In this study, we observed that approximately 30.3% of patients diagnosed with recently diagnosed type 2 diabetes mellitus also exhibited CKD, with the majority (92%) being in the early stages of the disease. Age, DBP, HbA1c and triglyceride levels were associated with the presence of early CKD in recently diagnosed type 2 diabetes mellitus patients. We also identified several clinical variables, including body weight, SBP, fasting glucose, and UACR, that exhibited significant associations with eGFR. Furthermore, we found that SBP, fasting blood glucose, log triglyceride level, and eGFR were significantly associated with UACR in this cohort. Notably, our findings also indicated a mutual influence between eGFR and UACR.
The association between type 2 diabetes mellitus and DKD has been extensively discussed in numerous studies. Various factors have been identified to be associated with CKD. In a German study, a comparison was made between type 2 diabetes mellitus patients with or without CKD using large databases15. The study specifically focused on type 2 diabetes mellitus patients with an eGFR less than 60 mL/min/1.73 m2 or those with an eGFR greater than 60 mL/min/1.73 m2 but with albuminuria (UACR > 30 mg/g). The study's findings revealed that type 2 diabetes mellitus patients with CKD were older, had a longer duration of type 2 diabetes mellitus, had a higher incidence of higher triglyceride levels, and were more likely to be female. Furthermore, a significantly higher level of HbA1c and blood pressure were observed in type 2 diabetes mellitus patients with CKD. These results were similar to our study, except that we did not find a higher percentage of female patients in the CKD group, and our study only included patients recently diagnosed with type 2 diabetes mellitus. Another cross-sectional study also identified old age and an HbA1c level greater than 7% as significant risk factors for the development of advanced CKD (eGFR < 60 mL/min/1.73 m2) in patients with type 2 diabetes mellitus16. In contrast to our study, we specifically focused on recently diagnosed type 2 diabetes mellitus patients with early-stage CKD. Regardless of the stage of CKD, old age and higher HbA1c levels were both significant risk factors for the development of CKD in type 2 diabetes mellitus patients.
Consistent with prior literature, SBP exhibited a negative correlation with eGFR 17, 18. Additionally we found that fasting blood glucose was positively associated with eGFR, which is in line with previous study 19. The positive association indicates higher fasting blood glucose may reflect kidney hyperfiltration. Even there’s no significant association between eGFR and HbA1c in our study. There’s study demonstrated the same trend that HbA1c had positive association with early CKD. However, when the disease progresses to CKD stage 3 or 4, the association between HbA1c and eGFR becomes negative20. Proper glycemic control remains crucial in slowing the decline of eGFR and improving renal function. Our findings regarding the association between body weight and eGFR differ from the previous study that reposted an association between higher BMI and worsened eGFR21. However, it is worth noting that conflicting results exist in the literature. Another study conducted by the Hong Kong Diabetes Registry revealed a negative correlation between CKD and BMI22. One hypothesis suggests that CKD may lead to malnutrition and sarcopenia, which could contribute to lower BMI. Due to the conflicting results, the role of body weight or BMI in predicting CKD in patients with recently diagnosed type 2 diabetes mellitus remains uncertain. Further research is requiring to better understand the impact of body weight on CKD in this population.
In this study, our findings are consistent with previous studies that have shown a positive association between SBP and fasting glucose levels with UACR17, 18, 23. Interestingly, we found that triglyceride levels were also positively associated with UACR, which has also been reported in previous research24. The underlying pathophysiological mechanism for this association is still unclear. However, it has been suggested that elevated triglyceride levels may impact the glomerulus and lead to glomerular injury.
This study also demonstrated that eGFR and UACR mutually influenced each other. Previous studies have shown that lower albuminuria is associated with CKD regression 25, and reduced eGFR may be associated with albuminuria 26. Additionally, other studies have reported that albuminuria and declining eGFR are both predictors of worsened cardiovascular or renal outcomes 27, 28. Just like a vicious cycle, albuminuria can lead to declining eGFR, and reduced eGFR can also result in more albuminuria. Therefore, early intervention to prevent the worsening of eGFR and albuminuria is crucial in patients with DKD.
This study focused on individuals with early CKD, specifically those in KDIGO CKD stage \(\le\)G3a. Previous research has shown that all-cause mortality increases from 1.1 per 100 person-years in CKD stage G3a to 4.8 per 100 person-years in CKD stage G3b 29. Hence, identifying the early CKD population is crucial, and early intervention may improve outcomes.
Patients with DKD are at an increased risk of other diabetic complications, such as hypoglycemia, ketoacidosis, retinopathy, neuropathy, and cardiovascular events8. Given the potential impact of DKD on patient health, multidisciplinary and comprehensive care should be offered to patients with DKD to prevent further progression of the disease. Lifestyle modifications such as smoking cessation and avoiding nephrotoxic agents should be emphasized, along with secondary prevention of cardiovascular events through the use of aspirin and statins. Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists have emerged as the drugs of choice for patients with DKD due to their proven benefits beyond glycemic control. In addition, angiotensin-converting enzyme inhibitors /angiotensin II receptor blockers should be used as first-line therapy for blood pressure control in DKD patients, unless contraindicated 8, 30.
The strength of this study lies in its use of a nationwide, multicenter diabetes registry cohort and the analysis of a large number of cases. Furthermore, the study focused on a group with early CKD, an area that has been sparsely investigated. The study also highlighted the possible risk factors for developing early CKD in type 2 diabetes mellitus diagnosed within one year and demonstrated the mutual influence between eGFR and albuminuria. However, there are also some limitations to the study. First, as it is a cross-sectional analysis, the causal relationship between the variables cannot be ascertained. Further research with longitudinal designs and broader patient populations is warranted to better understand the dynamic relationship between type 2 diabetes mellitus, CKD, eGFR, and UACR. Second, the inclusion of patients with type 2 diabetes mellitus diagnosed within one year may limit the generalizability to those with longer disease duration. Finally, some factors other than type 2 diabetes mellitus could influence eGFR and UACR in developing early CKD.
In conclusion, this study provides valuable insights of CKD in patients with type 2 diabetes mellitus diagnosed within one years, particularly in the early stages. The results of our study suggest that several factors are associated with an increased risk of developing early CKD in recently diagnosed patients with type 2 diabetes mellitus. Specifically, older age, higher levels of HbA1c, and elevated triglyceride levels were found to be significant risk factors. Besides, body weight, SBP, and fasting blood glucose are modifiable clinical variables that are closely associated with eGFR. Additionally, other factors such as SBP, fasting blood glucose, and triglyceride levels are associated with UACR. Furthermore, the findings indicate a mutual influence between UACR and eGFR. The study underscores the importance of managing modifiable factors in slowing the progression of CKD in patients with recently diagnosed type 2 diabetes mellitus. Further research is needed to evaluate the effects of such management strategies.