Simeon Pierre Choukem

Ketosis-Prone Type 2 Diabetes Mellitus and Human Herpesvirus 8 Infection in Sub-Saharan Africans

CONTEXT An atypical form of type 2 diabetes mellitus (DM-2) is revealed by ketosis (ketosis-prone type 2 diabetes mellitus), frequently occurring in individuals who are black and of African origin, and characterized by an acute onset requiring transient insulin therapy. Its sudden onset suggests precipitating factors. OBJECTIVE To investigate the putative role of human herpesvirus 8 (HHV-8) in the pathogenesis of ketosis-prone DM-2. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study in which antibodies were searched against latent and lytic HHV-8 antigens using immunofluorescence. The presence of HHV-8 in genomic DNA was investigated in 22 of the participants at clinical onset of diabetes. We also tested whether HHV-8 was able to infect human pancreatic beta cells in culture in vitro. The study was conducted at Saint-Louis University Hospital, Paris, France, from January 2004 to July 2005. All participants were black and of African origin: 187 were consecutive diabetic patients of whom 81 had ketosis-prone DM-2 and 106 had nonketotic DM-2, and 90 individuals were nondiabetic control participants who were matched for age and sex. MAIN OUTCOME MEASURES Seroprevalence of HHV-8 and percentage of patients with HHV-8 viremia at onset in ketosis-prone DM-2. RESULTS HHV-8 antibodies were found in 71 patients (87.7%) with ketosis-prone DM-2 vs 16 patients (15.1%) with nonketotic DM-2 (odds ratio, 39.9; 95% confidence interval, 17.1-93.4; P < .001) and 36 of the control participants (40.0%) (odds ratio, 10.7; 95% confidence interval, 4.9-23.4; P < .001). HHV-8 in genomic DNA was present in 6 of 13 patients with ketosis-prone DM-2 tested at acute onset and in 0 of 9 patients with nonketotic DM-2. HHV-8 proteins were present in human islet cells that were cultured for 4 days in the presence of HHV-8. CONCLUSIONS In this preliminary cross-sectional study, the presence of HHV-8 antibodies was associated with ketosis-prone DM-2 in patients of sub-Saharan African origin. Longitudinal studies are required to understand the clinical significance of these findings.

Multitissue Insulin Resistance Despite Near-Normoglycemic Remission in Africans With Ketosis-Prone Diabetes

OBJECTIVE—To characterize insulin action in Africans with ketosis-prone diabetes (KPD) during remission. RESEARCH DESIGN AND METHODS—At Saint-Louis Hospital, Paris, France, 15 African patients with KPD with an average 10.5-month insulin-free near-normoglycemic remission period (mean A1C 6.2%) were compared with 17 control subjects matched for age, sex, BMI, and geographical origin. Insulin stimulation of glucose disposal, and insulin suppression of endogenous glucose production (EGP) and nonesterified fatty acids (NEFAs), was studied using a 200-min two-step (10 mU · m−2 body surface · min−1 and 80 mU · m−2 · min −1 insulin infusion rates) euglycemic clamp with [6,6-2H2]glucose as the tracer. Early-phase insulin secretion was determined during an oral glucose tolerance test. RESULTS—The total glucose disposal was reduced in patients compared with control subjects (7.5 ± 0.8 [mean ± SE] vs. 10.5 ± 0.9 mg · kg−1 · min−1; P = 0.018). EGP rate was higher in patients than control subjects at baseline (4.0 ± 0.3 vs. 3.0 ± 0.1 mg · kg−1 · min−1; P = 0.001) and after 200-min insulin infusion (10 mU · m−2 · min−1: 1.6 ± 0.2 vs. 0.6 ± 0.1, P = 0.004; 80 mU · m−2 · min−1: 0.3 ± 0.1 vs. 0 mg · kg−1 · min−1, P = 0.007). Basal plasma NEFA concentrations were also higher in patients (1,936.7 ± 161.4 vs. 1,230.0 ± 174.1 μmol/l; P = 0.002) and remained higher after 100-min 10 mU · m−2 · min−1 insulin infusion (706.6 ± 96.5 vs. 381.6 ± 55.9 μmol/l; P = 0.015). CONCLUSIONS—The triad hepatic, adipose tissue, and skeletal muscle insulin resistance is observed in patients with KPD during near-normoglycemic remission, suggesting that KPD is a form of type 2 diabetes.

Prevalence and determinants of undiagnosed diabetes in an urban sub-Saharan African population.

AIMS To report the prevalence of undiagnosed diabetes and its determinants among adults Cameroonian urban dwellers. METHODS On May 17th 2011, a community-based combined screening for diabetes and hypertension was conducted simultaneously in four major Cameroonian cities. Adult participants were invited through mass media. Fasting blood glucose was measured in capillary blood. RESULTS Of the 2120 respondents, 1591 (52% being men) received a fasting glucose test. The median age was 43.7 years, and 64.2% were overweight or obese. The sex-specific age adjusted prevalence (for men and women) were 10.1% (95% confidence interval [CI]: 8.1-12.1%) and 11.2% (95%CI: 9.1-13.3%) for any diabetes, and 4.6% (95%CI: 2.6-6.6%) and 5.1% (95%CI: 3.0-7.2%) for screened-detected diabetes, respectively. The prevalence of diabetes increased with increasing age in men and women (all p ≤ 0.001 for linear trend). Older age (p<0.001), region of residence (p<0.001), excessive alcohol intake (p=0.02) were significantly associated with screened-detected diabetes, while physical inactivity, body mass index, and high waist girth were not significantly associated with the same outcome. CONCLUSIONS Prevalence of undiagnosed diabetes is very high among Cameroonian urban dwellers, indicating a potentially huge impact of screening for diabetes, thus the need for more proactive policies of early detection of the disease.

High birth weight in a suburban hospital in Cameroon: an analysis of the clinical cut-off, prevalence, predictors and adverse outcomes

Background and aims High birth weight (HBW) increases the risk of maternal and fetal morbidity and mortality. Its prevalence and adverse outcomes may be reduced if risk factors are identified and managed during pregnancy. The cut-off value for HBW remains debatable. The objectives of this study were to identify the optimal cut-off value and determine the prevalence, predictors and adverse outcomes of HBW in a suburban area of Cameroon. Design A 6-year retrospective register analysis and a 3-month prospective phase. Setting A secondary care level (regional) hospital in the city of Buea (southwest region of Cameroon). Participants Women who delivered in this hospital over a 6-year period (retrospective phase) and consenting pregnant mothers and their infants (singletons, born at >28 weeks gestation) (prospective phase). Outcome measures 90th centile of birth weights; prevalence of HBW defined as birth weight above the 90th centile; sociodemographic, maternal and obstetrical factors associated with HBW; maternal and neonatal adverse outcomes of HBW. Results Of the 4941 newborns reviewed in registers, the 90th centile of birth weights was 3850 g. Using this new cut-off, we obtained a prevalence of 14.0% for HBW in the 200 newborns included in the prospective phase. This was significantly higher than the prevalence (9.5%) yielded when the traditional cut-off of 4000 g was used (p=0.003). None of the factors assessed was independently associated with HBW. Newborns with HBW were more likely to have shoulder dystocia (p<0.01), and their mothers more likely to suffer from prolonged labour (p=0.01) and postpartum haemorrhage (p<0.01). Conclusions The results of this study suggest that the cut-off for HBW in this population should be 3850 g. Thus, 3 of every 10 babies born with HBW in this hospital are likely not receiving optimal postnatal care because 4000 g is currently used to qualify for additional support.

Blood pressure variables and prevalent electrocardiographic left ventricular hypertrophy in sub-Saharan African individuals with type 2 diabetes.

Background:  The aim of the present study was to investigate whether brachial blood pressure (BP) variables (systolic BP [SBP], diastolic BP [DBP], pulse [PP] and mean arterial pressure [MAP]) are similar determinants of prevalent electrocardiographic left ventricular hypertrophy (LVH) in sub‐Saharan Africans with type 2 diabetes (T2D).

Prevalence, substitute diagnostic tool, risk factors of diabetic polyneuropathy and foot care awareness in diabetic patients in a semi urban setting- Cameroon

Introduction : the world is facing an epidemic of Diabetes. Polyneuropathy is a length dependent symmetric sensorimotor type of neuropathy a main risk factor of diabetic foot ulcers. The diabetic neurological examination (DNE) score and yearly foot examinations have been recommended for clinical diagnosis of Diabetic polyneuropathy (DPN). The DNE score is lengthy. Other simple tools for accurate diagnosis exist. Risk factors for DPN are not known in our setting. The objectives were to determine the prevalence of Diabetic Polyneuropathy; To compare the Vibratory Perception Threshold (VPT), Monofilament score (MS) and Diabetic Neurological Symptom Score to the DNE score. Identify risk factors of DPN; To estimate Clinician and patient awareness of foot care. Methods : we conducted a cross sectional analytic study of diabetic patients in the Buea and Limbe regional hospitals during 4 months. Co-founders of diabetic polyneuropathy, alcoholics and HIV patients were excluded. Results : 360 patients with mean age of 56 years. 236(65.6%) women and 348(9.67%) T2DM were recruited. The prevalence of DPN was 30.6% (110) using the DNE score. VPT was most specific (96%), sensitive (94.6% and correlated (0.59) to the DNE score. The monofilament and DNS had sensitivities, specificities and correlations of (95.8%, 79.5%, r = 0.48) and (62.2%, 83.5%, r = 0.16) respectively. Determinants of DPN were age>60 years (p10 (p = 0.003), treatment with insulin and oral hypoglycaemics (p = 0.005), history of foot ulcer (p = 0.03), hypertension (p=0.04). During the preceding year, 264(73%) patients’ feet were not examined, 272(80%) did not check their foot wear before wearing, 255(71%) used razor to trim their nails, 144(40%) walked barefeet, and 72(21%) wore tight shoes.

The influence of diabetes on in-hospital complications and mortality in a Cardiovascular Intensive Care Unit in sub Saharan Africa

Introduction : patients living with type 2 diabetes are at increased risk of cardiovascular related death but there is little data on the influence of diabetes on early outcomes of cardiovascular emergencies (CVEs). This study aimed at describing the influence of diabetes on early outcome of patients admitted for CVEs. Methods : database of Cardiovascular Intensive Care Unit (CICU) of the Douala General Hospital was queried for patients admitted for CVEs between November 2012 and November 2015. We compared patients with and without known diabetes for sociodemographic profile and risk factors for CVEs using 2-sided tests (Chi-squared & one-way ANOVA). While Cox regression and Kaplan Meier survival models were used to compare in-hospital complications and mortality. Results : of the 333 patients admitted during the study period, 99 (29.7%) had a diagnosis of diabetes. Patients with diabetes were older (65.8 ± 13.8 vs 60.4 ± years, p<0.001) with a similar sex distribution to patients without diabetes. Hypertension (90.9% vs 68.4%, p < 0.001), dyslipidemia (44.4% vs 6.4%, p<0.001), sedentary lifestyle (68.7% vs 44.8%, p = 0.001) and gout (15.2% vs 6.8%, p = 0.02) were more frequent in patients with diabetes. Stroke (54.3% vs 37.2%), acute heart failure (26.3% vs 24.8%), acute coronary syndrome (6.1% vs 2.1%) and complications [(p<0.001): infectious (41.4% vs 23.5%), cardiovascular (16.2% vs 12.8%) and multi-systemic failure (9.1% vs 1.7%)] were also more frequent in patients with diabetes. Complications occurred much earlier (p<0.001), estimated survival time was shorter (p < 0.001) and mortality was higher in patients with diabetes [46.5% vs 25.6%, adjusted Hazard Ratio (aHR) for age & sex was 1.77 (95% CI: 1.18 – 2.64), adj-p = 0.005].

The association between antiretroviral therapy and selected cardiovascular disease risk factors in sub-Saharan Africa: A systematic review and meta-analysis.

Background With increasing adverse cardiovascular disease (CVD) outcomes in HIV/AIDS patients, the possible contribution of antiretroviral therapy (ART) to the prevailing CVD epidemic in sub-Saharan Africa (SSA) through its effect on CVD risk factors has rather been under investigated. This study aimed to assess the extent to which ART is associated with hypertension, diabetes mellitus (DM) and dyslipidemia in SSA. Methods This is a systematic review and meta-analysis of studies from SSA, published between January 1946 and December 2017, from Medline, Embase, Africa-wide Information, the Cochrane library, African Index and Medicus databases. Both observational and interventional studies with comparable ART-treated and ART-naïve populations were selected and data was extracted from eligible studies. Pooled estimates of the effect of ART on the outcomes of interest (hypertension, diabetes and abnormal lipid profiles) were obtained using random effects meta-analysis, and meta-regression analysis was used to explore between-study heterogeneity. Results Twenty cross-sectional studies were included involving 5386 participants. There was no association between ART use and hypertension (OR: 1.9, 95%CI: 0.96–3.76, n = 8, I2 = 73.8%) and DM (OR: 2.53, 95%CI: 0.87–7.35, n = 8, I2 = 73.8%). ART use was associated with high total cholesterol (OR: 3.85, 95%CI: 2.45–6.07, n = 8, I2 = 67.0%), high triglycerides (OR: 1.46, 95%CI: 1.21–1.75, n = 14, I2 = 10.0%) and high LDL-cholesterol (OR: 2.38, 95%CI: 1.43–3.95, n = 11, I2 = 87.6%). ART was associated with rather lower odds of having low HDL-cholesterol (OR: 0.53, 95%CI: 0.32–0.87, n = 8, I2 = 78.2%). There was evidence of between-study heterogeneity for all outcomes except high triglycerides. Conclusions ART appears to be associated with CVD risk in HIV/AIDS patients in SSA only through dyslipidemia but not through hypertension and DM, however, high quality and robust research in SSA is mandated to accurately ascertain the actual contribution of ART to the CVD burden in this part of the world. Nevertheless, HIV/AIDS patients should still benefit from systematic CVD screening alongside their regular care services. Trial registration Prospero Registration - CRD42016042306.

Markers of adiposity in HIV/AIDS patients: Agreement between waist circumference, waist-to-hip ratio, waist-to-height ratio and body mass index

Background Waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) are all independent predictors of cardio-metabolic risk and therefore important in HIV/AIDS patients on antiretroviral therapy at risk of increased visceral adiposity. This study aimed to assess the extent of agreement between these parameters and the body mass index (BMI), as anthropometric parameters and in classifying cardio-metabolic risk in HIV/AIDS patients. Methods A secondary analysis of data from a cross-sectional study involving 200 HIV/AIDS patients was done. Anthropometric parameters were measured from participants using standard guidelines and central obesity defined according to recommended criteria. Increased cardio-metabolic risk was defined according to the standard cut-off values for all four parameters. Data were analyzed using STATA version 14.1. Results The prevalence of WC-defined central obesity, WHR-defined central obesity and WHtR > 0.50 were 33.5%, 44.5% and 36.5%, respectively. The prevalence of BMI-defined overweight and obesity was 40.5%. After adjusting for gender and HAART status, there was a significant linear association and correlation between WC and BMI (regression equation: WC (cm) = 37.184 + 1.756 BMI (Kg/m2) + 0.825 Male + 1.002 HAART, (p < 0.001, r = 0.65)), and between WHtR and BMI (regression equation: WHtR = 0.223 + 0.011 BMI (Kg/m2)– 0.0153 Male + 0.003 HAART, (p < 0.001, r = 0.65)), but not between WHR and BMI (p = 0.097, r = 0.13). There was no agreement between the WC, WHtR and BMI, and minimal agreement between the WHR and BMI, in identifying patients with an increased cardio-metabolic risk. Conclusion Despite the observed linear association and correlation between these anthropometric parameters, the routine use of WC, WHR and WHtR as better predictors of cardio-metabolic risk should be encouraged in these patients, due to their minimal agreement with BMI in identifying HIV/AIDS patients with increased cardio-metabolic risk. HAART status does not appear to significantly affect the association between these anthropometric parameters.

Diagnostic and therapeutic challenges of an ambiguous cystic kidney disease in a resource limited setting: a case report

BackgroundUnilateral renal cystic disease is a rare condition that shares morphological similarities with multicystic dysplastic kidney, the former often distinguished from the latter on some clinical and histopathological grounds. However serious diagnostic and therapeutic dilemmas set in when there is a considerable overlap in the distinguishing features between these entities.Case presentationA 19-year-old African female presented with a chronic severe debilitating right lower quadrant abdominal pain refractory to analgesics. Biochemical investigations and imaging studies revealed a non-functional polycystic right kidney and no identifiable pelvicalyceal system or ureter but with preserved renal function. The marked overlap in clinical presentation between unilateral renal cystic disease and multicystic dysplastic kidney in this patient necessitated further investigation to pose an appropriate diagnosis. A right nephrectomy was performed and histopathological analysis of the resected kidney done, the results of which were more consistent with unilateral renal cystic disease. The post-operative course was favorable.ConclusionUnilateral renal cystic disease with an ipsilateral non-functional kidney and an atretic pelvicalyceal system is a very rare condition that needs to be distinguished from multicystic dysplastic kidney in order to guide management and set prognosis. A suspicion of either of these diseases therefore warrants a thorough clinical evaluation and the appropriate combination of biochemical and imaging investigations.