Metformin and contrast media--a dangerous combination?

Metformin is a biguanide used to treat type II diabetes mellitus. Since the recent introduction of this drug into the United States there has been considerable interest in metformin associated lactic acidosis (MALA) following intravenous contrast media. The Royal College of Radiologists published advice in November, 1996 (Advice to Members and Fellows with regard to metformin-induced lactic acidosis and X-ray contrast medium agents, RCR Publication) supporting the manufacturers' advice that metformin should not be used in the 48 h before or after intravenous (i.v.) contrast medium. We performed a systematic review of the literature and this has shown that almost all reported cases of MALA following i.v. contrast medium occurred where there was either pre-existing poor renal function or another contraindication to metformin usage. There has been only one reported case of lactic acidosis following the use of intravenous contrast medium in a patient with normal renal function. We suggest that the Royal College of Radiologists' advice should be modified and that it is safe to give i.v. contrast medium to patients on metformin with normal renal function.

Aggressive limb salvage using tibio-pedal bypass grafting with free tissue transfer in a diabetic patient.

A 63-year-old man presented with intermittent claudication, diabetes, and an ischaemic heel ulcer. After control of infection, the os calcis was left exposed. An aggressive combined infra-inguinal revascularization and reconstruction procedure involving free-tissue transfer resulted in rapid wound healing with independent walking by day 26. Recent improvements in surgical techniques mean that this approach should be considered in selected patients.

Mortality in diabetes mellitus: experience of a geographically defined population.

A population-based cohort study identified 915 deaths in 4186 patients with diabetes mellitus over a 5-year period. Ischaemic heart disease, cerebrovascular disease and malignant neoplasms were the major causes of death and accounted for 40%, 16%, and 14% of deaths, respectively, compared with 27%, 14%, and 25% of deaths in the non-diabetic population. Diabetic patients had a standardized mortality ratio (SMR) of 1.15 (95% Cl 1.08-1.22) (p less than 0.001). This excess risk of death was largely due to the excess death from ischaemic heart disease (SMR 1.55 (1.40-1.71); p less than 0.001) and the impact was greatest in middle-aged female patients. Stroke mortality was not significantly increased (SMR 1.09 (0.92-1.29)) while cancer mortality was reduced (SMR 0.75 (0.63-0.89); p less than 0.01). Death rates in diabetic male patients (SMR 1.04 (0.96-1.13)) did not differ significantly from those in non-diabetic male patients because the increased risk of ischaemic heart disease deaths (SMR 1.41 (1.22-1.62); p less than 0.001) was offset by the reduced risk of deaths from malignant neoplasms (SMR 0.65 (0.51-0.82); p less than 0.001). The reduction in cancer mortality did not reach statistical significance in diabetic women (SMR 0.82 (0.64-1.05)). Diabetic nephropathy and metabolic disasters were uncommon as causes of death.

Measuring outcome of diabetes: a retrospective survey.

The feasibility of using hospital discharge data to monitor six outcome indicators for diabetes care was assessed by reviewing retrospectively the occurrence of these events recorded in hospital records. The population studied was that of the Orkney Islands (19,500) over a 10-year period (1976-1985). During that time, 230 Orkney diabetic patients were treated in Orkney and/or Aberdeen hospitals. The six outcome indicators were: hospital admission rates for diabetic patients (609 in 230 patients), hospital admission rates specifically for diabetic ketoacidosis (29 in 20 patients), rates of diabetes-related lower limb amputations (36 in 23 patients), perinatal mortality rates related to maternal diabetes (nil), visual loss or blindness (13 eyes in 9 patients) and end-stage renal failure (one patient). Scottish Morbidity Returns (which collect data similar to that in the Hospital In-patient Enquiry in England) were shown by case note review to underestimate these outcomes by 41%. Cardiovascular disease, cerebrovascular disease, and peripheral vascular disease accounted for half of all in-patient bed use by diabetic patients (6077 of 13,951 days). The routinely available Scottish hospital discharge data, which are collected for a different purpose, are not sufficiently accurate or complete to reflect variations in actual diabetic events.

Angiotensin converting enzyme inhibitors may cause renal impairment in diabetes mellitus.

Angiotensin converting enzyme (ACE) inhibitors have been recommended for the treatment of diabetic nephropathy. However, it should be remembered that diabetic patients may also develop atheromatous renal artery stenosis. In such patients ACE inhibitors may have adverse effects on renal function. Careful investigation and monitoring is essential when ACE inhibitors are used in diabetes.

Comparison of propranolol and metoprolol in the management of hyperthyroidism.

1 Propranolol and metoprolol were both effective in controlling the symptoms and signs of hyperthyroidism. 2 Propranolol caused a highly significant increase in serum reverse T3 concentrations with lesser changes in other serum thyroid hormone levels, whereas metoprolol did not have this effect. 3 Steady-state plasma propranolol and metoprolol levels showed marked inter-individual variation. Metoprolol concentrations showed relatively little intra-individual variability, and could be related to the clinical efficacy of the drug, whereas no such relationship was demonstrated for propranolol.

Coagulation and fibrinolysis in thyroid disease.

The levels of components of the coagulation mechanism and fibrinolytic system in 20 hyperthyroid patients and 9 hypothyroid patients were compared with those of 20 euthyroid control subjects. The mean levels of fibrinolytic activity and plasminogen were significantly reduced in the hyperthyroid patients while mean levels of alpha1-antitrypsin and C1 inactivator were increased. Patients with hypothyroidism had significantly increased levels of fibrinolytic activity and alpha2-macroglobulin, a prolonged partial thromboplastin time, and reduced levels of factor XII and antithrombin III.

Metabolic effects of salbutamol: comparison of aerosol and intravenous administration.

The effects of intravenous salbutamol (4 mug/kg) were compared with those of aerosol salbutamol (200 mug) in 10 asthmatic patients in a double-blind placebo-controlled study. Both methods of administration produced equal bronchodilatation. Intravenous salbutamol caused significant increases in plasma insulin and glucose levels and a fall in serum potassium concentration in addition to tachycardia and tremor, whereas aerosol salbutamol produced only a small transient increase in the plasma glucose level. The initially raised non-esterified fatty acid levels decreased significantly after aerosol and placebo but not after intravenous salbutamol.

Comparison of propranolol and practolol in the management of hyperthyroidism.

Twenty-one hyperthyroid patients participated in an 8-week double-blind crossover trial of propranolol and practolol, and the effecte of these drugs on the clinical and metabolic features of the disease were studied. Propranolol was marginally more effective than practolol, as measured by the hyperthyroid diagnostic index and anxiety scale. Propranolol produced a significant reduction in the serum concentration ratio of tri-iodothyronine to thyroxine, compatible with partial inhibition of peripheral deiodination of thyroxine. Adverse reactions occurred more frequently with propranolol than with practolol. In veiw of the efficacy of practoloo, further trials in hyperthyroid patients of newer beta1-adrenoceptor antagonists, preferably without partial agonist activity, are indicated.

Lack of effect of bumetanide on body potassium content in hypertension.

1 Twelve patients with mild hypertension were treated with bumetanide for a six-month period. No evidence was found of hypokalaemia or decreased total exchangeable potassium in subjects with or without additional potassium supplements. 2 Bumetanide was well tolerated by all patients. It caused hyperuricaemia but no episodes of gout occurred. Minor abnormalities of liver function were noted. 3 Bumetanide did not have a sustained antihypertensive action.