{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:58:03Z","timestamp":1790740683969,"version":"4.1.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2020,8,22]],"date-time":"2020-08-22T00:00:00Z","timestamp":1598054400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,22]],"date-time":"2020-08-22T00:00:00Z","timestamp":1598054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007514","name":"Universit\u00e0 di Pisa","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007514","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/hypothesis<\/jats:title>\n                    <jats:p>\n                      The glucosuria induced by sodium\u2013glucose cotransporter 2 (SGLT2) inhibition stimulates endogenous (hepatic) glucose production (EGP), blunting the decline in HbA\n                      <jats:sub>1c<\/jats:sub>\n                      . We hypothesised that, in response to glucosuria, a renal signal is generated and stimulates EGP. To examine the effect of acute administration of SGLT2 inhibitors on EGP, we studied non-diabetic individuals who had undergone renal transplant with and without removal of native kidneys.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This was a parallel, randomised, double-blind, placebo-controlled, single-centre study, designed to evaluate the effect of a single dose of dapagliflozin or placebo on EGP determined by stable-tracer technique. We recruited non-diabetic individuals who were 30\u201365\u00a0years old, with a BMI of 25\u201335\u00a0kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      and stable body weight (\u00b12\u00a0kg) over the preceding 3\u00a0months, and HbA\n                      <jats:sub>1c<\/jats:sub>\n                      &lt;42\u00a0mmol\/mol (6.0%). Participants had undergone renal transplant with and without removal of native kidneys and were on a stable dose of immunosuppressive medications. Participants received a single dose of dapagliflozin 10\u00a0mg or placebo on two separate days, at a 5- to 14-day interval, according to randomisation performed by our hospital pharmacy, which provided dapagliflozin and matching placebo, packaged in bulk bottles that were sequentially numbered. Both participants and investigators were blinded to group assignment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty non-diabetic renal transplant patients (ten with residual native kidneys, ten with bilateral nephrectomy) participated in the study. Dapagliflozin induced greater glucosuria in individuals with residual native kidneys vs nephrectomised individuals (8.6\u2009\u00b1\u20091.1 vs 5.5\u2009\u00b1\u20090.5\u00a0g\/6\u00a0h;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02; data not shown). During the 6\u00a0h study period, plasma glucose decreased only slightly and similarly in both groups, with no difference compared with placebo (data not shown). Following administration of placebo, there was a progressive time-related decline in EGP that was similar in both nephrectomised individuals and individuals with residual native kidneys. Following dapagliflozin administration, EGP declined in both groups, but the differences between the decrement in EGP with dapagliflozin and placebo in the group with bilateral nephrectomy (\u0394\u2009=\u20091.11\u2009\u00b1\u20090.72\u00a0\u03bcmol\u00a0min\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00a0kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) was significantly lower (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03) than in the residual native kidney group (\u0394\u2009=\u20092.56\u2009\u00b1\u20090.33\u00a0\u03bcmol min\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00a0kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ). In the population treated with dapagliflozin, urinary glucose excretion was correlated with EGP (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.34,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Plasma insulin, C-peptide, glucagon, prehepatic insulin:glucagon ratio, lactate, alanine and pyruvate concentrations were similar following placebo and dapagliflozin treatment. \u03b2-Hydroxybutyrate increased with dapagliflozin treatment in the residual native kidney group, while a small increase was observed only at 360\u00a0min in the nephrectomy group. Plasma adrenaline (epinephrine) did not change after dapagliflozin and placebo treatment in either group. Following dapagliflozin administration, plasma noradrenaline (norepinephrine) increased slightly in the residual native kidney group and decreased in the nephrectomy group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>In nephrectomised individuals, the hepatic compensatory response to acute SGLT2 inhibitor-induced glucosuria was attenuated, as compared with individuals with residual native kidneys, suggesting that SGLT2 inhibitor-mediated stimulation of hepatic glucose production via efferent renal nerves occurs in an attempt to compensate for the urinary glucose loss (i.e. a renal\u2013hepatic axis).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      NCT03168295\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Funding<\/jats:title>\n                    <jats:p>This protocol was supported by Qatar National Research Fund (QNRF) Award No. NPRP 8-311-3-062 and NIH grant DK024092-38.<\/jats:p>\n                    <jats:p>Graphical abstract<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-020-05254-w","type":"journal-article","created":{"date-parts":[[2020,8,22]],"date-time":"2020-08-22T00:02:27Z","timestamp":1598054547000},"page":"2423-2433","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Increase in endogenous glucose production with SGLT2 inhibition is attenuated in individuals who underwent kidney transplantation and bilateral native nephrectomy"],"prefix":"10.1007","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6301-9161","authenticated-orcid":false,"given":"Giuseppe","family":"Daniele","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Solis-Herrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Dardano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Tura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Giusti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jancy J.","family":"Kurumthodathu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Campi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Saba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Tregnaghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Francesca","family":"Egidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Abdul-Ghani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"DeFronzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5388-0270","authenticated-orcid":false,"given":"Stefano","family":"Del Prato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,22]]},"reference":[{"issue":"2","key":"5254_CR1","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1172\/JCI70704","volume":"124","author":"A Merovci","year":"2014","unstructured":"Merovci A, Solis-Herrera C, Daniele G et al (2014) Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest 124(2):509\u2013514. https:\/\/doi.org\/10.1172\/JCI70704","journal-title":"J Clin Invest"},{"issue":"2","key":"5254_CR2","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1172\/JCI72227","volume":"124","author":"E Ferrannini","year":"2014","unstructured":"Ferrannini E, Muscelli E, Frascerra S et al (2014) Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest 124(2):499\u2013508. https:\/\/doi.org\/10.1172\/JCI72227","journal-title":"J Clin Invest"},{"issue":"7","key":"5254_CR3","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.2337\/db17-0100","volume":"66","author":"H Jobori","year":"2017","unstructured":"Jobori H, Daniele G, Cersosimo E et al (2017) Empagliflozin and kinetics of renal glucose transport in healthy individuals and individuals with type 2 diabetes. Diabetes 66(7):1999\u20132006. https:\/\/doi.org\/10.2337\/db17-0100","journal-title":"Diabetes"},{"issue":"18","key":"5254_CR4","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.1161\/CIRCULATIONAHA.110.991869","volume":"123","author":"F Mahfoud","year":"2011","unstructured":"Mahfoud F, Schlaich M, Kindermann I et al (2011) Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation 123(18):1940\u20131946. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.110.991869","journal-title":"Circulation"},{"key":"5254_CR5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3389\/fphys.2012.00010","volume":"3","author":"MP Schlaich","year":"2012","unstructured":"Schlaich MP, Hering D, Sobotka P et al (2012) Effects of renal denervation on sympathetic activation, blood pressure, and glucose metabolism in patients with resistant hypertension. Front Physio 3:10. https:\/\/doi.org\/10.3389\/fphys.2012.00010","journal-title":"Front Physio"},{"issue":"5","key":"5254_CR6","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.2337\/dc19-2177","volume":"43","author":"C Solis-Herrea","year":"2020","unstructured":"Solis-Herrea C, Daniele G, Alatrach M et al (2020) Increase in endogenous glucose production with SGLT2 inhibition is unchanged by renal denervation and correlates strongly with the increase in urinary glucose excretion. Diabetes Care 43(5):1065\u20131069. https:\/\/doi.org\/10.2337\/dc19-2177","journal-title":"Diabetes Care"},{"issue":"3","key":"5254_CR7","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/s0169-2607(02)00097-4","volume":"71","author":"A Mari","year":"2003","unstructured":"Mari A, Stojanovska L, Proietto J, Thorburn AW (2003) A circulatory model for calculating non-steady-state glucose fluxes. Validation and comparison with compartmental models. Comput Methods Prog Biomed 71(3):269\u2013281. https:\/\/doi.org\/10.1016\/s0169-2607(02)00097-4","journal-title":"Comput Methods Prog Biomed"},{"issue":"5","key":"5254_CR8","doi-asserted-by":"publisher","first-page":"E794","DOI":"10.1152\/ajpendo.2000.278.5.E794","volume":"278","author":"A Natali","year":"2000","unstructured":"Natali A, Gastaldelli A, Camastra S et al (2000) Dose-response characteristics of insulin action on glucose metabolism: a nonsteady-state approach. Am J Physiol Endocrinol Metab 278(5):E794\u2013E801. https:\/\/doi.org\/10.1152\/ajpendo.2000.278.5.E794","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"2","key":"5254_CR9","doi-asserted-by":"publisher","first-page":"E532","DOI":"10.1152\/ajpendo.00127.2009","volume":"297","author":"S Bonuccelli","year":"2009","unstructured":"Bonuccelli S, Muscelli E, Gastaldelli A et al (2009) Improved tolerance to sequential glucose loading (Staub-Traugott effect): size and mechanisms. Am J Physiol Endocrinol Metab 297(2):E532\u2013E537. https:\/\/doi.org\/10.1152\/ajpendo.00127.2009","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"8","key":"5254_CR10","doi-asserted-by":"publisher","first-page":"2154","DOI":"10.2337\/dc12-2391","volume":"36","author":"D Polidori","year":"2013","unstructured":"Polidori D, Sha S, Sunder Mudaliar S et al (2013) Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study. Diabetes Care 36(8):2154\u20132161. https:\/\/doi.org\/10.2337\/dc12-2391","journal-title":"Diabetes Care"},{"issue":"3","key":"5254_CR11","doi-asserted-by":"publisher","first-page":"E399","DOI":"10.1152\/ajpendo.1990.258.3.E399","volume":"258","author":"DC Simonson","year":"1990","unstructured":"Simonson DC, DeFronzo RA (1990) Indirect calorimetry: methodological and interpretative problems. Am J Phys 258(3):E399\u2013E412. https:\/\/doi.org\/10.1152\/ajpendo.1990.258.3.E399","journal-title":"Am J Phys"},{"issue":"3","key":"5254_CR12","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/0026-0495(88)90110-2","volume":"37","author":"E Ferrannini","year":"1988","unstructured":"Ferrannini E (1988) The theoretical bases of indirect calorimetry: a review. Metabolism 37(3):287\u2013301. https:\/\/doi.org\/10.1016\/0026-0495(88)90110-2","journal-title":"Metabolism"},{"issue":"1","key":"5254_CR13","doi-asserted-by":"publisher","first-page":"133","DOI":"10.2215\/CJN.04010609","volume":"5","author":"R Santer","year":"2010","unstructured":"Santer R, Calado J (2010) Familial renal glucosuria and SGLT2: from a mendelian trait to a therapeutic target. Clin J Am Soc Nephrol 5(1):133\u2013141. https:\/\/doi.org\/10.2215\/CJN.04010609","journal-title":"Clin J Am Soc Nephrol"},{"issue":"1","key":"5254_CR14","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/j.1463-1326.2011.01511.x","volume":"14","author":"RA DeFronzo","year":"2012","unstructured":"DeFronzo RA, Davidson JA, Del Prato S (2012) The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab 14(1):5\u201314. https:\/\/doi.org\/10.1111\/j.1463-1326.2011.01511.x","journal-title":"Diabetes Obes Metab"},{"issue":"6","key":"5254_CR15","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s10286-010-0065-7","volume":"20","author":"DS Goldstein","year":"2010","unstructured":"Goldstein DS (2010) Catecholamines 101. Clin Auton Res 20(6):331\u2013352. https:\/\/doi.org\/10.1007\/s10286-010-0065-7","journal-title":"Clin Auton Res"},{"issue":"4","key":"5254_CR16","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1016\/j.transproceed.2010.03.125","volume":"42","author":"G Mosconi","year":"2010","unstructured":"Mosconi G, Panicali L, Persici E et al (2010) Native kidney function after renal combined with other solid organs in preemptive patients. Transplant Proc 42(4):1017\u20131020. https:\/\/doi.org\/10.1016\/j.transproceed.2010.03.125","journal-title":"Transplant Proc"},{"issue":"1","key":"5254_CR17","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1097\/00007890-199801150-00019","volume":"65","author":"M Pascual","year":"1998","unstructured":"Pascual M, Rabito CA, Tolkoff-Rubin N et al (1998) Contribution of native kidney function to total glomerular filtration rate after combined kidney-pancreas transplantation. Transplantation 65(1):99\u2013103. https:\/\/doi.org\/10.1097\/00007890-199801150-00019","journal-title":"Transplantation"},{"issue":"12","key":"5254_CR18","doi-asserted-by":"publisher","first-page":"2885","DOI":"10.1007\/s00125-015-3771-9","volume":"58","author":"K Rafiq","year":"2015","unstructured":"Rafiq K, Fujisawa Y, Sherajee SJ et al (2015) Role of the renal sympathetic nerve in renal glucose metabolism during the development of type 2 diabetes in rats. Diabetologia 58(12):2885\u20132898. https:\/\/doi.org\/10.1007\/s00125-015-3771-9","journal-title":"Diabetologia"},{"issue":"10","key":"5254_CR19","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1016\/j.molmet.2017.07.005","volume":"6","author":"KH Chhabra","year":"2017","unstructured":"Chhabra KH, Morgan DA, Tooke BP, Adams JM, Rahmouni K, Low MJ (2017) Reduced renal sympathetic nerve activity contributes to elevated glycosuria and improved glucose tolerance in hypothalamus-specific Pomc knockout mice. Mol Metab 6(10):1274\u20131285. https:\/\/doi.org\/10.1016\/j.molmet.2017.07.005","journal-title":"Mol Metab"},{"issue":"10","key":"5254_CR20","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.1007\/s00125-018-4669-0","volume":"61","author":"MC Thomas","year":"2018","unstructured":"Thomas MC, Cherney DZI (2018) The actions of SGLT2 inhibitors on metabolism, renal function and blood pressure. Diabetologia 61(10):2098\u20132107. https:\/\/doi.org\/10.1007\/s00125-018-4669-0","journal-title":"Diabetologia"},{"issue":"5","key":"5254_CR21","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1038\/nm.3828","volume":"21","author":"C Bonner","year":"2015","unstructured":"Bonner C, Kerr-Conte J, Gmyr V et al (2015) Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat Med 21(5):512\u2013517. https:\/\/doi.org\/10.1038\/nm.3828","journal-title":"Nat Med"},{"issue":"6","key":"5254_CR22","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1007\/s00125-019-4849-6","volume":"62","author":"RE Kuhre","year":"2019","unstructured":"Kuhre RE, Ghiasi SM, Adriaenssens AE et al (2019) No direct effect of SGLT2 activity on glucagon secretion. Diabetologia 62(6):1011\u20131023. https:\/\/doi.org\/10.1007\/s00125-019-4849-6","journal-title":"Diabetologia"},{"issue":"6","key":"5254_CR23","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.2337\/db17-1278","volume":"67","author":"R Martinez","year":"2018","unstructured":"Martinez R, Al-Jobori H, Ali AM et al (2018) Endogenous glucose production and hormonal changes in response to canagliflozin and liraglutide combination therapy. Diabetes 67(6):1182\u20131189. https:\/\/doi.org\/10.2337\/db17-1278","journal-title":"Diabetes"},{"issue":"11","key":"5254_CR24","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.2337\/dc15-2688","volume":"39","author":"G Daniele","year":"2016","unstructured":"Daniele G, Xiong J, Solis-Herrera C et al (2016) Dapagliflozin enhances fat oxidation and ketone production in patients with type 2 diabetes. Diabetes Care 39(11):2036\u20132041. https:\/\/doi.org\/10.2337\/dc15-2688","journal-title":"Diabetes Care"},{"issue":"6","key":"5254_CR25","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1172\/JCI108038","volume":"55","author":"J McGarry","year":"1975","unstructured":"McGarry J, Wright PH, Foster DW (1975) Hormonal control of ketogenesis. Rapid activation of hepatic ketogenic capacity in fed rats by anti-insulin serum and glucagon. J Clin Invest 55(6):1202\u20131209. https:\/\/doi.org\/10.1172\/JCI108038","journal-title":"J Clin Invest"},{"issue":"6","key":"5254_CR26","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1111\/dom.12881","volume":"19","author":"H Al Jobori","year":"2017","unstructured":"Al Jobori H, Daniele G, Adams J et al (2017) Determinants of the increase in ketone concentration during SGLT2 inhibition in NGT, IFG and T2DM patients. Diabetes Obes Metab 19(6):809\u2013813. https:\/\/doi.org\/10.1111\/dom.12881","journal-title":"Diabetes Obes Metab"},{"issue":"1","key":"5254_CR27","doi-asserted-by":"publisher","first-page":"e0190430","DOI":"10.1371\/journal.pone.0190430","volume":"13","author":"A Solazzo","year":"2018","unstructured":"Solazzo A, Testa F, Giovanella S et al (2018) The prevalence of autosomal dominant polycystic kidney disease (ADPKD): a meta-analysis of European literature and prevalence evaluation in the Italian province of Modena suggest that ADPKD is a rare and underdiagnosed condition. PLoS One 13(1):e0190430. https:\/\/doi.org\/10.1371\/journal.pone.0190430","journal-title":"PLoS One"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-020-05254-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00125-020-05254-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-020-05254-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,21]],"date-time":"2021-08-21T19:07:00Z","timestamp":1629572820000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00125-020-05254-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,22]]},"references-count":27,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["5254"],"URL":"https:\/\/doi.org\/10.1007\/s00125-020-05254-w","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,22]]},"assertion":[{"value":"31 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 August 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}