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

Giuseppe Penno, Anna Solini, Enzo Bonora, Cecilia Fondelli, Emanuela Orsi, Gianpaolo Zerbini, Susanna Morano, Franco Cavalot, Olga Lamacchia, Luigi Laviola, Antonio Nicolucci, Giuseppe Pugliese, Renal Insufficiency And Cardiovascular Events Study Group, Giuseppe Pugliese, Giuseppe Penno, Anna Solini, Enzo Bonora, Emanuela Orsi, Roberto Trevisan, Luigi Laviola, Antonio Nicolucci, Giuseppe Pugliese, Salvatore De Cosmo, Gabriella Gruden, Susanna Morano, Giuseppe Penno, Francesco Pugliese, Giampaolo Zerbini, Luigi Laviola, Anna Solini, Roberto Trevisan, Giuseppe Pugliese, Paola Simonelli, Laura Salvi, Giulia Mazzitelli, Alessandra Bazuro, Aurora Frasheri, Paolo Cavallo-Perin, Gabriella Gruden, Bartolomeo Lorenzati, Mariella Trovati, Giovanni Anfossi, Franco Cavalot, Massimo Chirio, Giampaolo Zerbini, Valentina Martina, Emanuela Orsi, Laura Montefusco, Antonio Pontiroli, Marco Laneri, Maura Arosio, Alessia Dolci, Roberto Trevisan, Anna Corsi, Enzo Bonora, Giacomo Zoppini, Angelo Avogaro, Monica Vedovato, Elisa Pagnin, Giuseppe Penno, Laura Pucci, Daniela Lucchesi, Eleonora Russo, Monia Garofolo, Anna Solini, Francesco Dotta, Cecilia Fondelli, Laura Nigi, Susanna Morano, Alessandra Gatti, Raffaella Buzzetti, Mauro Cignarelli, Olga Lamacchia, Sabina Pinnelli, Francesco Giorgino, Luigi Laviola, Sebastio Perrini, Giorgio Sesti, Francesco Andreozzi, Marco Giorgio Baroni, Giuseppina Frau, Giuseppe Penno, Anna Solini, Enzo Bonora, Cecilia Fondelli, Emanuela Orsi, Gianpaolo Zerbini, Susanna Morano, Franco Cavalot, Olga Lamacchia, Luigi Laviola, Antonio Nicolucci, Giuseppe Pugliese, Renal Insufficiency And Cardiovascular Events Study Group, Giuseppe Pugliese, Giuseppe Penno, Anna Solini, Enzo Bonora, Emanuela Orsi, Roberto Trevisan, Luigi Laviola, Antonio Nicolucci, Giuseppe Pugliese, Salvatore De Cosmo, Gabriella Gruden, Susanna Morano, Giuseppe Penno, Francesco Pugliese, Giampaolo Zerbini, Luigi Laviola, Anna Solini, Roberto Trevisan, Giuseppe Pugliese, Paola Simonelli, Laura Salvi, Giulia Mazzitelli, Alessandra Bazuro, Aurora Frasheri, Paolo Cavallo-Perin, Gabriella Gruden, Bartolomeo Lorenzati, Mariella Trovati, Giovanni Anfossi, Franco Cavalot, Massimo Chirio, Giampaolo Zerbini, Valentina Martina, Emanuela Orsi, Laura Montefusco, Antonio Pontiroli, Marco Laneri, Maura Arosio, Alessia Dolci, Roberto Trevisan, Anna Corsi, Enzo Bonora, Giacomo Zoppini, Angelo Avogaro, Monica Vedovato, Elisa Pagnin, Giuseppe Penno, Laura Pucci, Daniela Lucchesi, Eleonora Russo, Monia Garofolo, Anna Solini, Francesco Dotta, Cecilia Fondelli, Laura Nigi, Susanna Morano, Alessandra Gatti, Raffaella Buzzetti, Mauro Cignarelli, Olga Lamacchia, Sabina Pinnelli, Francesco Giorgino, Luigi Laviola, Sebastio Perrini, Giorgio Sesti, Francesco Andreozzi, Marco Giorgio Baroni, Giuseppina Frau

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.

Research design and 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.

Trial registration: ClinicalTrials.gov NCT00715481.

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Source: PubMed

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