{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T17:08:22Z","timestamp":1774112902974,"version":"3.50.1"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["PCEGP3_186978"],"award-info":[{"award-number":["PCEGP3_186978"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/hypothesis<\/jats:title>\n                    <jats:p>Subcutaneous insulin delivery in individuals with insulin-deficient type 1 diabetes bypasses the portal circulation, disrupting the physiological porto-systemic insulin gradient and affecting postprandial hepatic glucose regulation. However, direct, non-invasive measurement of these liver-specific dynamics and their deviation from normal physiology in individuals with type 1 diabetes is challenging. To address this, we integrated metabolic imaging with whole-body tracer dilution to map postprandial glucose metabolism in both the liver and systemically in adults with type 1 diabetes and healthy control individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this cross-sectional study, ten adults with type 1 diabetes and ten healthy control individuals with similar age, BMI and gender distributions were enrolled. After an overnight fast, participants ingested 60\u202fg [6,6\u2032-\n                      <jats:sup>2<\/jats:sup>\n                      H\n                      <jats:sub>2<\/jats:sub>\n                      ]-glucose (D-Glc); subcutaneous insulin was administered to type 1 diabetes participants according to their carbohydrate-to-insulin ratio. Interleaved deuterium metabolic imaging (DMI) and\n                      <jats:sup>13<\/jats:sup>\n                      C-magnetic resonance spectroscopy (\n                      <jats:sup>13<\/jats:sup>\n                      C-MRS) at 7\u00a0T were performed from pre-ingestion to 150\u202fmin post-ingestion to quantify hepatic D-Glc and glycogen concentrations. Blood samples were collected to measure plasma glucose, insulin and glucagon. Postprandial glucose\u2013insulin dynamics were quantified using the single tracer oral minimal model, accounting for non-steady-state insulin exposure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At baseline, individuals with type 1 diabetes had significantly higher plasma glucose concentrations than control individuals (10.7\u00b12.3 and 5.2\u00b10.4 mmol\/l, respectively;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.001), while preprandial glycogen levels did not differ significantly. Following D-Glc administration, hepatic D-Glc increased more markedly in the individuals with type 1 diabetes compared with the control group (peak values 4.7\u00b12.0 and 3.0\u00b10.8 mmol\/l, respectively;\n                      <jats:italic>p<\/jats:italic>\n                      =0.02). In the postprandial period, glycogen levels did not significantly rise at 150\u202fmin in type 1 diabetes, whereas a clear increase was observed in control individuals (iAUC\n                      <jats:sub>0\u2013180<\/jats:sub>\n                      =2.4 mol\/l \u00d7 min). Despite similar systemic insulin exposure and no significant differences in postprandial glucagon concentrations between groups, individuals with type 1 diabetes demonstrated significantly reduced suppression of endogenous glucose production (\n                      <jats:italic>p<\/jats:italic>\n                      =0.001) but similar insulin-dependent glucose disposal. Hierarchical clustering identified two distinct type 1 diabetes subgroups: Subgroup 1 exhibited a steeper increase in both hepatic and systemic D-Glc profiles, while subgroup 2 showed a divergent D-Glc trajectory and net glycogen depletion relative to accumulation in subgroup 1 (iAUC\n                      <jats:sub>0\u2013180<\/jats:sub>\n                      =\u22123.0 vs 2.5\u202fmol\/l \u00d7 min,\n                      <jats:italic>p<\/jats:italic>\n                      =0.04), despite no overt clinical differences between subgroups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>\n                      By integrating DMI\/\n                      <jats:sup>13<\/jats:sup>\n                      C-MRS liver imaging with systemic stable-isotope modelling, this comparative study demonstrates significantly altered hepatic glucose metabolism in adults with well-managed type 1 diabetes vs control individuals, together with substantial phenotypic heterogeneity within the type 1 diabetes cohort. These findings highlight the potential of non-invasive metabolic phenotyping to resolve metabolic alterations and inter-individual variation in type 1 diabetes, which are essential steps towards the provision of precision medicine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-026-06677-7","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T14:03:00Z","timestamp":1770991380000},"page":"1301-1316","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel deuterium metabolic imaging technique reveals distinct patterns of postprandial hepatic glucose homeostasis in individuals with type 1 diabetes and healthy control individuals: a case\u2013control study"],"prefix":"10.1007","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8067-0417","authenticated-orcid":false,"given":"Alessandro","family":"Brunasso","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9519-4949","authenticated-orcid":false,"given":"Naomi F.","family":"Lange","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5676-3187","authenticated-orcid":false,"given":"Simone","family":"Poli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6124-5915","authenticated-orcid":false,"given":"Michele","family":"Schiavon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1028-9445","authenticated-orcid":false,"given":"David","family":"Herzig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4908-0596","authenticated-orcid":false,"given":"Chiara","family":"Dalla Man","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8618-6875","authenticated-orcid":false,"given":"Roland","family":"Kreis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1993-7672","authenticated-orcid":false,"given":"Lia","family":"Bally","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"6677_CR1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/S0140-6736(13)60591-7","volume":"383","author":"MA Atkinson","year":"2014","unstructured":"Atkinson MA, Eisenbarth GS, Michels AW (2014) Type 1 diabetes. Lancet 383:69\u201382. https:\/\/doi.org\/10.1016\/S0140-6736(13)60591-7","journal-title":"Lancet"},{"key":"6677_CR2","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1007\/s00125-021-05397-4","volume":"64","author":"DM Nathan","year":"2021","unstructured":"Nathan DM (2021) Realising the long-term promise of insulin therapy: the DCCT\/EDIC study. Diabetologia 64:1049\u20131058. https:\/\/doi.org\/10.1007\/s00125-021-05397-4","journal-title":"Diabetologia"},{"key":"6677_CR3","doi-asserted-by":"publisher","first-page":"286","DOI":"10.3945\/an.112.002089","volume":"3","author":"MC Moore","year":"2012","unstructured":"Moore MC, Coate KC, Winnick JJ, An Z, Cherrington AD (2012) Regulation of hepatic glucose uptake and storage in vivo. Adv Nutr 3:286\u2013294. https:\/\/doi.org\/10.3945\/an.112.002089","journal-title":"Adv Nutr"},{"key":"6677_CR4","doi-asserted-by":"publisher","first-page":"126974","DOI":"10.1172\/jci.insight.126974","volume":"4","author":"DS Edgerton","year":"2019","unstructured":"Edgerton DS, Scott M, Farmer B et al (2019) Targeting insulin to the liver corrects defects in glucose metabolism caused by peripheral insulin delivery. JCI Insight 4:126974. https:\/\/doi.org\/10.1172\/jci.insight.126974","journal-title":"JCI Insight"},{"key":"6677_CR5","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1172\/jci27073","volume":"116","author":"DS Edgerton","year":"2006","unstructured":"Edgerton DS, Lautz M, Scott M et al (2006) Insulin\u2019s direct effects on the liver dominate the control of hepatic glucose production. J Clin Invest 116:521\u2013527. https:\/\/doi.org\/10.1172\/jci27073","journal-title":"J Clin Invest"},{"key":"6677_CR6","doi-asserted-by":"publisher","first-page":"3946","DOI":"10.2337\/db14-0266","volume":"63","author":"DS Edgerton","year":"2014","unstructured":"Edgerton DS, Moore MC, Winnick JJ et al (2014) Changes in glucose and fat metabolism in response to the administration of a hepato-preferential insulin analog. Diabetes 63:3946\u20133954. https:\/\/doi.org\/10.2337\/db14-0266","journal-title":"Diabetes"},{"key":"6677_CR7","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.diabres.2006.11.011","volume":"77","author":"HJ Woerle","year":"2007","unstructured":"Woerle HJ, Neumann C, Zschau S et al (2007) Impact of fasting and postprandial glycemia on overall glycemic control in type 2 diabetes. Diabetes Res Clin Pract 77:280\u2013285. https:\/\/doi.org\/10.1016\/j.diabres.2006.11.011","journal-title":"Diabetes Res Clin Pract"},{"key":"6677_CR8","first-page":"233","volume":"11","author":"I Sarikaya","year":"2021","unstructured":"Sarikaya I, Schierz J-H, Sarikaya A (2021) Liver: glucose metabolism and 18F-fluorodeoxyglucose PET findings in normal parenchyma and diseases. Am J Nucl Med Mol Imaging 11:233\u2013249","journal-title":"Am J Nucl Med Mol Imaging"},{"key":"6677_CR9","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1007\/s00125-023-06055-7","volume":"67","author":"J Basset-Sagarminaga","year":"2023","unstructured":"Basset-Sagarminaga J, Van De Weijer T, Iozzo P, Schrauwen P, Schrauwen-Hinderling V (2023) Advances and challenges in measuring hepatic glucose uptake with FDG PET: implications for diabetes research. Diabetologia 67:407\u2013419. https:\/\/doi.org\/10.1007\/s00125-023-06055-7","journal-title":"Diabetologia"},{"key":"6677_CR10","doi-asserted-by":"publisher","first-page":"e4926","DOI":"10.1002\/nbm.4926","volume":"36","author":"A Gursan","year":"2023","unstructured":"Gursan A, Hendriks AD, Welting D, De Jong PA, Klomp DWJ, Prompers JJ (2023) Deuterium body array for the simultaneous measurement of hepatic and renal glucose metabolism and gastric emptying with dynamic 3D deuterium metabolic imaging at 7 T. NMR Biomed 36:e4926. https:\/\/doi.org\/10.1002\/nbm.4926","journal-title":"NMR Biomed"},{"key":"6677_CR11","doi-asserted-by":"publisher","first-page":"eaat7314","DOI":"10.1126\/sciadv.aat7314","volume":"4","author":"HM De Feyter","year":"2018","unstructured":"De Feyter HM, Behar KL, Corbin ZA et al (2018) Deuterium metabolic imaging (DMI) for MRI-based 3D mapping of metabolism in vivo. Sci Adv 4:eaat7314. https:\/\/doi.org\/10.1126\/sciadv.aat7314","journal-title":"Sci Adv"},{"key":"6677_CR12","doi-asserted-by":"publisher","first-page":"1198578","DOI":"10.3389\/fphys.2023.1198578","volume":"14","author":"AD Hendriks","year":"2023","unstructured":"Hendriks AD, Veltien A, Voogt IJ, Heerschap A, Scheenen TWJ, Prompers JJ (2023) Glucose versus fructose metabolism in the liver measured with deuterium metabolic imaging. Front Physiol 14:1198578. https:\/\/doi.org\/10.3389\/fphys.2023.1198578","journal-title":"Front Physiol"},{"key":"6677_CR13","doi-asserted-by":"publisher","first-page":"e5123","DOI":"10.1002\/nbm.5123","volume":"37","author":"S Poli","year":"2024","unstructured":"Poli S, Emara AF, Lange NF, Ballabani E et al (2024) Interleaved trinuclear MRS for single-session investigation of carbohydrate and lipid metabolism in human liver at 7T. NMR Biomed 37:e5123. https:\/\/doi.org\/10.1002\/nbm.5123","journal-title":"NMR Biomed"},{"issue":"1","key":"6677_CR14","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1111\/dom.16001","volume":"27","author":"S Poli","year":"2025","unstructured":"Poli S, Lange NF, Brunasso A et al (2025) In vivo mapping of postprandial hepatic glucose metabolism using dynamic magnetic resonance spectroscopy combined with stable isotope flux analysis in Roux-en-Y gastric bypass adults and non-operated controls: a case\u2013control study. Diabetes Obes Metab 27(1):196\u2013206. https:\/\/doi.org\/10.1111\/dom.16001","journal-title":"Diabetes Obes Metab"},{"key":"6677_CR15","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1002\/mrm.29696","volume":"90","author":"KM Nam","year":"2023","unstructured":"Nam KM, Gursan A, Bhogal AA et al (2023) Deuterium echo-planar spectroscopic imaging (EPSI) in the human liver in vivo at 7 T. Magnetic Resonance Med 90:863\u2013874. https:\/\/doi.org\/10.1002\/mrm.29696","journal-title":"Magnetic Resonance Med"},{"key":"6677_CR16","doi-asserted-by":"publisher","first-page":"118639","DOI":"10.1016\/j.neuroimage.2021.118639","volume":"244","author":"L Ruhm","year":"2021","unstructured":"Ruhm L, Avdievich N, Ziegs T et al (2021) Deuterium metabolic imaging in the human brain at 9.4 Tesla with high spatial and temporal resolution. NeuroImage 244:118639. https:\/\/doi.org\/10.1016\/j.neuroimage.2021.118639","journal-title":"NeuroImage"},{"key":"6677_CR17","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s41747-024-00464-y","volume":"8","author":"F Pan","year":"2024","unstructured":"Pan F, Liu X, Wan J et al (2024) Advances and prospects in deuterium metabolic imaging (DMI): a systematic review of in vivo studies. Eur Radiol Exp 8:65. https:\/\/doi.org\/10.1186\/s41747-024-00464-y","journal-title":"Eur Radiol Exp"},{"key":"6677_CR18","doi-asserted-by":"publisher","unstructured":"Wodtke P, McLean MA et al (2026) Deuterium metabolic imaging of the human abdomen at clinical field strength. Invest Radiol 61:1\u20139. https:\/\/doi.org\/10.1097\/RLI.0000000000001170","DOI":"10.1097\/RLI.0000000000001170"},{"key":"6677_CR19","doi-asserted-by":"publisher","unstructured":"De Feyter HM, Thomas MA, Behar KL, De Graaf RA (2021) NMR visibility of deuterium-labeled liver glycogen in vivo. Magn Reson Med 86:62\u201368. https:\/\/doi.org\/10.1002\/mrm.28717","DOI":"10.1002\/mrm.28717"},{"key":"6677_CR20","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1126\/science.1948033","volume":"254","author":"DL Rothman","year":"1991","unstructured":"Rothman DL, Magnusson I, Katz LD, Shulman RG, Shulman GI (1991) Quantitation of hepatic glycogenolysis and gluconeogenesis in fasting humans with 13 C NMR. Science 254:573\u2013576. https:\/\/doi.org\/10.1126\/science.1948033","journal-title":"Science"},{"key":"6677_CR21","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1002\/nbm.3531","volume":"29","author":"T Buehler","year":"2016","unstructured":"Buehler T, Bally L, Dokumaci AS, Stettler C, Boesch C (2016) Methodological and physiological test-retest reliability of 13 C-MRS glycogen measurements in liver and in skeletal muscle of patients with type 1 diabetes and matched healthy controls. NMR Biomed 29:796\u2013805. https:\/\/doi.org\/10.1002\/nbm.3531","journal-title":"NMR Biomed"},{"key":"6677_CR22","doi-asserted-by":"publisher","first-page":"E55","DOI":"10.1152\/ajpendo.00190.2001","volume":"284","author":"R Basu","year":"2003","unstructured":"Basu R, Di Camillo B, Toffolo G et al (2003) Use of a novel triple-tracer approach to assess postprandial glucose metabolism. Am J Physiol Endocrinol Metab 284:E55\u2013E69. https:\/\/doi.org\/10.1152\/ajpendo.00190.2001","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"6677_CR23","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1073\/pnas.4.12.370","volume":"4","author":"JA Harris","year":"1918","unstructured":"Harris JA, Benedict FG (1918) A biometric study of human basal metabolism. Proc Natl Acad Sci USA 4:370\u2013373. https:\/\/doi.org\/10.1073\/pnas.4.12.370","journal-title":"Proc Natl Acad Sci USA"},{"key":"6677_CR24","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.3390\/nu9111163","volume":"9","author":"A Chatelan","year":"2017","unstructured":"Chatelan A, Beer-Borst S, Randriamiharisoa A et al (2017) Major differences in diet across three linguistic regions of Switzerland: results from the First National Nutrition Survey menuCH. Nutrients 9:1163. https:\/\/doi.org\/10.3390\/nu9111163","journal-title":"Nutrients"},{"key":"6677_CR25","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1002\/dta.2765","volume":"12","author":"A Thomas","year":"2020","unstructured":"Thomas A, Yang R, Petring S, Bally L, Thevis M (2020) Simplified quantification of insulin, its synthetic analogs and C-peptide in human plasma by means of LC-HRMS. Drug Test Anal 12:382\u2013390. https:\/\/doi.org\/10.1002\/dta.2765","journal-title":"Drug Test Anal"},{"key":"6677_CR26","doi-asserted-by":"publisher","first-page":"E161","DOI":"10.1152\/ajpendo.00358.2014","volume":"309","author":"R Visentin","year":"2015","unstructured":"Visentin R, Dalla Man C, Basu R, Basu A, Rizza RA, Cobelli C (2015) Hepatic insulin sensitivity in healthy and prediabetic subjects: from a dual- to a single-tracer oral minimal model. Am J Physiol Endocrinol Metab 309:E161\u2013E167. https:\/\/doi.org\/10.1152\/ajpendo.00358.2014","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"6677_CR27","doi-asserted-by":"publisher","first-page":"2472","DOI":"10.1109\/TBME.2006.883792","volume":"53","author":"C Dalla Man","year":"2006","unstructured":"Dalla Man C, Camilleri M, Cobelli C (2006) A system model of oral glucose absorption: validation on gold standard data. IEEE Trans Biomed Eng 53:2472\u20132478. https:\/\/doi.org\/10.1109\/TBME.2006.883792","journal-title":"IEEE Trans Biomed Eng"},{"key":"6677_CR28","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.1109\/TBME.2017.2784101","volume":"65","author":"M Schiavon","year":"2018","unstructured":"Schiavon M, Dalla Man C, Cobelli C (2018) Modeling subcutaneous absorption of fast-acting insulin in type 1 diabetes. IEEE Trans Biomed Eng 65:2079\u20132086. https:\/\/doi.org\/10.1109\/TBME.2017.2784101","journal-title":"IEEE Trans Biomed Eng"},{"key":"6677_CR29","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1109\/TBME.2019.2919250","volume":"67","author":"M Schiavon","year":"2020","unstructured":"Schiavon M, Visentin R, Giegerich C, Klabunde T, Cobelli C, Dalla Man C (2020) Modeling subcutaneous absorption of long-acting insulin glargine in type 1 diabetes. IEEE Trans Biomed Eng 67:624\u2013631. https:\/\/doi.org\/10.1109\/TBME.2019.2919250","journal-title":"IEEE Trans Biomed Eng"},{"key":"6677_CR30","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1089\/dia.2020.0027","volume":"22","author":"M Schiavon","year":"2020","unstructured":"Schiavon M, Visentin R, Giegerich C et al (2020) In silico head-to-head comparison of insulin glargine 300 U\/ml and insulin degludec 100 U\/ml in type 1 diabetes. Diabetes Technol Ther 22:553\u2013561. https:\/\/doi.org\/10.1089\/dia.2020.0027","journal-title":"Diabetes Technol Ther"},{"key":"6677_CR31","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1111\/dme.12337","volume":"31","author":"M Takayama","year":"2014","unstructured":"Takayama M, Yamauchi K, Aizawa T (2014) Quantification of insulin. Diabet Med 31:375\u2013376. https:\/\/doi.org\/10.1111\/dme.12337","journal-title":"Diabet Med"},{"key":"6677_CR32","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.2337\/dc13-1120","volume":"37","author":"M Schiavon","year":"2014","unstructured":"Schiavon M, Dalla Man C, Kudva YC, Basu A, Cobelli C (2014) Quantitative estimation of insulin sensitivity in type 1 diabetic subjects wearing a sensor-augmented insulin pump. Diabetes Care 37:1216\u20131223. https:\/\/doi.org\/10.2337\/dc13-1120","journal-title":"Diabetes Care"},{"key":"6677_CR33","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.2337\/db05-1692","volume":"55","author":"R Basu","year":"2006","unstructured":"Basu R, Dalla Man C, Campioni M et al (2006) Effects of age and sex on postprandial glucose metabolism. Diabetes 55:2001\u20132014. https:\/\/doi.org\/10.2337\/db05-1692","journal-title":"Diabetes"},{"key":"6677_CR34","doi-asserted-by":"publisher","first-page":"E1152","DOI":"10.1152\/ajpendo.00486.2007","volume":"295","author":"C Dalla Man","year":"2008","unstructured":"Dalla Man C, Toffolo G, Basu R, Rizza RA, Cobelli C (2008) Use of labeled oral minimal model to measure hepatic insulin sensitivity. Am J Physiol Endocrinol Metab 295:E1152\u2013E1159. https:\/\/doi.org\/10.1152\/ajpendo.00486.2007","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"6677_CR35","unstructured":"MATLAB Help Center (2025) Documentation of MATLAB. Available from https:\/\/it.mathworks.com\/help\/releases\/R2024a\/. Accessed 17 Apr 2024"},{"key":"6677_CR36","doi-asserted-by":"publisher","first-page":"2400","DOI":"10.2337\/db17-0433","volume":"66","author":"GM Kowalski","year":"2017","unstructured":"Kowalski GM, Moore SM, Hamley S, Selathurai A, Bruce CR (2017) The effect of ingested glucose dose on the suppression of endogenous glucose production in humans. Diabetes 66:2400\u20132406. https:\/\/doi.org\/10.2337\/db17-0433","journal-title":"Diabetes"},{"key":"6677_CR37","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1210\/jc.2015-4251","volume":"101","author":"KM Utzschneider","year":"2016","unstructured":"Utzschneider KM, Kratz M, Damman CJ, Hullarg M (2016) Mechanisms linking the gut microbiome and glucose metabolism. J Clin Endocrinol Metab 101:1445\u20131454. https:\/\/doi.org\/10.1210\/jc.2015-4251","journal-title":"J Clin Endocrinol Metab"},{"key":"6677_CR38","doi-asserted-by":"publisher","first-page":"1419329","DOI":"10.3389\/fendo.2024.1419329","volume":"15","author":"L Zhang","year":"2024","unstructured":"Zhang L, Qin Y, Huang Y et al (2024) Abnormal late postprandial glucagon response in type 1 diabetes is a function of differences in stimulated C-peptide concentrations. Front Endocrinol 15:1419329. https:\/\/doi.org\/10.3389\/fendo.2024.1419329","journal-title":"Front Endocrinol"},{"key":"6677_CR39","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1111\/jdi.13486","volume":"12","author":"A Ito","year":"2021","unstructured":"Ito A, Horie I, Miwa M et al (2021) Impact of glucagon response on early postprandial glucose excursions irrespective of residual \u03b2-cell function in type 1 diabetes: a cross-sectional study using a mixed meal tolerance test. J Diabetes Invest 12:1367\u20131376. https:\/\/doi.org\/10.1111\/jdi.13486","journal-title":"J Diabetes Invest"},{"key":"6677_CR40","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1111\/cen.12546","volume":"81","author":"PR Van Dijk","year":"2014","unstructured":"Van Dijk PR, Logtenberg SJJ, Gans ROB, Bilo HJG, Kleefstra N (2014) Intraperitoneal insulin infusion: treatment option for type 1 diabetes resulting in beneficial endocrine effects beyond glycaemia. Clin Endocrinol 81:488\u2013497. https:\/\/doi.org\/10.1111\/cen.12546","journal-title":"Clin Endocrinol"},{"key":"6677_CR41","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1111\/tri.12919","volume":"30","author":"V Delaune","year":"2017","unstructured":"Delaune V, Berney T, Lacotte S, Toso C (2017) Intraportal islet transplantation: the impact of the liver microenvironment. Transpl Int 30:227\u2013238. https:\/\/doi.org\/10.1111\/tri.12919","journal-title":"Transpl Int"},{"key":"6677_CR42","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1016\/j.diabres.2015.05.002","volume":"109","author":"L Bally","year":"2015","unstructured":"Bally L, Buehler T, Dokumaci AS, Boesch C, Stettler C (2015) Hepatic and intramyocellular glycogen stores in adults with type 1 diabetes and healthy controls. Diabetes Res Clin Pract 109:e1\u2013e3. https:\/\/doi.org\/10.1016\/j.diabres.2015.05.002","journal-title":"Diabetes Res Clin Pract"},{"key":"6677_CR43","doi-asserted-by":"publisher","first-page":"49","DOI":"10.2337\/diabetes.51.1.49","volume":"51","author":"MG Bischof","year":"2002","unstructured":"Bischof MG, Bernroider E, Krssak M et al (2002) Hepatic glycogen metabolism in type 1 diabetes after long-term near normoglycemia. Diabetes 51:49\u201354. https:\/\/doi.org\/10.2337\/diabetes.51.1.49","journal-title":"Diabetes"},{"key":"6677_CR44","doi-asserted-by":"publisher","first-page":"2248","DOI":"10.1210\/jc.2015-1055","volume":"100","author":"SJ Perano","year":"2015","unstructured":"Perano SJ, Rayner CK, Kritas S et al (2015) Gastric emptying is more rapid in adolescents with type 1 diabetes and impacts on postprandial glycemia. J Clin Endocrinol Metab 100:2248\u20132253. https:\/\/doi.org\/10.1210\/jc.2015-1055","journal-title":"J Clin Endocrinol Metab"},{"key":"6677_CR45","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1007\/s00125-022-05796-1","volume":"65","author":"RJ Jalleh","year":"2022","unstructured":"Jalleh RJ, Jones KL, Rayner CK, Marathe CS, Wu T, Horowitz M (2022) Normal and disordered gastric emptying in diabetes: recent insights into (patho)physiology, management and impact on glycaemic control. Diabetologia 65:1981\u20131993. https:\/\/doi.org\/10.1007\/s00125-022-05796-1","journal-title":"Diabetologia"},{"key":"6677_CR46","doi-asserted-by":"publisher","first-page":"2269","DOI":"10.1210\/jc.2017-02811","volume":"103","author":"R Lupoli","year":"2018","unstructured":"Lupoli R, Creanza A, Griffo E et al (2018) Gastric emptying impacts the timing of meal glucose peak in subjects with uncomplicated type 1 diabetes. J Clin Endocrinol Metab 103:2269\u20132276. https:\/\/doi.org\/10.1210\/jc.2017-02811","journal-title":"J Clin Endocrinol Metab"},{"key":"6677_CR47","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1042\/bj2830759","volume":"283","author":"A Gardemann","year":"1992","unstructured":"Gardemann A, Watanabe Y, Gro\u00dfe V, Hesse S, Jungermann K (1992) Increases in intestinal glucose absorption and hepatic glucose uptake elicited by luminal but not vascular glutamine in the jointly perfused small intestine and liver of the rat. Biochem J 283:759\u2013765. https:\/\/doi.org\/10.1042\/bj2830759","journal-title":"Biochem J"},{"key":"6677_CR48","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/0016-5085(93)90711-K","volume":"105","author":"M Horowitz","year":"1993","unstructured":"Horowitz M, Jones K, Edelbroek MAL, Smout AJPM, Read NW (1993) The effect of posture on gastric emptying and intragastric distribution of oil and aqueous meal components and appetite. Gastroenterology 105:382\u2013390. https:\/\/doi.org\/10.1016\/0016-5085(93)90711-K","journal-title":"Gastroenterology"},{"key":"6677_CR49","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1172\/JCI118379","volume":"97","author":"R Taylor","year":"1996","unstructured":"Taylor R, Magnusson I, Rothman DL et al (1996) Direct assessment of liver glycogen storage by 13C nuclear magnetic resonance spectroscopy and regulation of glucose homeostasis after a mixed meal in normal subjects. J Clin Invest 97:126\u2013132. https:\/\/doi.org\/10.1172\/JCI118379","journal-title":"J Clin Invest"},{"key":"6677_CR50","doi-asserted-by":"publisher","first-page":"E102","DOI":"10.1152\/ajpendo.00511.2024","volume":"329","author":"A Brunasso","year":"2025","unstructured":"Brunasso A, Dalla Man C, Poli S et al (2025) Modeling hepatic glucose tracer kinetics from isotope dilution technique and deuterium metabolic imaging in postbariatric surgery and nonoperated individuals. Am J Physiol Endocrinol Metab 329:E102\u2013E116. https:\/\/doi.org\/10.1152\/ajpendo.00511.2024","journal-title":"Am J Physiol Endocrinol Metab"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-026-06677-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00125-026-06677-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-026-06677-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T16:46:12Z","timestamp":1774111572000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00125-026-06677-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,13]]},"references-count":50,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["6677"],"URL":"https:\/\/doi.org\/10.1007\/s00125-026-06677-7","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,13]]},"assertion":[{"value":"14 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"We thank all study participants for their time and commitment. We gratefully acknowledge the contributions of A. F. Emara, A. Buser, E. Ballabani and A. Melmer and of the study nurse team (V. Br\u00e4gger, J. F. Rodrigues Cunha Freitas, S. Tenisch) for their assistance with conducting the experiments, caring for study participants and support with data collection (all University Hospital Bern\/University of Bern), as well as L. Meiller and V. Sauvinet (CRNH Lyon) for the measurement of plasma glucose isotopic enrichment. We also thank the research administration team of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism (University Hospital Bern\/University of Bern) for their support in the logistical management of the study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"The data that support the findings of this study are available from the corresponding author upon reasonable request.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"The project received support from the Swiss National Science Foundation (PCEGP3_186978), the Diabetes Center Bern, the Translational Imaging Center (TIC) of Sitem-Insel, and Luc Tappy (Emeritus Professor of the Institute of Physiology, University of Lausanne, Switzerland) who kindly contributed to the purchase of [6,6\u2032-\n                      2\n                      H\n                      2\n                      ]-glucose. AB is supported by Piano Nazionale di Ripresa e Resilienza (PNRR) Next Generation EU ex Ministerial Decree (DM) 118\/23.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"DH, RK and LB designed the study. SP, NFL, AB, DH, RK and LB prepared and processed the data. All authors contributed to statistical analysis and interpretation of the results. AB, MS and CDM worked on the mathematical modelling analysis. AB, NFL and LB drafted the manuscript. NFL, SP, DH, RK and LB contributed to acquiring and managing the data. All authors contributed to the critical review of the manuscript. All authors approved the final version of the article, including the authorship list. LB is responsible for the integrity of the work as a whole.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}