title: Human Type 1 Diabetes Is Characterized by an Early, Marked, Sustained, and Islet-Selective Loss of Sympathetic Nerves.
abstract: In humans, the glucagon response to moderate-to-marked insulin-induced hypoglycemia (IIH) is largely mediated by the autonomic nervous system. Because this glucagon response is impaired early in type 1 diabetes, we sought to determine if these patients, like animal models of autoimmune diabetes, have an early and severe loss of islet sympathetic nerves. We also tested whether this nerve loss is a permanent feature of type 1 diabetes, is islet-selective, and is not seen in type 2 diabetes. To do so, we quantified pancreatic islet and exocrine sympathetic nerve fiber area from autopsy samples of patients with type 1 or 2 diabetes and control subjects without diabetes. Our central finding is that patients with either very recent onset (<2 weeks) or long duration (>10 years) of type 1 diabetes have a severe loss of islet sympathetic nerves (Δ = -88% and Δ = -79%, respectively). In contrast, patients with type 2 diabetes lose no islet sympathetic nerves. There is no loss of exocrine sympathetic nerves in either type 1 or type 2 diabetes. We conclude that patients with type 1, but not type 2, diabetes have an early, marked, sustained, and islet-selective loss of sympathetic nerves, one that may impair their glucagon response to IIH.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA mundin@u.washington.edu.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Mundinger
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Mei
authors.affiliation: Department of Pathology, Southern General Hospital, Glasgow, Scotland, U.K.
authors.forename: Alan K
authors.initials: AK
authors.lastname: Foulis
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA.
authors.forename: Corinne L
authors.initials: CL
authors.lastname: Fligner
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA VA Puget Sound Health Care System, Seattle, WA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hull
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA VA Puget Sound Health Care System, Seattle, WA.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Taborsky
mesh_terms: D000293:Adolescent; D000328:Adult; D001341:Autonomic Nervous System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D005934:Glucagon