Insulin sensitivity and glucose effectiveness: minimal model analysis of regular and insulin-modified FSIGT

Abstract

The minimal model is widely used to evaluate insulin action on glucose disappearance from frequently sampled intravenous glucose tolerance tests (FSIGT). The common protocols are a regular (rFSIGT, single injection of 0.3 g/kg of glucose) and an insulin-modified test (mFSIGT, with an additional insulin administration at 20 min). This study compared the insulin sensitivity index (SI) and glucose effectiveness (SG) obtained in the same individual (16 normal subjects) with the two tests. SI was 7.11 ± 0.80 10−4 ⋅ min−1 ⋅ μU−1 ⋅ ml in rFSIGT and 6.96 ± 0.83 in mFSIGT ( P = 0.656), regression r = 0.92, P < 0.0001; SG was 0.0260 ± 0.0028 min−1 and 0.0357 ± 0.0052, respectively, statistically different ( P = 0.013) but still with a good regression ( r = 0.66, P = 0.0051). SG and insulin amount during the early period correlated ( r = 0.6, P = 0.015 in rFSIGT and r = 0.76, P = 0.0006 in mFSIGT). In summary, both FSIGTs with minimal model analysis provide the same SI, which is a very robust index. SG was different by 28% due probably to the relationship between SG and the amount of circulating insulin. In studies comparing groups, the simpler rFSIGT can still be used with the advantage of accounting for endogenous insulin, thus offering the possibility of direct inferences on the β-cell activity.

Importance of quantifying insulin secretion in relation to insulin sensitivity to accurately assess beta cell function in clinical studies

“…For medium size metabolic studies, measurement of beta cell function independently from the corresponding ones of insulin sensitivity, such as the first-phase insulin secretion indices from either the hyperglycemic clamp or the arginine test or the FSIGT are therefore advisable. In particular, in the insulin-modified FSIGT (29,30), insulin secretion is calculated during the first 8-10 min (AIR G ), while for the estimation of the parameter S I the delayed insulin action, i.e. after exogenous insulin administration from 20 min on, plays the major role.…”

“…An experimental procedure that includes determination of both insulin sensitivity and insulin secretion is the IVGTT (28,29) with frequent sampling at the beginning (i.e. FSIGT).…”

“…In both cases, regular and modified FSIGT, the solution of a system of differential equations yields S I , which quantifies the ability of insulin to enhance glucose uptake by insulin-dependent tissues and to inhibit liver glucose production. Regardless of the protocol used, S I is a robust parameter and turned out to be the same with regular and insulinmodified FSIGTs when performed in the same subjects (29). As regards the analysis of the commonly used, simple and widespread oral glucose tolerance test (OGTT), recently several formulas have been published to calculate insulin sensitivity indices (35)(36)(37); their validation in various clinical settings has yet to be established.…”

Circulating concentrations of asymmetrical dimethyl- L -arginine are increased in women with previous gestational diabetes

“…Venous plasma glucose concentrations were measured before and 1 h after the oral glucose load. Insulin resistance was evaluated by the insulin sensitivity index (S I ) during an insulin-modified intravenous glucose tolerance test (FSIGT) [23]. An S I value of 3·10 -4 min -1 ·ml·µU -1 was used to discriminate normal (S I ≥3·10 -4 min -1 ·ml·µU -1 ) from impaired insulin sensitivity (S I <3·10 -4 min -1 ·ml·µU -1 ), respectively.…”

Acute effects of hydrocortisone on the metabolic response to a glucose load: increase in the first-phase insulin secretion

“…We addressed this question using the intravenous glucose tolerance test (IVGTT), which provides a reliable measurement of the first-phase insulin secretion and allows an accurate calculation of the first-phase b-cell function (15)(16)(17). The precise timing and the known amount of glucose directly administered into the circulation, as well as the bypass of gastrointestinal effects that accompany a meal or an oral glucose load, make IVGTT the test of choice for studying the rapid changes in the b-cell response to glucose (18).…”