Importance of obtaining independent measures of insulin secretion and insulin sensitivity during the same test: results with the Botnia clamp.

OBJECTIVE To validate and apply a method for independent assessment of insulin secretion and insulin sensitivity (S(I)) during the same test; that is, an intravenous glucose tolerance test followed by a euglycemic-hyperinsulinemic clamp, also called the Botnia clamp. This test was then applied to nondiabetic subjects with (FH+) and without (FH-) a first-degree family history of diabetes. RESEARCH DESIGN AND METHODS The Botnia clamp measures the first-phase insulin response (FPIR) to 0.3g/kg glucose i.v. and insulin sensitivity (M-value) from a 2-h euglycemic clamp begun 60 min after the glucose bolus. The M-value obtained during the Botnia clamp was compared with M-values obtained during a regular euglycemic clamp without prior glucose bolus. Repeated tests were performed in random order in subjects with normal and abnormal glucose tolerance. Finally, the test was applied to subjects with and without a family history of type 2 diabetes. RESULTS S(I) and insulin secretion from this test showed a high degree of reproducibility, and the M-value obtained with the Botnia clamp correlated strongly with the M-value from a euglycemic clamp without prior glucose bolus (r = 0.953, P < 0.005). FH+ subjects showed decreased S(I) (P = 0.02), but similar FPIR, compared with FH- subjects. However, insulin secretion adjusted for the degree of insulin resistance was significantly impaired (P = 0.04). CONCLUSIONS In conclusion, the Botnia clamp provides reliable and independent measures of S(I) and beta-cell function during the same test. As illustrated above, knowledge of the degree of S(I) is mandatory when presenting data on insulin secretion.