Separate Impact of Obesity and Glucose Tolerance on the Incretin Effect in Normal Subjects and Type 2 Diabetic Patients
Open accessAbstract
OBJECTIVE—To quantitate the separate impact of obesity and hyperlycemia on the incretin effect (i.e., the gain in β-cell function after oral glucose versus intravenous glucose). RESEARCH DESIGN AND METHODS—Isoglycemic oral (75 g) and intravenous glucose administration was performed in 51 subjects (24 with normal glucose tolerance [NGT], 17 with impaired glucose tolerance [IGT], and 10 with type 2 diabetes) with a wide range of BMI (20–61 kg/m2). C-peptide deconvolution was used to reconstruct insulin secretion rates, and β-cell glucose sensitivity (slope of the insulin secretion/glucose concentration dose-response curve) was determined by mathematical modeling. The incretin effect was defined as the oral-to-intravenous ratio of responses. In 8 subjects with NGT and 10 with diabetes, oral glucose appearance was measured by the double-tracer technique. RESULTS—The incretin effect on total insulin secretion and β-cell glucose sensitivity and the GLP-1 response to oral glucose were significantly reduced in diabetes compared with NGT or IGT (P ≤ 0.05). The results were similar when subjects were stratified by BMI tertile (P ≤ 0.05). In the whole dataset, each manifestation of the incretin effect was inversely related to both glucose tolerance (2-h plasma glucose levels) and BMI (partial r = 0.27–0.59, P ≤ 0.05) in an independent, additive manner. Oral glucose appearance did not differ between diabetes and NGT and was positively related to the GLP-1 response (r = 0.53, P < 0.01). Glucagon suppression during the oral glucose tolerance test was blunted in diabetic patients. CONCLUSIONS—Potentiation of insulin secretion, glucose sensing, glucagon-like peptide-1 release, and glucagon suppression are physiological manifestations of the incretin effect. Glucose tolerance and obesity impair the incretin effect independently of one another.
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 study only tested young and healthy adults and did not confirm results in obese subjects or patients with impaired glucose metabolism.
“Also, we only tested young and healthy adults and did not confirm our results in obese subjects or patients with impaired glucose metabolism (18, 37).”
From Assessment of the incretin effect in healthy subjects: concordance between clamp and OGTT methods (2023) · cites this paper as [37]
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
Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus* (2002) · Diabetes Care · doi:10.2337/diacare.25.2007.s5 · Cited by 10,320 · see citing works
Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (1997) · Diabetes Care · doi:10.2337/diacare.20.7.1183 · Cited by 6,220 · see citing works
β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes
Butler, A. E., Janson, J., Bonner-Weir, S., Ritzel, R., Rizza, R. A., & Butler, P. C. (2003) · Diabetes · doi:10.2337/diabetes.52.1.102 · Cited by 4,011 · see citing works
Kahn, S. E. (2003) · Diabetologia · doi:10.1007/s00125-002-1009-0 · Cited by 2,166 · see citing works
Nauck, M. A., Heimesaat, M. M., Orskov, C., Holst, J. J., Ebert, R., & Creutzfeldt, W. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116186 · Cited by 1,651 · see citing works
Self-citationReduced incretin effect in Type 2 (non-insulin dependent) diabetes
Nauck, M., Stöckmann, F., Ebert, R., & Creutzfeldt, W. (1986) · Diabetologia · doi:10.1007/bf02427280 · Cited by 1,307 · see citing works
Zander, M., Madsbad, S., Madsen, J. L., & Holst, J. J. (2002) · The Lancet · doi:10.1016/s0140-6736(02)07952-7 · Cited by 1,297 · see citing works
Self-citationCauter, E. V., Mestrez, F., Sturis, J., & Polonsky, K. (1992) · Diabetes · doi:10.2337/diab.41.3.368 · Cited by 938 · see citing works
Plasma Insulin Responses to Oral and Intravenous Glucose: Studies in Normal and Diabetic Subjects*
Perley, M. J., & Kipnis, D. M. (1967) · Journal of Clinical Investigation · doi:10.1172/jci105685 · Cited by 917 · see citing works
Tissue and Plasma Concentrations of Amidated and Glycine-Extended Glucagon-Like Peptide I in Humans
Ørskov, C., Rabenhøj, L., Wettergren, A., Kofod, H., & Holst, J. J. (1994) · Diabetes · doi:10.2337/diab.43.4.535 · Cited by 916 · see citing works
Self-citationFerrannini, E., Natali, A., Bell, P., Cavallo-Perin, P., Lalic, N., & Mingrone, G. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119628 · Cited by 898 · see citing works
Self-citationNAUCK, M. A., HOMBERGER, E., SIEGEL, E. G., ALLEN, R. C., EATON, R. P., EBERT, R., & CREUTZFELDT, W. (1986) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-63-2-492 · Cited by 874 · see citing works
Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients
Toft-Nielsen, M.-B., Damholt, M. B., Madsbad, S., Hilsted, L. M., Hughes, T. E., Michelsen, B. K., & Holst, J. J. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.8.7750 · Cited by 869 · see citing works
Self-citationA Model-Based Method for Assessing Insulin Sensitivity From the Oral Glucose Tolerance Test
Mari, A., Pacini, G., Murphy, E., Ludvik, B. H., & Nolan, J. J. (2001) · Diabetes Care · doi:10.2337/diacare.24.3.539 · Cited by 805 · see citing works
Self-citationCauter, E. V., Mestrez, F., Sturis, J., et al. (1992) · Diabetes · doi:10.2337/diabetes.41.3.368 · Cited by 643 · see citing works
Abnormal Alpha-Cell Function in Diabetes: Response to Carbohydrate and Protein Ingestion
Müller, W. A., Faloona, G. R., Aguilar-Parada, E., & Unger, R. H. (1970) · New England Journal of Medicine · doi:10.1056/nejm197007162830301 · Cited by 626 · see citing works
Kolterman, O., Buse, J. B., Fineman, M. S., Gaines, E., Heintz, S., Bicsak, T. A., Taylor, K., Kim, D. S., Aisporna, M., Wang, Y., et al. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021545 · Cited by 549 · see citing works
Laferrère, B., Heshka, S., Wang, K., Khan, Y., McGinty, J., Teixeira, J., Hart, A. B., & Olivan, B. (2007) · Diabetes Care · doi:10.2337/dc06-1549 · Cited by 532 · see citing works
Vilsbøll, T., Krarup, T., Sonne, J., Madsbad, S., Vølund, A., Juul, A. G., & Holst, J. J. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021873 · Cited by 528 · see citing works
Self-citationFerrannini, E. (1998) · Endocrine Reviews · doi:10.1210/edrv.19.4.0336 · Cited by 451 · see citing works
Self-citationIncretins, insulin secretion and Type 2 diabetes mellitus
Vilsbøll, T., & Holst, J. J. (2004) · Diabetologia · doi:10.1007/s00125-004-1342-6 · Cited by 444 · see citing works
Self-citationVerdich, C., Toubro, S., Buemann, B., Lysgård Madsen, J., Juul Holst, J., & Astrup, A. (2001) · International Journal of Obesity · doi:10.1038/sj.ijo.0801655 · Cited by 434 · see citing works
Self-citationGastric emptying and release of incretin hormones after glucose ingestion in humans.
Schirra, J., Katschinski, M., Weidmann, C., Schäfer, T., Wank, U., Arnold, R., & Göke, B. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118411 · Cited by 426 · see citing works
Deacon, C. F., Nauck, M. A., Meier, J. J., Hücking, K., & Holst, J. J. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.10.6855 · Cited by 401 · see citing works
Self-citationAttenuated GLP-1 secretion in obesity: cause or consequence
Ranganath, L. R., Beety, J. M., Morgan, L. M., Wright, J. W., Howland, R., & Marks, V (1996) · Gut · doi:10.1136/gut.38.6.916 · Cited by 394 · see citing works
Intestinal Factors in the Control of Insulin Secretion
McIntyre, N. R., Holdsworth, C. D., & Turner, D. S. (1965) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-25-10-1317 · Cited by 387 · see citing works
Downregulation of GLP-1 and GIP Receptor Expression by Hyperglycemia
Xu, G., Kaneto, H., Laybutt, D. R., Duvivier-Kali, V. F., Trivedi, N., Suzuma, K., King, G. L., Weir, G. C., & Bonner‐Weir, S. (2007) · Diabetes · doi:10.2337/db06-1033 · Cited by 379 · see citing works
Jebb, S. A., Cole, T. J., Doman, D., Murgatroyd, P. R., & Prentice, A. M. (2000) · British Journal Of Nutrition · doi:10.1017/s0007114500000155 · Cited by 378 · see citing works
Reduced Incretin Effect in Type 2 Diabetes
Knop, F. K., Vilsbøll, T., Højberg, P. V., Larsen, S., Madsbad, S., Vølund, A., Holst, J. J., & Krarup, T. (2007) · Diabetes · doi:10.2337/db07-0100 · Cited by 349 · see citing works
Self-citationThe disposal of an oral glucose load in patients with non-insulin-dependent diabetes
Ferrannini, E., Simonson, D. C., Katz, L. D., Reichard, G., Bevilacqua, S., Barrett, E. J., Olsson, M., & DeFronzo, R. A. (1988) · Metabolism · doi:10.1016/0026-0495(88)90033-9 · Cited by 305 · see citing works
Self-citationMeal and oral glucose tests for assessment of β-cell function: modeling analysis in normal subjects
Mari, A., Schmitz, O., Gastaldelli, A., Oestergaard, T., Nyholm, B., & Ferrannini, E. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00093.2002 · Cited by 303 · see citing works
Self-citationDeacon, C. F. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.10.3575 · Cited by 303 · see citing works
GLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans
Näslund, E. B., Bogefors, J., Skogar, S., Grybäck, P., Jacobsson, H., Holst, J. J., & Hellström, P. M. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.277.3.r910 · Cited by 286 · see citing works
Self-citationFirth, R. G., Bell, P. M., Marsh, H. W., Hansen, I., & Rizza, R. A. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112467 · Cited by 280 · see citing works
Meier, J. J., Gethmann, A., Götze, O., Gallwitz, B., Holst, J. J., Schmidt, W. E., & Nauck, M. A. (2006) · Diabetologia · doi:10.1007/s00125-005-0126-y · Cited by 276 · see citing works
Self-citationVella, A. V., Bock, G., Giesler, P. D., Burton, D. B., Serra, D. B., Ligueros‐Saylan, M., Dunning, B. E., Foley, J. E., Rizza, R. A., & Camilleri, M. (2007) · Diabetes · doi:10.2337/db07-0136 · Cited by 200 · see citing works
Hvidberg, A., Nielsen, M.-B., Hilsted, J., Ørskov, C., & Holst, J. J. (1994) · Metabolism · doi:10.1016/0026-0495(94)90164-3 · Cited by 195 · see citing works
Self-citationKnop, F. K., Vilsbøll, T., Madsbad, S., Holst, J. J., & Krarup, T. (2007) · Diabetologia · doi:10.1007/s00125-006-0566-z · Cited by 191 · see citing works
Self-citationRegulation of hepatic glucose metabolism in humans
DeFronzo, R. A., & Ferrannini, E. (1987) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610030204 · Cited by 167 · see citing works
Self-citationVaag, A. A., Holst, J. J., Vølund, A., & Beck‐Nielsen, H. (1996) · European Journal of Endocrinology · doi:10.1530/eje.0.1350425 · Cited by 154 · see citing works
Self-citationNauck, M. A., El-Ouaghlidi, A., Gabrys, B., Hücking, K., Holst, J. J., Deacon, C. F., Gallwitz, B., Schmidt, W. E., & Meier, J. J. (2004) · Regulatory Peptides · doi:10.1016/j.regpep.2004.06.020 · Cited by 137 · see citing works
Self-citationLugari, R., Cas, A. D., Ugolotti, D., Barilli, A. L., Camellini, C., Ganzerla, G. C., Luciani, A., Salerni, B., Mittenperger, F., Nodari, S., et al. (2004) · Hormone and Metabolic Research · doi:10.1055/s-2004-814222 · Cited by 128 · see citing works
The entero-insular axis in type 2 diabetes - incretins as therapeutic agents
Creutzfeldt, W. (2001) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2001-18589 · Cited by 127 · see citing works
Wachters-Hagedoorn, R. E., Priebe, M. G., Heimweg, J., Heiner, A. M., Englyst, K. N., Holst, J. J., Stellaard, F., & Vonk, R. J. (2006) · Journal of Nutrition · doi:10.1093/jn/136.6.1511 · Cited by 124 · see citing works
Self-citationSalera, M., Giacomoni, P., Pironi, L., Cornia, G. L., Capelli, M., Marini, A. M., Benfenati, F., Miglioli, M., & Barbara, L. (1982) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-55-2-329 · Cited by 101 · see citing works
Nyholm, B., Walker, M., Gravholt, C. H., Shearing, P. A., Sturis, J., Alberti, K. G. M. M., Holst, J. J., & Schmitz, O. (1999) · Diabetologia · doi:10.1007/s001250051444 · Cited by 90 · see citing works
Self-citationImpact of incretin hormones on β-cell function in subjects with normal or impaired glucose tolerance
Muscelli, E., Mari, A., Natali, A., Astiarraga, B., Camastra, S., Frascerra, S., Holst, J. J., & Ferrannini, E. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00571.2005 · Cited by 88 · see citing works
Self-citationRelation between gastric emptying of glucose and plasma concentrations of glucagon-like peptide-1
Wishart, J. M., Horowitz, M., Morris, H. A., Jones, K. L., & Nauck, M. A. (1998) · Peptides · doi:10.1016/s0196-9781(98)00052-7 · Cited by 85 · see citing works
Effect of Pioglitazone on the Metabolic and Hormonal Response to a Mixed Meal in Type II Diabetes
Gastaldelli, A., Casolaro, A., Pettiti, M., Nannipieri, M., Ciociaro, D., Frascerra, S., Buzzigoli, E., Baldi, S., Mari, A., & Ferrannini, E. (2007) · Clinical Pharmacology & Therapeutics · doi:10.1038/sj.clpt.6100034 · Cited by 68 · see citing works
Self-citationLauritsen, K. B., Christensen, K. C., & Stokholm, K. H. (1980) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365528009181506 · Cited by 51 · see citing works
Heptulla, R. A., Tamborlane, W. V., Cavaghan, M. K., Bronson, M. L., Limb, C. J., Yong-Zhan, M. A., Sherwin, R. S., & Caprio, S. (2000) · Pediatric Research · doi:10.1203/00006450-200005000-00012 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Incretin hormones: Their role in health and disease
Nauck, M. A., & Meier, J. J. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13129 · Cited by 950 · see citing works
Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective
Zaccardi, F., Webb, D. R., Yates, T. E., & Davies, M. J. (2015) · Postgraduate Medical Journal · doi:10.1136/postgradmedj-2015-133281 · Cited by 570 · see citing works
The incretin system and its role in type 2 diabetes mellitus
Holst, J. J., Vilsboll, T., & Deacon, C. F. (2008) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.08.012 · Cited by 516 · see citing works
Self-citationNauck, M. A., & Meier, J. J. (2016) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(15)00482-9 · Cited by 503 · see citing works
Physiology of Proglucagon Peptides: Role of Glucagon and GLP-1 in Health and Disease
Sandoval, D. A., & D'Alessio, D. A. (2015) · Physiological Reviews · doi:10.1152/physrev.00013.2014 · Cited by 498 · see citing works
Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down?
Nauck, M. A., Vardarli, I., Deacon, C. F., Holst, J. J., & Meier, J. J. (2011) · Diabetologia · doi:10.1007/s00125-010-1896-4 · Cited by 465 · see citing works
Self-citationGastric Bypass vs Sleeve Gastrectomy for Type 2 Diabetes Mellitus
Lee, W. (2011) · Archives of Surgery · doi:10.1001/archsurg.2010.326 · Cited by 439 · see citing works
Nauck, M. A., Quast, D. R., Wefers, J., & Pfeiffer, A. F. H. (2021) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14496 · Cited by 388 · see citing works
Obesity, Polycystic Ovary Syndrome, and Infertility: A New Avenue for GLP-1 Receptor Agonists
Cena, H., Chiovato, L., & Nappi, R. E. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa285 · Cited by 356 · see citing works
Korner, J., Inabnet, W., Febres, G., Conwell, I. M., McMahon, D. J., Salas, R., Taveras, C., Schrope, B., & Bessler, M. (2009) · International Journal of Obesity · doi:10.1038/ijo.2009.79 · Cited by 338 · see citing works
Færch, K., Torekov, S. S., Vistisen, D., Johansen, N. B., Witte, D. R., Jonsson, A., Pedersen, O., Hansen, T., Lauritzen, T., Sandbæk, A., et al. (2015) · Diabetes · doi:10.2337/db14-1751 · Cited by 321 · see citing works
Self-citationHygum, K., Starup-Linde, J., Harsløf, T., Vestergaard, P., & Langdahl, B. (2017) · European Journal of Endocrinology · doi:10.1530/eje-16-0652 · Cited by 274 · see citing works
Nauck, M. A. (2010) · The American Journal of Medicine · doi:10.1016/j.amjmed.2010.11.002 · Cited by 295 · see citing works
Grasset, E., Puel, A., Charpentier, J., Collet, X., Christensen, J. E., Tercé, F., & Burcelin, R. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.04.013 · Cited by 280 · see citing works
Loss of Incretin Effect Is a Specific, Important, and Early Characteristic of Type 2 Diabetes
Holst, J. J., Knop, F. K., Vilsbøll, T., Krarup, T., & Madsbad, S. (2011) · Diabetes Care · doi:10.2337/dc11-s227 · Cited by 280 · see citing works
Self-citationInter-organ cross-talk in metabolic syndrome
Priest, C., & Tontonoz, P. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0145-5 · Cited by 279 · see citing works
Chang, C. L., Lin, Y., Bartolome, A. P., Chen, Y. C., Chiu, S., & Yang, W. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/378657 · Cited by 274 · see citing works
Færch, K., Borch‐Johnsen, K., Holst, J. J., & Vaag, A. A. (2009) · Diabetologia · doi:10.1007/s00125-009-1443-3 · Cited by 255 · see citing works
Self-citationCalanna, S., Christensen, M., Holst, J. J., Laferrère, B., Gluud, L. L., Vilsbøll, T., & Knop, F. K. (2013) · Diabetologia · doi:10.1007/s00125-013-2841-0 · Cited by 251 · see citing works
Self-citationRole of Reduced β-Cell Mass Versus Impaired β-Cell Function in the Pathogenesis of Type 2 Diabetes
Meier, J. J., & Bonadonna, R. C. (2013) · Diabetes Care · doi:10.2337/dcs13-2008 · Cited by 242 · see citing works
GLP-1 and energy balance: an integrated model of short-term and long-term control
Barrera, J. G., Sandoval, D. A., D'Alessio, D. A., & Seeley, R. J. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.77 · Cited by 220 · see citing works
Adipose Dipeptidyl Peptidase-4 and Obesity
Sell, H., Blüher, M., Klöting, N., Schlich, R., Willems, M., Ruppe, F., Knoefel, W. T., Dietrich, A., Fielding, B. A., Arner, P., et al. (2013) · Diabetes Care · doi:10.2337/dc13-0496 · Cited by 219 · see citing works
Meier, J. J., & Nauck, M. A. (2010) · Diabetes · doi:10.2337/db09-1899 · Cited by 215 · see citing works
Lipotoxicity disrupts incretin-regulated human β cell connectivity
Hodson, D. J., Mitchell, R. K., Bellomo, E. A., Sun, G., Vinet, L., Meda, P., Li, D., Li, W.-H., Bugliani, M., Marchetti, P., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci68459 · Cited by 210 · see citing works
Kahles, F., Meyer, C., Möllmann, J., Diebold, S., Findeisen, H. M., Lebherz, C., Trautwein, C., Koch, A., Tacke, F., Marx, N., et al. (2014) · Diabetes · doi:10.2337/db14-0100 · Cited by 212 · see citing works
Hwang, I., Park, Y. J., Kim, Y.-R., Kim, Y. N., Ka, S., Lee, H., Seong, J. K., Seok, Y., & Kim, J. B. (2015) · The FASEB Journal · doi:10.1096/fj.14-265983 · Cited by 206 · see citing works
Insulin Regulates Glucagon-Like Peptide-1 Secretion from the Enteroendocrine L Cell
Lim, G. E., Huang, G. J., Flora, N., LeRoith, D., Rhodes, C. J., & Brubaker, P. L. (2009) · Endocrinology · doi:10.1210/en.2008-0726 · Cited by 200 · see citing works
Knop, F. K., Aaboe, K., Vilsbøll, T., Vølund, A., Holst, J. J., Krarup, T., & Madsbad, S. (2011) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01549.x · Cited by 195 · see citing works
Self-citationFerrannini, E., & Mingrone, G. (2009) · Diabetes Care · doi:10.2337/dc08-1762 · Cited by 191 · see citing works
Self-citationGasbjerg, L. S., Helsted, M. M., Hartmann, B., Jensen, M. H., Gabe, M. B. N., Sparre-Ulrich, A. H., Veedfald, S., Stensen, S., Lanng, A. R., Bergmann, N. C., et al. (2019) · Diabetes · doi:10.2337/db18-1123 · Cited by 193 · see citing works
Self-citationIncretin hormones and type 2 diabetes
Nauck, M. A., & Müller, T. D. (2023) · Diabetologia · doi:10.1007/s00125-023-05956-x · Cited by 190 · see citing works
Incretin hormones and the satiation signal
Holst, J. J. (2013) · International Journal of Obesity · doi:10.1038/ijo.2012.208 · Cited by 189 · see citing works
Self-citationMathematical modeling of the glucose–insulin system: A review
Palumbo, P. J., Ditlevsen, S., BERTUZZI, A., & Gaetano, A. D. (2013) · Mathematical Biosciences · doi:10.1016/j.mbs.2013.05.006 · Cited by 183 · see citing works
Nannipieri, M., Mari, A., Anselmino, M., Baldi, S., Barsotti, E., Guarino, D., Camastra, S., Bellini, R., Berta, R. D., & Ferrannini, E. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0446 · Cited by 176 · see citing works
Self-citationPathophysiology of prediabetes
Ferrannini, E., Gastaldelli, A., & Iozzo, P. (2011) · Medical Clinics of North America · doi:10.1016/j.mcna.2010.11.005 · Cited by 177 · see citing works
Self-citationLund, A., Vilsbøll, T., Bagger, J. I., Holst, J. J., & Knop, F. K. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00665.2010 · Cited by 169 · see citing works
Self-citationBreton, J., Galmiche, M. C., & Déchelotte, P. (2022) · Microorganisms · doi:10.3390/microorganisms10020452 · Cited by 170 · see citing works
Secretion of Glucose-Dependent Insulinotropic Polypeptide in Patients With Type 2 Diabetes
Calanna, S., Christensen, M., Holst, J. J., Laferrère, B., Gluud, L. L., Vilsbøll, T., & Knop, F. K. (2013) · Diabetes Care · doi:10.2337/dc13-0465 · Cited by 158 · see citing works
Self-citationRevisiting the role of glucagon in health, diabetes mellitus and other metabolic diseases
Hædersdal, S., Andersen, A., Knop, F. K., & Vilsbøll, T. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00817-4 · Cited by 164 · see citing works
Carr, R. D., Larsen, M. O., Jelic, K., Lindgren, O., Vikman, J., Holst, J. J., Deacon, C. F., & Åhrén, B. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2054 · Cited by 154 · see citing works
Self-citationThe role of glucagon‐like peptide‐1 impairment in obesity and potential therapeutic implications
Madsbad, S. (2014) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12119 · Cited by 146 · see citing works
Duarte, A. I., Candeias, E., Correia, S. C., Santos, R. X., Carvalho, C., Cardoso, S., Plácido, A. I., Santos, M. S., Oliveira, C. R., & Moreira, P. I. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.01.008 · Cited by 142 · see citing works
β-Cell function in type 2 diabetes
Ferrannini, E., & Mari, A. (2014) · Metabolism · doi:10.1016/j.metabol.2014.05.012 · Cited by 140 · see citing works
Self-citationEffects of GLP-1 and Incretin-Based Therapies on Gastrointestinal Motor Function
Marathe, C. S., Rayner, C. K., Jones, K. L., & Horowitz, M. (2011) · Experimental Diabetes Research · doi:10.1155/2011/279530 · Cited by 138 · see citing works
Pancreatic β-Cell Proliferation in Obesity
Linnemann, A. K., Baan, M., & Davis, D. B. (2014) · Advances in Nutrition · doi:10.3945/an.113.005488 · Cited by 132 · see citing works
Glucagon-Like Peptide-1: New Regulator in Lipid Metabolism
Bu, T., Sun, Z., Pan, Y., Deng, X., & Yuan, G. (2024) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2023.0277 · Cited by 131 · see citing works
Physiology of Incretins in Health and Disease
Deacon, C. F., & Åhrén, B. (2011) · The Review of Diabetic Studies · doi:10.1900/rds.2011.8.293 · Cited by 126 · see citing works
GLP-1 physiology in obesity and development of incretin-based drugs for chronic weight management
Holst, J. J. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01113-9 · Cited by 125 · see citing works
Self-citationEffect of endogenous GLP-1 on insulin secretion in type 2 diabetes
Salehi, M., Aulinger, B., Prigeon, R. L., & D'Alessio, D. A. (2010) · Diabetes · doi:10.2337/db09-1253 · Cited by 124 · see citing works
Glucagon antagonism as a potential therapeutic target in type 2 diabetes
Bagger, J. I., Knop, F. K., Holst, J. J., & Vilsbøll, T. (2011) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01427.x · Cited by 124 · see citing works
Self-citationJiménez, A., Casamitjana, R., Viaplana-Masclans, J., Lacy, A. M., & Vidal, J. (2013) · Diabetes Care · doi:10.2337/dc12-1535 · Cited by 123 · see citing works
Arjmand, G., Abbaszadeh, M., Fardaei, M., & Eftekhari, M. H. (2022) · Scientific Reports · doi:10.1038/s41598-021-04258-9 · Cited by 110 · see citing works
DPP-4 inhibitors in the treatment of type 2 diabetes
Duez, H., Cariou, B., & Staels, B. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.11.028 · Cited by 113 · see citing works
Hansen, K. B., Vilsbøll, T., Bagger, J. I., Holst, J. J., & Knop, F. K. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0119 · Cited by 110 · see citing works
Self-citationβ‐cell function assessment from modelling of oral tests: an effective approach
Mari, A., & Ferrannini, E. (2008) · Diabetes, Obesity and Metabolism · doi:10.1111/j.1463-1326.2008.00946.x · Cited by 112 · see citing works
Self-citationHeuvelman, V. D., Van Raalte, D. H., & Smits, M. M. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvz323 · Cited by 106 · see citing works
Mechanisms for the Antihyperglycemic Effect of Sitagliptin in Patients with Type 2 Diabetes
Muscelli, E., Casolaro, A., Gastaldelli, A., Mari, A., Seghieri, G., Astiarraga, B., Chen, Y., Alba, M., Holst, J. J., & Ferrannini, E. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1205 · Cited by 103 · see citing works
Self-citationMingrone, G., Nolfe, G., Gissey, G. C., Iaconelli, A., Leccesi, L., Guidone, C., Nanni, G., & Holst, J. J. (2009) · Diabetologia · doi:10.1007/s00125-009-1288-9 · Cited by 103 · see citing works
Self-citationZarrinpar, A., & Loomba, R. S. (2012) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.12084 · Cited by 102 · see citing works
Successful weight loss maintenance includes long-term increased meal responses of GLP-1 and PYY3-36
Iepsen, E. W., Lundgren, J., Holst, J. J., Madsbad, S., & Torekov, S. S. (2016) · European Journal of Endocrinology · doi:10.1530/eje-15-1116 · Cited by 101 · see citing works
Self-citationLiraglutide for Type 2 diabetes and obesity: a 2015 update
Iepsen, E. W., Torekov, S. S., & Holst, J. J. (2015) · Expert Review of Cardiovascular Therapy · doi:10.1586/14779072.2015.1054810 · Cited by 101 · see citing works
Self-citationIncretins in obesity and diabetes
Chia, C. W., & Egan, J. M. (2020) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14211 · Cited by 93 · see citing works
Glucose-dependent insulinotropic polypeptide (GIP)
Müller, T. D., Adriaenssens, A. E., Ahrén, B., Blüher, M., Birkenfeld, A. L., Campbell, J. E., Coghlan, M. P., D’Alessio, D. D., Deacon, C. F., DelPrato, S., et al. (2025) · Molecular Metabolism · doi:10.1016/j.molmet.2025.102118 · Cited by 98 · see citing works
Self-citationKnop, F. K. (2009) · Diabetologia · doi:10.1007/s00125-009-1511-8 · Cited by 93 · see citing works
Michaliszyn, S. F., Mari, A., Lee, S., Bacha, F. F., Tfayli, H. M., Farchoukh, L. O., Ferrannini, E., & Arslanian, S. A. (2014) · Diabetes · doi:10.2337/db13-1951 · Cited by 92 · see citing works
Self-citationClarifying the Role of Incretin-Based Therapies in the Treatment of Type 2 Diabetes Mellitus
Campbell, R. K. (2011) · Clinical Therapeutics · doi:10.1016/j.clinthera.2011.04.015 · Cited by 92 · see citing works
Recent advances in clinical practice challenges and opportunities in the management of obesity
Acosta, A., Abu Dayyeh, B. K., Port, J. D., & Camilleri, M. (2014) · Gut · doi:10.1136/gutjnl-2013-306235 · Cited by 91 · see citing works
Yabe, D., Kuroe, A., Lee, S., Watanabe, K., Hyo, T., Hishizawa, M., Kurose, T., Deacon, C. F., Holst, J. J., Hirano, T., et al. (2010) · Journal of Diabetes Investigation · doi:10.1111/j.2040-1124.2010.00010.x · Cited by 90 · see citing works
Self-citationJunker, A. E., Gluud, L. L., Holst, J. J., Knop, F. K., & Vilsbøll, T. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12462 · Cited by 88 · see citing works
Self-citationDollerup, O. L., Trammell, S. A. J., Hartmann, B., Holst, J. J., Christensen, B., Møller, N., Gillum, M. P., Treebak, J. T., & Jessen, N. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-01081 · Cited by 77 · see citing works
Self-citationHygum, K., Starup‐Linde, J., & Langdahl, B. L. (2019) · Osteoporosis and Sarcopenia · doi:10.1016/j.afos.2019.05.001 · Cited by 86 · see citing works
Glucagon-Like Peptide-1 (GLP-1) in the Integration of Neural and Endocrine Responses to Stress
Diz-Chaves, Y., Herrera-Pérez, S., González-Matías, L. C., Lamas, J. A., & Mallo, F. (2020) · Nutrients · doi:10.3390/nu12113304 · Cited by 84 · see citing works
Limited Recovery of β-Cell Function After Gastric Bypass Despite Clinical Diabetes Remission
Dutia, R., Brakoniecki, K., Bunker, P., Paultre, F., Homel, P., Carpentier, A. C., McGinty, J., & Laferrère, B. (2013) · Diabetes · doi:10.2337/db13-1176 · Cited by 84 · see citing works
Hare, K. J., Vilsbøll, T., Holst, J. J., & Knop, F. K. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00700.2009 · Cited by 84 · see citing works
Self-citationPotential role of skeletal muscle glucose metabolism on the regulation of insulin secretion
Mizgier, M. L., Casas, M., Contreras‐Ferrat, A. E., Llanos, P., & Galgani, J. E. (2014) · Obesity Reviews · doi:10.1111/obr.12166 · Cited by 84 · see citing works
Yang, W., Jiang, W., & Guo, S. (2023) · Nutrients · doi:10.3390/nu15214671 · Cited by 93 · see citing works
Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity
Anandhakrishnan, A., & Korbonits, M. (2016) · World Journal of Diabetes · doi:10.4239/wjd.v7.i20.572 · Cited by 81 · see citing works
Smushkin, G., & Vella, A. V. (2010) · Medicine · doi:10.1016/j.mpmed.2010.08.008 · Cited by 80 · see citing works
Sun, Y., Jin, C., Zhang, X., Jia, W., Le, J., & Ye, J. (2018) · Nutrition and Diabetes · doi:10.1038/s41387-018-0061-x · Cited by 77 · see citing works
Incretin physiology and pathophysiology from an A sian perspective
Cho, Y. M. (2014) · Journal of Diabetes Investigation · doi:10.1111/jdi.12305 · Cited by 75 · see citing works
What is GLP-1 really doing in obesity?
Hira, T., Pinyo, J., & Hara, H. (2020) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2019.09.003 · Cited by 74 · see citing works
Woerle, H. J., Carneiro, L., Derani, A., Göke, B., & Schirra, J. (2012) · Diabetes · doi:10.2337/db11-1701 · Cited by 73 · see citing works
Hepatogenous diabetes: Is it time to separate it from type 2 diabetes?
Orsi, E., Grancini, V., Menini, S., Aghemo, A., & Pugliese, G. (2016) · Liver International · doi:10.1111/liv.13337 · Cited by 73 · see citing works
Intact Glucagon-like Peptide-1 Levels are not Decreased in Japanese Patients with Type 2 Diabetes
Lee, S., Yabe, D., Nohtomi, K., Takada, M., Morita, R., Seino, Y., & Hirano, T. (2010) · Endocrine Journal · doi:10.1507/endocrj.k09e-269 · Cited by 73 · see citing works
Jensen, D. H., Aaboe, K., Henriksen, J. E., Vølund, A., Holst, J. J., Madsbad, S., & Krarup, T. (2012) · Diabetologia · doi:10.1007/s00125-012-2459-7 · Cited by 70 · see citing works
Self-citationPerreault, L., & Færch, K. (2013) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2013.10.008 · Cited by 71 · see citing works
Incretin Hormones in Obesity and Related Cardiometabolic Disorders: The Clinical Perspective
Michałowska, J. M., Miller‐Kasprzak, E., & Bogdański, P. (2021) · Nutrients · doi:10.3390/nu13020351 · Cited by 69 · see citing works
Mechanisms Underlying Type 2 Diabetes Remission After Metabolic Surgery
Pérez‐Pevida, B., Escalada, J., Miras, A. D., & Frühbeck, G. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00641 · Cited by 67 · see citing works
Obesity - an indication for GLP-1 treatment? Obesity pathophysiology and GLP-1 treatment potential
Torekov, S. S., Madsbad, S., & Holst, J. J. (2011) · Obesity Reviews · doi:10.1111/j.1467-789x.2011.00860.x · Cited by 65 · see citing works
Self-citationAlpha-cell paracrine signaling in the regulation of beta-cell insulin secretion
Holter, M. M., Saikia, M., & Cummings, B. P. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.934775 · Cited by 63 · see citing works
Matikainen, N., Bogl, L. H., Hakkarainen, A., Lundbom, J., Lundbom, N., Kaprio, J., Rissanen, A., Holst, J. J., & Pietiläinen, K. H. (2014) · Diabetes Care · doi:10.2337/dc13-1283 · Cited by 63 · see citing works
Self-citationRole of the incretin pathway in the pathogenesis of type 2 diabetes mellitus
Kennedy, L., & Freeman, J. S. (2009) · Cleveland Clinic Journal of Medicine · doi:10.3949/ccjm.76.s5.03 · Cited by 62 · see citing works
Predictors of Long-Term Diabetes Remission After Metabolic Surgery
Lee, M. H., Lee, W., Chong, K., Chen, J., Ser, K., Lee, Y.-C., & Chen, S. (2015) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-015-2808-1 · Cited by 63 · see citing works
Kim, M. K., Chae, Y., Kim, H. D., Yang, E. K., Cho, E., Choi, S., Cheong, Y.-H., Kim, H.-S., Kim, H. J., Jo, Y. W., et al. (2011) · Life Sciences · doi:10.1016/j.lfs.2011.10.007 · Cited by 63 · see citing works
GLP-1: A Mediator of the Beneficial Metabolic Effects of Bariatric Surgery?
Manning, S., Pucci, A. B. F., & Batterham, R. L. (2015) · Physiology · doi:10.1152/physiol.00027.2014 · Cited by 63 · see citing works
Huber, H., Schieren, A., Holst, J. J., & Simon, M.-C. (2024) · The American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2024.01.007 · Cited by 62 · see citing works
Self-citationDaniele, G., Iozzo, P., Molina‐Carrión, M., Lancaster, J. L., Ciociaro, D., Cersósimo, E., Tripathy, D., Triplitt, C. L., Fox, P. T., Musi, N., et al. (2015) · Diabetes · doi:10.2337/db14-1718 · Cited by 62 · see citing works
Self-citationKnop, F. K. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00137.2010 · Cited by 62 · see citing works
The Role of cAMP in Beta Cell Stimulus–Secretion and Intercellular Coupling
Stožer, A., Leitgeb, E. P., Pohorec, V., Dolenšek, J., Bombek, L. K., Gosak, M., & Klemen, M. S. (2021) · Cells · doi:10.3390/cells10071658 · Cited by 64 · see citing works
Lee, W., Almulaifi, A. M., Chong, K., Chen, S., Tsou, J. J., Ser, K., Lee, Y.-C., & Chen, J. (2015) · Obesity Surgery · doi:10.1007/s11695-015-1603-0 · Cited by 61 · see citing works
- Authors
- Muscelli, E., Mari, A., Casolaro, A., Camastra, S., Seghieri, G., Gastaldelli, A., Holst, J. J., & Ferrannini, E.
- Affiliations
- University of Pisa (IT)
- National Research Council (IT)
- Division of Internal Medicine, Spedali Riuniti, Pistoia, Italy
- University of Copenhagen (DK)
- Corresponding author
- Ferrannini, Ele
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2008-05-01
- Volume
- 57
- Issue
- 5
- Pages
- 1340-1348
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2145818242
- Cited by
- 409
- References
- 50
- Citations by year
- 2026: 9 · 2025: 4 · 2024: 17 · 2023: 19 · 2022: 23 · 2021: 21 · 2020: 17 · 2019: 22 · 2018: 20 · 2017: 27 · 2016: 22 · 2015: 35 · 2014: 35 · 2013: 34 · 2012: 20
- FWCI
- 18.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- incretin effect, obesity, glucose tolerance, type 2 diabetes, impaired glucose tolerance, beta-cell function, beta-cell glucose sensitivity, glucagon-like peptide-1, glucagon suppression, insulin secretion, body mass index, hyperglycemia
- MeSH terms
- Insulin Secretion, Adult, Blood Glucose, Diabetes Mellitus, Type 2, Female, Glucose Tolerance Test, Humans, Hypoglycemic Agents, Insulin, Male, Middle Aged, Obesity, Reference Values, Body Mass Index, Insulin-Secreting Cells
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
