Biomedical subjects
Publications and source records attributed to D R Hadden.
We report a four-generation kindred with the complex of myxomas, spotty pigmentation and endocrine overactivity. This kindred demonstrates a relatively limited phenotypic expression with predominance of cutaneous features. Male-to-male transmission confirms the autosomal dominant nature of the condition. We propose that pilonidal sinus may be an associated manifestation in this kindred.
There is still disagreement concerning the optimal procedure for the diagnosis of milder degrees of hyperglycaemia in pregnancy. We have compared the results of a 75 g oral glucose tolerance test (OGTT) and a standardised breakfast test performed one week apart in 102 non-diabetic women with a singleton pregnancy. There was poor correlation between the two tests (r = 0.15) at two hours, and neither test was predictive of adverse maternal or fetal outcome. One hundred and four patients with impaired glucose tolerance, diagnosed at 30 weeks' gestation by 75 g OGTT, subsequently had a breakfast and lunch meal profile. There was no significant correlation between the two-hour OGTT value and either the two hour post-breakfast value (r = 0.35) or the maximum profile value (r = 0.33). Using the WHO diagnostic criterion of > 8 mmol/l for the OGTT and a maximum glucose concentration > 6.8 mmol/l for the meal profile, there was no relationship between an abnormal result in either test and pregnancy outcome. In our obstetric environment, the 75 g OGTT, a standardised breakfast test, and a structured meal profile, all failed to provide a useful indication of pregnancy outcome in mothers not already known to have diabetes.
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Self-reported dietary intake was estimated from 3-day prospective food diaries completed by Type 2 diabetic patients in the UK Prospective Diabetes Study. All patients had received individual dietary advice and had been randomly allocated to diet, sulphonylurea or insulin therapy 3 months after diagnosis. A total of 132 patients (120 white Caucasian, 12 Asian) stratified for gender, obesity and allocated therapy with mean age 55 years (SD 8), body mass index 28 kg m-2 (SD 4), and with a diabetes duration of 3 to 6 years were selected at random from 5 of 23 clinical centres. Patients reported a similar proportion of their energy intake as carbohydrate (43%) to the general population and had not increased to the recommended 50-55%. Their protein intake (21%) was higher than the advised 10-15%. Estimated energy intake from fat (37%) was close to that recommended for diabetic patients (30-35%) and was lower than that reported for the UK population (40%). The estimated polyunsaturated/saturated fat intake ratio (0.48) was higher than that reported for the UK population (0.35) compared with the recommended 1.0. Mean fibre intake at 22 g day-1 was less than the recommended 30 g day-1. The 8 male Asian patients took a higher proportion of their dietary intake as fat (46% vs 37%) and lower as protein (14% vs 21%) than the male white Caucasian patients. No significant differences were seen in estimated nutrient constituents between patients allocated to diet, sulphonylurea or insulin therapy as part of the UK Prospective Diabetes Study and followed for mean 4.2 years (SD1.6). This suggests that dietary factors will not confound UK Prospective Diabetes Study treatment related analyses.
During the period 1989-1994, 462 cases of insulin-dependent diabetes mellitus were registered among children from Northern Ireland aged under 15 years. The estimated completeness of the register was 98.8% (95% confidence interval (CI) 97.7%, 99.9%). A standardised rate of 19.6 (95% CI 17.8, 21.4) per 100 000 person years was obtained, placing Northern Ireland near the top of the range of published incidence in the United Kingdom, with a rate close to that reported for Scotland. In an analysis based on 217 postcode sectors, areas with a high population density and the most material deprivation were observed to have the lowest incidence rates. After inclusion of population density in a Poisson regression analysis, the component of deprivation which was found to be most significant was household crowding. Relative to children living in areas of low population density, there was a reduced risk for children in medium (relative incidence 0.85 (95% confidence limits CI 0.67, 1.09)) and high (0.62 (95% CI 0.48,0.80)) population density areas. Similarly, relative to children living in areas with low levels of household crowding, there was a reduced risk for children in medium (relative incidence 0.73 (95% CI 0.58,0.93)) and high (0.67 (95% CI 0.53, 0.83)) levels of household crowding. Tests for space-time clustering at diagnosis and at birth were negative. A possible explanation for the differences in incidence rate observed in this study is that exposure to infections very early in childhood is a protective factor. Later infections may act as either initiators or promoters of diabetes, but the absence of space-time clustering suggests that no single specific infectious agent is responsible.
We assessed the clinical characteristics of newly-diagnosed diabetic patients presenting to the Mulago Hospital Diabetic Clinic for the first time between 1 January 1993 and 10 August 1994. There were 252 patients: 117 men and 135 women. Mean age at onset of diabetes was 45 years (range 2-87 years) and peak incidence was at 40-49 years. Body mass index (BMI) was available in only 71 patients, of whom 53.5% (33.8% female, 19.7% male) were overweight (BMI > 25 in women, in > 27 men) and 11.3% (8.5% men, 2.8% women) were underweight (BMI < 20). Obesity was more marked in young women. Almost all patients presented with the classical symptoms of diabetes, and the majority were severely hyperglycaemic. A family history of diabetes was identified in 16%. Concurrent illnesses at diagnosis of diabetes were unusual. Sepsis was commonest (11.9%), followed by malaria (7.8%), tuberculosis (1.2%), AIDS (1.2%) and pancreatitis (0.8%). Peripheral neuropathy was present in 46.4% of patients, hypertension (BP > 150/100) in 27.3%, impotence in 22.2% of the men, proteinuria in 17.1%, ischaemic heart disease in 4.8%, foot ulcers in 4.0% and cataracts in 3.2%. Insulin was the most commonly prescribed treatment (52.8%); 31% of patients received oral hypoglycaemic agents, only 15.1% were managed on diet only, and 1.2% opted for herbal medicine.
We report a family in which a phenotype of acromegaloid facial appearance (AFA) and generalised hypertrichosis terminalis segregates through three generations. Congenital hypertrichosis terminalis and AFA have been previously reported as independent autosomal dominant traits. This is the first report to delineate an autosomal dominant transmission of the combined phenotype.
The aim of the diabetes specialist is to provide a service to the pregnant diabetic woman so that she will present to her obstetrician with such well-controlled plasma glucose levels that her pregnancy will proceed without any diabetes-related problem, and she will be delivered of a normal baby, of normal size, at the normal full-term gestation, by the normal route. There are some problems in achieving this aim. The exact definition of hyperglycaemia in pregnancy is still a matter of dispute. Screening methods to identify the problem differ widely. Many centres have developed joint diabetes/antenatal clinics, but there are practical problems with such an approach. Pre-pregnancy counselling, and discussion of contraceptive measures is an important task for the diabetologist and requires up-to-date knowledge. Control of plasma glucose requires alteration of insulin doses as pregnancy proceeds. Mothers with retinal, renal or cardiac problems will need special care. The medical problems which develop, and the management of blood glucose during labour and delivery, mean that the diabetes team must be very adjacent to the obstetric service, and a centralised approach offers many advantages. The postpartum state, and the long-term outcome for both mother and baby, remain both an interest and a responsibility for the obstetric physician.
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OBJECTIVE: To report our experience of 41 patients with phaeochromocytoma. DESIGN: Retrospective study. SETTING: Teaching hospital, United Kingdom. SUBJECTS: Forty-one patients who presented with phaeochromocytoma 1970-1991. INTERVENTIONS: Removal of tumour (n = 38). MAIN OUTCOME MEASURES: Mortality, morbidity, and recurrence. RESULTS: Thirty-four patients had sporadic tumours, five had the multiple endocrine neoplasia (MEN) type 2 syndrome, and two had non-MEN familial phaeochromocytoma. Thirty-six patients (88%) presented with symptoms of catecholamine excess, and 37 (90%) were hypertensive. The diagnosis was confirmed biochemically in 37. Tumours were located using computed tomography (n = 26), vascular studies (n = 11), and ultrasonography (n = 3). Thirty-eight patients had their tumours resected, of whom 10 (27%) developed complications. There were no postoperative deaths. Two patients were managed conservatively, and one died before diagnosis. Six patients developed recurrent tumours a mean of five years after the initial operation, and another patient had an inoperable tumour at initial diagnosis; four of these seven died from metastatic disease. Metaiodobenzylguanidine (MIBG) scans were positive in three of the patients who developed recurrences. CONCLUSIONS: Patients with phaeochromocytoma can now be operated on safely but prolonged follow-up is essential.
The prevalence of hypertension and its relationship to nephropathy were measured in a hospital-based diabetic clinic. Six hundred patients (300 insulin treated, 300 non-insulin treated) were randomly selected from a clinic population of 1054 insulin treated and 1039 non-insulin treated subjects. Eighty-three percent of patients with insulin treated diabetes and 72% of patients with non-insulin treated diabetes were studied. Blood pressure data from the Belfast MONICA project were used for the control group. In patients with insulin treated diabetes (age 25-64 years) the prevalence of a systolic blood pressure > 160 mmHg or a diastolic blood pressure > 95 mmHg or on treatment for hypertension (WHO criteria) was 19.1% in males (NS, vs. control group) and 17.8% in females (NS); the prevalence of a systolic blood pressure > 140 mmHg and diastolic blood pressure > 90 mmHg was 17.6% in males (NS, vs. control group) and 9.5% in females (NS). In patients with non-insulin treated diabetes (age 35-65 years) the prevalence of hypertension by WHO criteria (see above) was 26.8% in males (NS, vs. control group) and 28.9% in females (NS); the prevalence of a systolic blood pressure > 140 mmHg and diastolic blood pressure > 90 mmHg was 21.4% in males (NS, vs. control group) and 17.8% in females (NS).(ABSTRACT TRUNCATED AT 250 WORDS)
This study followed up a cohort of patients with microalbuminuria identified on a spot morning urine sample 8 years earlier and aimed to determine if a spot morning urinary albumin concentration was able to identify patients with non-insulin treated diabetes at increased risk of mortality and progression to nephropathy. In 1984, 47 of 216 patients chosen by random selection from our teaching hospital-based diabetes clinic were identified as having microalbuminuria (urinary albumin concentration 35-300 micrograms ml-1). Subjects were compared with an age-matched control group from the 1984 cohort who did not have microalbuminuria. Eight years later, 22 of 47 (46.8%) patients with microalbuminuria had died compared to 10 of 47 (21.3%) patients without albuminuria (p < 0.05). The majority of deaths were from cardiovascular disease (53.1%). Logistic regression showed microalbuminuria to be an independent predictor of mortality, not influenced by age, duration of diabetes, blood pressure, glycosylated haemoglobin or creatinine at the initial examination. Eight years later, in the group with initial microalbuminuria, eight still had microalbuminuria and five patients had developed nephropathy. In the group without albuminuria in 1984, only one patient had progressed to microalbuminuria and no patients to nephropathy. In conclusion, a spot urinary albumin concentration is of value in identifying patients with an increased risk of mortality or progression to nephropathy, and is simple to obtain at a clinic.
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In normal pregnancy, the maternal adrenal gland adapts to the physiologic changes necessary to sustain gestation. These changes protect the fetus and the mother, allowing for increased shunting of nutrients to the fetus and protection of immunologic rejection. The adrenal disorders pertinent to pregnancy include overactive and underactive secretion of adrenocortical hormones and tumors that secrete too much catecholamine. In addition, iatrogenic hypercortisolemia may be necessary to treat the mother for underlying diseases. The impact of iatrogenic hypercortisolemia on the fetus is addressed also.
We studied insulin and C-peptide levels in patients with non-insulin-dependent diabetes mellitus (NIDDM) during standard oral or intravenous glucose tolerance tests (GTT) at the time of diagnosis and after 3 months dietary therapy. On the second occasion they also had an 'augmented' GTT, in which slow intravenous infusion of glucose raised basal plasma glucose to a level similar to that at the time of diagnosis. Eight patients had oral tests, and seven patients intravenous tests. In both groups, dietary therapy significantly reduced fasting and peak plasma glucose (p < 0.05 for oral; p < 0.01 for intravenous GTT). Serum insulin levels during conventional oral GTT were not significantly different after dietary therapy compared to diagnosis, but were significantly higher during the 'augmented' oral GTT (p < 0.05). In those patients who underwent intravenous GTT, there was a significant increase in both the total amount of insulin secreted (0-60 min) and in first-phase insulin secretion (0-10 min) during the 'augmented' test compared to diagnosis (p < 0.01), but first-phase insulin secretion during the conventional intravenous GTT was unchanged. Serum C-peptide responses were also greater during 'augmented' tests (p < 0.05), similar in pattern to serum insulin. There is a relative deficiency in insulin secretion in untreated NIDDM, which can be reversed by dietary therapy. It is essential to study insulin and C-peptide secretion in controlled 'fasting' glucose conditions.
The debate continues on how to screen for microalbuminuria in clinical practice in patients with insulin-dependent diabetes mellitus. Our study assesses the value of a spot morning urine specimen obtained at a clinic visit. In 1984, as part of a randomised survey of our diabetes clinic, 43 of 249 patients with insulin treated diabetes mellitus, were found to have microalbuminuria (urinary albumin concentration 35-300 ug ml-1) on a spot morning urine sample. These subjects were compared with an age-matched control group from the 1984 cohort who did not have microalbuminuria. Eight years later, in the group with microalbuminuria, 10 had died compared to six in the control group (p = 0.17) with 62.5% of all deaths being from cardiovascular disease. In the group with microalbuminuria, 10 of 27 still had incipient nephropathy while five had progressed to nephropathy. In the group without microalbuminuria only three of 33 patients had progressed to microalbuminuria while none had progressed to nephropathy. In conclusion a spot morning urine sample is a useful screening test to identify patients at risk of progression to nephropathy.
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OBJECTIVE: To identify perinatal risk factors for childhood insulin-dependent diabetes mellitus (IDDM) and determine if they differ between early-onset and late-onset disease. RESEARCH DESIGN AND METHODS: We selected 258 diabetic children in Northern Ireland and 271 diabetic children in Scotland from population-based registers. For each diabetic child, five matched control subjects were drawn from the same population. All perinatal data were recorded routinely at birth. Odds ratios (ORs) were estimated for parental age, social class, breast-feeding, deprivation measures, and other perinatal variables. RESULTS: Scottish data indicated an increased risk among children born to older mothers (OR = 2.43, 95% confidence interval [CI] 1.49-3.97 for mothers > or = 35 years of age relative to those < 25 years of age). Northern Ireland data showed no such effect. Only Northern Ireland data showed an excess risk in children of professional or managerial families (OR = 1.51, 95% CI 1.11-2.04). A small but nonsignificant reduction in risk among breast-fed children was observed only after adjustment for social class (OR = 0.76, 95% CI 0.54-1.07). Deprivation measures were associated with reductions in risk. Children delivered by cesarean section were at increased risk in both Northern Ireland (OR = 1.66, 95% CI 1.10-2.50) and Scottish (OR = 1.70, 95% CI 1.12-2.59) data. In Northern Ireland data only, children of first pregnancies were at increased risk (OR = 1.41, 95% CI 1.03-1.93). Both data sets indicated that a first pregnancy was a more important risk factor for early-onset disease than for late-onset disease. CONCLUSIONS: Many reported risk factors are weak and show inconsistencies between studies. They may be secondary to more direct, as-yet-undiscovered risk factors. Although irrelevant in the majority of cases, the increased risk associated with delivery by cesarean section deserves further study.