title: HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study.
abstract: OBJECTIVE
  To examine the association of hemoglobin (Hb) A1c variability with microvascular complications in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study.
  
  
  METHODS
  Serial (3-5) HbA1c values collected in a 2-year period before enrollment were available from 8,260 subjects from 9 centers (of 15,773 patients from 19 centers). HbA1c variability was measured as the intraindividual SD of 4.52 ± 0.76 values. Diabetic retinopathy (DR) was assessed by dilated funduscopy. Chronic kidney disease (CKD) was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate (eGFR) was calculated from serum creatinine.
  
  
  RESULTS
  Median and interquartile range of average HbA1c (HbA1c-MEAN) and HbA1c-SD were 7.57% (6.86-8.38) and 0.46% (0.29-0.74), respectively. The highest prevalence of microalbuminuria, macroalbuminuria, reduced eGFR, albuminuric CKD phenotypes, and advanced DR was observed when both HbA1c parameters were above the median and the lowest when both were below the median. Logistic regression analyses showed that HbA1c-SD adds to HbA1c-MEAN as an independent correlate of microalbuminuria and stages 1-2 CKD and is an independent predictor of macroalbuminuria, reduced eGFR, and stages 3-5 albuminuric CKD, whereas HbA1c-MEAN is not. The opposite was found for DR, whereas neither HbA1c-MEAN nor HbA1c-SD affected nonalbuminuric CKD.
  
  
  CONCLUSIONS
  In patients with type 2 diabetes, HbA1c variability affects (albuminuric) CKD more than average HbA1c, whereas only the latter parameter affects DR, thus suggesting a variable effect of these measures on microvascular complications.
authors.affiliation: Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy. giuseppe.pugliese@uniroma1.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Penno
authors.forename: Anna
authors.initials: A
authors.lastname: Solini
authors.forename: Enzo
authors.initials: E
authors.lastname: Bonora
authors.forename: Cecilia
authors.initials: C
authors.lastname: Fondelli
authors.forename: Emanuela
authors.initials: E
authors.lastname: Orsi
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Zerbini
authors.forename: Susanna
authors.initials: S
authors.lastname: Morano
authors.forename: Franco
authors.initials: F
authors.lastname: Cavalot
authors.forename: Olga
authors.initials: O
authors.lastname: Lamacchia
authors.forename: Luigi
authors.initials: L
authors.lastname: Laviola
authors.forename: Antonio
authors.initials: A
authors.lastname: Nicolucci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pugliese
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D003925:Diabetic Angiopathies / Q000453:epidemiology*; D003928:Diabetic Nephropathies / Q000453:epidemiology*; D003930:Diabetic Retinopathy / Q000453:epidemiology / Q000209:etiology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology / Q000209:etiology
chemical_list: D006442:Glycated Hemoglobin