title: The effect of cumulative glycemic burden on the incidence of diabetic foot disease.
abstract: BACKGROUND
  Glycemic control is a known modifiable risk factor for diabetic foot disease. Prior attempts to define its relationship with diabetic foot ulcer and Charcot arthropathy fail to account for variability in control and duration of diabetic disease. We developed a novel metric to reflect aggregate disease exposure in a diabetic, termed cumulative glycemic burden. We hypothesized that it would be positively associated with both diabetic foot ulcer and radiographically diagnosed Charcot arthropathy.
  
  
  METHODS
  Patients aged 18 to 90 years with ≥3 hemoglobin A1c (HbA1c) values were identified retrospectively at a single institution over a 15-year period. Primary outcomes were ICD-9 diagnosis of foot ulcer and radiographically diagnosed Charcot arthropathy. Cumulative glycemic burden was calculated by trapezoidal integration of the area under a curve defined by HbA1c values above 7 over time. Patients were stratified into quartiles based on cumulative glycemic burden (excellent, good, fair, and poor control). χ2tests compared the proportion of foot ulcer and Charcot across quartiles. Regression analysis identified associated demographic and comorbidity factors with diabetic foot disease. Statistical significance was set at P < .05.
  
  
  RESULTS
  Out of 22,913 diabetics, 1643 (7.2%) had a foot ulcer; 54 out of 771 diabetics (7.0%) had radiographic Charcot arthropathy. There was a statistically significant stepwise increase in the incidence of foot ulcer with increasing cumulative glycemic burden by patient quartile (5.2 vs. 6.4 vs. 7.9 vs. 13.9%; P < .001). No significant trend was seen between incidence of Charcot arthropathy and greater cumulative glycemic burden (7.8 vs. 5.6 vs. 4.4 vs. 10.0%; P = .469). Peripheral vascular disease was most strongly associated with diabetic foot ulcer. Hypertension and diabetic neuropathy were independently associated with Charcot arthropathy.
  
  
  CONCLUSIONS
  Increasing cumulative glycemic burden is positively associated with diabetic foot ulcer. Greater attention should be paid towards the most poorly controlled diabetics with the longest duration of disease to reduce their risk. Cumulative glycemic burden is not associated with Charcot arthropathy.
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University, Chicago, IL, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Dekker
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. c-qin@northwestern.edu.
authors.forename: Charles
authors.initials: C
authors.lastname: Qin
authors.affiliation: Department of Orthopaedic Surgery, University of Rochester, Rochester, NY, USA.
authors.forename: Bryant S
authors.initials: BS
authors.lastname: Ho
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University, Chicago, IL, USA.
authors.forename: Anish R
authors.initials: AR
authors.lastname: Kadakia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism*; D017719:Diabetic Foot / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D038321:Glycemic Index / Q000502:physiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
keywords: Charcot arthropathy; Cumulative glycemic burden; Diabetic foot disease; Diabetic foot ulcer