Diabetes Metab J.  2023 Jul;47(4):535-546. 10.4093/dmj.2022.0112.

Glycemic Control and Adverse Clinical Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus: Results from KNOW-CKD

• Heo GY
• Koh HB
• Kim HW
• Park JT
• Yoo TH
• Kang SW
• Kim J
• Kim SW
• Kim YH
• Sung SA
• Oh KH
• Han SH

• KMID: 2544732
• DOI: http://doi.org/10.4093/dmj.2022.0112

Abstract

Background
The optimal level of glycosylated hemoglobin (HbA1c) to prevent adverse clinical outcomes is unknown in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM).
Methods
We analyzed 707 patients with CKD G1-G5 without kidney replacement therapy and T2DM from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD), a nationwide prospective cohort study. The main predictor was time-varying HbA1c level at each visit. The primary outcome was a composite of development of major adverse cardiovascular events (MACEs) or all-cause mortality. Secondary outcomes included the individual endpoint of MACEs, all-cause mortality, and CKD progression. CKD progression was defined as a ≥50% decline in the estimated glomerular filtration rate from baseline or the onset of end-stage kidney disease.
Results
During a median follow-up of 4.8 years, the primary outcome occurred in 129 (18.2%) patients. In time-varying Cox model, the adjusted hazard ratios (aHRs) for the primary outcome were 1.59 (95% confidence interval [CI], 1.01 to 2.49) and 1.99 (95% CI, 1.24 to 3.19) for HbA1c levels of 7.0%–7.9% and ≥8.0%, respectively, compared with <7.0%. Additional analysis of baseline HbA1c levels yielded a similar graded association. In secondary outcome analyses, the aHRs for the corresponding HbA1c categories were 2.17 (95% CI, 1.20 to 3.95) and 2.26 (95% CI, 1.17 to 4.37) for MACE, and 1.36 (95% CI, 0.68 to 2.72) and 2.08 (95% CI, 1.06 to 4.05) for all-cause mortality. However, the risk of CKD progression did not differ between the three groups.
Conclusion
This study showed that higher HbA1c levels were associated with an increased risk of MACE and mortality in patients with CKD and T2DM.

Keyword

Cardiovascular diseases; Diabetes mellitus, type 2; Glycated hemoglobin A; Renal insufficiency, chronic

Figure

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  Fig. 1. Kaplan–Meier failure curves for (A) the primary composite outcome and individual secondary outcomes of (B) major cardiovascular events, (C) all-cause mortality, and cumulative incidence function of (D) renal outcome according to glycosylated hemoglobin (HbA1c) levels of <7.0%, 7.0%–7.9%, and ≥8.0%. Log-rank test (A) P=0.02, (B) P=0.19, (C) P=0.03, (D) P=0.08.

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  Fig. 2. Subgroup analysis for showing the effect of glycosylated hemoglobin levels on the risk of the composite outcomea. Hazard ratios were adjusted for age, sex, body mass index, Charlson comorbidity index, socioeconomic status, smoking status, systolic blood pressure, use of renin angiotensin aldosterone system inhibitors, statins, estimated glomerular filtration rate (eGFR), serum albumin, low-density lipoprotein cholesterol, and urine protein/creatinine ratio. BMI, body mass index; CVD, cardiovascular disease; hs-CRP, high-sensitive C-reactive protein. aPrimary composite outcome included major adverse cardiovascular event, cardiac death or all-cause death, whichever came first.

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