Turner syndrome in diverse populations.

Turner syndrome (TS) is a common multiple congenital anomaly syndrome resulting from complete or partial absence of the second X chromosome. In this study, we explore the phenotype of TS in diverse populations using clinical examination and facial analysis technology. Clinical data from 78 individuals and images from 108 individuals with TS from 19 different countries were analyzed. Individuals were grouped into categories of African descent (African), Asian, Latin American, Caucasian (European descent), and Middle Eastern. The most common phenotype features across all population groups were short stature (86%), cubitus valgus (76%), and low posterior hairline 70%. Two facial analysis technology experiments were conducted: TS versus general population and TS versus Noonan syndrome. Across all ethnicities, facial analysis was accurate in diagnosing TS from frontal facial images as measured by the area under the curve (AUC). An AUC of 0.903 (p < .001) was found for TS versus general population controls and 0.925 (p < .001) for TS versus individuals with Noonan syndrome. In summary, we present consistent clinical findings from global populations with TS and additionally demonstrate that facial analysis technology can accurately distinguish TS from the general population and Noonan syndrome.

My flanks aches: Emphysematous pyelonephritis in a newly diagnosed case of diabetes mellitus.

Emphysematous pyelonephritis (EPN) is a rare, severe necrotising infection of the renal parenchyma and surrounding tissues. It is usually life-threatening and should be promptly treated. Here, we report a clinical case of a 54-year-old male who presented with the left flank pains of 3-week duration. The flank pain was described as dull, constant with associated fever. He was diagnosed with diabetes mellitus (DM) while on admission. A clinical diagnosis of the left pyelonephritis was made. The abdominopelvic computed tomography scan confirmed bilateral EPN by showing a thin film of perinephric fluid (13.2 ml) in the left lower pole. He was managed conservatively with fluid therapy, adequate glycaemic control and intravenous antibiotics with no percutaneous drainage done. This highlights the importance of early initiation of appropriate medical treatment to avoid interventional urological procedures of nephrectomy. It also highlights the importance of clinical suspicion of EPN in patients presenting with symptoms of urinary tract infection and DM.

Genome-wide association study identifies African-ancestry specific variants for metabolic syndrome.

The metabolic syndrome (MetS) is a constellation of metabolic disorders that increase the risk of developing several diseases including type 2 diabetes and cardiovascular diseases. Although genome-wide association studies (GWAS) have successfully identified variants associated with individual traits comprising MetS, the genetic basis and pathophysiological mechanisms underlying the clustering of these traits remain unclear. We conducted GWAS of MetS in 1427 Africans from Ghana and Nigeria followed by replication testing and meta-analysis in another continental African sample from Kenya. Further replication testing was performed in an African American sample from the Atherosclerosis Risk in Communities (ARIC) study. We found two African-ancestry specific variants that were significantly associated with MetS: SNP rs73989312[A] near CA10 that conferred increased risk (P=3.86 × 10(-8), OR=6.80) and SNP rs77244975[C] in CTNNA3 that conferred protection against MetS (P=1.63 × 10(-8), OR=0.15). Given the exclusive expression of CA10 in the brain, our CA10 finding strengthens previously reported link between brain function and MetS. We also identified two variants that are not African specific: rs76822696[A] near RALYL associated with increased MetS risk (P=7.37 × 10(-9), OR=1.59) and rs7964157[T] near KSR2 associated with reduced MetS risk (P=4.52 × 10(-8), Pmeta=7.82 × 10(-9), OR=0.53). The KSR2 locus displayed pleiotropic associations with triglyceride and measures of blood pressure. Rare KSR2 mutations have been reported to be associated with early onset obesity and insulin resistance. Finally, we replicated the LPL and CETP loci previously found to be associated with MetS in Europeans. These findings provide novel insights into the genetics of MetS in Africans and demonstrate the utility of conducting trans-ethnic disease gene mapping studies for testing the cosmopolitan significance of GWAS signals of cardio-metabolic traits.

C-reactive protein (CRP) promoter polymorphisms influence circulating CRP levels in a genome-wide association study of African Americans.

C-reactive protein (CRP) is an acute phase reactant protein produced primarily by the liver. Circulating CRP levels are influenced by genetic and non-genetic factors, including infection and obesity. Genome-wide association studies (GWAS) provide an unbiased approach towards identifying loci influencing CRP levels. None of the six GWAS for CRP levels has been conducted in an African ancestry population. The present study aims to: (i) identify genetic variants that influence serum CRP in African Americans (AA) using a genome-wide association approach and replicate these findings in West Africans (WA), (ii) assess transferability of major signals for CRP reported in European ancestry populations (EA) to AA and (iii) use the weak linkage disequilibrium (LD) structure characteristic of African ancestry populations to fine-map the previously reported CRP locus. The discovery cohort comprised 837 unrelated AA, with the replication of significant single-nucleotide polymorphisms (SNPs) assessed in 486 WA. The association analysis was conducted with 2 366 856 genotyped and imputed SNPs under an additive genetic model with adjustment for appropriate covariates. Genome-wide and replication significances were set at P < 5 × 10(-8) and P < 0.05, respectively. Ten SNPs in (CRP pseudogene-1) CRPP1 and CRP genes were associated with serum CRP (P = 2.4 × 10(-09) to 4.3 × 10(-11)). All but one of the top-scoring SNPs associated with CRP in AA were successfully replicated in WA. CRP signals previously identified in EA samples were transferable to AAs, and we were able to fine-map this signal, reducing the region of interest from the 25 kb of LD around the locus in the HapMap CEU sample to only 8 kb in our AA sample.

Case Report of Graves' Disease in a 45-Year-Old Woman Secondary to Herceptin Treatment for Breast Cancer.

Graves' disease is the most common cause of thyrotoxicosis and is characterized by ophthalmopathy with proptosis, chemosis, or conjunctival injection; pretibial myxedema; and thyroid acropachy. It is an autoimmune disease that can be genetic or influenced by coexisting environmental factors such as exposure to anticancer drugs, including immune checkpoint inhibitors. The incidence rate of breast cancer is increasing due to rising awareness of risk factors and screening for breast cancer, and the mortality rate is decreasing due to recent advances in cancer treatment. However, there are side effects that are attributed to these treatment modalities, manifesting in various forms in breast cancer survivors, which are reflected in the patient in this case study.

Telemedicine ready or not? A cross-sectional assessment of telemedicine maturity of federally funded tertiary health institutions in Nigeria.

Introduction and objective: Telemedicine has reinforced its position as a means for the continuity of healthcare services and a cost-effective approach to improving health equity as demonstrated during the COVID-19 pandemic. The preparedness of health systems for telemedicine is an indicator of the scalability of their services, especially during catastrophes. We aimed to assess the maturity and preparedness of federally funded tertiary health institutions in Nigeria, to deploy telemedicine as such data are currently lacking and are required to drive improvements in health services delivery. Methods: We conducted a cross-sectional survey of thirty randomly selected federally funded tertiary health institutions in Nigeria using the Pan American Health Organization's tool for assessing the maturity level of health institutions to implement telemedicine between 17 September 2020 and 1 September 2021. Descriptive statistics were used for overall maturity levels and non-parametric tests to compare scores for overall maturity and specific Pan American Health Organization domains per region. The level of significance was set at p-value <0.05. Results: The response rate was 77.4% (24 of 30 randomly polled federally funded tertiary health institutions responded). Overall, the median telemedicine maturity level was 2.0 (1.75) indicating a beginner level. No significant inter-zonal difference in the median overall maturity level (p = 0.87). The median maturity levels for telemedicine readiness in specific domains were organizational readiness - 2.0 (2.0), processes 1.0 (1.0), digital environment 2.0 (3.0), human resources 2.0 (1.0), regulatory issues - 1.5 (1.0) and expertise 2.0 (2.0); mostly at beginner level, with no inter-zonal differences. Most participating institutions had no initiatives in place for domains of processes and regulatory issues. Conclusions: The current telemedicine maturity level of federally funded tertiary health institutions in Nigeria is at the beginner level. This behoves policy-makers to advance the implementation and deployment of telemedicine nationwide as part of digital quality healthcare, to improve health equity and to ensure continuity of healthcare services in the event of another pandemic.

Prevalence of haemoglobin A1c based dysglycaemia among adult community dwellers in selected states in Nigeria: a descriptive cross-sectional study.

Background: Type 2 diabetes mellitus (T2DM) is a disease of public health importance globally with an increasing burden of undiagnosed pre-diabetes and diabetes in low- and middle-income countries, Nigeria in particular. Pre-diabetes and diabetes are established risk factors for cardiovascular complications. However, data are scanty on the current prevalence of these conditions in Nigeria, based on haemoglobin A1c (HbA1c) diagnosis as recommended by the WHO in 2009. We aimed to determine the prevalence of pre-diabetes, diabetes, and undiagnosed diabetes among the adult population of Nigeria using HbA1c. Methodology: A cross-sectional, multi-site population study was carried out in selected states in Nigeria (namely, Ekiti, Lagos, Osun, Oyo, and Kwara states) involving 2,708 adults (≥18 years) in rural and urban community dwellers, without prior diagnosis of pre-diabetes or diabetes. Participants with ongoing acute or debilitating illnesses were excluded. Data were collected using an interviewer-administered pretested, semi-structured questionnaire. Socio-demographic, clinical (weight, height, blood pressure, etc.), and laboratory characteristics of participants including HbA1c were obtained. Data were analysed using STATA version 16. Results: The mean age of participants was 48.1 ± 15.8 years, and 65.5% were female. The overall prevalence of pre-diabetes and undiagnosed diabetes was 40.5% and 10.7%, respectively, while the prevalence of high blood pressure was 36.7%. The prevalence of pre-diabetes was the highest in Lagos (48.1%) and the lowest in Ekiti (36.7%), while the prevalence of diabetes was the highest in Kwara (14.2%) and the lowest in Ekiti (10%). There was a significant association between age of the participants (p< 0.001), gender (p = 0.009), educational status (p = 0.008), occupation (p< 0.001), tribe (p = 0.004), marital status (p< 0.001), blood pressure (p< 0.001), and their diabetic or pre-diabetic status. Independent predictors of diabetes and pre-diabetes include excess weight gain, sedentary living, and ageing. Participants within the age group 45-54 years had the highest total prevalence (26.6%) of pre-diabetes and diabetes. Conclusion: Over half of the respondents had pre-diabetes and diabetes, with a high prevalence of undiagnosed diabetes. A nationwide screening campaign will promote early detection of pre-diabetes and undiagnosed diabetes among adult Nigerians. Health education campaigns could be an effective tool in community settings to improve knowledge of the risk factors for diabetes to reduce the prevalence of dysglycaemia.

Genome-wide associated loci influencing interleukin (IL)-10, IL-1Ra, and IL-6 levels in African Americans.

Interleukins (ILs) are key mediators of the immune response and inflammatory process. Plasma levels of IL-10, IL-1Ra, and IL-6 are associated with metabolic conditions, show large inter-individual variations, and are under strong genetic control. Therefore, elucidation of the genetic variants that influence levels of these ILs provides useful insights into mechanisms of immune response and pathogenesis of diseases. We conducted a genome-wide association study (GWAS) of IL-10, IL-1Ra, and IL-6 levels in 707 non-diabetic African Americans using 5,396,780 imputed and directly genotyped single nucleotide polymorphisms (SNPs) with adjustment for gender, age, and body mass index. IL-10 levels showed genome-wide significant associations (p < 5 × 10(-8)) with eight SNPs, the most significant of which was rs5743185 in the PMS1 gene (p = 2.30 × 10(-10)). We tested replication of SNPs that showed genome-wide significance in 425 non-diabetic individuals from West Africa, and successfully replicated rs17365948 in the YWHAZ gene (p = 0.02). IL-1Ra levels showed suggestive associations with two SNPs in the ASB3 gene (p = 2.55 × 10(-7)), ten SNPs in the IL-1 gene family (IL1F5, IL1F8, IL1F10, and IL1Ra, p = 1.04 × 10(-6) to 1.75 × 10(-6)), and 23 SNPs near the IL1A gene (p = 1.22 × 10(-6) to 1.63 × 10(-6)). We also successfully replicated rs4251961 (p = 0.009); this SNP was reported to be associated with IL-1Ra levels in a candidate gene study of Europeans. IL-6 levels showed genome-wide significant association with one SNP (RP11-314E23.1; chr6:133397598; p = 8.63 × 10(-9)). To our knowledge, this is the first GWAS on IL-10, IL-1Ra, and IL-6 levels. Follow-up of these findings may provide valuable insight into the pathobiology of IL actions and dysregulations in inflammation and human diseases.

Clinical features, predictive factors and outcome of hyperglycaemic emergencies in a developing country.

BACKGROUND: Hyperglycaemic emergencies are common acute complications of diabetes mellitus (DM) but unfortunately, there is a dearth of published data on this entity from Nigeria. This study attempts to describe the clinical and laboratory scenario associated with this complication of DM. METHODS: This study was carried out in DM patients who presented to an urban hospital in Nigeria with hyperglycaemic emergencies (HEs). The information extracted included biodata, laboratory data and hospitalization outcome. Outcome measures included mortality rates, case fatality rates and predictive factors for HEs mortality. Statistical tests used are chi2, Student's t test and logistic regression. RESULTS: A total of 111 subjects with HEs were recruited for the study. Diabetes ketoacidosis (DKA) and hyperosomolar hyperglycaemic state (HHS) accounted for 94 (85%) and 17 (15%) respectively of the HEs. The mean age (SD) of the subjects was 53.9 (14.4) years and their ages ranged from 22 to 86 years. DKA occurred in all subjects with type 1 DM and 73 (81%) of subjects with type 2 DM. The presence of HSS was noted in 17 (19%) of the subjects with type 2 DM.Hypokalaemia (HK) was documented in 41 (37%) of the study subjects. Elevated urea levels and hyponatraemia were noted more in subjects with DKA than in those subjects with HHS (57.5%,19% vs 53%,18%). The mortality rate for HEs in this report is 20% and the case fatality rates for DKA and HHS are 18% and 35% respectively.The predictive factors for HEs mortality include, sepsis, foot ulceration, previously undetected DM, hypokalaemia and being elderly. CONCLUSION: HHS carry a higher case fatality rate than DKA and the predictive factors for hyperglycaemic emergencies' mortality in the Nigerian with DM include foot ulcers, hypokalaemia and being elderly.

Diabetes foot ulceration in a Nigerian hospital: in-hospital mortality in relation to the presenting demographic, clinical and laboratory features.

This prospective study assessed in-hospital mortality from diabetic foot ulcer in relation to the demographic, clinical and laboratory features at presentation. Forty-two patients admitted with diabetic foot ulcer were followed up from admission till discharge from hospital. Those who survived or died were compared for any differences in demographic, clinical and laboratory parameters at presentation. The mean age and duration of diabetes for the 42 patients were 56.1 +/- 1.9 years and 8.3 +/- 1.1 years, respectively. The in-hospital mortality rate amongst the 42 subjects was 40.5%. Ulcer grade > or =4, leucocytosis and anaemia were more prevalent in those who demised in comparison with survivors.

Type 2 diabetes complications and comorbidity in Sub-Saharan Africans.

BACKGROUND: Context-specific evidence of the spectrum of type 2 diabetes (T2D) burden is essential for setting priorities and designing interventions to reduce associated morbidity and mortality. However, there are currently limited data on the burden of T2D complications and comorbidity in sub-Saharan Africa (SSA). METHODS: T2D complications and comorbidities were assessed in 2,784 participants with diabetes enrolled from tertiary health centres and contextualised in 3,209 individuals without diabetes in Nigeria, Ghana and Kenya. T2D complications and comorbidities evaluated included cardiometabolic, ocular, neurological and renal characteristics. FINDINGS: The most common complications/comorbidities among the T2D participants were hypertension (71%; 95% CI 69-73), hyperlipidaemia (34%; 95% CI 32-36), and obesity (27%; 95% CI 25-29). Additionally, the prevalence of cataracts was 32% (95% CI 30-35), diabetic retinopathy 15% (95% CI 13-17), impaired renal function 13% (95% CI 12-15), and erectile dysfunction (in men) 35% (95% CI 32-38). T2D population-attributable fraction for these comorbidities ranged between 6 and 64%. INTERPRETATION: The burden of diabetes complications and comorbidity is substantial in SSA highlighting the urgent need for innovative public health strategies that prioritise promotion of healthy lifestyles for prevention and early detection of T2D. Also needed are strategies to strengthen health care system capacities to provide treatment and care for diabetes complications.

ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response.

Genome analysis of diverse human populations has contributed to the identification of novel genomic loci for diseases of major clinical and public health impact. Here, we report a genome-wide analysis of type 2 diabetes (T2D) in sub-Saharan Africans, an understudied ancestral group. We analyze ~18 million autosomal SNPs in 5,231 individuals from Nigeria, Ghana and Kenya. We identify a previously-unreported genome-wide significant locus: ZRANB3 (Zinc Finger RANBP2-Type Containing 3, lead SNP p = 2.831 × 10-9). Knockdown or genomic knockout of the zebrafish ortholog results in reduction in pancreatic ß-cell number which we demonstrate to be due to increased apoptosis in islets. siRNA transfection of murine Zranb3 in MIN6 ß-cells results in impaired insulin secretion in response to high glucose, implicating Zranb3 in ß-cell functional response to high glucose conditions. We also show transferability in our study of 32 established T2D loci. Our findings advance understanding of the genetics of T2D in non-European ancestry populations.

A comparison of the anti-diabetic potential of d-ribose-l-cysteine with insulin, and oral hypoglycaemic agents on pregnant rats.

Over 18% of pregnant women are affected by diabetes mellitus (DM) and Insulin has been the commonest drug used in its treatment. There are reports of noncompliance to insulin due to trypanophobia, with suggestions for the use of oral hypoglycaemic agents (OHAs). However, the opposing views about the benefits and risk of oral hypoglycaemic agents (OHAs) warrant a continuous search for an alternative regimen. Therefore, this study is aimed at comparing the antidiabetic effects of d-ribose-l-cysteine (riboceine) with vildagliptin, glibenclamide, metformin, glipizide and insulin in diabetes in pregnancy. Forty (40) female Sprague-Dawley (SD) rats were mated with twenty (20) male SD rats. Diabetes was induced by streptozotocin and the female SD rats were divided into 8 groups of five (5) rats each. The animals were administered either of the OHAs vildagliptin, glibenclamide, metformin, glipizide and riboceine for a period of 19 gestational days. The results showed that streptozotocin (STZ) significantly (p < 0.05) decreased the weights of the animals, increased malondialdehyde, blood glucose levels and altered reproductive hormones. These effects of STZ were better ameliorated in animals that received insulin and riboceine compared to the other OHAs. While progesterone levels were significantly (p < 0.05) higher in animals that received riboceine compared to insulin. Glibenclamide increased (p < 0.05) foetal weights compared to non-diabetic animals. In conclusion, glibenclamide may be a threat to mother`s life in the management of diabetes in pregnancy however, riboceine as well as vildagliptin, metformin and glipizide are effective oral hypoglycaemic agents which could serve as a potent adjuvant comparable to insulin in the management of diabetes during gestation.

Testicular Dysfunction is a Common Feature in Men with Type 2 Diabetes Mellitus in a Nigerian Tertiary Hospital.

BACKGROUND: Hypogonadism in male patients with diabetes mellitus is associated with older age, obesity and poor glycaemic control. The patterns of sperm count, testicular volume, sperm motility and morphology have also been reported to be abnormal in these patients, though reports are conflicting. The objectives of this study were to assess gonadal function and sperm parameters in Nigerian males with diabetes mellitus. METHODS: A study sample of 150 males consisting of 108 patients and 56 age-matched controls were recruited. The ADAM questionnaire was used to obtain a clinical score for hypogonadism. Laboratory parameters measured were fasting plasma glucose, serum LH, FSH, free testosterone, total cholesterol, LDL, HDL and triglyceride. Testicular volume was measured with a Prader orchidometer. Total sperm count, sperm morphology and motility were assessed. RESULTS: Hypogonadism was present in 38.9% of males with diabetes compared to 3.6% in controls. The patients with diabetes had significantly lower sperm count, reduced sperm motility with increased abnormal forms than the controls (p<0.001, p<0.001). Only 8.5% of the patients did not demonstrate any abnormality in testicular function. CONCLUSION: Poor sperm function was more common than hypogonadism and was associated with poor glycaemic control (p<0.001). Likewise, hypogonadism was significantly associated with poor glycaemic control (p<0.001).

Expert Opinion: Patient Selection for Premixed Insulin Formulations in Diabetes Care.

Premixed insulins are an important tool for glycemic control in persons with diabetes. Equally important in diabetes care is the selection of the most appropriate insulin regimen for a particular individual at a specific time. Currently, the choice of insulin regimens for initiation or intensification of therapy is a subjective decision. In this article, we share insights, which will help in rational and objective selection of premixed formulations for initiation and intensification of insulin therapy. The glycemic status and its variations in a person help to identify the most appropriate insulin regimen and formulation for him or her. The evolution of objective glucometric indices has enabled better glycemic monitoring of individuals with diabetes. Management of diabetes has evolved from a 'glucocentric' approach to a 'patient-centered' approach; patient characteristics, needs, and preferences should be evaluated when considering premixed insulin for treatment of diabetes.Funding: Novo Nordisk, India.

A genome-wide search for linkage to renal function phenotypes in West Africans with type 2 diabetes.

BACKGROUND: Reduced renal function often is a major consequence of diabetes and hypertension. Although several indices of renal function (eg, creatinine clearance) are clearly heritable and show linkage to several genomic regions, the specific underlying genetic determinants are still being sought. The purpose of this study is to conduct a genome-wide search for regions linked to 3 renal function phenotypes, serum creatinine, creatinine clearance, and glomerular filtration rate (GFR), in persons with type 2 diabetes. METHODS: A genome-wide panel of 372 autosomal short tandem repeat markers at an average spacing of 9 centimorgan were typed in 691 patients with type 2 diabetes (321 sib pairs and 36 half-sib pairs) in an affected sib pair study in West Africa. Linkage analysis was conducted with the 3 phenotypes by using a multipoint variance components linkage method. RESULTS: Creatinine clearance showed higher logarithm of odds (LOD) score than the other 2 phenotypes. Linkage to creatinine clearance was observed on chromosomes 16 (marker D16S539, LOD score of 3.56, empirical P = 0.0001), 17 (D17S1298, LOD score of 2.08, empirical P = 0.0018), and 7 (D7S1818, LOD score of 1.84, nominal P = 0.00181, empirical P = 0.0022). Maximum LOD scores for serum creatinine were observed on chromosomes 10 (D10S1432, LOD score of 2.53, empirical P = 0.0001) and 3 (D3S2418, LOD score of 2.21, empirical P = 0.0003) and for GFR on chromosomes 6 (D6S1040, LOD score of 2.08, empirical P = 0.0001) and 8 (D8S256, LOD score of 1.80, empirical P = 0.0001). Several of these results are replications of significant findings from other genome scans. CONCLUSION: A genome-wide scan for serum creatinine, creatinine clearance, and GFR in a West African sample showed linkage regions that may harbor genes influencing variation in these phenotypes. Potential candidate genes in these regions that have been implicated in diabetic nephropathy and/or renal damage in models of hypertension include CYBA (or P22PHOX) (16q24), NOX1 (10q22), and NOX3 (6q25.1-q26).

Polymorphism of the endothelial nitric oxide synthase gene is associated with diabetic retinopathy in a cohort of West Africans.

PURPOSE: In addition to chronic hyperglycemia, there is increasing evidence that genetic factors may be important in the development of diabetes retinopathy (DR). Specifically, polymorphisms of the endothelial nitric oxide synthase gene (eNOS) have been reported to be associated with multiple health conditions including DR, hypertension, nephropathy, and cardiovascular diseases in several ethnic groups. However, there is a paucity of similar data in African Americans and other African populations. To address this issue, we investigated the potential association between polymorphisms of the eNOS gene and diabetes-related phenotypes in 384 persons with type 2 diabetes and 191 controls from two West African countries (Ghana and Nigeria). METHODS: We genotyped the deletion/insertion (4a/b) and the G894T polymorphisms of eNOS gene in a total of 575 persons. RESULTS: The b/b genotype of the polymorphism was associated with a 2.4 fold increased risk of DR (95% CI 1.39-4.09). In contrast, we did not observe any association between the genotypes or alleles of G894T polymorphism with DR, hypertension, or nephropathy. CONCLUSIONS: We observed a significant association between the 4a/b polymorphism of the eNOS and DR in our West African cohort.

Prognostic indices of diabetes mortality.

INTRODUCTION: Diabetes mellitus is an important cause of morbidity and mortality worldwide and the burden associated with it is felt more in developing countries. Communicable diseases, as opposed to non-communicable diseases, remain a top priority in developing countries like Nigeria. This report sets out to highlight the current status of diabetes-related hospitalizations in Nigeria and also to make comparisons with past reports. This goal will be achieved primarily by determining the prognostic factors associated with diabetes mortality and also noting the duration of hospital stay for the major causes of diabetes deaths. METHOD: From January through December 2006, subjects with diabetes mellitus (DM) in a tertiary hospital in Nigeria were prospectively studied after admission to assess their shortterm outcome which was defined as death. The total mortality, causes of death, associated complications and duration of hospital stay were noted. The predictive factors for DM morbidity were evaluated using chi test, logistic regression. Students t test was computed for quantitative data. RESULTS: A total of 1,327 subjects were admitted to the Medical wards for the duration of the study and the crude death rate was 11%. DM related admissions made up 206 (15%) of all the medical admissions and the case fatality rate was 33 (16%). The most common reasons for DM admission were hyperglycaemic emergencies (HE), 88 (40%) and hypertension, 44 (21%). The most common causes of deaths were HE, 15 (46%) and DM foot ulcers (DFU), 10 (30%) while DFU and cerebrovascular accident (CVA) had the highest case fatality rates of 28% and 25% respectively. DFU had the most prolonged duration of admission ranging from 15-122 days. DFU, CVD and having type 2 DM were highly predictive of fatal outcomes. The odds ratio and 95% CI for these factors were 4.5 (1.5-12.7), 3.0 (0.9-9.92 and 3.1 (0.7-14) respectively. CONCLUSION: DFU and HE are potentially remediable causes of mortality in DM. DFU as seen by the prolonged hospital stay imposes a huge burden on health resources. Better and early intervention of DFU is necessary to reduce the resultant disease burden.

Genome-wide analysis identifies an african-specific variant in SEMA4D associated with body mass index.

OBJECTIVE: The prevalence of obesity varies between ethnic groups. No genome-wide association study (GWAS) for body mass index (BMI) has been conducted in continental Africans. METHODS: We performed a GWAS for BMI in 1,570 West Africans (WA). Replication was conducted in independent samples of WA (n = 1,411) and African Americans (AA) (n = 9,020). RESULTS: We identified a novel genome-wide significant African-specific locus for BMI (SEMA4D, rs80068415; minor allele frequency = 0.008, P = 2.10 × 10-8 ). This finding was replicated in independent samples of WA (P = 0.013) and AA (P = 0.017). Individuals with obesity had higher serum SEMA4D levels compared to those without obesity (P < 0.0001), and elevated levels of serum SEMA4D were associated with increased obesity risk (OR = 4.2, P < 1 × 10-4 ). The prevalence of obesity was higher in individuals with the CT versus TT genotypes (55.6% vs. 22.9%). CONCLUSIONS: A novel variant in SEMA4D was significantly associated with BMI. Carriers of the C allele were 4.6 BMI units heavier than carriers of the T allele (P = 0.0007). This variant is monomorphic in Europeans and Asians, highlighting the importance of studying diverse populations. While there is evidence for the involvement of SEMA4D in inflammatory processes, this study is the first to implicate SEMA4D in obesity pathophysiology.

Genomewide scan and fine mapping of quantitative trait loci for intraocular pressure on 5q and 14q in West Africans.

PURPOSE: High intraocular pressure (IOP) is a major risk factor for glaucoma, one of the leading causes of blindness worldwide. Because it has been demonstrated that African populations are at increased risk for glaucoma, the authors investigated the genetic basis of IOP in a sample of West Africans with type 2 diabetes (T2D) from Ghana and Nigeria. METHODS: Genomewide linkage analysis was conducted for loci linked to IOP (measured by applanation tonometry) in 244 affected sibling pairs with T2D using 372 autosomal short-tandem repeat markers at an average spacing of 9 cM. RESULTS: Multipoint variance components linkage analyses revealed suggestive linkage on chromosome 5 (5q22) with a logarithm of odds (LOD) score of 2.50 (nominal P = 0.0003; empiric P = 0.0004) and on chromosome 14 (14q22) with an LOD score of 2.95 (nominal P = 0.0001; empiric P = 0.0003). Fine mapping at a marker density of 2 cM in the 5q region confirmed the linkage signal, with an increase in peak LOD score to 4.91. CONCLUSIONS: The strong signal on chromosome 5 lies in the region in which a novel gene, WDR36, in the GLC1G locus was recently identified as causative for adult-onset primary open-angle glaucoma and provides additional evidence that chromosome 5 contains susceptibility loci for glaucoma in multiple human populations. The evidence provided in this study is particularly important given the evolutionary history of these West African populations and the recent ancestral relationship to African Americans-a population with one of the highest rates of diabetes and associated complications (including glaucoma) in the world.