Hyperinsulinaemia and syndrome X.
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Biomedical subjects
Publications and source records attributed to D R Hadden.
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Using carefully selected relatively non-obese non insulin dependent diabetic patients, we were not able to show differences in standard measures of insulin production or insulin action between patients treated with a long acting crystalline zinc insulin, with glibenclamide, or with metformin for a six week period. All three drugs were hypoglycaemic, but a fall in basal hepatic glucose output measured by the 3H3 glucose technique was only seen in those patients who had an initial fasting plasma glucose above 12.0 mmol/l, irrespective of treatment.
Urine albumin excretion was studied by two widely accepted methods in 210 patients with insulin-dependent diabetes mellitus and related to the mean of serial glycosylated haemoglobin (HbA1) measurements made every 3 months during the previous 6 years. Microalbuminuria (albumin excretion rate > 20 micrograms/min) was present in 9.5 per cent of patients when defined by a 24-hour collection and 8.1 per cent of patients when defined by a timed overnight urine sample. Those with microalbuminuria, as estimated from a timed overnight urine sample, had a longer duration of diabetes but otherwise did not differ in age, duration of diabetes or arterial blood pressure from patients whose albumin excretion rate was 20 micrograms/min or less irrespective of the method of urine collection. The mean and the most recent HbA1 levels differed significantly between the normal and the microalbuminuric groups when defined by the 24-hour albumin excretion rate (p < 0.001, p < 0.01), but no significant difference between these groups was found when albumin excretion rates were calculated from the timed overnight urine sample. Albumin excretion rate, examined in relation to mean HbA1, increased significantly with worsening glycaemic control whether measured over 24 hours or overnight (p < 0.05, p < 0.01). These findings support an association between glycaemic control and microalbuminuria, but the correlation is weak, dependent on the method of urine collection and is just as good for a relatively short-term as for a long-term measure of average blood glucose.
Four out of twenty-three acromegalic patients selected for treatment with external megavoltage pituitary irradiation between 1961 and 1975 developed progressive visual failure. They had received megavoltage external irradiation through multiple portals from a cobalt-60 unit over a period of 3 weeks. Visual deterioration began 2 months to 6 years after irradiation. In two patients the optic nerves were explored. In both, post-mortem later confirmed radiation damage to the optic nerves and hypothalamus. In one case there was also necrosis of the right frontal lobe with necrosis and inflammation of the bone surrounding the pituitary fossa. In the two other patients, extensive clinical and neuroradiological investigation excluded the presence of a suprasellar mass as a cause for this visual failure and a clinical diagnosis of radiation necrosis was made.
Microvascular disease is the predominant manifestation of the juvenile-onset diabetic after the third decade of survival, while large vessel atheroma is the major problem in the long-term survival of the maturity-onset diabetic. From the experience of a diabetic-eye clinic, we would estimate that only about 3% of patients attending a hospital diabetic clinic would have a severe form of diabetic retinopathy which might need specialized ophthalmic photocoagulation treatment. The long-term visual prognosis for patients treated in this way remains under review. Among metabolic factors associated with vascular disease, a deficiency of HDL cholesterol may be important in the future prognosis of maturity-onset diabetes.
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Serum cholesterol and high-density lipoprotein (HDL) cholesterol concentrations were measured in 192 diabetics (94 with juvenile-onset and 98 with maturity-onset diabetes) and 177 non-diabetic controls. Hb A1C, an index of blood sugar control, was also measured in the diabetics. Serum cholesterol concentrations were similar in all the diabetics and controls, but HDL cholesterol concentrations were lower in patients with maturity-onset diabetes than in those with juvenile-onset diabetes and controls. There was no correlation in diabetics between HDL cholesterol and Hb A1C. We conclude that HDL cholesterol concentrations are abnormally low in patients with maturity-onset diabetes but essentially normal in those with juvenile-onset diabetes. They are not related to diabetic control.
1. Catecholamine sensitivity in hyper- and hypothyroidism has been studied using a standardised isoprenaline sensitivity test. 2. Seven patients with hyperthyroidism and seven with hypothyroidism were tested both when showing evidence of thyroid dysfunction and again when euthyroid. 3. No significant differences were seen in heart rate responses to isoprenaline when patients became euthyroid compared to their response when either hyperthyroid or hypothyroid. 4. These results indicate that sensitivity to catecholamines is not altered in thyroid dysfunction and, in particular, that hypersensitivity does not occur in spontaneous hyperthyroidism.
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A case is described of an ectopic ACTH syndrome associated with malacoplakia.
Plasma immunoreactive secretin levels were measured in 22 newly diagnosed non-ketotic, maturity-onset diabetics and 10 healthy control subjects during 50 gram oral glucose tolerance test (OGTT). The test was repeated in the diabetic group after 6 months' dietary treatment. At diagnosis the fasting secretin levels in the diabetics were higher than in control subjects but fell within the normal range following dietary treatment. In the diabetics there was a significant positive correlation between the fasting glucose and fasting secretin levels at the time of diagnosis. Suppression of secretin levels occurred during the OGTT, both in diabetic and control subjects.
Analysis of the first six months of intensive dietary management of 57 maturity onset diabetics showed that a large proportion of such patients could be satisfactorily controlled without the need of either oral hypoglycaemic agents or insulin. A dietitian's assessment of the patient's adherence to the prescribed diet allowed groups of good and poor dieters to be selected. Among the poor dieters the plasma insulin and triglyceride levels were significantly increased though plasma glucose levels were not significantly higher. Dietary adherence may thus be an prognostic risk factor in this group of diabetic patients.
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A patient with idiopathic marrow hypoplasia associated with short stature and other anomalies (Fanconi's anaemia) is described: treatment with human growth hormone for one year did not accelerate his growth rate or significantly affect his anaemia: androgen treatment considerably improved both features. Endocrine studies suggest that though he had poor and insufficient production of endogenous growth hormone to insulin-induced hypoglycaemia, the major defect in this syndrome is determined more at the end-organ than at the pituitary or gonadal level.