An empirical index of insulin sensitivity from short IVGTT: validation against the minimal model and glucose clamp indices in patients with different clinical characteristics
Open accessAbstract
Aims/hypothesis Minimal model analysis for insulin sensitivity has been validated against the glucose clamp and is an accepted method for estimating insulin sensitivity from IVGTT. However minimal model analysis requires a 3 h test and relevant expertise to run the mathematical model. The aim of this study was to suggest a simple predictor of minimal model analysis index using only 1 h IVGTT.Methods We studied participants with different clinical characteristics who underwent 3 h regular (n = 336) or insulin-modified (n = 160) IVGTT, or 1 h IVGTT and euglycaemic-hyperinsulinaemic clamp (n = 247). Measures of insulin sensitivity were insulin sensitivity index estimated by minimal model analysis (S(I)) and the mean glucose infusion rate (clamp) (M). A calculated S(I) (CS(I)) predictor, CS(I) = Alpha X K(G)/(DeltaAUC(INS)/T), was suggested, based on the calculation of the rate of glucose disappearance K(G) and the suprabasal AUC of insulin concentration DeltaAUC(INS) over T = 40 min. For all the participants, alpha was assumed equal to the regression line slope between K(G)/(DeltaAUC(INS)/T) and S(I) in control participants.Results CS(I) and S(I) showed high correlation (R(2) = 0.68-0.96) and regression line slopes of approximately one in the majority of groups. CS(I) tended to overestimate S(I) in type 2 diabetic participants, but results were more reliable when CS(I) was computed with insulin-modified rather than regular IVGTT. CS(I) showed behaviours similar to S(I) as regards relationships with BMI, acute insulin response and sex. CS(I) showed good correlation with M (R(2) = 0.82).Conclusions/interpretation A short test can achieve a good approximation of minimal model analysis and clamp insulin sensitivity. The importance of a method such as CS(I) is that it allows analysis of IVGTT datasets with samples limited to 1 h.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The insulin sensitivity index (CSI) from the 50-minute IVGTT is highly correlated with the Minimal Model insulin sensitivity index (SI) from a 3-hour IVGTT and with the glucose infusion rate during a hyperinsulinemic-euglycemic clamp, and has greater reproducibility than the Matsuda composite index (MISI) derived from an OGTT.
“CSI is highly correlated with the Minimal Model insulin sensitivity index (SI) obtained from a 3-hour IVGTT, as well as the glucose infusion rate during a hyperinsulinemic-euglycemic clamp [19]. This method has also been used to assess insulin sensitivity in response to acute exercise [20,21], and has greater reproducibility than the Matsuda composite index (MISI) derived from an OGTT [20].”
From Twelve weeks of sprint interval training improves indices of cardiometabolic health similar to traditional endurance training despite a five-fold lower exercise volume and time commitment (2016) · cites this paper as [19]
Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502 · see citing works
Bergman, R. N., Phillips, L. S., & Cobelli, C. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110398 · Cited by 1,640 · cited 1× · see citing works
“The existence of nonlinear inverse (hyperbolic) relationship between insulin sensitivity and insulin release was postulated some years ago [28] and several subsequent studies [29] have confirmed this finding, although it has recently been suggested that the hyperbola may not be evident in some groups of participants […”
ResultKahn, S. E., Prigeon, R. L., McCulloch, D. K., Boyko, E. J., Bergman, R. N., Schwartz, M. W., Neifing, J. L., Ward, W. K., Beard, J. C., & Palmer, J. P. (1993) · Diabetes · doi:10.2337/diab.42.11.1663 · Cited by 1,405 · see citing works
Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity.
Stümvoll, M., Mitrakou, A., Pimenta, W. P., Jenssen, T. G., Yki-Järvinen, H., van Haeften, T. W., Renn, W., & Gerich, J. E. (2000) · Diabetes Care · doi:10.2337/diacare.23.3.295 · Cited by 1,040 · see citing works
Toward Physiological Understanding of Glucose Tolerance: Minimal-Model Approach
Bergman, R. N. (1989) · Diabetes · doi:10.2337/diab.38.12.1512 · Cited by 1,001 · see citing works
Incorrect least-squares regression coefficients in method-comparison analysis.
Cornbleet, P. J., & Gochman, N. (1979) · Clinical Chemistry · doi:10.1093/clinchem/25.3.432 · Cited by 573 · see citing works
How to measure insulin sensitivity
Ferrannini, E., & Mari, A. (1998) · Journal of Hypertension · doi:10.1097/00004872-199816070-00001 · Cited by 506 · see citing works
A model of the kinetics of insulin in man
Sherwin, R. S., Kramer, K. J., Tobin, J. D., Insel, P. A., Liljenquist, J. E., Berman, M., & Andres, R. (1974) · Journal of Clinical Investigation · doi:10.1172/jci107697 · Cited by 460 · cited 1× · see citing works
“It is well known that the action of exogenous insulin on glucose disappearance is delayed [17], and hence we assumed a 5 min delay.”
BackgroundGroop, L., Forsblom, C. M., Lehtovirta, M., Tuomi, T., Karanko, S., Nissén, M., Ehrnstrom, B. O., Forsén, B., Isomaa, B., Snickars, B., et al. (1996) · Diabetes · doi:10.2337/diab.45.11.1585 · Cited by 384 · see citing works
Self-citationSaad, M. F., Anderson, R. L., Laws, A., Watanabe, R. M., Kades, W. W., Chen, Y. D. I., Sands, R. E., Pei, D., Savage, P. J., & Bergman, R. N. (1994) · Diabetes · doi:10.2337/diab.43.9.1114 · Cited by 376 · see citing works
Insulin resistance and hyperinsulinemia are already present in patients with incipient renal disease
Fliser, D., Pacini, G., Engelleiter, R., Kautzky‐Willer, A., Prager, R., Franek, E., & Ritz, E. (1998) · Kidney International · doi:10.1046/j.1523-1755.1998.00898.x · Cited by 358 · see citing works
Self-citationBeta cell function and its relation to insulin action in humans: a critical appraisal
Ferrannini, E., & Mari, A. (2004) · Diabetologia · doi:10.1007/s00125-004-1381-z · Cited by 259 · see citing works
Clausen, J. O., Borch-Johnsen, K., Ibsen, H., Bergman, R. N., Hougaard, P., Winther, K., & Pedersen, O. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118903 · Cited by 259 · see citing works
Amatuzio, D. S., Stutzman, F. L., Vanderbilt, M. J., et al. (1953) · Journal of Clinical Investigation · doi:10.1172/jci102755 · Cited by 213 · see citing works
Finegood, D. T., HRAMIAK, I. M., & Dupré, J. (1990) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-70-6-1538 · Cited by 186 · see citing works
Salinari, S., BERTUZZI, A., Asnaghi, S., Guidone, C., Manco, M., & Mingrone, G. (2008) · Diabetes Care · doi:10.2337/dc08-1314 · Cited by 157 · see citing works
Kautzky-Willer, A., Krssak, M., Winzer, C., Pacini, G., Tura, A., Farhan, S., Wagner, O., Brabant, G., Horn, R., Stingl, H., et al. (2003) · Diabetes · doi:10.2337/diabetes.52.2.244 · Cited by 150 · see citing works
Self-citationLaakso, M., Zilinskaite, J., Hansen, T. F., Boesgaard, T. W., Vänttinen, M., Stančáková, A., Jansson, P., Pellmé, F., Holst, J. J., Kuulasmaa, T., et al. (2007) · Diabetologia · doi:10.1007/s00125-007-0899-2 · Cited by 145 · see citing works
Self-citationAnderson, R. L., Hamman, R. F., Savage, P. J., Saad, M. F., Laws, A., Kades, W. W., Sands, R., & Cefalu, W. T. (1995) · American Journal of Epidemiology · doi:10.1093/aje/142.7.724 · Cited by 138 · see citing works
Standardization of insulin immunoassays: report of the American Diabetes Association Workgroup
Marcovina, S., Bowsher, R. R., Miller, W. G., Staten, M., Myers, G., Caudill, S. P., Campbell, S. E., Steffes, M. W., & Workgroup, F. T. I. S. (2007) · Clinical Chemistry · doi:10.1373/clinchem.2006.082214 · Cited by 136 · see citing works
Galvin, P., Ward, G. M., Walters, J. M., Pestell, R. G., Koschmann, M., Vaag, A. A., Martin, I. K., Best, J. D., & ALFORD, F. P. (1992) · Diabetic Medicine · doi:10.1111/j.1464-5491.1992.tb01732.x · Cited by 112 · see citing works
U.K. Prospective Diabetes Study
Turner, R. C., Cull, C. A., & Holman, R. R. (1996) · Diabetes Care · doi:10.2337/diacare.19.2.182 · Cited by 111 · see citing works
Pacini, G., Tonolo, G., Sambataro, M. P., Maioli, M., Ciccarese, M., Brocco, E., Avogaro, A., & Nosadini, R. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.274.4.e592 · Cited by 109 · see citing works
Self-citationZhang, Y., Wat, N. M. S., STRATTON, I. M., Warren-Perry, M., Orho, M., Groop, L., & Turner, R. C. (1996) · Diabetologia · doi:10.1007/s001250050605 · Cited by 96 · see citing works
Self-citationKautzky‐Willer, A., Pacinl, G., Niederle, B., Schernthaner, G., & Prager, R. (1992) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1992.tb02299.x · Cited by 87 · see citing works
Avogaro, A., Miola, M., Favaro, A., Gottardo, L., Pacini, G., Manzato, E., Zambon, S., Sacerdoti, D., de Kreutzenberg, S., Piliego, T., et al. (2001) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2001.00856.x · Cited by 73 · see citing works
Self-citationLudvik, B. H., Markolf Hanefeld, E., & Pacini, G. (2007) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2007.00752.x · Cited by 64 · see citing works
Self-citationHaffner, S. M., D’Agostino, R., Festa, A., Bergman, R. N., Mykkänen, L. M., Karter, A. J., Saad, M. F., & Wagenknecht, L. E. (2003) · Diabetes Care · doi:10.2337/diacare.26.10.2796 · Cited by 61 · see citing works
Avogaro, A., Watanabe, R. M., Dall’Arche, A., de Kreutzenberg, S. V., Tiengo, A., & Pacini, G. (2004) · Diabetes Care · doi:10.2337/diacare.27.6.1369 · Cited by 57 · see citing works
Self-citationThe hyperbolic equilibrium between insulin sensitivity and secretion
Pacini, G. (2006) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2005.10.014 · Cited by 46 · see citing works
Self-citationEstévez, D. A. G., Araújo‐Vilar, D., Saavedra, Á., Fiestras-Janeiro, M. G., & Cabezas-Cerrato, J. (2004) · Metabolism · doi:10.1016/j.metabol.2004.06.014 · Cited by 40 · see citing works
Assessment of insulin sensitivity with minimal model: role of model assumptions
Mari, A. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.272.5.e925 · Cited by 33 · see citing works
Pacini, G., Ahrén, M., & Åhrén, B. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90575.2008 · Cited by 27 · see citing works
Self-citationTura, A., Mari, A., Prikoszovich, T., Pacini, G., & Kautzky‐Willer, A. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03178.x · Cited by 24 · see citing works
Self-citationMorbiducci, U., Benedetto, G. D., Kautzky‐Willer, A., Pacini, G., & Tura, A. (2007) · Clinical Science · doi:10.1042/cs20060203 · Cited by 13 · see citing works
Self-citationViviani, G. L., & Pacini, G. (1999) · Aging Clinical and Experimental Research · doi:10.1007/bf03399659 · Cited by 9 · see citing works
Self-citationInsulin Secretion in IDDM Patients Who Have Undergone Successful Pancreas–Kidney Transplantation
Rigotti, P., Pacini, G., Baldan, N., et al. (1998) · Transplantation Proceedings · doi:10.1016/s0041-1345(97)01428-0 · Cited by 4 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Gillen, J. B., Martin, B. J., MacInnis, M. J., Skelly, L. E., Tarnopolsky, M. A., & Gibala, M. J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0154075 · Cited by 363 · see citing works
“604), KG is the glucose disappearance rate (mmol/L; calculated as the slope of log [glucose]), ΔAUCINS is the insulin area under the curve above basal (uIU/ml) and T is the time between 10 and 50 minutes (40 minutes) from which KG and ΔAUCINS were calculated [19].”
MethodInfluentialOrtega, J. F., Hamouti, N., Fernández-Elías, V. E., & Mora-Rodriguez, R. (2014) · Applied Physiology Nutrition and Metabolism · doi:10.1139/apnm-2013-0507 · Cited by 14 · see citing works
- Authors
- Tura, A., Sbrignadello, S., Succurro, E., Groop, L., Sesti, G., & Pacini, G.
- Affiliations
- National Research Council (IT)
- Magna Graecia University (IT)
- University of Helsinki (FI)
- Corresponding author
- Pacini, G.
- Venue
- Diabetologia
- Published
- 2009-10-30
- Volume
- 53
- Issue
- 1
- Pages
- 144-152
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2153797852
- Cited by
- 71
- References
- 37
- Citations by year
- 2026: 1 · 2024: 4 · 2023: 1 · 2021: 10 · 2020: 6 · 2019: 6 · 2018: 5 · 2017: 8 · 2016: 6 · 2015: 3 · 2014: 9 · 2013: 4 · 2012: 3
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Eli Lilly and Company
- Sanofi
- Universität Wien
- Medizinische Universität Wien
- European Association for the Study of Diabetes
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- insulin sensitivity, insulin sensitivity index, minimal model analysis, hyperinsulinemic-euglycemic clamp, glucose infusion rate, glucose disappearance rate, type 2 diabetes, acute insulin response, body mass index, sex differences
- MeSH terms
- Adult, Blood Glucose, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Glucose Tolerance Test, Humans, Hyperinsulinism, Hyperparathyroidism, Insulin, Kidney Diseases, Middle Aged, Models, Biological, Regression Analysis, Reproducibility of Results, Glucose Clamp Technique, Body Mass Index, Glucose Intolerance, Area Under Curve
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
