Impaired glucose tolerance (IGT) and Type II (noninsulin-dependent) diabetes mellitus result from different contributions of deficient insulin secretion and impaired insulin sensitivity [1±8]. Routine quantification of these abnormalities is rarely done as simple, user friendly methods have not been validated or received general approval [9,10]. The choice of therapy might depend on the causative pathophysiology in a patient and, with the prospect of insulin-sensitising drugs as well as life-style changes to improve insulin sensitivity, routine assessment of insulin sensitivity might become more appropriate than at present [11, Diabetologia (1999) AbstractAims/hypothesis. Adequate comparison of the relative performance of insulin sensitivity tests is not yet available. We compared the discrimination of four insulin sensitivity tests, commonly used in vivo, across a range of glucose tolerance. Methods. Normal (n = 7), impaired glucose tolerant (n = 8) and Type II (non-insulin-dependent) diabetic subjects (n = 9) had in random order two tests from the following: frequently sampled insulin-modified intravenous glucose tolerance test (FSIVGTT-MinMod); homeostasis model assessment (HOMA) and 2-h continuous infusion of glucose with model assessment (CIGMA) with immunoreactive or specific insulin; short insulin tolerance tests (ITT). The discriminatory power of tests was assessed by the ratio of the within-subject standard deviation to the underlying between-subject standard deviation (discriminant ratio ± DR). The degree to which tests measured the same variable was assessed by comparing rank correlation with the maximum expected correlation given the imprecision of the tests. The unbiased lines of equivalence taking into account the precision of tests were constructed.Results. Reciprocal fasting plasma insulin (FPI ±1 ), HOMA %S and 2-h CIGMA %S, had similar DRs with ITT being less informative. The FSIVGTT-MinMod analysis was able to assess 13 out of 24 subjects and had a performance similar to ITT. Using specific rather than immunoreactive insulin for HOMA-CIG-MA did not improve the DR. Reciprocal fasting plasma insulin FPI ±1 , HOMA %S, 2-h CIGMA %S and S I FSIVGTT intercorrelated more than 90 % of the expected rank correlation given the imprecision of the tests, but ITT gave only limited correlation. Conclusion/interpretation. The HOMA-CIGMA test with immunoreactive insulin provides similar information in distinguishing insulin sensitivity between subjects with normal glucose tolerance, those with impaired glucose tolerance and those with Type II diabetes as does FSIVGTT, whereas ITT is less informative. [Diabetologia (1999) 42: 678±687]

Adequate comparisons of the relative performance of different tests of beta-cell function are not available. We compared discrimination of commonly used in vivo tests of beta-cell function across a range of glucose tolerance in seven subjects with normal glucose tolerance (NGT), eight subjects with impaired glucose tolerance (IGT), and nine subjects with type 2 diabetes. In random order, each subject underwent two of each of the following tests: 1) frequently sampled 0.3-g/kg intravenous glucose tolerance test (FSIVGTT) with MinMod analysis; 2) homeostasis model assessment (HOMA) from three samples at 5-min intervals with a model incorporating immunoreactive or specific insulin measurements; and 3) continuous infusion of 180 mg x min(-1) x m(-2) glucose with model assessment (CIGMA) of three samples at 50, 55, and 60 min (1-h CIGMA) and at 110, 115, and 120 min (2-h CIGMA). The discrimination of each test was assessed by the ratio of the within-subject SD to the underlying between-subject SD, the discriminant ratio (DR). The degree to which tests measured the same physiological variable was assessed using Pearson's correlation coefficient adjusted for attenuation due to test imprecision. An unbiased line of equivalence, taking into account the imprecision of both tests, was used to compare results. Beta-cell function assessed from HOMA and beta-cell function assessed from CIGMA (CIGMA%beta) (using immunoreactive insulin) had higher DRs than first-phase intravenous glucose tolerance test-derived incremental insulin peak, area, insulin-to-glucose index, and acute insulin response to glucose from FSIVGTT-MinMod. CIGMA%beta (immunoreactive insulin) had the highest DR. FSIVGTT-derived first-phase insulin response tests correlated only moderately with HOMA and CIGMA. Using specific rather than immunoreactive insulin for HOMA and CIGMA did not improve discriminatory power. Simple tests such as HOMA and CIGMA, using immunoreactive insulin, offer better beta-cell function discrimination across subjects with NGT, IGT, and type 2 diabetes than measurements derived from FSIVGTT first-phase insulin response.

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