Subcutaneous aprotinin causes local hyperaemia

Williams, Gareth; Pickup, John C.; Bowcock, S.A.; Cooke, E. D.; Keen, H.

doi:10.1007/bf00297388

Cited by 23 publications

(6 citation statements)

References 12 publications

(21 reference statements)

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“…However, early successes with this treatment have not been maintained [66]; in our experience with subcutaneously-resistant patients, aprotinin has been of no use. The alternative theory to explain this syndrome is that insulin absorption from subcutaneously injected sites is poor and erratic because of variably impaired blood flow [47] -indeed it has been suggested that aprotinin itself may improve insulin absorption by inducing local hyperaemia [67]. Anecdotally, both local and systemic vasodilator therapy has not proved useful [68]; but recently, addition of prostaglandins to the injected insulin has been shown to improve absorption [69], though it is uncertain whether this effect will be therapeutically useful.…”

Section: Insulin Resistance Syndromesmentioning

confidence: 99%

Brittle diabetes — present concepts

1985

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Brittle" diabetes is one of the most poorly defined terms of modem medicine: it is emotive, subjective and imprecise. None the less it is an attractively appropriate descriptive term when clearly defined, and could usefully replace the many synonyms, such as "superlabile", "oscillatory" and "unstable". Woodyatt [1] was the first to describe patients with diabetes as "brittle". He defined such patients as "... insulin-dependent diabetics whose control is so fragile that they are subject to frequent and precipitous fluctuations between hyperglycaemia and insulin reactions and in whom causes of instability have been excluded." Used correctly this definition has proved useful although it has often been grossly abused. Rosenbloom [2], when discussing brittle diabetes in children, narrowed the definition to "those children whose sensitivity to insulin is such that a dosage change of 10% will result in either ketonaemia or reactions". Colwell [3] stated that "unstable diabetes is characterised by irregular, unpredictable behaviour of glycaemia and glycosuria with all insulins, especially the depot varieties, even though the food supply and amount of exercise are constant." These definitions, although useful, are rather restrictive and exclude those patients with predominantly hyperglycaemic or hypoglycaemic instability, which often form two distinct clinical subgroupings. In addition, it is now possible to define the cause of instability in many "brittle" patients (even if treatment remains difficult), and this would take many cases outside Woodyatt's definition. For these reasons, a more useful definition is that proposed by Tattersall in 1977 [4]... "insulindependent diabetics whose lives are constantly disrupted by episodes of hypo-or hyperglycaemia, whatever the cause". The concept of life disruption is an important one, which usefully separates problematic from non-problematic unstable diabetic patients.

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Section: Insulin Resistance Syndromesmentioning

confidence: 99%

Brittle diabetes — present concepts

1985

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“…Note that two out of five of the subjects experienced hypoglycemic symptoms during the study. This contrasts with the shortlived effect of aprotinin (7,11,12), which also accelerates insulin absorption, in part through increased local hyperemia at the injection site. T h e IRI-enhancing effect of aprotinin extended from 15 to 60 min after the injection, with the peak IRI occurring at 45 min.…”

Section: Resultsmentioning

confidence: 53%

“…This effect is evident whether increased flow is achieved through exercise (3,4), an increase in local temperature (5), or injection of a vasodilator (6). Some workers attribute the facilitatory effect of aprotinin on insulin absorption to its vasodilatory rather than its antiprotease action (7). This has, however, been challenged (8).…”

mentioning

confidence: 96%

Insulin Absorption Accelerated by Alpha-Adrenergic Blockade at Injection Site

et al. 1987

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The effect of the addition of phenoxybenzamine to a regular insulin preparation on the absorption of insulin and plasma glucose concentrations was investigated in five normal subjects. The addition of phenoxybenzamine (20 micrograms) to insulin (0.2 U/kg body wt) resulted in an acceleration of insulin absorption, with a higher and earlier peak insulin concentration at 45 min and higher insulin concentrations throughout the 180 min of investigation. With phenoxybenzamine, plasma glucose concentrations fell more rapidly; nadirs were lower and more rapidly achieved. Two subjects experienced hypoglycemic symptoms when phenoxybenzamine was added to insulin. It is concluded that the addition of phenoxybenzamine to subcutaneously injected insulin increases the bioavailability of insulin for at least 3 h, which leads to a greater fall in plasma glucose concentrations.

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“…The photoelectric technique, however, does not allow discrimination between blood flow changes in the skin and the subcutaneous tissue. Therefore, th~ flow increase registered by Williams et al [9] might well have been an effect of the injection trauma in the cutaneous tissues. The local t33Xe clearance technique, on the other hand, reflects the circulation selectively within the depot area and, thus, shows that blood flow was indeed higher in this area when aprotinin was given with the insulin.…”

Section: Discussionmentioning

confidence: 85%

“…By using a photoelectric measuring principle, hyperaemia in the tissues beneath the measuring probe following the injection of aprotinin has also recently been reported [9]. The photoelectric technique, however, does not allow discrimination between blood flow changes in the skin and the subcutaneous tissue.…”

Section: Discussionmentioning

confidence: 99%

Influence of aprotinin on insulin absorption and subcutaneous blood flow in Type 1 (insulin-dependent) diabetes

Linde

Gunnarsson

1985

Diabetologia

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Ten normal-weight Type 1 (insulin-dependent) diabetic patients (12 h postprandial) with normal insulin requirement were given 125I-labelled soluble insulin (10 U) in the thigh together with aprotinin (10000 KIU) or its diluent on two consecutive mornings. Disappearance of 125I-radioactivity was followed continuously for 3 h by external detection and plasma free insulin measured by radioimmunoassay. Subcutaneous blood flow following aprotinin or diluent was studied concomitantly in the contralateral thigh by external monitoring of locally injected 133Xenon. Plasma free insulin increased significantly faster (p less than 0.05) and the insulin area under the curve was significantly (p less than 0.05) greater during the first hour after injection of insulin with aprotinin. Subcutaneous blood flow (rate constants for 133Xenon) was significantly higher with aprotinin (p less than 0.05), the highest flow occurring early after injection. In conclusion, subcutaneously injected soluble insulin is more rapidly absorbed by addition of aprotinin to the insulin solution in Type 1 diabetes. Blood flow increase at the injection site may explain part of this effect.

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Subcutaneous aprotinin causes local hyperaemia

Cited by 23 publications

References 12 publications

Brittle diabetes — present concepts

Brittle diabetes — present concepts

Insulin Absorption Accelerated by Alpha-Adrenergic Blockade at Injection Site

Influence of aprotinin on insulin absorption and subcutaneous blood flow in Type 1 (insulin-dependent) diabetes

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