Distribution of autoantibodies to glutamic acid decarboxylase across the spectrum of diabetes mellitus seen in South Africa.

AIMS: This study investigated the association between glutamic acid decarboxylase antibodies (GAD-AB) and Type 1, Type 2, pancreatic and lipoatrophic diabetes mellitus (DM) in South African patients. METHODS: Four groups were selected: group A, 100 Black Type 1 DM patients (age at onset < 35 years, body mass index (BMI) < 27 kg/m2 and insulin dependent within 1 year of presentation); group B, 80 Black Type 2 DM patients (age at onset > 35 years, BMI > 27 kg/m2 and controlled on oral hypoglycaemic agents for at least 1 year after presentation); group C, 10 patients of varying ethnicity with DM or impaired glucose tolerance secondary to chronic pancreatitis; group D, five patients of varying ethnicity with DM associated with total lipodystrophy. Fifty healthy Black control subjects were also studied (group E). Serum GAD-AB and random C-peptide levels were measured by radioimmunoassay. RESULTS: Mean C-peptide concentration was significantly lower in Type 1 DM patients than Type 2 DM patients (P < 0.00001). Forty-four patients with Type 1 DM were GAD-AB-positive compared to two patients with Type 2 DM. Two control subjects were also GAD-AB-positive. No patient in the other groups had a titre > 1 U/ml. Type 1 DM patients who were GAD-AB-positive did not differ from those who were GAD-AB-negative for age at onset, duration of DM or C-peptide concentrations. CONCLUSIONS: Auto-immune beta-cell destruction has an important role in the pathogenesis of Type 1 DM amongst African patients. However, Type 2 African DM patients and other diabetes subtypes are largely GAD-AB-negative.

Thyroid-associated ophthalmopathy in black South African patients with Graves' disease: relationship to antiflavoprotein antibodies.

Thyroid-associated ophthalmopathy (TAO) is a progressive eye disorder associated with Graves' hyperthyroidism, which is generally considered to have an autoimmune etiology. Eye muscle membrane proteins of 64 kd are good markers of ophthalmopathy in patients with thyroid autoimmunity. The 64-kd protein is now shown from a partial sequence to be the flavoprotein subunit (Fp) of mitochondrial succinate dehydrogenase. Hyperthyroidism due to Graves' disease is increasing in incidence among urban black female Africans, possibly because of exposure to environmental risk factors such as increased dietary iodine ingestion and stress. Ophthalmopathy is frequently observed in this clinical context, but its association with serum autoantibodies reactive with Fp has not been examined. We studied 19 black South African patients with Graves' disease during the course of prolonged antithyroid drug administration, of whom 10 had congestive ophthalmopathy, but no clinical evidence for eye muscle damage at the onset. Anti-Fp antibodies were detected in 2 of these patients, as well as in 2 of the 9 patients who did not have overt eye disease. Additionally, the antibodies became positive in 3 patients with ophthalmopathy in whom tests were negative initially, remained positive in 1 patient throughout the study period and became negative in 1 patient with positive tests initially. Ophthalmopathy did not develop in any of the 9 patients who lacked this complication on presentation. The reasons why we failed to demonstrate a close relationship between anti-Fp antibodies and the eye muscle component of ophthalmopathy are unclear although one possibility is that ocular myopathy is an uncommon manifestation in African thyrotoxic patients compared with those of Caucasian origin. The relationship between anti-Fp antibodies and eye muscle inflammation in patients with thyroid autoimmunity of different ethnic origins and environmental settings, needs to be addressed in a large prospective study.

Thyrotropin receptor antibodies in black South African patients with Graves' disease and their response to medical therapy.

Graves' disease is increasing in incidence amongst urban black South Africans. The pathogenic role of thyrotropin receptor antibodies (TRAb), crucial in other populations, has not been formally evaluated in African communities. We therefore prospectively investigated the prevalence of TRAb in 30 consecutive urban black South African patients with classical Graves' disease at the onset of their illness. This was compared with the frequency of thyroid microsomal and thyroglobulin antibodies in the same patients. Ten patients with euthyroid goitres unrelated to Graves' disease and 10 healthy controls were also studied. Twenty of the hyperthyroid patients were retested 4-6 months after starting carbimazole therapy and ten of them again after 1 year. Initially 83% of patients were positive for TRAb as against 54% for thyroid microsomal and 1 7% for thyroglobulin antibodies. After 4-6 months of treatment, 65% of patients still had elevated (>15% inhibition of binding) TRAb titres, while at 1 year this had dropped to 40% (4 out of 10 patients). All positive patients had relapsed biochemically, while TRAb negative patients were all in remission. We conclude that TRAb are a sensitive and specific marker of Graves' disease in black South Africans and closely parallels the response to medical therapy at 1 year. However, their predictive value for delayed relapse requires the study of a larger cohort of patients over a longer time-frame.

Clinical characteristics and outcome of hyperglycaemic emergencies in Johannesburg Africans.

In this prospective analysis we investigated the clinical characteristics of black South African diabetic patients admitted to hospital with hyperglycaemic emergencies. The study cases were selected from the medical admissions to an urbanized, Johannesburg academic hospital over a period of 12 months. Only patients with severe diabetic ketoacidosis (DKA) or hyperosmolar non-ketotic hyperglycaemia (HNKH) as defined in the text were included. Over the study period, we identified 58 patients with severe DKA (M: 32, F: 26) and 24 with HNKH (M: 14, F:10). Thirty-two of the patients with DKA (55.2%) were classified as having non-insulin dependent (Type 2) diabetes mellitus (NIDDM). Compared to the 26 subjects with insulin-dependent (Type 1) diabetes mellitus (IDDM), the NIDDM patients were older (51.7 vs 27.7 years) and had a significantly higher body mass index (BMI) (29.4 vs 23.5 kg m(-2), p = 0.002), and glucose levels 47.5 vs 34 mmol l(-1) p = 0.004). Mortality from DKA was 6.8 % and from HNKH 16.6%. Infection was the leading precipitating factor for both DKA and HNKH, followed by first presentation and noncompliance. We conclude that the majority of urban African patients admitted to hospital with DKA have NIDDM. Mortality from DKA among the black Africans in Johannesburg is low and comparable to the mortality in western Europe.

Microalbuminuria is not associated with cardiovascular disease in patients with homozygous familial hypercholesterolaemia.

Microalbuminuria is thought to be a predictor of cardiovascular disease (CVD). A high prevalence of microalbuminuria might therefore be expected in patients with homozygous familial hypercholesterolaemia (HFH), as they develop severe premature atherosclerosis. We tested for this in 15 HFH patients (M = 9, F = 6; mean age 19.3 years). Urinary albumin excretion (UAER) were normal in all patients [corrected]. In addition, there was no difference in the mean urinary albumin excretion rate (UAER) between those with documented CVD (n = 8; UAER = 5.17 micrograms/min) and those without (n = 7; UAER = 3.60 micrograms/min). There is therefore no association between microalbuminuria and CVD in HFH.

Renal and neuromuscular respiratory failure--is this a syndrome associated with cantharidin poisoning?

OBJECTIVE: To describe the clinical and laboratory features of patients with renal and neuromuscular respiratory failure due to suspected cantharidin poisoning. DESIGN: Retrospective record review of cases with neuromuscular respiratory failure. SETTING: Intensive Care Unit (ICU), Hillbrow Hospital, Johannesburg. PATIENTS: Out of a total of 47 patients with neuromuscular respiratory failure admitted to the ICU between January 1983 and December 1990, 10 with suspected cantharidin poisoning were selected and studied further. OUTCOME MEASURES: Description of clinical features, laboratory data, treatment and prognosis. RESULTS: In 10 of the 47 patients, the cause of renal and neuromuscular respiratory failure that which precipitated the need for ICU admission was suspected to be cantharidin poisoning. This was based on the history and clinical and laboratory features. In 4 cases trace amounts of cantharidin were detected in blood and/or urine, strengthening the diagnosis. There were 8 males and 2 females. All had evidence of renal injury and 9 had gastro-intestinal symptoms. All presented with fixed dilated pupils, varying cranial nerve palsies and muscle weakness, usually ascending and progressive, necessitating admission to the ICU. All but 1 of the patients were mechanically ventilated, 5 required significant inotropic support of the blood pressure, and 6 dialysed. Four patients died soon after admission and the remainder survived with relatively complete return of neurological function. CONCLUSION: This study highlights the possibility that cantharidin poisoning may be a cause of a 'Guillain-Barrè-like' syndrome.