Maternal and neonatal outcomes following the introduction of oral hypoglycaemic agents for gestational diabetes mellitus were comparable to insulin monotherapy in two historical cohorts.

BACKGROUND: Gestational diabetes mellitus (GDM), a disorder of glucose intolerance first encountered during pregnancy, has far-reaching implications for both mother and child. Insulin therapy remains the 'gold standard' of care, with oral hypoglycaemic agents (OHAs) increasingly being viewed as potential alternatives. OBJECTIVES: To compare maternal and neonatal outcomes in two cohorts of women with GDM exposed to either insulin monotherapy or OHAs. METHODS: A retrospective medical record review at Chris Hani Baragwanath Academic Hospital in South Africa was conducted for women with GDM diagnosed using the 100 g oral glucose tolerance test and/or random capillary blood glucose >11.1 mmol/L in 2010 - 2014. The findings were compared with a previous audit at the same clinic for the period 1992 - 2002. Variables of interest included maternal demographics, maternal comorbidities, glycaemic indices, treatments used during pregnancy, and obstetric and neonatal outcomes. RESULTS: A total of 192 women with GDM were identified for 2010 - 2014, and there were 348 women in the previous audit (1992 - 2002). Baseline characteristics and outcomes of women in the two cohorts were similar apart from earlier presentation (mean (standard deviation) gestational age (GA) 27 (7.5) weeks v. 28.3 (6.4) weeks; p=0.04), lower GA at delivery (36.3 (3.6) weeks v. 37 (1.6) weeks); p=0.008) and lower macrosomia rates (12.5% v. 4.9%; p=0.011) in the later cohort. When comparing the individual OHAs against insulin in the later cohort, both agents were comparable to insulin in terms of maternal and neonatal outcomes. CONCLUSIONS: This study contributes to the paucity of data on the safety of OHAs in GDM pregnancy in terms of maternal and neonatal outcomes. OHAs were shown to be an effective alternative to insulin for women with GDM in whom lifestyle measures fail, particularly in a resource-poor setting.

Phaeochromocytoma in black South Africans - a 30-year audit.

OBJECTIVE: Phaeochromocytomas are catecholamine-secreting tumours, the majority of which arise from the adrenal medulla. Untreated, they are potentially lethal; early diagnosis and treatment offer a good chance of cure. They are rarely reported in blacks. The clinical presentation and outcome of phaeochromocytoma in a large cohort of black South Africans is reviewed. METHODS: Patients' records in a tertiary care university hospital were reviewed. Fifty-four black patients presenting with phaeochromocytoma between 1980 and 2009 were included. The clinical presenting features, tumour localisation and outcome were assessed. RESULTS: Fifty-four (41 female, 13 male; age range 8 - 57 years) patients were identified. Five (9%) had familial syndromes; 49 (91%) were deemed sporadic. All tumours were intra-abdominal: 34 (61%) were adrenal and 22 (39%) extra-adrenal in origin. The most common symptoms were headache (77%), palpitations (77%), and sweating (74%). All were hypertensive, almost equally divided between paroxysmal and sustained hypertension. Six (11%) presented in congestive cardiac failure including 2 with catecholamine-induced myocarditis. Two patients had features which simulated hypertrophic obstructive cardiomyopathy. Nine women presented in pregnancy: there was no maternal mortality; fetal mortality included 1 early neonatal death and 1 intrauterine death. There were 4 deaths: 1 from postoperative haemorrhage, 1 from multisystem crisis, 1 from metastatic medullary thyroid carcinoma, and 1 from catecholamine-induced myocarditis. CONCLUSION: Phaeochromocytoma is an important although rare tumour in blacks, with similar clinical presentations and complications to those in white patients. Timely diagnosis and appropriate treatment resulted in a favourable outcome in over 90% of patients in this study.

Audit of the outcome of pregnancy in diabetic women in Soweto, South Africa, 1992 - 2002.

OBJECTIVE: To audit the outcome of pregnancy among diabetic black women in Soweto following the introduction of a specialised service. DESIGN AND METHODS: An analysis of patients' records was conducted for the period 1992 - 2002. Maternal characteristics, aspects of treatment and its complications, mode of delivery and perinatal outcome are reported. The incidence of postpartum glucose intolerance in women with gestational diabetes was assessed. Major outcomes from this study are compared with those of an earlier study conducted from 1983 to 1992. RESULTS: A total of 733 diabetic pregnancies was managed over 11 years: 348 women had gestational diabetes, 172 had type 1 diabetes and 213 had type 2 diabetes. Insulin was used in all but 23 women. Mean (+/- standard deviation (SD)) capillary blood glucose levels varied between 5.7 (+/- 0.72) and 6.2 (+/- 0.95) mmol/l in the 3 groups. Severe maternal hypoglycaemia was most common in the type 1 diabetes group (14%). Mean (+/- SD) neonatal weight varied between 2 922.3 g #x0028;+/- 753) and 3 073.3 g (+/- 727). Caesarean section rates exceeded 60% in all 3 groups. Overall, 13.1% of women had hypertension, 31.3% of whom had proteinuric hypertension. There were no cases of progressive pre-eclampsia. The combined perinatal mortality (PMN) rate was 3.7%, compared with 15.6% in the 'control' group. Major congenital malformations occurred in 11 pregnancies (1.5%). There were 2 maternal deaths. Postpartum impaired glucose tolerance/diabetes occurred in 25.9% of women with gestational diabetes. Combining the 2 studies (1983 - 1992 and 1992 - 2002), 1 087 pregnancies were managed over 20 years using a similar protocol. There were no significant differences in major outcomes between the 2 studies. The overall PMN of 4.5% is significantly lower than that of the combined 'control' group (19.9%). Postpartum glucose intolerance was documented in 28.5% of women. CONCLUSIONS: The institution of a specialised service for pregnant diabetic women from Soweto for a sustained period of 20 years proved feasible and was of significant benefit. The interventions, centred around a diabetes nurse educator, were relatively simple and easy to implement. Late presentation/referral of patients remains a problem. Persistence of glucose intolerance postpartum in women with gestational diabetes was common and provides an opportunity for preventive measures to be introduced.

Long-term (20 years) outcome and mortality of Type 1 diabetic patients in Soweto, South Africa.

AIMS: To assess the long-term (20 years) mortality, with causes of death, in a cohort of Type 1 diabetic patients resident in Soweto, South Africa. METHODS: A cohort of Type 1 diabetic patients attending the Diabetic Clinic of Baragwanath Hospital, Soweto were studied in 1982. They were followed over the subsequent 20 years, the final investigation being in 2002. Numbers dying during the period were recorded, as well as year of death and cause. The complication status of survivors was also assessed. RESULTS: Of the original cohort of 88 Type 1 patients, 21 died during the follow-up period. There were 39 lost to follow-up, giving a crude 20 years' mortality of 43%. Kaplan-Meier analysis showed mortality hazard of 33%. Of those dying, most (9/21) were as a result of renal failure. Other causes were hypoglycaemia (6), ketoacidosis (2), infection (2) and undetermined (2). Of the survivors, comparing data at 0 and 20 years' follow-up, there was a significant increase in rates of retinopathy (P<0.02) and hypertension (P<0.005), but not of other complications. CONCLUSIONS: This is the first long-term outcome study of Type 1 diabetes in sub-Saharan Africa. Although the mortality was substantial, it is similar to equivalent studies of United States (US) Afro-Americans with Type 1 diabetes. The major cause of death was renal failure related to diabetic nephropathy, and reflects lack of adequate facilities for renal replacement therapy. Despite the deprivation, poverty, political upheaval and recent AIDS epidemic in Soweto, Type 1 diabetes carries a reasonable long-term prognosis, and survivors are generally free of debilitating complications.

Phaeochromocytoma by way of case reports.

Endocrine causes of hypertension are relatively rare, but their detection offers a real chance for cure. This is particularly true of phaeochromocytoma, a catecholamine-producing tumour derived from chromaffin tissue, which, if left undetected, is invariably fatal. The lethal nature of this tumour is dependent on two major characteristics: firstly, its ability to secrete catecholamines in excess, resulting in potentially catastrophic consequences; and, secondly, its malignant potential. Approximately 5-10% of these tumours are malignant, which, if metastasised, are generally refractory to treatment. Clearly, however, because only one in 1,000 hypertensives is likely to harbour a phaeochromocytoma, it is not cost-effective option to screen all hypertensives for this cause. Rather, a selective approach is preferred in which a high index of suspicion for the clinical characteristics of this tumour is used to guide the physician. The following two case reports derived from our records at Chris Hani Baragwanath Hospital will illustrate many issues related to diagnosis and management of this fascinating tumour.

Phaeochromocytoma in pregnancy.

The diagnosis of phaeochromocytoma during pregnancy requires a high index of suspicion and is essential for the favourable outcome of mother and offspring. Delayed diagnosis is associated with considerable morbidity and mortality. The cases of 4 patients presenting with phaeochromocytoma during pregnancy over an 11-year period are presented.

Multiple endocrine neoplasia type 2A in a black South African family.

The genetic abnormality of multiple endocrine neoplasia type 2A (MEN 2A) has recently been elucidated. Over 95% of families with MEN 2A have an identifiable mutation of the RET proto-oncogene on chromosome 10. This report describes a black South African woman with MEN 2A in whom a mutation of the RET proto-oncogene was identified. Current genetic knowledge and recent changes in clinical practice are presented, with specific reference to the other family members found to be carrying the mutant RET gene.

Smoking habits of black South African patients with diabetes mellitus.

Cigarette smoking is a major arteriosclerotic risk factor, and this is enhanced by the presence of diabetes mellitus. Although smoking rates are increasing in many African countries, they have been little studied. We have critically assessed smoking among black diabetic and general medical patients at Baragwanath Hospital in Soweto, South Africa. As well as direct questioning of patients, we also used urinary cotinine:creatinine ratio as an objective marker. The admitted smoking rate was 16% in 118 diabetic patients, compared with 22% in 105 medical patients. Using a validated biochemical index of smoking (urinary cotinine:creatinine > 1.0 microgram mg-1) the rates were 37% and 33%, respectively. Most of the excess however was due to women who took snuff, and when excluded, the estimated real rates were 20% (diabetic) and 24% (medical). Amongst diabetic smokers mean cotinine:creatinine ratio was higher than in medical smokers (4.7 +/- 6.0 v 1.8 +/- 2.0 micrograms mg-1) despite admitted similar smoking consumption. A separate control group of British smokers had a mean level of 3.6 +/- 1.3 though their consumption was twice that of the South African groups. We conclude that smoking is common among South African black diabetic patients (20%), though it is less than reported figures for the black general population (28%), and British diabetic patients (35%). Questionnaire studies may seriously underestimate smoking rates, though this effect is considerably less in African compared with British smokers. Urinary cotinine also allows quantification of the 'smoking load', which is rarely reflected by admitted cigarette consumption.

Pheochromocytoma associated with clinical and echocardiographic features simulating hypertrophic obstructive cardiomyopathy.

Left ventricular hypertrophy simulating hypertrophic obstructive cardiomyopathy is a rare complication of pheochromocytoma. In this report, two cases of pheochromocytoma with this complication are described. Successful tumor removal in both cases led to relief of symptoms, normalization of BP, regression of abnormal clinical features, normalization of the ECGs, but only partial regression of the echocardiographic features despite prolonged follow-up of 24 and 32 months, respectively.

Mortality and outcome of insulin-dependent diabetes in Soweto, South Africa.

Sixty-four insulin-dependent (Type 1) diabetic patients (IDDM) in Soweto, South Africa were followed over a 10-year period. Patients were assessed in 1982 and again in 1992. There were 10 deaths (16%), half of which were due to renal failure. Ketoacidosis, hypoglycaemia, and sepsis accounted for the rest. At the 10-year follow-up mean age (+/- SD) was 32.4 +/- 5.0 years and diabetes duration 13.6 +/- 2.6 years. Retinopathy affected 52%, peripheral neuropathy 42%, and nephropathy 28% (all significantly increased from the 1982 assessment). Microalbuminuria and autonomic neuropathy were also common. Serum cholesterol was over 6.5 mmol l-1 in 19%, hypertension affected 22%, and 28% were cigarette smokers; though no patient had evidence of macroangiopathy. We conclude that IDDM in South Africa is associated with excess mortality, a significant proportion of which is related to nephropathy. Diabetes of long duration is now not uncommon in South Africa, and although diabetic complications frequently occur, most patients have good life quality and freedom from large vessel disease.

Hyperosmolar non-ketotic diabetic coma as a cause of emergency hyperglycaemic admission to Baragwanath Hospital.

There were 136 emergency hyperglycaemic admissions to Baragwanath Hospital over a 6-month period during 1992-1993, representing 1.2% of the total number of medical admissions; 24 (18%) patients died. Diabetic keto-acidosis (DKA) accounted for 88 (65%) admissions (mortality rate 9%) while 16 admissions (12%) were as a result of hyperosmolar non-ketotic coma (HNKC), defined as hyperglycaemia, dehydration and an altered level of consciousness with a plasma osmolality > or = 330 and an arterial pH > or = 7.30, with absent or minimal ketonuria. Of these 16 patients, 9 (56%) were known to have diabetes mellitus. Patients with HNKC were significantly older than those with DKA (P < 0.001) and other patients with nonketotic hyperglycaemia (P < 0.05). The overall mortality rate was 44%; prophylactic low-molecular-weight heparin appeared of benefit (P < 0.05).

Autonomic neuropathy in African diabetic patients.

To determine the prevalence and extent of autonomic neuropathy amongst Africans with insulin-dependent diabetes mellitus (IDDM), we investigated 50 such patients at our clinic. Mean age (+/- 1 s.d.) was 26 +/- 6 years, male:female ratio was equal (25M:25F) and duration of diabetes was 4.0 +/- 3.0 years. A battery of six validated tests of autonomic function was performed, testing both sympathetic and parasympathetic systems. Overall 16 (32%) had evidence of autonomic damage, affecting parasympathetic only in 14, and both sympathetic and parasympathetic in two. Those with autonomic neuropathy had a significantly longer diabetes duration than those without (6.0 +/- 2.8 years versus 3.1 +/- 2.7 years, P < 0.005), but there was no difference in glycosylated haemoglobin (HbA1) between the two groups. Autonomic neuropathy was also not significantly associated with peripheral neuropathy or other diabetic complications. Autonomic neuropathy carries a poor prognosis in IDDM and this high prevalence in a group of patients with relatively short diabetes duration gives cause for concern.

The age of onset and sex distribution of insulin-dependent diabetes mellitus in Africans in South Africa.

Type I (insulin-dependent) diabetes mellitus (IDDM) appears to be rare in indigenous African populations, but little detailed information has been published. We have therefore analysed the age of onset of diabetes in 176 African patients with IDDM (age of onset < 35 years), and in 149 consecutive white patients of European extraction for comparison. In the Africans the peak age of onset occurred at 22-23 years (median 22 years) with an earlier peak from 14 to 17 years. In the Whites, the peak was found at 12-13 years (median 12 years). In only 7% of Africans did diabetes start under the age of 12 years. There was a slight female preponderance in the Africans, especially at the ages of greatest incident (20-25 years)-F:M 1.55:1. When patients with duration of diabetes less than 5 years only were analysed (the period during which early mortality among African patients was greatly reduced) the patterns of age distribution were similar to the total respective groups. A peak incidence in the winter months was noted.

Hypoglycaemic admissions among diabetic patients in Soweto, South Africa.

An audit of hypoglycaemic admissions among diabetic patients to Baragwanath Hospital, Soweto, South Africa was carried out prospectively during a recent 5-month period. A total of 51 episodes of biochemically confirmed hypoglycaemia (blood glucose < 2.2 mmol l-1 with coma or pre-coma, and requiring intravenous glucose) were observed in 43 patients. There was a wide range of ages (22-88 years) and an excess of males (27 M:16 F). Fourteen (33%) cases were associated with sulphonylurea (gliclazide) treatment. Doses of insulin or sulphonylureas were not excessive. The major cause precipitating the event was a missed meal (36%), though alcohol (22%), gastrointestinal upset (20%), and inappropriate treatment (18%) were also important contributory factors. Following recovery from the event, doses of drugs or insulin were frequently reduced, and three patients were successfully taken off insulin, and six off gliclazide. There was no mortality in this series, and no obvious long-term morbidity. We conclude that severe hypoglycaemia is a frequent and important acute diabetic complication in Soweto. Patient education and care in prescribing for Type 2 diabetic patients may help reduce its occurrence and severity.

Patterns of insulin dependence in an African diabetic clinic.

Analysis of the age of onset of diabetes amongst insulin-treated patients in a large African diabetic clinic revealed a bimodal type of distribution, 23 per cent having an age of onset before 30 years and 77 per cent with onset at greater than or equal to 30 years of age. All 66 of the young insulin-treated group (21.7 +/- 4.8 years (mean +/- 1 SD)), and a random selection of 50 older insulin-treated patients (49.7 +/- 10 years), were studied. The older group were better controlled (HbA1 8.4 +/- 1.7 per cent vs. 10.8 +/- 2.6 per cent, p less than 0.001), on lower doses of insulin (49 +/- 23 vs. 71 +/- 23 u/day, p less than 0.001) and had higher body mass index (26.0 +/- 5.6 vs. 21.8 +/- 3.5, p less than 0.001). Serum C-peptide (0.24 +/- 0.15 vs. 0.07 +/- 0.10 nmol/l, p less than 0.0001), and C-peptide/glucose ratio (2.57 +/- 2.65 vs. 0.56 +/- 0.98 nmol/mmol x 10(2), p less than 0.001) were very significantly higher in older patients. Patients with later onset disease thus had better preservation of pancreatic function, higher body mass index and better glycaemic control on lower doses of insulin. These features suggest that older insulin-treated patients could in fact be 'Type 2' or non-insulin dependent patients, and the condition may be controllable with diet and/or oral hypoglycaemic agents, at least in some.

Phaeochromocytoma. A report of 10 patients.

A spectrum of presentation of phaeochromocytoma in black South Africans is described. Ten patients were reviewed over a 9-year period. Sweating, headache, and palpitations were prominent symptoms in 9 patients; postural dizziness occurred in 5; gastro-intestinal symptoms in 7; diabetes in 3; and hypertension in all. One patient developed a phaeochromocytoma crisis, characterised by hypotension and pulmonary oedema, before operation. One woman presented in pregnancy. Urinary vanillylmandelic acid was elevated in 9 out of 10 subjects tested; plasma catecholamines were elevated in 6 out of 6 tested. Computed tomography detected 7 adrenal tumours and 3 paragangliomas. All patients were stabilised pre-operatively with alpha- and/or beta-receptor blockers. Intraoperative pressor crises were controlled with sodium nitroprusside, phentolamine, or magnesium sulphate infusions. At operation all tumours appeared benign, each was successfully removed, and the diagnosis confirmed on histological examination. There was no operative mortality. Two patients had residual hypertension. This study highlights the various challenges presented by this catecholamine-producing tumour.