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This study investigated the impact of DM on nigrostriatal dopaminergic vulnerability independently of disease severity in drug-na\u00efve PD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study analyzed two independent cohorts of PD patients (multi-center PPMI\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009174, single-center UniBS\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200995). Patients with and without DM were first compared and then matched for age, sex, and clinical severity. All patients underwent baseline\n                      <jats:sup>123<\/jats:sup>\n                      I-FP-CIT imaging to quantify dopamine transporter binding. Dopaminergic binding, neural reserve index and molecular connectivity patterns were compared between severity-matched groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients with DM were older, predominantly male, and exhibited worse non-motor and cognitive symptoms. After severity matching, PD-DM exhibited more preserved nigrostriatal dopamine uptake compared to PD-n. PD-DM also showed fewer nigrostriatal dopaminergic connectivity alterations (10% vs. 21%) and reduced neural reserve index in the left putamen and \u2013 only in the single-center cohort- whole striatum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In drug-na\u00efve PD patients, comorbid diabetes is associated with comparable clinical severity despite milder dopaminergic loss. This suggests an increased dopamine system vulnerability linked to DM, reducing the efficiency and compensatory mechanisms of nigrostriatal dopaminergic networks in PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-026-08011-0","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T23:22:23Z","timestamp":1781911343000},"page":"6274-6288","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dopaminergic nigrostriatal vulnerability in Parkinson\u2019s Disease with diabetes: evidence from severity-matched cohorts"],"prefix":"10.1007","volume":"53","author":[{"given":"Alice","family":"Galli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Zatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Lupini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Paola","family":"Caminiti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Rizzardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Lucchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Bertagna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Paghera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago Fleming","family":"Outeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Perani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Padovani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2029-6606","authenticated-orcid":false,"given":"Andrea","family":"Pilotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,20]]},"reference":[{"key":"8011_CR1","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1002\/mds.27498","volume":"33","author":"MA Sacheli","year":"2018","unstructured":"Sacheli MA, Murray DK, Vafai N, Cherkasova MV, Dinelle K, Shahinfard E, et al. 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Here are attached the full financial disclosures not related to the present work: Alice Galli is supported by #NEXTGENERATIONEU (NGEU), Mission 1, Component 4 (CUP D82B23003790008). Silvia Paola Caminiti is supported by #NEXTGENERATIONEU (NGEU) and fundedby the Ministry of University and Research (MUR), National Recovery and Resilience Plan(NRRP), project MNESYS (PE0000006) \u2013 A multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022).Alessandro Padovani received grant support from Ministry of Health (MINSAL) and Ministry of Education, Research and University (MIUR), IMI H2020 initiative (IMI2-2018-15-06) and received speaker honoraria from Biogen, Lundbeck, Lilli, Roche Pharma.Andrea Pilotto received grant support from IMI H2020 initiative (IMI2-2018-15-06), Ministry of Health (MINSAL) Ministry of Education, Research and University (MIUR), Airalzh, LIMPE-DIsmoV Academy and received honoraria from the Movement Disorder Society, Abbvie, Bial, Eli Lilly, Lundbeck, Roche, Zambon Pharma.PPMI \u2013 a public-private partnership \u2013 is funded by the Michael J. Fox Foundation forParkinson\u2019s Research and funding partners, including 4D Pharma, Abbvie, AcureX, Allergan,Amathus Therapeutics, Aligning Science Across Parkinson's, AskBio, Avid Radiopharmaceuticals, BIAL, Biogen, Biohaven, BioLegend, BlueRock Therapeutics, Bristol-Myers Squibb, Calico Labs, Celgene, Cerevel Therapeutics, Coave Therapeutics, DaCapo Brainscience, Denali, Edmond J. Safra Foundation, Eli Lilly, Gain Therapeutics, GE HealthCare, Genentech, GSK, Golub Capital, Handl Therapeutics, Insitro, Janssen Neuroscience, Lundbeck, Merck, Meso Scale Discovery,Mission Therapeutics, Neurocrine Biosciences, Pfizer, Piramal, Prevail Therapeutics, Roche,Sanofi, Servier, Sun Pharma Advanced Research Company, Takeda, Teva, UCB, Vanqua Bio, Verily, Voyager Therapeutics, the Weston Family Foundation and Yumanity Therapeutics.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"PPMI cohort - The institutional review board approved the study at each site, and informed consent was obtained from all individual participants included in the study. UniBS cohort- The research protocol was approved by the Ethics Committee of the Brescia Hospital, Brescia, Italy (DNA study, NP 1471). Written informed consent was collected from each participant and the study was conducted in accordance with the declaration of Helsinki.","order":2,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}