title: Near-normoglycaemia and development of neuropathy: a 24-year prospective study from diagnosis of type 1 diabetes.
abstract: OBJECTIVE
  Complete prevention of diabetic neuropathies has not been previously demonstrated. We sought to determine whether long-term near-normoglycaemia maintained from the diagnosis of type 1 diabetes is associated with polyneuropathy and cardiac autonomic dysfunction.
  
  
  METHODS
  Prospective observational study over 24 years.
  
  
  METHODS
  Ambulatory care.
  
  
  METHODS
  32 newly diagnosed patients with type 1 diabetes aged 20.3 ± 1.0 years, duration of diabetes 2.7 ± 0.3 weeks.
  
  
  METHODS
  Insulin therapy according to standards of care.
  
  
  METHODS
  Motor and sensory nerve conduction velocity (MNCV and SNCV), heart rate variability (HRV), and confirmed clinical polyneuropathy measured at 15 time points over 24 years and quantitative sensory testing (QST) determined over 20-22 years.
  
  
  RESULTS
  11 patients were well controlled over 24 years with mean glycated haemoglobin (HbA1c) <7.0% (6.5 ± 0.1%; group 1), whereas 21 patients were poorly controlled (mean HbA1c ≥ 7.0%: 8.3 ± 0.2%; group 2). After 24 years, MNCV was faster in group 1 versus group 2 in the median (55.5 ± 1.6 vs 48.9 ± 1.6 m/s), ulnar (56.5 ± 1.5 vs 49.3 ± 1.7 m/s) and peroneal nerve (44.7 ± 1.6 vs 36.8 ± 2.5 m/s), while SNCV was faster in the median (53.6 ± 1.6 vs 45.5 ± 2.8 m/s), ulnar (54.7 ± 1.8 vs 43.0 ± 3.9 m/s), and sural nerve (44.5 ± 1.8 vs 35.5 ± 2.6 m/s; all p<0.05). The annual decline in peroneal MNCV and sural SNCV in group 1 was sixfold and threefold faster in group 2 than in group 1, respectively. Likewise, impairment in QST and HRV developed at faster rates in group 2. After 24 years, 64% of patients in group 2, but none in group 1, developed confirmed clinical polyneuropathy.
  
  
  CONCLUSIONS
  Near-normoglycaemia maintained from the diagnosis of type 1 diabetes over 24 years was associated with a complete prevention of the decline in hyperglycaemia-related peripheral and autonomic nerve function, and development of confirmed clinical polyneuropathy.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Dan
authors.initials: D
authors.lastname: Ziegler
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Margarete
authors.initials: M
authors.lastname: Behler
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Schroers-Teuber
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000328:Adult; D001341:Autonomic Nervous System / Q000503:physiopathology*; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D017776:Autonomic Pathways / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D003929:Diabetic Neuropathies / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006331:Heart Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006339:Heart Rate; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000150:complications*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009431:Neural Conduction; D010525:Peripheral Nerves / Q000503:physiopathology; D011115:Polyneuropathies / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D011446:Prospective Studies; D012016:Reference Values; D012684:Sensory Thresholds; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin