Effect of Intensive Glycemic Control on Risk of Lower Extremity Amputation

J Am Coll Surg. 2018 Dec;227(6):596-604. doi: 10.1016/j.jamcollsurg.2018.09.021. Epub 2018 Oct 16.


Background: Diabetes mellitus is a major risk factor for peripheral arterial disease and lower extremity amputation (LEA). We evaluated the effects of intensive glucose control (IGC) on risk of LEA in patients with type 2 diabetes during a randomized-controlled multicenter trial.

Study design: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial randomized patients with type 2 diabetes to IGC (HbA1c target < 6.0%) or standard glycemic control (SGC; HbA1c target 7.0% to 7.9%). Using analysis of mean HbA1c, we examined relationships between glycemic control and incident/recurrent LEA during the clinical trial/follow-up.

Results: Mean post-randomization HbA1c over the course of the trial and post-trial follow-up was 7.3% ± 0.9% (6.8% ± 0.8% in the IGC arm, 7.7% ± 0.7% in the SGC arm). There were 124 participants who had at least 1 LEA during the study period; 73 were randomized to the SGC arm and 51 to the IGC arm (p = 0.049). Randomization to IGC was associated with decreased LEA rate (HR 0.69, 95% CI 0.483 to 0.987, p = 0.042). In multivariable models, mean HbA1c was a powerful predictor of LEA (HR 2.07 per 1% increase in HbA1c, 95% CI 1.67 to 2.57, p < 0.0001). Post-randomization mean HbA1c remained a strong predictor of LEA after controlling for other important covariates and competing risk of death (HR 1.94 per 1% increase in HbA1c, 95% CI 1.52 to 2.46, p < 0.0001).

Conclusions: In patients with type 2 diabetes, IGC was associated with a reduction in the risk for LEA. After 3.7 years of IGC, there was an enduring protective effect against LEA. Improved glycemic control was a strong predictor of decreased risk for subsequent LEA. This study suggests that tight glycemic control, even over a short time period, has potential to reduce risk of limb loss.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Amputation, Surgical*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / etiology
  • Diabetic Angiopathies / therapy
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / metabolism
  • Humans
  • Lower Extremity*
  • Male
  • Middle Aged
  • Peripheral Arterial Disease / blood
  • Peripheral Arterial Disease / etiology
  • Peripheral Arterial Disease / therapy


  • Blood Glucose
  • Glycated Hemoglobin A