Hemoglobin A1c variability as an independent correlate of cardiovascular disease in patients with type 2 diabetes: A cross-sectional analysis of the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study

Giuseppe Penno, Anna Solini, Giacomo Zoppini, Emanuela Orsi, Cecilia Fondelli, Gianpaolo Zerbini, Susanna Morano, Franco Cavalot, Olga Lamacchia, Roberto Trevisan, Monica Vedovato, Giuseppe Pugliese

Research output: Contribution to journalArticle

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Abstract

Background: Previous reports have clearly indicated a significant relationship between hemoglobin (Hb) A1c change from one visit to the next and microvascular complications, especially nephropathy (albuminuria and albuminuric chronic kidney disease, CKD). In contrast, data on macrovascular disease are less clear. This study was aimed at examining the association of HbA1c variability with cardiovascular disease (CVD) 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 obtained during the 2-year period preceding recruitment, including that obtained at the enrolment, were available from 8,290 subjects from 9 centers (out of 15,773 patients from 19 centers). Average HbA1c and HbA1c variability were calculated as the intra-individual mean (HbA1c-MEAN) and standard deviation (HbA1c-SD), respectively, of 4.52±0.76 values. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events. Diabetic retinopathy (DR) was assessed by dilated fundoscopy. CKD was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate, as calculated from serum creatinine.Results: HbA1c-MEAN, but not HbA1c-SD, was significantly higher (P1c-MEAN, and 0.47 (0.29-0.75) and 0.46 (0.28-0.73), respectively, for HbA1c-SD. Logistic regression analyses showed that HbA1c-MEAN, but not HbA1c-SD (and independent of it), was a significant correlate of any CVD. Similar findings were observed in subjects with versus those without any coronary or cerebrovascular event or myocardial infarction. Conversely, none of these measures were associated with stroke, whereas both correlated with any lower limb vascular event and HbA1c-SD alone with ulceration/gangrene. All these associations were independent of known CVD risk factors and microvascular complications (DR and CKD).Conclusions: In patients with type 2 diabetes, HbA1c variability has not a major impact on macrovascular complications, at variance with average HbA1c, an opposite finding as compared with microvascular disease, and particularly nephropathy.Trial registration: ClinicalTrials.Gov NCT00715481.

Original languageEnglish
Article number98
JournalCardiovascular Diabetology
Volume12
Issue number1
DOIs
Publication statusPublished - Jul 5 2013

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Type 2 Diabetes Mellitus
Multicenter Studies
Renal Insufficiency
Hemoglobins
Cardiovascular Diseases
Cross-Sectional Studies
Chronic Renal Insufficiency
Albuminuria
Diabetic Retinopathy
Blood Vessels
Gangrene
Diabetic Nephropathies
Glomerular Filtration Rate
Lower Extremity
Creatinine
Logistic Models
Stroke
Myocardial Infarction
Regression Analysis
Serum

Keywords

  • Chronic kidney disease
  • Hemoglobin A1c
  • Retinopathy
  • Risk factors
  • Type 2 diabetes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Hemoglobin A1c variability as an independent correlate of cardiovascular disease in patients with type 2 diabetes : A cross-sectional analysis of the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study. / Penno, Giuseppe; Solini, Anna; Zoppini, Giacomo; Orsi, Emanuela; Fondelli, Cecilia; Zerbini, Gianpaolo; Morano, Susanna; Cavalot, Franco; Lamacchia, Olga; Trevisan, Roberto; Vedovato, Monica; Pugliese, Giuseppe.

In: Cardiovascular Diabetology, Vol. 12, No. 1, 98, 05.07.2013.

Research output: Contribution to journalArticle

Penno, Giuseppe ; Solini, Anna ; Zoppini, Giacomo ; Orsi, Emanuela ; Fondelli, Cecilia ; Zerbini, Gianpaolo ; Morano, Susanna ; Cavalot, Franco ; Lamacchia, Olga ; Trevisan, Roberto ; Vedovato, Monica ; Pugliese, Giuseppe. / Hemoglobin A1c variability as an independent correlate of cardiovascular disease in patients with type 2 diabetes : A cross-sectional analysis of the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study. In: Cardiovascular Diabetology. 2013 ; Vol. 12, No. 1.
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T1 - Hemoglobin A1c variability as an independent correlate of cardiovascular disease in patients with type 2 diabetes

T2 - A cross-sectional analysis of the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study

AU - Penno, Giuseppe

AU - Solini, Anna

AU - Zoppini, Giacomo

AU - Orsi, Emanuela

AU - Fondelli, Cecilia

AU - Zerbini, Gianpaolo

AU - Morano, Susanna

AU - Cavalot, Franco

AU - Lamacchia, Olga

AU - Trevisan, Roberto

AU - Vedovato, Monica

AU - Pugliese, Giuseppe

PY - 2013/7/5

Y1 - 2013/7/5

N2 - Background: Previous reports have clearly indicated a significant relationship between hemoglobin (Hb) A1c change from one visit to the next and microvascular complications, especially nephropathy (albuminuria and albuminuric chronic kidney disease, CKD). In contrast, data on macrovascular disease are less clear. This study was aimed at examining the association of HbA1c variability with cardiovascular disease (CVD) 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 obtained during the 2-year period preceding recruitment, including that obtained at the enrolment, were available from 8,290 subjects from 9 centers (out of 15,773 patients from 19 centers). Average HbA1c and HbA1c variability were calculated as the intra-individual mean (HbA1c-MEAN) and standard deviation (HbA1c-SD), respectively, of 4.52±0.76 values. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events. Diabetic retinopathy (DR) was assessed by dilated fundoscopy. CKD was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate, as calculated from serum creatinine.Results: HbA1c-MEAN, but not HbA1c-SD, was significantly higher (P1c-MEAN, and 0.47 (0.29-0.75) and 0.46 (0.28-0.73), respectively, for HbA1c-SD. Logistic regression analyses showed that HbA1c-MEAN, but not HbA1c-SD (and independent of it), was a significant correlate of any CVD. Similar findings were observed in subjects with versus those without any coronary or cerebrovascular event or myocardial infarction. Conversely, none of these measures were associated with stroke, whereas both correlated with any lower limb vascular event and HbA1c-SD alone with ulceration/gangrene. All these associations were independent of known CVD risk factors and microvascular complications (DR and CKD).Conclusions: In patients with type 2 diabetes, HbA1c variability has not a major impact on macrovascular complications, at variance with average HbA1c, an opposite finding as compared with microvascular disease, and particularly nephropathy.Trial registration: ClinicalTrials.Gov NCT00715481.

AB - Background: Previous reports have clearly indicated a significant relationship between hemoglobin (Hb) A1c change from one visit to the next and microvascular complications, especially nephropathy (albuminuria and albuminuric chronic kidney disease, CKD). In contrast, data on macrovascular disease are less clear. This study was aimed at examining the association of HbA1c variability with cardiovascular disease (CVD) 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 obtained during the 2-year period preceding recruitment, including that obtained at the enrolment, were available from 8,290 subjects from 9 centers (out of 15,773 patients from 19 centers). Average HbA1c and HbA1c variability were calculated as the intra-individual mean (HbA1c-MEAN) and standard deviation (HbA1c-SD), respectively, of 4.52±0.76 values. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events. Diabetic retinopathy (DR) was assessed by dilated fundoscopy. CKD was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate, as calculated from serum creatinine.Results: HbA1c-MEAN, but not HbA1c-SD, was significantly higher (P1c-MEAN, and 0.47 (0.29-0.75) and 0.46 (0.28-0.73), respectively, for HbA1c-SD. Logistic regression analyses showed that HbA1c-MEAN, but not HbA1c-SD (and independent of it), was a significant correlate of any CVD. Similar findings were observed in subjects with versus those without any coronary or cerebrovascular event or myocardial infarction. Conversely, none of these measures were associated with stroke, whereas both correlated with any lower limb vascular event and HbA1c-SD alone with ulceration/gangrene. All these associations were independent of known CVD risk factors and microvascular complications (DR and CKD).Conclusions: In patients with type 2 diabetes, HbA1c variability has not a major impact on macrovascular complications, at variance with average HbA1c, an opposite finding as compared with microvascular disease, and particularly nephropathy.Trial registration: ClinicalTrials.Gov NCT00715481.

KW - Chronic kidney disease

KW - Hemoglobin A1c

KW - Retinopathy

KW - Risk factors

KW - Type 2 diabetes

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