title: Glycemic control and extended hemodialysis survival in patients with diabetes mellitus: comparative results of traditional and time-dependent Cox model analyses.
abstract: OBJECTIVE
  The benefits and risks of aggressive glycemic control in diabetes mellitus complicated by end-stage kidney failure remain uncertain but have importance because of the large patient population with inferior overall prognosis. Recent large observational studies with differing methodologies reached somewhat contrasting conclusions regarding the association of hemoglobin A1c with survival in diabetic chronic hemodialysis patients.
  
  
  METHODS
  This study supplements the authors' previous analysis (which found no correlation) by extending the follow-up period to 3 years and using time-dependent survival models with repeated measures. Among 24,875 nationally distributed study patients, 94.5% had type 2 diabetes, allowing additional analysis in the subset with type 1 diabetes. Data were collected at baseline and every quarter to a maximum of 3 years' follow-up.
  
  
  RESULTS
  Adjusted standard and time-dependent Cox models indicated that only extremes of glycemia were associated with inferior survival. There was no effect modification by serum albumin levels, a marker of protein nutrition status, and no trend associated with random glucose measurements in a post hoc analysis. In type 1 diabetic patients, upper extreme hemoglobin A1c values indicated lower survival risk.
  
  
  CONCLUSIONS
  Sustained extremes of glycemia were only variably and weakly associated with decreased survival in this population. In the absence of randomized, controlled trials, these results suggest that aggressive glycemic control cannot be routinely recommended for all diabetic hemodialysis patients on the basis of reducing mortality risk. Physicians are encouraged to individualize glycemic targets based on potential risks and benefits in diabetic ESRD patients.
authors.affiliation: Renal Unit, Joslin Diabetes Center, Boston, MA 02215, USA. mark.williams@joslin.harvard.edu
authors.forename: Mark E
authors.initials: ME
authors.lastname: Williams
authors.forename: Eduardo
authors.initials: E
authors.lastname: Lacson
authors.forename: Weiling
authors.initials: W
authors.lastname: Wang
authors.forename: J Michael
authors.initials: JM
authors.lastname: Lazarus
authors.forename: Raymond
authors.initials: R
authors.lastname: Hakim
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D016009:Chi-Square Distribution; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000401:mortality / Q000628:therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000401:mortality / Q000628:therapy*; D003928:Diabetic Nephropathies / Q000097:blood / Q000401:mortality / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000097:blood / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009656:North America; D009752:Nutritional Status; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000401:mortality*; D018570:Risk Assessment; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D012709:Serum Albumin; C517652:hemoglobin A1c protein, human