Relationship between insulin sensitivity and insulin secretion rate: not necessarily hyperbolic

There is general acceptance that the physiological relationship between insulin sensitivity and insulin secretion is hyperbolic. This conclusion has evolved from studies in which one test assessed both variables, and changes in plasma insulin concentration were used as a surrogate measure for insulin secretion rate. The aim of this study was to see if a hyperbolic relationship would also emerge when separate and direct measures were used to quantify both insulin sensitivity and insulin secretion rate.

Steady-state plasma glucose (SSPG) was determined in 146 individuals without diabetes using the insulin suppression test, with 1/SSPG used to quantify insulin sensitivity. The graded-glucose infusion test was used to quantify insulin secretion rate. Plasma glucose and insulin concentrations obtained during an oral glucose tolerance test (OGTT) were used to calculate surrogate estimates of insulin action and insulin secretion rate. A hyperbolic relationship was assumed if the β coefficient was near -1 using the following model: log (insulin secretion measure) = constant + β × log (insulin sensitivity measure).

OGTT calculations of insulin sensitivity (Matsuda) and plasma insulin response [ratio of insulin/glucose area-under-the-curve (AUC) or insulin total AUC] provided the expected hyperbolic relationship [β = -0.95, 95% CI (-1.09, -0.82); -1.06 (-1.14, -0.98)]. Direct measurements of insulin sensitivity and insulin secretion rate did not yield the same curvilinear relationship [β = -1.97 (-3.19, -1.36)].

These findings demonstrate that the physiological relationship between insulin sensitivity and insulin secretion rate is not necessarily hyperbolic, but will vary with the method(s) by which it is determined.