Optimal FBG levels and Progression of Diabetic Kidney Disease

Worldwide, the prevalence of end-stage kidney disease (ESKD) is increasing; the leading cause of ESKD is diabetes. The incidence of diabetic kidney disease has been shown to decrease with decreases in blood glucose levels in patients with diabetes. However, according to Hae Hyuk Jung, MD, PhD, there are few data available on the optimal blood glucose target associated with slowed progression of diabetic kidney disease.

Dr. Jung conducted a retrospective cohort study to examine the appropriate on-treatment glycemic levels associated with slowing diabetic kidney disease progression. Results were reported online in JAMA Network Open [doi:10.1001/jamanetworkopen.2021.27387].

The study exposure was on-treatment fasting blood glucose (FBG) level. The primary outcome of interest was a composite of doubling of serum creatinine, ESKD, or death from chronic kidney disease (CKD).

The study was conducted among retrospective cohorts generated from data from the National Health Information Database in Korea; patients with CKD were identified from a cohort of adults 40 to 74 years of age in the nationwide health screening survey in 2009 or 2010, when the survey initially included data on serum creatinine.

Following application of inclusion and exclusion criteria, the study cohort included 183,049 participants using antihyperglycemic agents; mean age was 61.7 years and  54.1% (n=99,110) were men. Of those, 131,401 individuals had CKD  (mean age, 62.4 years; 54.2% men [n=71,280], and 51,648 individuals without CKD (mean age, 59.6 years; 53.9% [n=27,830] men). Among the 183,049 participants, 72,268 had CKD with dipstick albuminuria, 74,717 had estimated glomerular filtration rate (eGFR) of 15 to less than 60 mL/min/1.73 m², and 64,861 were from the general population.

The distribution of follow-up FBG levels was widespread. The rate of inadequately decreased FBG level was higher among participants in the albuminuria group, and the rate of excessively decreased FBG level was higher in the population with decreased eGFR, compared with the general population.

During 9 years of follow-up, the primary composite outcome of major kidney events was found in 15.4% (n=11,120) of participants in the albuminuria population, 10.8% (n=8048) in the decreased eGFR population, and 4.3% (n=2787) in the general population.

Overall, on-treatment FBG level had a J-shaped cure for hazard ratios of major kidney events; the HR was lowest at FBG levels between 110 mg/dL and 160 mg/dL. In the albuminuria population, there was an association between FBG levels of 126 mg/dL to less than 140 mg/dL (HR, 0.87; 95% confidence interval [CI], 0.81-0.94) and 140 mg/dL to less than 160 mg/dL (HR, 0.90; 95% CI, 0.84-0.96) and decreased risk of the composite outcome. 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.

In the decreased eGFR population, there were associations with 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) and increased risk of the primary composite outcome compared with levels of 110 mg/dL to less than 126 mg/dL.

Among patients without 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.

In patients without albuminuria at baseline, there were associations between FBG levels of 140 mg/dL to less than 160 mg/dL (HR, 1.14; 985% CI, 1.09-1.20) and increased risk of new-onset albuminuria. There were no associations between levels of 100 mg/dL to less than 110 mg/dL compared with FBG levels of 110 mg/dL to less than 126 mg/dL.

In analyses of all-cause mortality, levels of FBG 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, and 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 among 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.

Limitations to the study findings included the lack of data on hemoglobin A1c necessitating use of FBG level only to assess glycemic status, not distinguishing between type 1 and type 2 diabetes, and limiting the study population to Korean adults 40 to 74 years of age with no known cardiovascular or cancer disease, possibly limiting the generalizability of the findings to other populations.

In conclusion, Dr. Jung said, “This study’s findings suggest that timely blood glucose control is important for preventing diabetic kidney disease and that intensive versus standard glycemic control may not be associated with greater protection for the progression of established diabetic  kidney disease. An individualized and comprehensive approach is necessary for treating patients with diabetes and CKD. Nonetheless, careful glycemic control may still be associated with decreasing overall health risks among patients with CKD, particularly those with no albuminuria.”

Takeaway Points

1. Results of a Korean study designed to examine the optimal on-treatment glycemic levels associated with slowing progression of diabetic kidney disease.
2. Among participants with albuminuria, there was an association between a fasting blood glucose (FBG) level of 126 mg/dL to less than 140 mg/dL and 140 mg/dL to less than 160 mg/dL and decreased risk of the composite outcome of serum creatinine doubling, end-stage kidney disease, or death from chronic kidney disease.
3. In patients without albuminuria at baseline, there were associations between FBG levels of 140 mg/dL to less than 160 mg/dL (HR, 1.14; 985% CI, 1.09-1.20) and increased risk of new-onset albuminuria.