title: Retinal neurodegeneration in patients with type 1 diabetes mellitus: the role of glycemic variability.
abstract: OBJECTIVE
  Recent studies have identified neuroretinal abnormalities in persons affected by diabetes mellitus, before the onset of microvascular alterations. However, the role of glycemic variability (GV) on early retinal neurodegeneration is still not clarified.
  
  
  METHODS
  To explore the relationship between glycemic control and neuroretinal characteristics, 37 persons with Type 1 diabetes mellitus (Type 1 DM) divided into two groups with no signs (noRD) and with mild non-proliferative diabetic retinopathy (NPDR) compared to 13 healthy control participants (C) were recruited. All persons underwent an optical coherence tomography with automatic segmentation of all neuroretinal layers. Measurements of mean of nasal (N)/temporal (T)/superior (S)/inferior (I) macular quadrants for individual layer were also calculated. Metabolic control was evaluated by glycated hemoglobin (HbA1c), and indexes of GV were calculated from continuous glucose monitoring.
  
  
  RESULTS
  The difference among the three groups in terms of RNFL thickness was significantly dependent on quadrant (F(6;132) = 2.315; p = 0.037). This interaction was due to a specific difference in RNFL-N thickness, where both Type 1 DM groups showed a similar reduction versus C (-3.9 for noDR and -4.9 for NPDR), without any relevant difference between them (-1.0). Inner nuclear layer (INL) was increased in all quadrants in the two Type 1 DM groups compared to C (mean difference = 7.73; 95% CI: 0.32-15.14, p = 0.043; mean difference = 7.74; 95% CI: 0.33-15.15, p = 0.043, respectively). A negative correlation between RNFL-N and low blood glucose index (r = -0.382, p = 0.034) and positive correlation between INL and continuous overall net glycemic action -1, -2, -4 h (r = 0.40, p = 0.025; r = 0.39, p = 0.031; r = 0.41, p = 0.021, respectively) were observed in Type 1 DM patients. The triglycerides were positively and significantly correlated to INL (r = 0.48, p = 0.011), in Type 1 DM subjects. GV and triglycerides resulted both independent predictors of increased INL thickness. No correlation was found with HbA1c.
  
  
  CONCLUSIONS
  Early structural damage of neuroretina in persons with Type 1 DM patients is related to glucose fluctuations. GV should be addressed, even in the presence of a good metabolic control.
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.|Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, Rome, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Picconi
authors.affiliation: IRCCS-G.B. Bietti Foundation, Rome, Italy.
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Parravano
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.|Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, Rome, Italy.
authors.forename: Dorina
authors.initials: D
authors.lastname: Ylli
authors.affiliation: Service of Medical Statistics and Information Technology, Fatebenefratelli Foundation for Health Research and Education, AFaR Division, Rome, Italy.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Pasqualetti
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.|Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Coluzzi
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.|Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Giordani
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.|Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Malandrucco
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Lauro
authors.affiliation: IRCCS-G.B. Bietti Foundation, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Scarinci
authors.affiliation: IRCCS-G.B. Bietti Foundation, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Giorno
authors.affiliation: IRCCS-G.B. Bietti Foundation, Rome, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Varano
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. frontoni@uniroma2.it.|Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, Rome, Italy. frontoni@uniroma2.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Frontoni
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology; D005260:Female; D038321:Glycemic Index / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012162:Retinal Degeneration / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology; D041623:Tomography, Optical Coherence
chemical_list: D001786:Blood Glucose
keywords: Glycemic variability; Retinal neurodegeneration; Type 1 diabetes mellitus