Human Type 1 Diabetes Is Characterized by an Early, Marked, Sustained, and Islet-Selective Loss of Sympathetic Nerves

• Published in: Diabetes (New York, N.Y.) Vol. 65; no. 8; pp. 2322 - 2330
• Main Authors: Mundinger, Thomas O., Mei, Qi, Foulis, Alan K., Fligner, Corinne L., Hull, Rebecca L., Taborsky, Gerald J.
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.08.2016
• Subjects: Adolescent; Adult; Autonomic Nervous System - metabolism; Autonomic Nervous System - pathology; Autonomic Nervous System - physiopathology; Child; Diabetes; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Diabetes Mellitus, Type 2 - physiopathology; Female; Glucagon - metabolism; Humans; Hypoglycemia; Hypoglycemia - metabolism; Hypoglycemia - pathology; Hypoglycemia - physiopathology; Immunohistochemistry; Insulin; Islet Studies; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Islets of Langerhans - physiopathology; Male; Middle Aged; Nervous system; Pancreas - metabolism; Pancreas - pathology; Pancreas - physiopathology; Sympathetic Nervous System - metabolism; Sympathetic Nervous System - pathology; Sympathetic Nervous System - physiopathology; Young Adult
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db16-0284

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.