Mortality from diabetic nephropathy in the United Kingdom.

Deaths in diabetic subjects dying under 50 years of age in the United Kingdom during 1979 have been analysed with special reference to diabetic nephropathy. Fifteen percent of 447 deaths were from nephropathy. Uraemic deaths from nephropathy were particularly common in those whose diabetes was diagnosed under 31 years old, and responsible for over one-quarter of deaths in this age group. Most deaths from nephropathy occur before 30 years' duration of diabetes and are rare in those of longer duration, suggesting that some diabetic patients are more and others less prone to this complication. There were more men than women in a ratio of approximately 1.3:1. Severe retinopathy is usually present in end-stage renal failure causing blindness in one out of three cases, and impaired vision in a further one out of three. Blind patients were not otherwise more severely affected by diabetic complications than others. It is estimated that approximately three-quarters of the diabetic subjects who develop end-stage renal failure from nephropathy may be suitable for dialysis or transplantation.

Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy.

In a survey of 46 randomly selected diabetic patients on biguanide therapy, 30% had malabsorption of vitamin B12. Withdrawal of the drug resulted in normal absorption in only half of those with malabsorption. In most patients with persistent malabsorption, the results of absorption tests with exogenous intrinsic factor suggested the diagnosis of coincidental intrinsic factor deficiency. Further considerations, however, led to the concept that biguanides can induce malabsorption by two different mechanisms. One of these is temporary and unrelated to intrinsic factor secretion and the other is permanent and mediated by depression of intrinsic factor secretion.

Urological aspects of diabetes.

Diabetes mellitus, which is a common metabolic disorder, classically presents with urological symptoms. In the assessment of patients referred to a urological service, complaining of urological symptoms including incontinence, diabetes may be overlooked in the search for other causes or contributory factors. Conversely, the diabetic patient presenting with such symptoms requires careful investigation if therapy is to have a rational basis.

Relevance of colour vision and diabetic retinopathy to self-monitoring of blood glucose.

A study was performed to determine the effect of colour vision defects and diabetic retinopathy on diabetic patients' ability to use a visual method of measuring their own blood glucose concentrations. Forty-eight diabetics whose colour vision and retinal status was assessed by an ophthalmologist carried out 311 blood glucose estimations using oxidase-peroxidase test strips which were then compared with laboratory values. There was a trend towards poor performance with advancing age but neither colour vision nor diabetic retinopathy had a significant effect on patients' ability to use this visual method of estimating blood glucose concentrations. The vast majority of diabetics who will benefit from being able to monitor their own blood glucose control should have no difficulty in using a visual method of testing, even if they do have defects of colour vision.

Diagnostic imaging in diabetes mellitus.

Diagnostic imaging techniques have an important role in supplementing the clinical evaluation of the diabetic. These are discussed in relation to the pathophysiologic changes: vascular degeneration, neurologic and infective changes, and maternal-fetal influences during pregnancy.

Sulphonylureas and cardiovascular disease: a problem for few diabetics.

Because of the doubts cast on the safety of the sulphonylureas we analysed 1000 consecutive referrals to a diabetic clinic to identify the number of new patients equally suitable for treatment with a sulphonylurea or insulin. After excluding previously diagnosed and treated diabetics and those with a non-diabetic glucose tolerance test there were 531 new diabetics. Youth and insulin dependency, old age or obesity accounted for 390. A further 40 required diet alone, 50 had concomitant disease or socio-domestic circumstances influencing treatment choice, and 10 had secondary diabetes. Thus, only 41 diabetics (7.7% of new patients or 4.1% of total clinic referrals) appeared suitable for optional sulphonylurea or insulin therapy. We conclude that there are relatively few diabetics for whom the questionable safety of the sulphonylureas poses a therapeutic problem, and equally few who would be available for any further long-term, random-allocation trials of their effects upon the cardiovascular system.

Blood glucose control and glomerular capillary basement membrane thickening in experimental diabetes.

Glomerular capillary basement membrane thickness (BMT) was measured in 23 rats which had had streptozocin-induced diabetes for 14 months and in 12 age-matched controls. Diabetic rats were randomly allocated to different groups, either receiving no treatment or treated with a low carbohydrate diet or insulin, or both. Control rats were randomly allocated to a normal or low carbohydrate diet. Among the diabetic rats mean plasma glucose concentrations for the groups ranged from 27-4 mmol/l (494 mg/100 ml) in the untreated rats to 9-8 mmol/l (177 mg/100 ml) in those receiving both a low carbohydrate diet and insulin. A highly significant positive relation was found between BMT and plasma glucose concentration for individual rats. When BMT was corrected for body weight a similar relation was observed.

Neonatal acidosis associated with transient methylmalonicaciduria and vitamin B12 deficiency.

Investigation of a neonate presenting with a metabolic acidosis, vomiting and an apnoeic attack revealed abnormal urinary excretion of methylmalonic acid (MMA) associated with a low serum vitamin B12. Restriction of dietary protein was followed by normalisation of acid-base balance. Reintroduction of normal daily protein intake did not precipitate flrther acidosis or increased excretion of MMA. The transient methylmalonicaciduria was probably due to deficiency of vitamin B12.

Hypoaldosteronism in three sibs due to 18-dehydrogenase deficiency.

Three sibs all presented in the early neonatal period with a salt-losing syndrome. The salt-losing form of congenital adrenal hyperplasia was diagnosed and appropriate treatment with glucocorticosteroids, mineralocorticosteroids, and additional dietary salt started. Although early life was maintained with difficulty, with age all 3 children required decreasing amounts of replacement steroids to maintain normal plasma electrolyte balance. They were reinvestigated at the ages of 15 years and 8 years (twins), when cortisol synthesis and metabolism proved normal, but aldosterone synthesis was blocked by deficiency of 18-dehydrogenase. Rational treatment of these cases of a salt-losing syndrome in which aldosterone synthesis alone is blocked due to lack of the enzyme 18-dehydrogenase requires the administration of a mineralocorticosteroid drug only. Since deoxycorticosterone (acetate or pivalate) requires intramuscular administration, as life-long therapy oral fludrocortisone is preferable. Although fludrocortisone has glucocorticoid activity, the "hydrocortisone equivalent" effect of the small dosage used was unlikely to inhibit either pituitary corticotrophin or growth hormone production.

Diabetic complications in a patient with coexisting anterior hypopituitarism.

We present a patient who developed insulin-requiring diabetes several years after the onset of symptoms of anterior hypopituitarism. It is likely that the hypopituitarism protected him against the development of diabetic retinopathy and glomerular basement membrane thickening but not against neuropathy and atheroma. The significance of this in relation to the growth-hormone-microangiopathy hypothesis is discussed.