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

Published on Apr 1, 1998in American Journal of Physiology-endocrinology and Metabolism4.125
· DOI :10.1152/ajpendo.1998.274.4.E592
Giovanni Pacini54
Estimated H-index: 54
(National Research Council),
Giancarlo Tonolo31
Estimated H-index: 31
(University of Sassari)
+ 5 AuthorsR. Nosadini16
Estimated H-index: 16
(University of Sassari)
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.
  • References (33)
  • Citations (87)
📖 Papers frequently viewed together
603 Citations
10 Authors (Steven E. Kahn, ..., Jerry P. Palmer)
1,151 Citations
815 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Ta-Chen NiH-Index: 2
#2Marilyn AderH-Index: 28
Last. Richard N. BergmanH-Index: 96
view all 3 authors...
Minimal model analysis with the frequently sampled intravenous glucose tolerance test provides an effective way to measure two important metabolic parameters in vivo under non-steady-state conditions: glucose effectiveness ( S G ) and insulin sensitivity ( S I ). Two questions regarding the validity of S G and S I have recently emerged. First, S G from the minimal model is suspected to be overestimated. Second, the occurrence of S I values indistinguishable from zero (“zero- S I ”) is not neglig...
39 CitationsSource
This study examined whether insulin secretion, insulin sensitivity, glucose effectiveness, and hepatic extraction of insulin are altered in subjects with impaired glucose tolerance (IGT). The frequ...
51 CitationsSource
#1Mohammed F. SaadH-Index: 74
#2Garry M. SteilH-Index: 42
Last. Richard N. BergmanH-Index: 96
view all 8 authors...
The insulin-modified frequently sampled Intravenous glucose tolerance test (FSIGTT) with minimal model analysis (MINMOD) was compared with the tolbutamide protocol and the glucose clamp in 35 nondiabetic subjects (age 38 ± 2 years [mean ± SE], BMI 27.2 ± 0.9 kg/m 2 ). Each subject underwent two FSIGTTs, one with tolbutamide (300 mg) and the other with insulin (0.03 U/kg) and a euglycemic hyperinsulinemic clamp (40 mU · m −2 · min −1 ). Insulin sensitivity was determined from each FSIGTT with MIN...
57 CitationsSource
Insulin sensitivity is frequently assessed with the minimal model (MM) and the insulin-modified intravenous glucose tolerance test (MIVGTT). To ascertain the validity of this approach, the mechanisms by which the MM estimates glucose effectiveness and insulin sensitivity (SG and SI, respectively) from the data are analyzed theoretically. Published data and new labeled MIVGTTs in normal and non-insulin-dependent diabetic (NIDDM) subjects are used as reference data. One reason for the reported dif...
27 CitationsSource
#1Marilyn AderH-Index: 28
#2Ta-Chen NiH-Index: 2
Last. Richard N. BergmanH-Index: 96
view all 3 authors...
Glucose tolerance is determined by both insulin action and insulin-independent effects, or “glucose effectiveness,” which includes glucose-mediated stimulation of glucose uptake (R d ) and suppression of hepatic glucose output (HGO). Despite its importance to tolerance, controversy surrounds accurate assessment of glucose effectiveness. Furthermore, the relative contributions of glucose’s actions on R d and HGO under steady state and dynamic conditions are unclear. We performed hyperglycemic cla...
81 CitationsSource
#1Ananda BasuH-Index: 43
#2Andrea Caumo (UniSR: Vita-Salute San Raffaele University)H-Index: 35
Last. Robert A. RizzaH-Index: 81
view all 7 authors...
People with NIDDM are resistant to insulin. The present studies sought to determine whether the ability of glucose to regulate its own metabolism in the presence of basal insulin concentrations is impaired. To address this question, basal insulin concentrations were maintained constant with an exogenous insulin infusion, while endogenous hormone secretion was inhibited by somatostatin. The integrated glycemic response above baseline during identical prandial glucose infusions was greater (1,411 ...
74 CitationsSource
#1Karl ThomasethH-Index: 26
#2Claudio Cobelli (UNIPD: University of Padua)H-Index: 88
Abstract In the identification of physiological systems it is often of practical interest knowing which time intervals during experiments provide most information on specific estimated model parameters. A common approach is based on visual inspection of the time courses of model output sensitivities determined for each parameter separately. This kind of analysis is however limited if strong correlation between parameter estimates is present. For this purpose, three approaches, based on different...
12 CitationsSource
#1James D. BestH-Index: 49
#2Steven E. KahnH-Index: 98
Last. Richard N. BergmanH-Index: 96
view all 6 authors...
230 CitationsSource
#1D. T. Finegood (U of A: University of Alberta)H-Index: 1
#2D. Tzur (U of A: University of Alberta)H-Index: 1
We previously demonstrated that minimal model-derived estimates of glucose effectiveness (SG), based on the frequently sampled intravenous glucose tolerance test (SGFSIGT), were reduced in islet-tr...
82 CitationsSource
Administration of exogenous insulin during an intravenous glucose tolerance test allows the use of the minimal model technique to determine the insulin sensitivity index in subjects with reduced endogenous insulin responses. To study the effect of different insulin administration protocols, we performed three intravenous glucose tolerance tests in each of seven obese subjects (age, 20-41 yr; body mass index, 30-43 kg/m2). Three different insulin administration protocols were used: a low-dose (0....
89 CitationsSource
Cited By87
#1Micaela Morettini (Marche Polytechnic University)H-Index: 7
#2Carlo Castriota (Marche Polytechnic University)
Last. Andrea TuraH-Index: 31
view all 7 authors...
BACKGROUND: This study aimed to design a simple surrogate marker (i.e., predictor) of the minimal model glucose effectiveness (SG), namely calculated SG (CSG), from a short insulin-modified intravenous glucose tolerance test (IM-IVGTT), and then to apply it to study women with previous gestational diabetes mellitus (pGDM). METHODS: CSG was designed using the stepwise model selection approach on a population of subjects (n=181) ranging from normal tolerance to type 2 diabetes mellitus (T2DM). CSG...
#1Veronica Falcone (Medical University of Vienna)H-Index: 2
#2Grammata Kotzaeridi (Medical University of Vienna)
Last. Christian S. Göbl (Medical University of Vienna)H-Index: 12
view all 11 authors...
#1Micaela Morettini (Marche Polytechnic University)H-Index: 7
#2Ludovica Ilari (Marche Polytechnic University)
Last. Laura Burattini (Marche Polytechnic University)H-Index: 18
view all 7 authors...
Sex differences may assume a key role in condition of impaired glucose metabolism and progression to type 2 diabetes, affecting insulin-dependent processes. However, the presence of sex differences in non-insulin-dependent processes (i.e. glucose effectiveness) has been scarcely investigated. The aim of this study was to detect the presence of sex differences in glucose effectiveness (SG), as assessed by minimal model analysis, in subjects with different degrees of glucose metabolism impairment....
#1Jie Zhang (SJTU: Shanghai Jiao Tong University)H-Index: 43
#2Huating Li (SJTU: Shanghai Jiao Tong University)H-Index: 20
Last. Wei Jia (SJTU: Shanghai Jiao Tong University)H-Index: 54
view all 14 authors...
Purpose The ileum-derived fibroblast growth factor 19 (FGF19) plays key roles in hepatic glucose homeostasis in animals in an insulin-independent manner. Here, we analyzed the association of FGF19 with glucose effectiveness (GE, the insulin-independent glucose regulation), as well as hepatic glucose production (HGP) in Chinese subjects.
1 CitationsSource
#1Micaela Morettini (Marche Polytechnic University)H-Index: 7
#2Francesco Di Nardo (Marche Polytechnic University)H-Index: 14
Last. Andrea TuraH-Index: 31
view all 8 authors...
Aims Minimal model analysis of intravenous glucose tolerance test (IVGTT) data represents the reference method to assess insulin sensitivity (SI) and glucose effectiveness (SG) that quantify the insulin-dependent and insulin-independent processes of glucose disappearance, respectively. However, test duration (3 h) and need for modeling expertise limit the applicability of this method. Aim of this study was providing a simple predictor of SG applicable to short test (1 h), as previously done with...
2 CitationsSource
#1Micaela Morettini (Marche Polytechnic University)H-Index: 7
#2Francesco Di Nardo (Marche Polytechnic University)H-Index: 14
Last. Laura Burattini (Marche Polytechnic University)H-Index: 18
view all 6 authors...
Glucose effectiveness (SG) represents the ability of glucose per se, under basal insulin concentrations, to stimulate its own uptake and to suppress its own production. SG and its two components BIE (Basal Insulin Effect) and GEZI (Glucose Effectiveness at Zero Insulin) are known to decline in subjects whose glycemic status worsens, but no study aimed to analyze whether changes may occur even before, when a normal glucose tolerance status is still preserved but insulin resistance has already ari...
1 CitationsSource
#1Giovanni PaciniH-Index: 54
#2Bo Ahrén (Lund University)H-Index: 88
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) stimulate insulin secretion. They are both released after meal ingestion, and therefore they might cooperate in their actions. However, whether there is a cooperative action of the two incretins is not known. This study therefore investigated the effects on insulin secretion and glucose disappearance of GLP-1 and GIP when given together with intravenous glucose both alone and in combination in mice. Four different...
5 CitationsSource
#1Peiwen Liang (SJTU: Shanghai Jiao Tong University)H-Index: 2
#2Liuqing Xi (SJTU: Shanghai Jiao Tong University)H-Index: 2
Last. Jie Hong (SJTU: Shanghai Jiao Tong University)H-Index: 32
view all 14 authors...
Objective To compare the prevalence of polycystic ovary syndrome (PCOS) and related clinical characteristics between metabolically unhealthy obese (MUO) and metabolically healthy obese (MHO) women of reproductive age. Design Cross-sectional clinical study. Setting Tertiary hospital. Patient(s) We studied 299 MUO and 122 MHO Chinese women matched on body mass index. Metabolically healthy obese was defined as obesity with no more than one metabolic abnormality. Diagnosis of PCOS was based on the r...
7 CitationsSource
#1Saloni Rathee (DCE: Delhi Technological University)H-Index: 1
#2Nilam (DCE: Delhi Technological University)H-Index: 2
Diabetes also known as diabetes mellitus is a chronic and complex metabolic disease due to the persistent raised blood glucose concentration for long duration. The mechanism behind the disturbed glucose-insulin dynamics is still not fully understood. The mathematical models which describe the glucose homeostasis, different aspects of diabetes and its consequences are growing rapidly, provide new insights into the biological mechanism involved and help in the management of diabetes. Here, contrib...
4 CitationsSource
#1Toh Peng Yeow (Penang Medical College)H-Index: 3
#2Giovanni Pacini (National Research Council)H-Index: 54
Last. Wan Nazaimoon Wan MohamudH-Index: 12
view all 11 authors...
Objective Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect are scarce. We examined the insulin resistance, β-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM. Research design and methods This case–control study recruited 25 A...
4 CitationsSource