Abstract
BackgroundThe Minimal Model, (MM), used to assess insulin sensitivity (IS) from Intra-Venous Glucose-Tolerance Test (IVGTT) data, suffers from frequent lack of identifiability (parameter estimates with Coefficients of Variation (CV) less than 52%). The recently proposed Single Delay Model (SDM) is evaluated as a practical alternative.MethodsThe SDM was applied to 74 IVGTTs from lean (19), overweight (22), obese (22) and morbidly obese (11) subjects. Estimates from the SDM (KxgI) were compared with the corresponding MM (SI), 1/HOMA-IR index and Euglycemic-Hyperinsulinemic Clamp (M-EHC over 7 subjects) estimates.ResultsKxgI was identifiable in 73 out of 74 subjects (CV = 69% in the 74th subject) and ranged from 1.25 × 10-5 to 4.36 × 10-4min-1pM-1; SI CV was >52% in 36 subjects (up to 2.36 × 109%) and presented 18 extreme values (≤ 1.5 × 10-12 or ≥ 3.99).KxgI correlated well with 1/HOMA-IR (r = 0.56, P < 0.001), whereas the correlations KxgI-SI and 1/HOMA-IR-SI were high (r = 0.864 and 0.52 respectively) and significant (P < 0.001 in both cases) only in the non-extreme SI sub-sample (56 subjects). Correlations KxgI vs. M-EHC and SI vs. M-EHC were positive (r = 0.92, P = 0.004 and r = 0.83, P = 0.02 respectively). KxgI decreased for higher BMI's (P < 0.001), SI significantly so only over the non-extreme-SI sub-sample. The Acute Insulin Response Index was also computed and the expected inverse (hyperbolic) relationship with the KxgI observed.ConclusionsPrecise estimation of insulin sensitivity over a wide range of BMI, stability of all other model parameters, closer adherence to accepted physiology make the SDM a useful alternative tool for the evaluation of insulin sensitivity from the IVGTT.
Highlights
The Minimal Model, (MM), used to assess insulin sensitivity (IS) from Intra-Venous Glucose-Tolerance Test (IVGTT) data, suffers from frequent lack of identifiability (parameter estimates with Coefficients of Variation (CV) less than 52%)
Insulin Resistance (IR), an impaired metabolic response to circulating insulin resulting in a decreased ability of the body to respond to the hormone by suppressing Hepatic Glucose Output and enhancing tissue glucose uptake, plays a central role in the development of Type 2 Diabetes Mellitus
The goal of the present study is to apply the same Single Delay Model (SDM) to a heterogeneous population, consisting of overweight, obese and morbidly obese subjects compared with lean individuals, in order to verify the performance of this model over the entire body mass index (BMI) range of interest for diabetologists
Summary
The Minimal Model, (MM), used to assess insulin sensitivity (IS) from Intra-Venous Glucose-Tolerance Test (IVGTT) data, suffers from frequent lack of identifiability (parameter estimates with Coefficients of Variation (CV) less than 52%). The Insulin Resistance Atherosclerosis Study (IRAS), for instance, performed on 398 black, 457 Hispanic, and 542 non-Hispanic white subjects, evaluated insulin sensitivity (SI) by the frequently sampled intravenous glucose tolerance test (IVGTT), analyzed by means of the Minimal Model (MM) [11]. The MM, introduced in the late seventies, suffers, from some relevant problems, one of which is the frequent occurrence of “zero-SI“ values, i.e. of very low point estimates of the insulin sensitivity index, in large clinical studies [12]
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