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Aim: To assess control and morbidity in patients with type 1 diabetes mellitus (T1 attending a tertiary adult diabetes clinic in Durban, South Africa. Methods: A retrospective chart review of all p...

Type 2 diabetes mellitus (T2DM), which was once thought to be rare in sub-Saharan Africa (SSA), is now well established in this region. The SSA region is undergoing a rapid but variable epidemiological transition fuelled by the pace of urbanization, with disease burden profiles shifting from communicable diseases to non-communicable diseases (NCDs). Information on the epidemiology of T2DM has increased, but wide variations in study methods, diagnostic biomarkers and criteria hamper analytical comparison, and data from high-quality studies are limited. The prevalence of T2DM is still low in some rural populations but moderate or high rates are reported in many countries/regions, with evidence for an increase in some. In addition, the proportion of undiagnosed T2DM is still high. The prevalence of T2DM is highest in African people living in urban areas, and the gradient between African people living in urban areas and people in the African diaspora is rapidly fading. However, data from longitudinal studies are lacking and there is limited information on chronic complications and the genetics of T2DM. The large unmet needs for T2DM care call for greater investment of resources into health systems to manage NCDs in SSA. Proposed health-system paradigms are being developed in some countries/regions. However, national NCD programmes need to be adequately funded and coordinated to stem the tide of T2DM and its complications.

Polygenic risk scores (PRS) can enhance risk stratification and are useful for precision medicine interventions. Here we show that African American Genome-wide Association Study (GWAS) derived PRS enhance prediction of lipid traits in Sub-Saharan Africans. Our PRS prediction varied greatly between South African Zulus (LDL-C, R2 = 8.49%) and Ugandans (LDL-C, R2= 0.043%), potentially attributable to environmental factors. Moreover, the PRS shown here had a higher discriminatory ability (AUC = 74.6%) than conventional risk factors (AUC= 67.8%) to identify extreme phenotypes. This work highlights the utility of PRS derived from relevant ethnic groups for identifying high-risk cases missed by conventional clinical factors.

OBJECTIVE South Africa has a high burden of HIV infection and anaemia. These conditions may cause HbA1c to over- or underestimate glycaemia; however, this has not been comprehensively investigated in African populations. We assessed the association of anaemia, HIV infection and antiretroviral therapy (ART) with HbA1c , and implications for the detection and diagnosis of diabetes, in a black South African population. RESEARCH DESIGN AND METHODS In this population-based cross-sectional study in eThekwini municipality (Durban), South Africa, we assessed HbA1c and conducted oral glucose tolerance tests (OGTTs), HIV diagnostic tests and full blood count measurements among 1067 participants without a history of diabetes diagnosis. Linear regression was used to examine differences in HbA1c by anaemia (comparator: no anaemia), or HIV and ART (comparator: no HIV) status. HbA1c -based diabetes prevalence was compared with OGTT-based prevalence among individuals with anaemia and with untreated and ART-treated HIV. RESULTS In adjusted analyses, normocytic and microcytic anaemia were associated with higher HbA1c compared with no anaemia, whereas macrocytic anaemia and ART-treated HIV were associated with lower HbA1c compared with no anaemia and no HIV, respectively. However, magnitudes of association were small (range: β = -3.4 mmol/mol or -0.31%, p

South Africa has a high burden of HIV infection and anaemia. These conditions may cause HbAIn this population-based cross-sectional study in eThekwini municipality (Durban), South Africa, we assessed HbAIn adjusted analyses, normocytic and microcytic anaemia were associated with higher HbAOur results suggest that anaemia and HIV status appear unlikely to materially affect the utility of HbA

ObjectivePolygenic prediction of type 2 diabetes in continental Africans is adversely affected by the limited number of genome-wide association studies (GWAS) of type 2 diabetes from Africa, and the poor transferability of European derived polygenic risk scores (PRS) in diverse ethnicities. We set out to evaluate if African American or multi-ethnic derived PRSs would improve polygenic prediction in continental Africans.Research Design and MethodsUsing the PRSice software, ethnic-specific PRSs were computed with weights from the type 2 diabetes GWAS of the Million Veteran Program (MVP) study. The South African Zulu study (1602 cases and 976 controls) was used as the target data set. Replication and assessment of the best predictive PRS association with age at diagnosis was done in the Africa America Diabetes Mellitus (AADM) study (1031 cases and 738 controls).ResultsThe African American derived PRS was more predictive of type 2 diabetes compared to the European and multi-ethnic derived scores. Notably, participants in the 10th decile of this PRS had a 3.19-fold greater risk (OR 3.19; 95%CI (1.94-5.29), p = 5.33 x10-6) of developing diabetes and were diagnosed 2.6 years earlier compared to those in the first decile.ConclusionsAfrican American derived PRS enhances polygenic prediction of type 2 diabetes in continental Africans. Improved representation of non-Europeans populations (including Africans) in GWAS, promises to provide better tools for precision medicine interventions in type 2 diabetes.

We assembled an ancestrally diverse collection of genome-wide association studies of type 2 diabetes (T2D) in 180,834 cases and 1,159,055 controls (48.9% non-European descent). We identified 277 loci at genome-wide significance (p-8), including 237 attaining a more stringent trans-ancestry threshold (p-9), which were delineated to 338 distinct association signals. Trans-ancestry meta-regression offered substantial enhancements to fine-mapping, with 58.6% of associations more precisely localised due to population diversity, and 54.4% of signals resolved to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying foundations for functional investigations. Trans-ancestry genetic risk scores enhanced transferability across diverse populations, providing a step towards more effective clinical translation to improve global health.

Background and aim The aim of this study was to assess the prevalence and characteristics of celiac disease (CD) in all patients with type 1 diabetes mellitus attending a tertiary adult diabetes clinic in Durban, South Africa. Methods This was a cross-sectional observational study that screened 202 patients; of these, 56.4% were African (Black), 31.7% Asian Indian, 4.5% White, and 7.4% mixed race. Demographic data, symptoms, and anthropometry were documented. Blood tests included anti-tissue transglutaminase antibody (tTG), anti-endomysial antibody (EMA), and anti-gliadin antibody (AGA). Endoscopy and duodenal biopsy were performed in patients with celiac antibodies. Diagnosis of CD was based on the modified Marsh classification. Results Mean age and mean duration of diabetes were 26.4 ± 11.4 and 10.7 ± 9.1 years, respectively. Celiac antibodies were found in 65 (32.2%) patients: EMA 7.4%, tTG immunoglobulin A (IgA) 8.4%, tTG immunoglobulin G 1.9%, AGA IgA 18.3%, and AGA immunoglobulin G 21.8%. Histological evidence of CD was found in 5.9% (n = 12/202): 2.5% were classed as definite CD (Marsh 3) and 3.4% as potential CD (Marsh 1). None of the patients with CD were symptomatic. The sensitivity of AGA IgA, EMA, and tTG IgA antibodies for detecting histologically proven CD was 66.7%, 50.0%, and 41.7%, respectively. Conclusion The prevalence of CD was similar to reports from western countries. No ethnic specific differences were noted. CD was silent in all patients in this study. The sensitivity of EMA and tTG antibodies was poor and merits further evaluation as screening tools for CD in South African patients with type 1 diabetes mellitus.

The presentation of primary hyperparathyroidism (PHPT) in most Western countries has evolved from the classic description of ‘stones, bones, and groans’ to becoming increasingly asymptomatic as a r...

Background: The mode of presentation, clinical, radiologic and laboratory characteristics of patients with acromegaly and the outcome following various modalities of treatment are not well document...

Objectives: To evaluate the characteristics and outcomes of treatment of patients with pheochromocytoma at Inkosi Albert Luthuli Central Hospital (ILACH) in Durban, South Africa over 14 years. Desi...

Background: Most patients diagnosed with diabetes mellitus

To compare the age at diagnosis and prevalence of islet autoantibody [glutamic acid decarboxylase (65 kDa) 65 and islet antigen 2] positivity in black and white participants with type 1 diabetes in South Africa, and to analyse the relationship between age at diagnosis and the presence of autoantibodies.Participants were recruited from diabetes outpatient departments and autoantibodies to glutamic acid decarboxylase (65 kDa) and islet antigen 2 were measured by enzyme-linked immunosorbent assay.We recruited 472 (353 black and 119 white) participants with type 1 diabetes. Age at diagnosis of diabetes was later in black (19.7 ± 10.5) than in white participants (12.7 ± 10.8 years; P 0.001) with a median (interquartile range) disease duration of 5.0 (2.0-10.0) and 8.5 (4.0-20.0) years (P 0.001), respectively. An older age at diagnosis (≥ 21 years) was more frequent in black (152 of 340, 45%) than in white participants (24 of 116, 21%; P 0.001). The prevalence of islet antigen 2 autoantibodies was 19% (66/352) in black and 41% in white participants (48/118; P 0.001). There was no significant difference in glutamic acid decarboxylase (65 kDa) autoantibody positivity between black (212/353, 60%) and white participants (77/117, 66%; P = 0.269). In black, but not white, participants the prevalence of both glutamic acid decarboxylase (65 kDa) and islet antigen 2 autoantibody positivity was significantly lower in participants diagnosed at age ≥ 21 years (P 0.001 for both comparisons).The older age at diagnosis, lower prevalence of islet antigen 2 autoantibodies and a distinct subgroup of participants with type 1 diabetes with age at diagnosis of 20 years in the black compared to white population suggest a difference in the immunological aetiology of type 1 diabetes in these two population groups.

Aims/hypothesis Genome-wide association studies (GWAS) for type 2 diabetes have uncovered >400 risk loci, primarily in populations of European and Asian ancestry. Here, we aimed to discover additional type 2 diabetes risk loci (including African-specific variants) and fine-map association signals by performing genetic analysis in African populations. Methods We conducted two type 2 diabetes genome-wide association studies in 4347 Africans from South Africa, Nigeria, Ghana and Kenya and meta-analysed both studies together. Likely causal variants were identified using fine-mapping approaches. Results The most significantly associated variants mapped to the widely replicated type 2 diabetes risk locus near TCF7L2 (p = 5.3 × 10−13). Fine-mapping of the TCF7L2 locus suggested one type 2 diabetes association signal shared between Europeans and Africans (indexed by rs7903146) and a distinct African-specific signal (indexed by rs17746147). We also detected one novel signal, rs73284431, near AGMO (p = 5.2 × 10−9, minor allele frequency [MAF] = 0.095; monomorphic in most non-African populations), distinct from previously reported signals in the region. In analyses focused on 100 published type 2 diabetes risk loci, we identified 21 with shared causal variants in African and non-African populations. Conclusions/interpretation These results demonstrate the value of performing GWAS in Africans, provide a resource to larger consortia for further discovery and fine-mapping and indicate that additional large-scale efforts in Africa are warranted to gain further insight in to the genetic architecture of type 2 diabetes. Electronic supplementary material The online version of this article (10.1007/s00125-019-4880-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Aim The study aimed to assess the prevalence of hypoglycaemia in subjects with type 1 diabetes (T1D) attending a public health tertiary diabetes clinic in Durban, South Africa. Methods Patients with T1D were enrolled at the time of clinic attendance. Data on hypoglycaemia over the previous 12 weeks were obtained from glucose meter downloads as well as diary records. Each patient completed the Hypoglycaemia Fear Survey questionnaire as well as an in-house questionnaire on hypoglycaemic episodes in the previous 12 months. Results A total of 151 subjects (58% female, 54% black African) were enrolled. “Any” hypoglycaemia occurred in 144 (95.4%) in the 12 months prior to clinic attendance. Of these, “severe” hypoglycaemia occurred in 107 (74.3%) and 22 (20.6%) had five or more severe episodes. The most frequent behavioural change in response to hypoglycaemia was insulin dose self-adjustment and the commonest worry was the possibility of becoming emotionally upset during hypoglycaemia. Conclusions In a tertiary diabetes clinic in Durban, South Africa, there was a high frequency of hypoglycaemia in patients with T1D and in the majority, at least one severe episode occurred in the 12 months prior to clinic attendance. The results indicate a need for further study and strategies to reduce the frequency and severity of hypoglycaemia.

There is a dearth of data on the burden and spectrum of non-alcoholic fatty liver disease (NAFLD) in African populations. The limited available information suggests that the prevalence of NAFLD in the general population is lowest for the Africa region. However, this is likely to be an underestimate and also does not take into consideration the long-term impact of rising rates of obesity, type-2 diabetes mellitus (T2DM) and high human immunodeficiency virus infection burden in Africa. A racial disparity in the prevalence of NAFLD has been observed in some studies but remains unexplained. There is an absence of data from population-based studies in Africa and this highlights the need for such studies, to reliably define the health service needs for this region. Screening for NAFLD at a population-based level using ultrasound is perhaps the ideal method for resource-poor settings because of its relative cost-effectiveness. What is required as a priority from Africa, are well-designed epidemiologic studies that screen for NAFLD in the general population as well as high-risk groups such as patients with T2DM or obesity.

Aims The impact of introducing new classes of glucose-lowering medication (GLM) on diabetes management remains unclear, especially outside North America and Western Europe. Therefore, we aimed to analyse trends in glycaemic control and the usage of new and old GLMs in people with type 2 diabetes from 2006 to 2015. Methods Summary data from clinical services from nine countries outside North America and Western Europe were collected and pooled for statistical analysis. Each site summarized individual-level data from out-patient medical records for 2006 and 2015. Data included: demographics; HbA1c and fasting plasma glucose levels; and the proportions of patients taking GLM as monotherapy, combination therapy and/or insulin. Results Between 2006 and 2015, glycaemic control remained stable, although body mass index and duration of diabetes increased in most sites. The proportion of people on GLM increased, and the therapeutic regimens became more complex. There were increases in the use of insulin and triple therapy in most sites, while monotherapy, particularly in relation to sulphonylureas, decreased. Despite the introduction of new GLMs, such as DPP-4 inhibitors, insulin use increased over time. Conclusions There was no clear evidence that the use of new classes of GLMs was associated with improvements in glycaemic control or reduced the reliance on insulin. These findings were consistent across a range of economic and geographic settings. Fil: Tabesh, Maryam. Monash University; Australia. Baker Heart and Diabetes Institute; Australia Fil: Magliano, Dianna J.. Monash University; Australia. Baker Heart and Diabetes Institute; Australia Fil: Tanamas, Stephanie K.. Baker Heart and Diabetes Institute; Australia Fil: Surmont, Filip. Astrazeneca; Reino Unido Fil: Bahendeka, Silver. Uganda Martyrs University; Uganda. St. Francis Hospital Nsambya; Uganda Fil: Chiang, Chern En. Taipei Veterans General Hospital; China Fil: Elgart, Jorge Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: Kalra, Sanjay. Bharti Research Institute of Diabetes and Endocrinology; India Fil: Krishnamoorthy, Satheesh. Dr A Ramachandran’s Diabetes Hospitals; India Fil: Luk, Andrea. Prince of Wales Hospital Hong Kong; Hong Kong Fil: Maegawa, Hiroshi. Shiga University of Medical Science; Japón Fil: Motala, Ayesha A.. University of KwaZulu Natal; Sudáfrica Fil: Pirie, Fraser. University of KwaZulu Natal; Sudáfrica Fil: Ramachandran, Ambady. Dr A Ramachandran’s Diabetes Hospitals; India Fil: Tayeb, Khaled. Diabetes Center at Al-Noor Specialist Hospital; Arabia Saudita Fil: Vikulova, Olga. FGBU “Endocrinology Research Center” Ministry of Health; Rusia Fil: Wong, Jencia. University of Sydney; Australia Fil: Shaw, Jonathan E.. Baker Heart and Diabetes Institute; Australia. Monash University; Australia

Background. The reported prevalence of low testosterone among men with type 2 diabetes mellitus (T2DM) is high. However, there is a dearth of information on the prevalence of androgen deficiency symptoms and low serum testosterone levels in men with T2DM from sub-Saharan Africa. Scanty data are available from Nigeria, Ghana and South Africa (SA). Objectives. To determine the prevalence of low serum testosterone and associated risk factors and the prevalence of androgen deficiency symptoms in men with T2DM. Methods. In a cross-sectional observational study, androgen deficiency symptoms in men with T2DM attending two outpatient diabetes clinics in Durban, KwaZulu-Natal Province, SA, were assessed using the Ageing Males’ Symptoms Scale (AMS) questionnaire and direct enquiry. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), luteinising hormone (LH), fructosamine, serum lipids and glycated haemoglobin (HbA1c) were measured and free testosterone (FT) was calculated. TT, SHBG and FT levels were measured in control subjects with no history of diabetes. Results. There were 148 men with T2DM in the study group and 50 control subjects in the control group. In the study group, the majority were black Africans (58.8%); Indians (39.2%) and whites (2.0%) constituted the remainder. The mean (standard deviation (SD)) age was 57.5 (11.2) years, the mean duration of diabetes 11.4 (8.9) years and the mean HbA1c 8.6% (1.9%). Of the study group, 85.8% had metabolic syndrome. Mean TT, SHBG and FT and median LH (interquartile range) in the study group were within normal ranges. However, mean (SD) serum TT and FT were lower in the study group than in the control subjects (14.5 (5.8) v. 18.8 (7.2) nmol/L; p

Objective Data on the prevalence of autoimmune thyroid disease (AITD) and gastric autoimmunity in type 1 diabetes mellitus (T1DM) in Africa are limited. The aim of this study was to assess the prevalence of antithyroid peroxidase (TPO-A) and antiparietal cell antibody (PCA) in patients with T1DM at a tertiary diabetes clinic in Durban, South Africa. Research design and methods This was a cross-sectional observational study among subjects attending the adult T1DM clinic at Inkosi Albert Luthuli Hospital. Information about history and clinical examination was collected. Blood tests included glutamic acid decarboxylase antibody (GADA), TPO-A, PCA, vitamin B12, folate, ferritin, thyroid stimulating hormone (TSH), free thyroxine, lipids and HbA1c. Results A total of 202 (M:F, 90:112) patients were recruited. The ethnic composition was African (black) (56.4%; n=114), Indian (31.7%; n=64), white (4.5%; n=9) and coloured (mixed race) (7.4%; n=15). Mean age and mean duration of diabetes were 26.4±11.4 and 10.7±9.1 years, respectively. Mean body mass index was 21.6±6.3 kg/m2. GADA was positive in 63.37% (n=128). The prevalence of TPO-A was 18.9% (n=39) and PCA 8.9% (n=17). The prevalence of overt hypothyroidism, subclinical hypothyroidism and Graves’ disease was 10.9%, 2.5% and 1.5%, respectively; vitamin B12 deficiency was noted in 3.5% (n=7) and iron deficiency in 19.3% (n=39). Conclusions Among patients with T1DM in this study, there was a high prevalence of coexistent AITD and gastric autoimmunity. Screening for hypothyroidism and thyroid autoimmunity should be undertaken in all patients at initial presentation. However, to assess the feasibility and optimal timing of subsequent testing in the African setting with limited resources, more collaborative research with longitudinal studies is required.

SummaryAims To describe the clinical, biochemical, radiological and histological features and to determine the outcome of all patients with pituitary tumours treated surgically at Inkosi Albert Luthuli Central Hospital (ILACH) in Durban over a 5-year period. Research design Retrospective chart review from 2008 to 2012. Clinical, biochemical and radiological data were collected before and 1 year after surgery. Histopathology findings and perioperative complications were recorded. Results Seventy patients were included (age 44·8 ± 14·9 years, 55·7% female). Headache (84·1%) and visual disturbances (78·3%) were the predominant presenting symptoms (84·1% and 78·3%). Most tumours were macroadenomas (97·1%). Trans-sphenoidal surgery was employed in the majority (90%). A single procedure was required in 55·7% patients, two procedures in 30% and up to six in others. Complete resection was achieved in only nine patients (12·8%), residual tumour postsurgery was found in 48 (68·6%), and no change in tumour size was found in 13 (18·6%) patients. Additional medical therapy was used in 22 (31·4%) and radiotherapy in 13 (18·6%). On biopsy, the most common pathology was nonfunctional adenoma in 33 (47·1%); 29 (41·4%) were secretory tumours, and 8 (11·4%) were craniopharyngiomas. Overall mortality was 4·3%. The commonest surgical complication was cerebrospinal fluid (CSF) leak (10%; n = 7). New postsurgical pituitary hypofunction occurred in 50 (71·4%) patients. The outcome at 1 year was similar to that on discharge. Conclusions Patients presenting to IALCH had large tumours, and complete resection was achieved in a minority. There was a low overall mortality but high rate of postsurgical pituitary hypofunction.

Background: A comprehensive approach to the control of type 2 diabetes is required to reduce mortality and morbidity. To improve diabetes management, in 2005 a protocol for the monitoring and management of type 2 diabetes, aligned to the 2003 Society for Endocrinology, Metabolism and Diabetes of South Africa (SEMDSA) guidelines, was introduced atAddington Hospital Medical Outpatients Department, Durban, South Africa.Method: Data were collected from 120 randomly selected patients with type 2 diabetes. The number of glycated haemoglobin (HbA1c) and lipid estimations, blood pressure (BP) measurements and body mass indices (BMIs) recorded in 2005 was compared with those recorded in 2008 and 2009. The mean levels of these parameters and the number of patients reaching goal in 2008 were compared with the figures for 2009.Results: In 2005, 18.8% of patients had HbA1c levels measured compared with 82.9% in 2009 (P < 0.01). The mean HbA1c was 6.9% (± 1.9) in 2008 and 6.4% (± 2.0) in 2009 (P = 0.1). BP and BMI was measured in over 93% of patients in 2005, 2008 and 2009. BP goals were attained by 21% of patients in 2008 and 30% in 2009 (P = 0.65). The mean BMI in 2008was 29.4 kg/m2 (24% achieved goal), and in 2009 it was 28.6kg/m2 (29% achieved goal; P = 0.267). Lipid estimations rose significantly from 26% in 2005 to 73% in 2009 (P < 0.01). There was no improvement in the number of patients reaching target lipid levels between 2008 and 2009.Conclusion: The monitoring protocol improved adherence to the SEMDSA 2003 guidelines from 2005 to 2009. Overall glycaemic control was within target, but attainment of most nonglycaemic goals was suboptimal and did not improve over the study period.

Objective: To determine the prevalence of liver function test abnormalities in South African black and Indian adult patients with type 2 diabetes mellitus attending a tertiary diabetes clinic. iabetes clinic. Recorded data included the past medical and drug history, history of alcohol abuse, anthropometry, lipid profile and liver function tests. Results: The charts of 313 patients were reviewed. Liver function test abnormalities were found in 146 patients (46.6%). Of these,15 patients had a history of alcohol abuse, or a past medical history that might explain the abnormality, and these patients were excluded from further analysis. Elevations in serum gamma-glutamyl transferase, alkaline phosphatase and alanine transaminase were found in 25.2% (n = 79), 23.3% (n = 73) and 15.3% (n = 48), respectively. Serum total cholesterol, triglycerides and low-density lipoprotein cholesterol were higher in the group with liver function test abnormalities when compared with subjects with normal results. Mean body mass index was similar in the two groups (32.5 vs. 33.2 kg/m2). Although morbidly obese patients (n = 42) demonstrated the highest frequency of liver enzyme derangements (54.8%), this was not statistically significant. Conclusion: There is a high prevalence of liver function test abnormalities in this group of patients with type 2 diabetes, and this is particularly so in the morbidly obese subjects. This is comparable with the reported prevalence in the Western world. Lipid abnormalities were more frequent in the group with liver enzyme derangements.Keywords: South African, type 2 diabetes, abnormal liver enzymes, prevalence

P>Objective We sought to determine whether autoimmunity is the predominant cause of Addison's disease in South Africa and whether human leucocyte antigen (HLA) DQ association exists. Design We compiled a national registry of patients from primary care, referral centres and private practices. Patients A total of 144 patients, 94 of European descent, 34 Mixed Ancestry, 5 Asian and 11 Black Africans (mean age 45 center dot 9 years, range 2 center dot 7-88 years; mean duration of disease 13 center dot 1 years, range 0-50 years) and controls were matched for gender and ethnicity. All potential causes were investigated. Results Fifty one per cent of cases (74 patients) were autoimmune in aetiology. Either 21-hydroxylase autoantibodies (72 patients, 50% of entire patient group) or adrenocortical autoantibodies (35 patients, 24%) were present, while 23% of patients had both. None of the Asian (n = 5) or Black (n = 11) patients had evidence of autoimmune disease. Overall 8% of patients had tuberculosis, 4% adrenoleucodystrophy, 1% adrenocorticotrophic hormone resistance syndrome and 6% X-linked adrenal hypoplasia. In those with autoimmune disease primary hypothyroidism (47%), premature ovarian failure (8%) and type 1 diabetes (7%) were the most prevalent accompanying autoimmune conditions. HLA DQB1*0201 alleles predominated in the autoimmune group (DQB1*0201: 65%vs 43% of controls P = 0 center dot 017) with the *0201/*0302 heterozygous genotype being the most prevalent (28%vs 8%P = 0 center dot 02). Conclusions While autoimmunity accounts for at least half of patients with Addison's disease in South Africa and is associated with HLA DQB1*0201, none of the Black Africans or Asians in this cohort had adrenal autoantibodies. Moreover, 21-hydroxylase autoantibodies were detectable in a higher proportion than adrenocortical autoantibodies, especially in those patients with a long history after disease onset.

Diabetes mellitus is a known independent risk factor for coronary artery disease (CAD) and other macrovascular complications, including stroke and peripheral vascular disease.

Peptide-YY (PYY) is secreted from endocrine L-cells of the gastrointestinal tract in response to caloric ingestion and may mediate postprandial satiety through the hypothalamic neuropeptide Y2 receptor (Y2R). We examined whether variants in the genes encoding PYY and Y2R might be associated with obesity-related phenotypes in humans. Among 101 subjects with severe early-onset obesity and a history of hyperphagia, we found two rare sequence variants—L73P and IVS2 + 32delG—in PYY and three rare missense mutations—L40F, F87I, and A172T—in Y2R. Although none of these were found in 100 normal-weight white control subjects, L73P in PYY and F87I and A172T in Y2R did not segregate with obesity in family studies, and family data were unavailable for IVS2 + 32delG in PYY and L40F in Y2R. Two common single nucleotide polymorphisms (SNPs), R72T and IVS3 + 68C>T, in PYY were in tight linkage disequilibrium but showed no association with BMI in a large white population. In the Y2R, two SNPs, 585T>C and 936T>C, were found and were in tight linkage disequilibrium. Men, homozygous for the rarer variant, had significantly lower BMI (P = 0.017), waist-to-hip ratio (P = 0.013), and, surprisingly, higher nonesterified fatty acid levels (P = 0.01). In conclusion, mutations in PYY and Y2R are not commonly found in humans with severe early-onset obesity. The relationship between common variants in Y2R and obesity-related traits deserves further exploration in other populations.

Until recently, there was a paucity of data on the epidemiology of diabetes mellitus in Africa. Over the past decade, information on the prevalence of type 2 diabetes has increased, albeit still limited, but there is still a lack of adequate data on type 1 diabetes in sub-Saharan Africa (SSA). For type 2 diabetes, although the prevalence is low in some rural populations, moderate and even high rates have been reported from other countries. In low diabetes prevalence populations, the moderate to high rates of impaired glucose tolerance is a possible indicator of the early stage of a diabetes epidemic. Diabetes prevalence is higher in urban, migrant and African-origin populations living abroad. There is evidence for a significant association with preventable and modifiable risk factors viz. adiposity, known diabetes, physical activity; but a dearth of data on the impact of dietary and genetic factors. For type 1 diabetes, the limited available data suggest that in SSA the frequency is low and that age of on...

Akram Shmendi,1 Fraser Pirie,2 Datshana P Naidoo,3 Boikhutso Tlou,4 Wilfred Pilloy,5 Ayesha A Motala2 1Department of Medicine, 2Department of Diabetes and Endocrinology, 3Department of Cardiology, 4Department of Biostatistics, 5Department of Nuclear Medicine, University of KwaZulu-Natal, Durban, South Africa Background: The relationship between myocardial perfusion imaging (MPI) abnormalities, diabetes mellitus, and glucose control in South African populations is unknown. It was hypothesized that in subjects undergoing MPI for suspected coronary artery disease (CAD), those with diabetes would have more extensive perfusion defects and that diabetes control would influence MPI abnormalities. The aim of this study was to examine the relationship between the severity of CAD diagnosed with MPI in subjects with and without diabetes and to determine the relationship between diabetes control and extent of CAD.Methods: This study was a retrospective chart review of 340 subjects in whom MPI scans were performed over a 12-month period.Results: Subjects with diabetes had a higher prevalence of abnormal MPI, with more extensive ischemia, compared with subjects without diabetes (85.6% versus 68%; odds ratio 2.81, P

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.

ObjectivesExisting electronic data capture options are often financially unfeasible in resource-poor settings or difficult to support technically in the field. To help facilitate large-scale multicenter studies in sub-Saharan Africa, the African Partnership for Chronic Disease Research (APCDR) has developed an open-source electronic questionnaire (EQ).Study Design and SettingTo assess its relative validity, we compared the EQ against traditional pen-and-paper methods using 200 randomized interviews conducted in an ongoing type 2 diabetes case–control study in South Africa.ResultsDuring its 3-month validation, the EQ had a lower frequency of errors (EQ, 0.17 errors per 100 questions; paper, 0.73 errors per 100 questions; P-value ≤0.001), and a lower monetary cost per correctly entered question, compared with the pen-and-paper method. We found no marked difference in the average duration of the interview between methods (EQ, 5.4 minutes; paper, 5.6 minutes).ConclusionThis validation study suggests that the EQ may offer increased accuracy, similar interview duration, and increased cost-effectiveness compared with paper-based data collection methods. The APCDR EQ software is freely available (https://github.com/apcdr/questionnaire).

Introduction Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterised by hypercalcaemia and elevated parathyroid hormone (PTH) levels. However, it remains a relatively underdiagnosed disease in the developing world primarily due to a lack of routine blood chemistry screening. The aim of this analysis was to evaluate the characteristics, management and outcome of patients with PHPT at a tertiary referral clinic in South Africa. Methods A retrospective analysis was undertaken on all patients with a diagnosis of PHPT attending the endocrinology clinic at a tertiary referral hospital in Durban, South Africa, between January 2003 and June 2009. Information on clinical presentation, past medical history, biochemistry, radiology, histology and surgical notes were recorded. Patients with multiple endocrine neoplasia were excluded. Results A total of 28 case records of PHPT were reviewed. The mean age at presentation was 60±14.5 years with a female preponderance (78.6%). The mode of presentation included referral for investigation of an abnormal serum calcium (n: 23), referral from urologist with nephrolithiasis (n: 3) and for investigation of bone disease (n: 2). Symptomatic disease was found in 26 patients (92.9%), including bone pain (75%), fatigue (46.4%) and abdominal pain (32.1%). Mean serum calcium was 3.0+0.39 (normal 2.08–2.65) mmol/L, serum intact PTH 34.7±41.5 (normal 1.2–8.5) pmol/L and serum alkaline phosphatase 206.3±340.2 (normal 53–141) mIU/L. Sestamibi scan was performed on 24 patients and an adenoma was identified in 83.3%. Of the 19 (68%) patients who had parathyroidectomy, an adenoma was identified as the cause in all cases where histology was available (n:18). Surgery was successful in 18 patients with only one patient requiring repeat parathyroidectomy for persistent hypercalcaemia. Postoperative hypocalcaemia developed in eight patients (42.1%) including four patients who required intravenous calcium infusion for symptomatic hypocalcaemia. Conclusions PHPT is a treatable disorder with good surgical success. Asymptomatic disease was uncommon in this group of patients. This is compatible with the symptomatic pattern of presentation reported in other developing countries.

A group of South African Indians with NIDDM participated in a study to evaluate the frequency of positive family histories of the disease and to determine the relative contribution of maternal or paternal genetic determinants. Information was elicited by means of an interview and recorded. Of the 1098 diabetic subjects studied 70% gave a positive family history of a first degree relative suffering from NIDDM. Three-generation transmission was recorded in 5.3% of the subjects. A significantly greater proportion of probands (40%) had a mother with NIDDM than those with a father (26%). A positive family history in an offspring was more common in female probands (10.6%) than males (5.5%). Twice as many probands with 3 generation transmission had a maternal grandmother suffering from NIDDM (2.5%) compared with those who had a paternal grandmother afflicted (1.2%) (P < 0.05), whereas the frequencies in the maternal (0.9%) and paternal (0.8%) grandfathers were similar. This study has highlighted, not only the high prevalence of a positive family history in South African Indians with NIDDM, but also a stronger maternal contribution to the putative gene responsible for the disease.

Diabetes is one of the most common noncommunicable diseases (NCD) globally and a leading cause of death in many countries; the global epidemic of type 2 diabetes will most affect the developing world. The burden of diabetes is related to its chronic complications, both the specific microvascular and the nonspecific macrovascular (atherosclerosis), making diabetes one of the leading causes of death in some countries and an enormous financial burden. The costs of diabetes care, both direct and indirect, are high. Single and multiple risk-factor intervention studies have provided evidence that targeting hyperglycemia and other nonglycemic risk factors reduces the risk of chronic complications; most national guidelines recommend intensified, multitargeted intervention of known modifiable risk factors. The aim in management is optimal control, both glycemic and non-glycemic (blood pressure, lipid and weight control). Management strategies for hyperglycemia include standard methods and individualized options. Given the complexities of the therapeutic choices (classes/agents) and regimens and on the basis of proven benefit, long familiarity, known side-effects, and reduced cost of sulfonylureas, biguanides, and insulin, one should start with standard methods. Despite the evidence for benefit of glycemic control, wide therapeutic choices and regimens and clearer targets for control, glycemic control is far from ideal. The cost-effectiveness of interventions to reduce the burden of diabetes-related complications compares favorably with that of other accepted uses of healthcare resources and provides convincing economic rationale for improving standards of care for patients with type 2 diabetes.

Type 1 diabetes is the consequence of exposure of genetically susceptible individuals to specific environmental precipitants. The innate immune system provides the initial response to exogenous antigen and links with the adaptive immune system. The aim of this study was to assess the role of polymorphisms occurring in the cytoplasmic region of toll-like receptor (TLR) 3 gene and immediate 5' sequence, in subjects of Zulu descent with type 1 diabetes in KwaZulu-Natal, South Africa. Seventy-nine subjects with type 1 diabetes and 74 healthy normal glucose tolerant gender-matched control subjects were studied. Parts of exon 4 and exon 3/intron 3 of the TLR3 gene were studied by polymerase chain reaction, direct sequencing and restriction enzyme digestion with Bts 1. Of the nine polymorphisms studied, a significant association with type 1 diabetes was found for the major allele in the 2593 C/T polymorphism and for the minor alleles in the 2642 C/A and 2690 A/G polymorphisms, which were found to be in complete linkage disequilibrium. Correction of the P-values for the number of alleles studied, however, rendered the results no longer significant. These results suggest that polymorphisms in the TLR3 gene, which is part of the innate immune system, may be associated with type 1 diabetes in this population.

Aims Previous cross-sectional studies have established that South African Indians have a high prevalence of Type 2 diabetes mellitus. A prospective community study was undertaken to determine the incidence of Type 2 diabetes and the risk factors associated with its development in a cohort of South African Indians who had been studied 10 years previously. Methods This is a report on 563 subjects who participated both at baseline and at the 10-year follow-up study. In the baseline study, 2479 subjects (> 15 years) were studied; using 1985 World Health Organization criteria for glucose tolerance based on 75 g oral glucose tolerance tests (OGTT), the crude prevalence of diabetes mellitus (Diabetes) was 9.8% and of impaired glucose tolerance (IGT) 5.8% (age and sex-adjusted prevalence 13% and 6.9%, respectively). Results At the 10-year follow-up study, 563 of the subjects who could be traced consented to a repeat OGTT; of these, 91 (16.2%) were classified as Diabetes and 41 (7.3%) as IGT. Of the subjects who did not have diabetes at baseline (n = 517), 49 (9.5%) progressed to diabetes (PTD) and 40 (7.7%) had IGT. The crude cumulative incidence of diabetes was 9.5% (rate of progression 0.95% per annum; incidence density 9.5/1000 person years) with an age and sex-adjusted cumulative incidence of 8.3% (rate of progression 0.95% per annum; incidence density 8.3/1000 person years). Examination of risk factors predictive of subsequent diabetes development was undertaken by analysis of baseline (year 0) variables in the 517 subjects who did not have diabetes at baseline. In multivariate analysis using a logistic regression model, the significant predictive risk factors for future diabetes included 2-h post load plasma glucose (2 PG) (P

People with newly diagnosed diabetes are faced with an overwhelming amount of information about their condition, new skills to learn and adaptation to a new lifestyle.

Defining normal adrenocortical responses (especially glucocorticoid responses) to various stimuli has been a topic of debate for many years in clinical endocrinology.

As 2009 draws to a close, there is time to reflect on the new-look JEMDSA. Through the tireless work of Professor Stephen Hough, a new publisher was found and the endocrine community drew together to ensure the success of JEMDSA as the official journal of six societies (SEMDSA, DESSA, NOFSA, SASOM, LASSA, and PAEDS-SA).

A number of landmark studies have made it abundantly clear that the goals of diabetes care involve striving for optimal metabolic and blood pressure control. The message is now loud and clear: lower HbA1C, lower lowdensity lipoprotein cholesterol, and lower blood pressure.

Type 2 diabetes is associated with a 2 - 4-fold increased risk of cardiovascular disease (CVD), and over half the excess mortality in subjects with type 2 diabetes is due to this complication. The development of macrovascular disease in type 2 diabetes is partly related to chronic hyperglycaemia, but also to other associated atherogenic factors, including dyslipidaemia, oxidative stress, endothelial damage, hypercoaguability and activation of inflammatory pathways.

The SEMDSA Congress, to be held on the Durban beachfront at the end of March 2004, promises to be an inspiring mix of international expertise and local input.