The euglycaemic hyperinsulinaemic clamp: an evaluation of current methodology

Area of Science:

• Endocrinology
• Metabolic Research
• Clinical Physiology

Background:

• Insulin resistance is crucial in disease states.
• New drugs targeting insulin-dependent metabolism are emerging.
• The euglycaemic hyperinsulinaemic clamp is increasingly used to measure insulin sensitivity in vivo.

Purpose of the Study:

• Evaluate the reproducibility of insulin sensitivity measurements using the clamp technique.
• Assess intersubject variation in insulin sensitivity.
• Determine the effects of hand warming on haemodynamic and metabolic responses during the clamp.

Main Methods:

• Two protocols were used: (i) repeated clamp measurements in healthy volunteers and hypertensive patients, and (ii) comparison of antecubital vs. 'arterialized' venous blood and effects of hand warming in healthy volunteers.
• Insulin sensitivity (M) was derived after 120 and 180 minutes of hyperinsulinaemia.
• Haemodynamic and metabolic parameters, including blood pressure, heart rate, venous oxygen saturation, and plasma glucose, were monitored.

Main Results:

• Clamp measurements of insulin sensitivity (M120 and M180) demonstrated good reproducibility in both volunteers and patients.
• Significant intersubject variation (20-40%) in insulin sensitivity was observed.
• Hand warming effectively arterialized venous blood, increasing glucose concentrations and M values, but also induced systemic vasodilation.

Conclusions:

• Euglycaemic hyperinsulinaemic clamp durations of 120 and 180 minutes provide reproducible measures of insulin sensitivity.
• The clamp technique is more robust in a crossover design due to significant intersubject variation.
• While hand warming aids arterialization and increases M values, its vasodilatory effects may confound measurements.