Evaluation of Serum Glucose and Kidney Disease Progression Among Patients With Diabetes

IMPORTANCE: The appropriate target of glycemic control in diabetic kidney disease is unclear. OBJECTIVE: To investigate optimal on-treatment glycemic levels associated with slowing of diabetic kidney disease progression. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted using nationwide Korean cohorts from the National Health Information Database from 2005 to 2019. Included individuals were adults with diabetes using antihyperglycemic agents with and without chronic kidney disease (CKD) identified from participants aged 40 to 74 years in a nationwide health screening survey conducted from 2009 to 2010. Data were analyzed from October 2020 through March 2021. EXPOSURE: On-treatment fasting blood glucose (FBG) level. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of doubling of serum creatinine, end-stage kidney disease, or death from CKD. RESULTS: Among 183 049 adults with diabetes using antihyperglycemic agents (mean [SD] age, 61.7 [8.4] years; 99 110 [54.1%] men), there were 131 401 individuals with dipstick albuminuria or an estimated glomerular filtration rate (eGFR) of 15 to 59 mL/min/1.73 m(2) (mean [SD] age, 62.4 [8.3] years; 71 280 [54.2%] men) and 51 648 individuals with no CKD (mean [SD] age, 59.6 [8.4] years; 27 830 [53.9%] men). During 9 years of follow-up, the primary outcome occurred among 13 802 individuals with CKD (10.5%) and 1421 individuals with no CKD (2.8%). On-treatment FBG level had a J-shaped hazard ratio (HR) curve for the primary outcome. Among patients with albuminuria, FBG levels of 126 mg/dL to less than 140 mg/dL (HR, 0.87; 95% CI, 0.81-0.94) and 140 mg/dL to less than 160 mg/dL (HR, 0.90; 95% CI, 0.84-0.96) were associated with decreased risk and levels of 160 mg/dL to less than 180 mg/dL were associated with increased risk (HR, 1.10; 95% CI, 1.03-1.18) compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with decreased eGFR, FBG levels of 80 mg/dL to less than 100 mg/dL (HR, 1.30; 95% CI, 1.20-1.42) and levels of 160 mg/dL to less than 180 mg/dL (HR, 1.13; 95% CI, 1.04-1.23) were associated with increased risk of the primary outcome compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with no CKD, FBG levels of 80 mg/dL to less than 100 mg/dL (HR, 1.29; 95% CI, 1.01-1.65) and levels of 126 mg/dL to less than 140 mg/dL (HR, 1.23; 95% CI, 1.03-1.47) were associated with increased risk compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with no albuminuria at baseline, FBG levels of 140 mg/dL to less than 160 mg/dL (HR, 1.14; 95% CI, 1.09-1.20) were associated with increased risk of new-onset albuminuria, while levels of 100 mg/dL to less than 110 mg/dL were not associated with increased risk compared with FBG levels of 110 mg/dL to less than 126 mg/dL. For all-cause mortality, while FBG levels of 160 mg/dL to less than 180 mg/dL (HR, 1.20; 95% CI, 1.12-1.28) were associated with increased risk among patients with albuminuria, FBG levels of 140 mg/dL to less than 160 mg/dL were associated with increased risk among patients with decreased eGFR (HR, 1.10; 95% CI, 1.04-1.16) and those with no CKD (HR, 1.10; 95% CI, 1.00-1.21) compared with levels of 110 mg/dL to less than 126 mg/dL. CONCLUSIONS AND RELEVANCE: These findings suggest that intensive vs standard glucose control may not be associated with increased protection for the progression of established diabetic kidney disease and that timely control is important for prevention. However, careful glycemic control would still be associated with improved overall outcomes among patients with CKD, particularly those with no albuminuria.