Ning Ding1, Lucia Kwak1, Shoshana H Ballew1, Bernard Jaar2, Ron C Hoogeveen3, Christie M Ballantyne3, A Richey Sharrett1, Aaron R Folsom4, Gerardo Heiss5, Maya Salameh6, Josef Coresh2, Alan T Hirsch7, Elizabeth Selvin2, Kunihiro Matsushita8. 1. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 2. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Johns Hopkins University School of Medicine, Baltimore, MD, USA. 3. Baylor College of Medicine, Houston, TX, USA. 4. University of Minnesota School of Public Health, Minneapolis, MN, USA. 5. University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, NC, USA. 6. Johns Hopkins University School of Medicine, Baltimore, MD, USA. 7. University of Minnesota School of Medicine, Minneapolis, MN, USA. 8. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: kmatsus5@jhu.edu.
Abstract
BACKGROUND AND AIMS: Traditional glycemic markers, fasting glucose and hemoglobin A1c (HbA1c), predict incident peripheral artery disease (PAD). However, it is unknown whether nontraditional glycemic markers, fructosamine, glycated albumin, and 1,5-anhydroglucitol, are associated with PAD and whether these glycemic markers demonstrate particularly strong associations with severe PAD, critical limb ischemia (CLI). METHODS: We quantified the associations of these five glycemic markers with incident PAD (hospitalizations with PAD diagnosis or leg revascularization) in 11,634 ARIC participants using Cox regression models. Participants were categorized according to diabetes diagnosis and clinical cut-points of glycemic markers (nontraditional glycemic markers were categorized according to percentiles corresponding to the HbA1c cut-points). RESULTS: Over a median follow-up of 20.7 years, there were 392 cases of PAD (133 were CLI with tissue loss). HbA1c was more strongly associated with incident PAD than fasting glucose, with adjusted hazard ratios (HR) 6.00 (95% CI, 3.73-9.66) for diagnosed diabetes with HbA1c ≥ 7% and 3.53 (2.39-5.22) for no diagnosed diabetes with HbA1c ≥ 6.5% compared to no diagnosed diabetes with HbA1c <5.7%. Three nontraditional glycemic markers demonstrated risk gradients intermediate between HbA1c and fasting glucose and their risk gradients were substantially attenuated after adjusting for HbA1c. All glycemic markers consistently demonstrated stronger associations with CLI than PAD without CLI (p for difference <0.02 for all glycemic markers). CONCLUSIONS: Nontraditional glycemic markers were associated with incident PAD independent of fasting glucose but not necessarily HbA1c. Our results also support the importance of glucose metabolism in the progression to CLI.
BACKGROUND AND AIMS: Traditional glycemic markers, fasting glucose and hemoglobin A1c (HbA1c), predict incident peripheral artery disease (PAD). However, it is unknown whether nontraditional glycemic markers, fructosamine, glycated albumin, and 1,5-anhydroglucitol, are associated with PAD and whether these glycemic markers demonstrate particularly strong associations with severe PAD, critical limb ischemia (CLI). METHODS: We quantified the associations of these five glycemic markers with incident PAD (hospitalizations with PAD diagnosis or leg revascularization) in 11,634 ARIC participants using Cox regression models. Participants were categorized according to diabetes diagnosis and clinical cut-points of glycemic markers (nontraditional glycemic markers were categorized according to percentiles corresponding to the HbA1c cut-points). RESULTS: Over a median follow-up of 20.7 years, there were 392 cases of PAD (133 were CLI with tissue loss). HbA1c was more strongly associated with incident PAD than fasting glucose, with adjusted hazard ratios (HR) 6.00 (95% CI, 3.73-9.66) for diagnosed diabetes with HbA1c ≥ 7% and 3.53 (2.39-5.22) for no diagnosed diabetes with HbA1c ≥ 6.5% compared to no diagnosed diabetes with HbA1c <5.7%. Three nontraditional glycemic markers demonstrated risk gradients intermediate between HbA1c and fasting glucose and their risk gradients were substantially attenuated after adjusting for HbA1c. All glycemic markers consistently demonstrated stronger associations with CLI than PAD without CLI (p for difference <0.02 for all glycemic markers). CONCLUSIONS: Nontraditional glycemic markers were associated with incident PAD independent of fasting glucose but not necessarily HbA1c. Our results also support the importance of glucose metabolism in the progression to CLI.
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