*Geek Box: Measuring Insulin Sensitivity

*Geek Box: Hyperinsulinemic-euglycemic clamp & HOMA-IR

You will inevitably come across certain investigative techniques in research papers, particularly if you have an interest in diabetes or fatty liver disease [or any condition defined by insulin resistance]. The hyperinsulinemic-euglycemic clamp is a means of assessing whole-body metabolism of glucose into peripheral tissues and the sensitivity  of tissues to insulin during a steady-state elevated glucose levels. To perform a hyperinsulinemic-euglycemic clamp, both glucose and insulin are infused [usually through a catheter in the forearm] together in order to create conditions of normal plasma glucose ranges [hence ‘euglycemic’], but elevated insulin [hence ‘hyperinsulinemic’]. Under these conditions, the rate of glucose infusion matches uptake of glucose by tissues, which reflects the sensitivity of these tissues to insulin. This method has a number of strengths, particularly the assessment of total body insulin sensitivity, but also requires laboratory facilities and greater expense.

The Homeostatic Model Assessment of Insulin Resistance [HOMA-IR] is another commonly used method, and as the name implies is used to determine insulin resistance using a calculation based off fasting blood glucose and insulin values. The mathematical model is based on endogenous fasting glucose levels being regulated by the capacity of bee-cells to produce insulin in response to blood glucose concentrations. A ratio of fasting blood glucose to fasting insulin levels is used to determine the resistance to insulin. A score of 1.0 and range of 0.5-1.4 indicates normal insulin sensitivity; above 1.9 indicates early insulin resistance, while over 2.9 indicates significant insulin resistance. Unlike the clamp, HOMA-IR may be used at scale in prospective studies, and was first used in the UK Prospective Diabetes Study to assess long-term follow-up of participants with type-2 diabetes. Of note, HOMA-IR has reasonably good correlation with the hyperinsulinemic-euglycemic clamp, which is stronger in people with T2DM than for people with normal glucose tolerance.