title: Diabetic Peripheral Neuropathy as a Predictor of Asymptomatic Myocardial Ischemia in Type 2 Diabetes Mellitus: A Cross-Sectional Study.
abstract: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes and has been associated with cardiovascular disease, the leading cause of mortality in diabetes. As asymptomatic myocardial ischemia (MI) is frequent in diabetes, we hypothesized that DPN may be associated with MI in patients with type 2 diabetes mellitus and no history of cardiovascular events.
  
  
  
  Eighty-two patients with DPN (n = 41) or without DPN (n = 41) were included. Among the DPN group, 15 had active foot ulcers. All subjects underwent Technetium-99 m sestamibi single-photon emission computed tomographic imaging for the estimation of myocardial ischemia, expressed as Summed Stress Score (SSS). The Neuropathy Disability Score (NDS) was used to quantify DPN and abnormal ratio of the longest electrocardiographic RR interval between the 28th and 32nd beats, after standing to the shortest interval between the 13th and 17th beats (RR ratio) was used as an index of cardiovascular autonomic neuropathy (CAN).
  
  
  
  Abnormal SSS was observed in 9.8% of patients without DPN and in 46.3% of patients with DPN (p < 0.001). In the multivariate analysis, NDS was the strongest predictor for SSS (β = 0.32, p = 0.003). When excluding patients with abnormal RR ratio (β = 0.32, p = 0.003) or with foot ulcers (β = 0.24, p = 0.04), this association remained significant. The RR ratio was also significantly associated with SSS in univariate (ρ = -0.30, p = 0.005) and multiple regressions (β = 0.24, p = 0.02).
  
  
  
  MI was strongly associated with DPN, and this association remained significant in patients with normal RR ratio. These results suggest that DPN assessment could help in identifying patients at risk of cardiovascular disease (CVD).
authors.affiliation: Microcirculation Lab, Joslin-Beth Israel Deaconess Foot Center and Rongxiang Xu, MD, Center for Regenerative Therapeutics, Harvard Medical School, Boston, MA, USA. dbaltzis@bidmc.harvard.edu.|Diabetes Center, Papageorgiou General Hospital, Thessaloniki, Greece. dbaltzis@bidmc.harvard.edu.|Third Department of Internal Medicine, Papageorgiou General Hospital, Thessaloniki, Greece. dbaltzis@bidmc.harvard.edu.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Baltzis
authors.affiliation: Microcirculation Lab, Joslin-Beth Israel Deaconess Foot Center and Rongxiang Xu, MD, Center for Regenerative Therapeutics, Harvard Medical School, Boston, MA, USA.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Roustit
authors.affiliation: Department of Nutrition and Dietetics, Alexander Technological Educational Institute, Thessaloniki, Greece.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Grammatikopoulou
authors.affiliation: Third Department of Nuclear Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Katsaboukas
authors.affiliation: Third Department of Nuclear Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Vassileios
authors.initials: V
authors.lastname: Athanasiou
authors.affiliation: Third Department of Nuclear Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Iakovou
authors.affiliation: Microcirculation Lab, Joslin-Beth Israel Deaconess Foot Center and Rongxiang Xu, MD, Center for Regenerative Therapeutics, Harvard Medical School, Boston, MA, USA.
authors.forename: Aristidis
authors.initials: A
authors.lastname: Veves
authors.affiliation: Diabetes Center, Papageorgiou General Hospital, Thessaloniki, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Manes
authors.affiliation: Third Department of Internal Medicine, Papageorgiou General Hospital, Thessaloniki, Greece.
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Trakatelli
mesh_terms: D000368:Aged; D058070:Asymptomatic Diseases; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003929:Diabetic Neuropathies / Q000150:complications*; D004185:Disability Evaluation; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006115:Greece; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D013223:Statistics as Topic; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
keywords: Cardiovascular autonomic neuropathy; Diabetes; Diabetic foot ulcer; Diabetic peripheral neuropathy; Myocardial ischemia; Type 2 diabetes mellitus