. RESULTS: The average age was 48 years with a female predominance (M: F of 0.6). The literacy rate was 65.2% and 44.7% of participants were from rural areas. The prevalence of hypercholesterolemia, hyperLDLemia, hypoHDLemia, hypertriglyceridemia and mixed hyperlipidemia were 56%, 22.5%, 12.4%, 7.11% and 1.9% respectively. One in four was obese (BMI> 30kg/m2) and 34.8% had abdominal obesity. The main factors significantly associated with dyslipidemia were obesity, urban dwelling, physical inactivity and a family history of dyslipidemia. CONCLUSION: The prevalence of dyslipidemia, obesity and other risk factors in the population was high needing immediate care for those affected and implementation of prevention strategies.

Good clinical practice in resource-limited settings: translating theory into practice.

A Good Clinical Practices (GCPs) course, based on the combination of theoretical modules with a practical training in real-life conditions, was held in 2010 in Burkina Faso. It was attended by 15 trainees from nine African, Asian, and Latin American countries. There were some discrepancies between the average good results at the end of the theoretical phase and the GCP application during the first days of the practical phase, underlying the difficulties of translating theoretical knowledge into good practices. Most of the findings were not unexpected and reflected the challenges commonly faced by clinical investigators in resource-poor contexts (i.e., the high workload at peripheral health facilities, the need to conciliate routine clinical activities with clinical research, and the risk of creating a double standard among patients attending the same health facility [free care for recruited patients versus user fees for non-recruited patients with the same medical condition]). Even if limited in number and time, these observations suggest that a theoretical training alone may not be sufficient to prepare trainees for the challenges of medical research in real-life settings. Conversely, when a practical phase immediately follows a theoretical one, trainees can immediately experience what the research methodology implicates in terms of work organization and relationship with recruited and non-recruited patients. This initial experience shows the complexity of translating GCP into practice and suggests the need to rethink the current conception of GCP training.

Prevalence and determinants of hypertension and associated cardiovascular risk factors: data from a population-based, cross-sectional survey in Saint Louis, Senegal.

BACKGROUND: The incidence of cardiovascular disease is growing worldwide and this is of major public health concern. In sub-Saharan Africa, there is a lack of epidemiological data on the prevalence and distribution of risk factors of cardiovascular disease. This study aimed at assessing the prevalence of hypertension and other cardiovascular risk factors among an urban Senegalese population. METHODS: Using an adaptation of the WHO STEPwise approach to chronic disease risk-factor surveillance, we conducted a population-based, cross-sectional survey from 3 to 30 May 2010 on 1 424 participants aged over 15 years. Socio-demographic and behavioural risk factors were collected in step 1. Physical anthropometryc measurements and blood pressure were documented in step 2. Blood tests (cholesterol, fasting blood glucose, and creatinine levels) were carried out in step 3. RESULTS: The prevalence of hypertension was 46% (95% CI: 43.4-48%), with a higher prevalence in females (47.9%) than males (41.7%) (p = 0.015), and 50% of these hypertensive were previously undiagnosed. Mean age was 53.6 years (SD: 15.8). In known cases of hypertension, the average length of its evolution was 6 years 9 months (range 1 month to 60 years). Hypertension was significantly associated with age (p = 0.001), socio-professional category (p = 0.003), dyslipidaemia (p < 0.001), obesity (p < 0.001), physical inactivity (p < 0.001), diabetes (p < 0.001) and stroke (p < 0.001). CONCLUSION: We found a high prevalence of hypertension and other cardiovascular risk factors in this population. There is need of a specific programme for the management and prevention of cardiovascular disease in this population.