Volume 24, Issue 7 p. 513-518

THE EUGLYCAEMIC HYPERINSULINAEMIC CLAMP: AN EVALUATION OF CURRENT METHODOLOGY

Andrew D. Morris

Corresponding Author

Andrew D. Morris

Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Glasgow, United Kingdom

Dr AD Morris, University Department of Medicine, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom. Email: [email protected]Search for more papers by this author
Shinchiro Ueda

Shinchiro Ueda

Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Glasgow, United Kingdom

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John R. Petrie

John R. Petrie

Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Glasgow, United Kingdom

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John MC Connell

John MC Connell

Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Glasgow, United Kingdom

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Henry L. Elliott

Henry L. Elliott

Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Glasgow, United Kingdom

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Richard Donnelly

Richard Donnelly

Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Glasgow, United Kingdom

*Department of Pharmacology, University of Sydney and The Diabetes Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.

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First published: 28 June 2007
Citations: 29

SUMMARY

1. The recognition of the role of insulin resistance in disease states and the recent development of new drugs that modify insulin-dependent metabolism has led to increased use of the euglycaemic hyperinsulinaemic clamp to measure in vivo insulin sensitivity, but several key aspects of the technique are poorly documented in the literature.

2. We have evaluated the reproducibility and intersubject variation of measurements of insulin sensitivity in groups of insulin-sensitive and insulin-resistant subjects and assessed the effects of hand warming on haemodynamic and metabolic responses.

3. Subjects participated in one of two protocols: (i) 18 healthy male volunteers and 18 patients with hypertension and glucose intolerance were clamped on two occasions, 1 week apart with measurements of insulin sensitivity (M) derived after 120 and 180 min of hyperinsulinaemia; and (ii) six healthy volunteers were clamped on one occasion with simultaneous sampling of antecubital and ‘arterialized’ (dorsal hand) venous blood for comparison of plasma glucose concentrations and oxygen saturation and a further six volunteers were clamped on two occasions with and without the use of hand warming.

4. Measurements of M derived after 120 min (M120) and 180 min (M180) of hyperinsulinaemia were reproducible: the coefficients of repeatability (mg/kg per min) of M120 and M180 were 1.0 and 0.9 for volunteers and 1.0 and 1.0 for the patient group, respectively. The intersubject variation in insulin stimulus was high: coefficients of variation for M180 were 22% for volunteers compared with 38% for the patient group. In volunteers compared with the patient group, hand warming significantly increased venous oxygen saturations (95 ± 2 vs 79 ± 18%, respectively) and glucose concentrations (5.2 ± 0.2 vs 4.5 ± 0.4 mmol/L, respectively) and measurements of M were significantly higher using arterialized compared with antecubital venous blood. However, local hand warming was associated with systemic vasodilatation: blood pressure decreased (e.g. 6mmHg diastolic; P < 0.05) with a compensatory increase in heart rate (8 b.p.m.).

5. In conclusion, clamps of 120 and 180 min duration yielded measurements of M that were reproducible. The technique is much more robust when used in the context of a crossover design because of the significant (20–40%) intersubject variation in M, even among apparently homogeneous male volunteers. Hand warming effectively arterializes venous blood and gives significantly higher M values, but induces systemic vasodilatation, which may confound measurements of M.

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