Long-term Results in Treatment of Diabetes Mellitus with the Sulphonylureas

Gorman, Christina; Weaver, J. A.

doi:10.1136/bmj.2.5161.1214

Cited by 10 publications

(3 citation statements)

References 7 publications

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“…On the basis of our previous experience with the sulphonylureas (Gorman and Weaver, 1959;Hadden et al, 1962) and the results of this trial we find 1,000 mg. of acetohexamide to be roughly equivalent to 2,250 mg. of tolbutamide and 500 mg. of chlorpropamide. Our results compare fairly closely with those of Owen (1962), who specifically studied the hypoglycaemic potency of these sulphonylureas in six " maturity onset " diabetics.…”

Section: Discussionsupporting

confidence: 55%

Acetohexamide in Treatment of Diabetes Mellitus

Montgomery¹,

Rastogi²,

Weaver³

1964

BMJ

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animals, either as a whole or at the various times of killing. Grain counts were therefore made, but again no significant differences were found. DiscussionSince this study was begun Danowski et al. (1962) have shown that when leucine and tolbutamide are taken together the degree of hypoglycaemia is no greater than with tolbutamide alone, but the addition of leucine prolonged the duration of the hypoglycaemia. The leucine also increased tolbutamide-induced hypophosphataemia. Danowski et al. therefore suggested that sufficient extra insulin was released to produce further hypophosphataemia, but not further hypoglycaemia. Our studies have shown that tolbutamide can " sensitize " normal individuals to the hypoglycaemic effect of leucine, so it does appear that this is a general property of the sulphonylureas. Fajans et al. (1963) have clearly demonstrated that leucine-induced hypoglycaemia after chlorpropamide administration is associated with increased circulating insulin (immuno-assay) levels. They also found that, although oral leucine had no consistent effects on the blood sugar when administered intravenously, there was a small but fairly consistent fall in the blood sugar. This evidence would support Cochrane's (1960) hypothesis that the level of leucine in the plasma normally exerts some control over the rate of insulin release. If this hypothesis is correct, then the controlling effect must normally be small. However, in certain conditions-genetic predisposition, islet-cell tumours, and during sulphonylurea therapy-the normal effect of leucine is magnified.The sensitizing effect of the sulphonylureas may be due to a variety of effects, but the two most likely hypotheses would seem to be (a) that the drugs increase leucine uptake by the islets, or (b) that by stimulating insulin clearance from the islets they render the mechanisms of control of insulin production more sensitive to changes in plasma leucine (or glucose).The latter situation might apply with /l-cell adenomata, where insulin synthesis and release are also increased by leucine. Our studies lend no support to the first hypothesis. Only in unphysiological amounts does tolbutamide affect in vitro leucine metabolism by muscle. And, although the autoradiographic method is only likely to reveal relatively gross differences in leucine uptake by the islets, our small study did not reveal any such difference. The method of studying the metabolism of isolated mammalian islets (Keen et al., 1963) may offer a more sensitive method of studying both hypotheses. SummaryAfter the administration of tolbutamide normal individuals become sensitive to the hypoglycaemic effect of the amino-acid L-leucine. This effect could not, however, be demonstrated after the administration of another hypoglycaemic drug, phenformin. In vitro studies with the rat diaphragm failed to reveal any effect of tolbutamide upon leucine metabolism except in concentrations greater than those achieved therapeutically. No difference could be demonstrated in the uptake of injected 14C-leucine...

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Section: Discussionsupporting

confidence: 55%

Acetohexamide in Treatment of Diabetes Mellitus

Montgomery¹,

Rastogi²,

Weaver³

1964

BMJ

Self Cite

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“…It has been considered that patients with a fasting value over this level would not respond or would prove difficult, whilst patients with fasting blood sugar value below 300 mg would respond reason ably satisfactorily (Dunlop, 1957). It is appreciated that by his scheme a few patients may have missed the benefits of oral agents but Gorman and Weaver (1959) have recently shown that in a group of patients who failed to respond to sulphonylurca treatment, 44% had average initial blood sugars greater than 300 mg/100 ml where as only 3% of successes had average initial figures in excess of this. …”

Section: Initial Oral Treatment Of Elderly Diabetic Patientsmentioning

confidence: 99%

“…Initial failures have been reported in varying incidences from 10% (Walker et al, 1957) to 30%. Whilst Gorman andWeaver (1959) record a 10% failure rate in patients age 70-80 and 50% failure in patients over 80 years. These rates of initial failures are high and lack of selection of material is probably the most likely explanation and selection would in fact explain the low incidence found in the present study.…”

Section: Dosage Of Tolbutamidementioning

confidence: 99%