Evaluation of Coomassie dye binding method for microprotein assay in diabetic proteinuria.

A simple and relatively cheap method for quantitating diabetic microproteinuria with Coomassie brilliant blue dye binding method was evaluated. It provides a proportional reactivity to urinary albumin as measured by the more expensive immunoassay. The significant correlation between haemoglobin A1 and microproteinuria shows that the quantity of urinary protein is affected by metabolic control of diabetes.

Aprotinin induced lipohypertrophy and glomerulonephritis in an insulin dependent diabetic.

In an insulin dependent diabetic who was hyperglycaemic and ketotic despite 3,000 u of insulin injected subcutaneously in 2 divided doses daily, 50 u of intravenous insulin infused over 24 hr restored normal glucose homeostasis. A combination of insulin (800 u) and aprotinin (10,000 u) given twice daily also produced adequate glucose homeostasis for a period of 12 months. The patient then developed local hypertrophy of subcutaneous tissue at the injection site and her diabetic control deteriorated. Non-selective proteinuria followed and she developed nephrotic syndrome. Renal biopsy revealed a membraneous glomerulonephritis with subepithelial immune complexes, appearances consistent with a drug-induced glomerulonephritis. Withdrawal of aprotinin led to a gradual remission of nephrotic syndrome and proteinuria over several months. During this period, her diabetes was well controlled with continuous subcutaneous infusion of insulin at a dose of 500 u/24 hr. This case report demonstrates: the effective use of aprotinin for prolonged periods in insulin dependent diabetics with abnormal absorption of subcutaneously injected insulin; aprotinin induced lipohypertrophy which was not observed when insulin was injected alone; aprotinin-associated glomerulonephritis and nephrotic syndrome; the effective use of CSII--at higher insulin doses--in such patients with subcutaneous malabsorption of insulin.

Exocrine pancreatic function in diabetes mellitus.

An investigation of serum immunoreactive trypsin concentration and pancreatic isoamylase activity in patients with diabetes mellitus has shown that exocrine pancreatic deficit is maximal in insulin dependent diabetics, intermediate in those controlled with sulphonylureas, and absent in patients controlled with biguanides or diet or both. A significant correlation between the serum concentrations of both these pancreatic enzymes and C peptide was found. Serum pancreatic enzyme concentrations were not related to glycosylated haemoglobin concentrations, the dosage of insulin, or the age of onset of diabetes. The concentration of immunoreactive trypsin was found to be low in most of the insulin dependent diabetics in whom this enzyme was measured at the time of the clinical onset of diabetes. Thus exocrine pancreatic deficit in diabetes closely parallels the endocrine beta cell deficit and occurs concurrently with, or antedates, the clinical presentation of type I diabetes. It is therefore possible that in type I diabetes similar mechanisms are entailed in the pathogenesis of impaired endocrine and exocrine pancreatic function.

Hyperthyroidism and acute bronchial asthma.

Asthma may be very mild, at times hard to diagnose; beta blockade should be used only with great caution. An asthmatic who becomes thyrotoxic should be closely monitored for deterioration of the asthma.

Diarrhea and metformin in a diabetic clinic.

In a questionnaire-based survey of 285 randomly selected diabetic patients, diarrhea was found to occur in 8%; this was found to be similar to that in 150 nondiabetic control patients attending other medical clinics (8%). When the diabetic patients were divided into separate therapeutic groups, metformin-treated (with or without sulfonylureas) patients had a markedly greater prevalence of diarrhea (20%) than those not on this drug (6%). A majority of patients with metformin-associated diarrhea had soiling of clothes as a problem, while at least two complained of frank loss of control over their anal sphincter. These patients did not have autonomic neuropathy, and in all who stopped this drug, diarrhea settled within 2-5 days. Only 6% of insulin-dependent diabetic individuals (IDD) had diarrhea, one of whom had explosive nocturnal stools with incontinence and features diagnostic of autonomic neuropathy. Metformin is by far the commonest cause of diarrhea and incontinence in our diabetic clinic, where it is used routinely. In contrast, diarrhea due to autonomic neuropathy is rare.

Low pancreatic lipase in insulin-dependent diabetics.

Serum samples obtained from 20 insulin-dependent diabetics (IDD), 23 non-insulin-dependent diabetics (NIDD) and 30 controls were assayed for their pancreatic lipase activity, immunoreactive trypsin concentration and glycosylated haemoglobin (HbA1) respectively. The distribution of serum pancreatic lipase activity in normal subjects and diabetics was nonparametric. The median serum lipase activity in IDDs (86 U/l) was significantly lower that that in controls (131 U/l, p less than 0.002) and NIDDs (126 U/l, p less than 0.001). There was a significant correlation between serum pancreatic lipase activity and serum IRT concentration (r = 0.65, p less than 0.001). Neither pancreatic lipase activity nor IRT was related to HbA1 concentrations. These data show for the first time that serum pancreatic lipase activity is diminished in IDDs.

Para-aminosalicylic acid-induced hypoglycaemia in a patient with diabetic nephropathy.

A 62-year-old Indian with diabetic nephropathy controlled with metformin, developed miliary tuberculosis for which he was treated with rifampicin, isoniazid and ethambutol. Soon afterwards he developed cholestatic hepatitis and visual disturbance. Rifampicin and ethambutol were stopped. Streptomycin caused vertigo and had to be stopped. The introduction of para-aminosalicylic acid (PAS) led to hypoglycaemic coma. Metformin was stopped. Hypoglycaemic coma recurred. PAS was stopped and the patient's blood glucose concentrations became normal. Treatment with isoniazid and ethambutol led to total recovery from pulmonary tuberculosis. The induction of hypoglycaemia with PAS in this patient suggests a potential role for PAS in the treatment of diabetes mellitus.

Instability of cerebral blood-flow in insulin-dependent diabetics.

Cerebral blood-flow (CBF) was measured in 23 insulin-dependent diabetics before and 2--3 h after insulin/breakfast. In 10 of these patients CBF changed significantly during the day, with a significant fall in 9. In 3 patients who had the greatest falls in CBF there was a concomitant sensation of an impending faint. Thus CBF is unstable in insulin-dependent diabetics in contrast to control subjects in who there is little or no variation. Sudden falls in CBF in insulin-dependent diabetics may explain the symptoms of impending faint without hypoglycaemia; such falls would also be relevant to the pathogenesis of strokes in these patients.

Low-dose insulin infusions in diabetic patients with high insulin requirements.

Six patients with high insulin requirements (range 120-3000 units daily) have been infused with much smaller doses (range 50-63 units daily) of insulin intravenously. All six maintained adequate glucose homoestasis on this regimen. It is suggested that subcutaneous tissue at the site of injection may alter insulin or impair its absorption. Insulin resistance in some patients may be due to these mechanisms.

Cerebral blood flow in diabetes mellitus: evidence of abnormal cerebrovascular reactivity.

Cerebral blood flow (CBF) was studied at normocapnia and after a challenge with 5% CO2 in 59 diabetic patients and 28 controls. There was a significant age-related decline in CBF in both groups, which suggests that diabetes does not affect the rate of decrease of CBF with age. After CO2 challenge CBF increased in most of the controls; in the patients CBF increased in 23, decreased in 26, and remained stable in 10. Thus the reactivity of cerebral blood vessels in diabetics is altered. Diabetics have diminished cerebrovascular reserve and are thus at increased risk of cerebrovascular disease because they are unable to compensate when necessary with an increased CBF.