Glycemic control and cardiovascular mortality in hemodialysis patients with diabetes: a 6-year cohort study

Abstract

Previous observational studies using differing methodologies have yielded inconsistent results regarding the association between glycemic control and outcomes in diabetic patients receiving maintenance hemodialysis (MHD). We examined mortality predictability of A1C and random serum glucose over time in a contemporary cohort of 54,757 diabetic MHD patients (age 63 ± 13 years, 51% men, 30% African Americans, 19% Hispanics). Adjusted all-cause death hazard ratio (HR) for baseline A1C increments of 8.0-8.9, 9.0-9.9, and ≥10%, compared with 7.0-7.9% (reference), was 1.06 (95% CI 1.01-1.12), 1.05 (0.99-1.12), and 1.19 (1.12-1.28), respectively, and for time-averaged A1C was 1.11 (1.05-1.16), 1.36 (1.27-1.45), and 1.59 (1.46-1.72). A symmetric increase in mortality also occurred with time-averaged A1C levels in the low range (6.0-6.9%, HR 1.05 [95% CI 1.01-1.08]; 5.0-5.9%, 1.08 [1.04-1.11], and ≤5%, 1.35 [1.29-1.42]) compared with 7.0-7.9% in fully adjusted models. Adjusted all-cause death HR for time-averaged blood glucose 175-199, 200-249, 250-299, and ≥300 mg/dL, compared with 150-175 mg/dL (reference), was 1.03 (95% CI 0.99-1.07), 1.14 (1.10-1.19), 1.30 (1.23-1.37), and 1.66 (1.56-1.76), respectively. Hence, poor glycemic control (A1C ≥8% or serum glucose ≥200 mg/dL) appears to be associated with high all-cause and cardiovascular death in MHD patients. Very low glycemic levels are also associated with high mortality risk.

FIG. 1.

HRs of all-cause mortality of the entire range of A1C in 54,757 MHD patients using standard Cox proportional hazards regression (A), a time-averaged model (B), and HRs of all-cause mortality of serum glucose in 50,383 diabetic MHD patients using standard Cox proportional hazards regression (C) and a time-averaged model (D). Case-mix model is adjusted for age, sex, race and ethnicity, categories of dialysis vintage, primary insurance, marital status, dialysis dose as indicated by Kt/V (single pool), and residual renal function during the entry quarter. MICS-adjusted model includes all of the case-mix covariates as well as BMI, nPCR, serum levels of albumin, total iron-binding capacity, ferritin, creatinine, phosphorus, calcium, bicarbonate, blood white blood cell count, lymphocyte percentage, and hemoglobin.

FIG. 2.

HRs of all-cause mortality for the dichotomized A1C >7% in different subgroups of 54,757 MHD patients (A) and HRs of all-cause mortality for the dichotomized glucose >150 mg/dL in different subgroups of 50,383 MHD patients (B). Fully adjusted model is controlled for age, sex, race and ethnicity, categories of dialysis vintage, primary insurance, marital status, dialysis dose as indicated by Kt/V (single pool), residual renal function during the entry quarter, BMI, nPCR, serum levels of albumin, total iron-binding capacity, ferritin, creatinine, phosphorus, calcium, bicarbonate, blood white blood cell count, lymphocyte percentage, and hemoglobin.

FIG. 3.

HRs of cardiovascular mortality of the entire range of A1C in 54,757 MHD patients using standard Cox proportional hazards regression (A), a time-averaged model (B), and HRs of cardiovascular mortality of serum glucose in 50,383 diabetic MHD patients using standard Cox proportional hazards regression (C) and a time-averaged model (D). Case-mix model is adjusted for age, sex, race and ethnicity, categories of dialysis vintage, primary insurance, marital status, dialysis dose as indicated by Kt/V (single pool), and residual renal function during the entry quarter. MICS-adjusted model includes all of the case-mix covariates as well as BMI, nPCR, serum levels of albumin, total iron-binding capacity, ferritin, creatinine, phosphorus, calcium, bicarbonate, blood white blood cell count, lymphocyte percentage, and hemoglobin.