title: Long-term Glycemic Variability and Risk of Adverse Outcomes: A Systematic Review and Meta-analysis.
abstract: OBJECTIVE
  Glycemic variability is emerging as a measure of glycemic control, which may be a reliable predictor of complications. This systematic review and meta-analysis evaluates the association between HbA1c variability and micro- and macrovascular complications and mortality in type 1 and type 2 diabetes.
  
  
  METHODS
  Medline and Embase were searched (2004-2015) for studies describing associations between HbA1c variability and adverse outcomes in patients with type 1 and type 2 diabetes. Data extraction was performed independently by two reviewers. Random-effects meta-analysis was performed with stratification according to the measure of HbA1c variability, method of analysis, and diabetes type.
  
  
  RESULTS
  Seven studies evaluated HbA1c variability among patients with type 1 diabetes and showed an association of HbA1c variability with renal disease (risk ratio 1.56 [95% CI 1.08-2.25], two studies), cardiovascular events (1.98 [1.39-2.82]), and retinopathy (2.11 [1.54-2.89]). Thirteen studies evaluated HbA1c variability among patients with type 2 diabetes. Higher HbA1c variability was associated with higher risk of renal disease (1.34 [1.15-1.57], two studies), macrovascular events (1.21 [1.06-1.38]), ulceration/gangrene (1.50 [1.06-2.12]), cardiovascular disease (1.27 [1.15-1.40]), and mortality (1.34 [1.18-1.53]). Most studies were retrospective with lack of adjustment for potential confounders, and inconsistency existed in the definition of HbA1c variability.
  
  
  CONCLUSIONS
  HbA1c variability was positively associated with micro- and macrovascular complications and mortality independently of the HbA1c level and might play a future role in clinical risk assessment.
authors.affiliation: Institute of Population Health, Centre for Primary Care, University of Manchester, Manchester, U.K. catherine.gorst@postgrad.manchester.ac.uk.
authors.forename: Catherine
authors.initials: C
authors.lastname: Gorst
authors.affiliation: Royal Stoke University Hospital, University Hospitals of North Midlands, Stoke-on-Trent, U.K. Keele Cardiovascular Research Group, Institute of Science and Technology in Medicine and Institute of Primary Care and Health Science, University of Keele, Stoke-on-Trent, U.K.
authors.forename: Chun Shing
authors.initials: CS
authors.lastname: Kwok
authors.affiliation: Central University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K.
authors.forename: Saadia
authors.initials: S
authors.lastname: Aslam
authors.affiliation: Farr Institute, University of Manchester, Manchester, U.K.
authors.forename: Iain
authors.initials: I
authors.lastname: Buchan
authors.affiliation: Institute of Population Health, Centre for Primary Care, University of Manchester, Manchester, U.K.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Kontopantelis
authors.affiliation: Epidemiology Group, Institute of Applied Health Sciences, School of Medicine, Medical Sciences, and Nutrition, University of Aberdeen, Aberdeen, Scotland, U.K.
authors.forename: Phyo K
authors.initials: PK
authors.lastname: Myint
authors.affiliation: Royal Stoke University Hospital, University Hospitals of North Midlands, Stoke-on-Trent, U.K.
authors.forename: Grant
authors.initials: G
authors.lastname: Heatlie
authors.affiliation: University East Anglia, Norwich, Norfolk, U.K.
authors.forename: Yoon
authors.initials: Y
authors.lastname: Loke
authors.affiliation: Manchester Diabetes Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K. Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, Manchester, U.K.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Rutter
authors.affiliation: Royal Stoke University Hospital, University Hospitals of North Midlands, Stoke-on-Trent, U.K. Keele Cardiovascular Research Group, Institute of Science and Technology in Medicine and Institute of Primary Care and Health Science, University of Keele, Stoke-on-Trent, U.K. Farr Institute, University of Manchester, Manchester, U.K.
authors.forename: Mamas A
authors.initials: MA
authors.lastname: Mamas
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D002318:Cardiovascular Diseases / Q000150:complications; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications* / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000401:mortality; D003925:Diabetic Angiopathies / Q000097:blood / Q000150:complications*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human