Abstract
Objectives Recent studies have shown that the slightly elevated circulating levels of ketone bodies (KBs) played a significant role in the treatment of various diseases. This study is aimed at investigating the association between different levels of KBs and kidney function in patients with type 2 diabetes mellitus (T2DM). Methods A retrospective study of 955 patients with T2DM (426 women and 529 men) admitted to our hospital from December 2017 to September 2019 was conducted. Patients were divided into different groups in line with the levels of KBs (low-normal group: 0.02-0.04 mmol/L, middle-normal group: 0.05-0.08 mmol/L, high-normal group: 0.09-0.27 mmol/L, and slightly elevated group: >0.27 and <3.0 mmol/L). Results In the present study, individuals with high-normal levels of KBs had the lowest risk of diabetic kidney disease (DKD) and increased peak systolic velocity (PSV); those with middle-normal levels of KBs had the lowest risk of increased renal arterial resistive index (RI), with a positive correlation between increased α1-microglobulin and KB concentration. In addition, the indicators of glomerulus, renal tubules, and renal arteries were all poor with slightly elevated circulating levels of KBs, and KB concentration lower than 0.09 mmol/L can be applied as the threshold for low risk of renal function damage. Conclusions In summary, slightly elevated circulating levels of ketone bodies are not of benefit for renal function in patients with type 2 diabetes mellitus.
Highlights
Diabetic kidney disease (DKD) is one of the most important complications of diabetes, as well as the main reason of endstage renal disease and renal replacement therapy, which remarkably reduces the quality of life and increases the mortality of diabetic patients [1]
Multiple linear regression analysis showed that sex, BMI, BUN, 2-hour plasma glucose (2hPG), heart rate (HR), and drinking were significantly associated with Ketone bodies (KBs) in type 2 diabetes mellitus (T2DM) patients, and 2hPG was the most influence on KBs according to standardization coefficient
DKD and peak systolic velocity (PSV) were found to be significantly decreased in the high-normal KB group; resistive index (RI) was notably reduced in the middle-normal KB group, α1-MG was positively associated with KB concentration, and the indicators of glomerulus, renal tubules, and renal arteries were all poor in the slightly elevated KB group, suggesting that there is no evidence indicating that slightly elevated circulating levels of KBs have a positive influence on patients with T2DM
Summary
Diabetic kidney disease (DKD) is one of the most important complications of diabetes, as well as the main reason of endstage renal disease and renal replacement therapy, which remarkably reduces the quality of life and increases the mortality of diabetic patients [1]. A relevant feature of SGLT-2 inhibitors in the treatment of diabetic patients is an increase in circulating levels of KBs, which plays a significant role in the cardiovascular and kidney protection because of the use of KBs as energy substrates and their potential interactions with G-protein coupled receptors and other signaling pathways [6]. Recent clinical studies have demonstrated that slightly elevated circulating levels of KBs play a significant role in the treatment of various diseases, such as Journal of Diabetes Research heart failure, neurodegenerative disease, and cancer [3, 4, 6, 7]. Some studies suggested that microvascular complications were found to be increased in diabetic patients who had elevated ketones compared to those with normal ketone levels [8]
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