Diabetes mellitus is a significant public health problem worldwide, and its rising incidence is a significant contributor to the burden of cardiovascular and renal complications.[1] The 11^th  edition of the International Diabetes Federation (IDF) Diabetes Atlas estimates that there were 589 million adults aged 20-79 years with diabetes globally in 2024, or 11.1% of the global adult population.[2] This is expected to rise to 853 million by 2050, which underscores the importance of early detection and prevention of diabetes related complications.[3] Type 2 diabetes mellitus (T2DM) is the most common form of diabetes and is linked to a progressive metabolic syndrome characterized by insulin resistance, dyslipidaemia, endothelial dysfunction, and chronic low-grade inflammation.[4] Diabetic kidney disease (DKD) is one of its microvascular complications of interest, as renal

abnormalities may occur subtly without presenting with any clinical changes in renal function.[5]

The hallmark of diabetic kidney disease is persistent albuminuria, reduced estimated glomerular filtration rate (eGFR), or both.[6] Albuminuria is a major early sign of renal microvascular damage and is independently related to the subsequent progression of chronic kidney disease and cardiovascular events.[7] Improving Global Outcomes (KDIGO) guidelines state that a UACR of ≥30 mg/g is a sign of moderately increased albuminuria if the abnormality persists.[8] Importantly, albuminuria may occur despite preserved eGFR, indicating that apparently normal renal filtration does not necessarily exclude early diabetic kidney injury.[9]

Insulin resistance is known to play a crucial role in the pathogenesis of diabetic kidney disease via several interrelated mechanisms such as oxidative stress, activation of inflammatory pathways, impairment of endothelial function, changes in glomerular haemodynamics and enhanced sodium retention in the kidney.[10] The triglyceride-glucose (TyG) index has emerged as a simple and inexpensive surrogate marker of insulin resistance, calculated using fasting triglyceride and fasting plasma glucose concentrations.[11] 

Previous research has demonstrated an association between elevated TyG index values and albuminuria in patients with T2DM. In a study of 1,872 people with T2DM, there was a close association between a higher TyG index and the presence of albuminuria. Similarly, a 2024 Pakistani study involving 218 patients demonstrated a positive relationship between the TyG index and UACR, supporting its potential relevance in identifying diabetic renal involvement.[12, 13]

Although there have been improvements in screening for DKD, there are still many clinical challenges in identifying patients who develop albuminuria while maintaining normal BP and preserved eGFR. These patients might exhibit early microvascular and metabolic alterations that are not detected by standard measures of BP and serum creatinine. In this relatively early stage of the disease, the relationship between the TyG and albuminuria could be of interest in understanding the link between insulin resistance and subclinical renal injury. In addition, the TyG index is a simple test that is routinely assessed in patients with T2DM, and thus could be an accessible marker for identifying patients who may benefit from reduced renal monitoring. This population of patients is of special interest for early risk stratification, and the evidence presented here may have implications for the significance of the inclusion of metabolic indices in the standard care of diabetics. Therefore, this study aimed to determine the association of the triglyceride-glucose index with albuminuria in normotensive patients with type 2 diabetes mellitus and preserved renal function.

Diabetes mellitus is a significant public health problem worldwide, and its rising incidence is a significant contributor to the burden of cardiovascular and renal complications.[1] The 11^th  edition of the International Diabetes Federation (IDF) Diabetes Atlas estimates that there were 589 million adults aged 20-79 years with diabetes globally in 2024, or 11.1% of the global adult population.[2] This is expected to rise to 853 million by 2050, which underscores the importance of early detection and prevention of diabetes related complications.[3] Type 2 diabetes mellitus (T2DM) is the most common form of diabetes and is linked to a progressive metabolic syndrome characterized by insulin resistance, dyslipidaemia, endothelial dysfunction, and chronic low-grade inflammation.[4] Diabetic kidney disease (DKD) is one of its microvascular complications of interest, as renal abnormalities may occur subtly without presenting with any clinical changes in renal function.[5]

The hallmark of diabetic kidney disease is persistent albuminuria, reduced estimated glomerular filtration rate (eGFR), or both.[6] Albuminuria is a major early sign of renal microvascular damage and is independently related to the subsequent progression of chronic kidney disease and cardiovascular events.[7] Improving Global Outcomes (KDIGO) guidelines state that a UACR of ≥30 mg/g is a sign of moderately increased albuminuria if the abnormality persists.[8] Importantly, albuminuria may occur despite preserved eGFR, indicating that apparently normal renal filtration does not necessarily exclude early diabetic kidney injury.[9]

Insulin resistance is known to play a crucial role in the pathogenesis of diabetic kidney disease via several interrelated mechanisms such as oxidative stress, activation of inflammatory pathways, impairment of endothelial function, changes in glomerular haemodynamics and enhanced sodium retention in the kidney.[10] The triglyceride-glucose (TyG) index has emerged as a simple and inexpensive surrogate marker of insulin resistance, calculated using fasting triglyceride and fasting plasma glucose concentrations.[11] 

Previous research has demonstrated an association between elevated TyG index values and albuminuria in patients with T2DM. In a study of 1,872 people with T2DM, there was a close association between a higher TyG index and the presence of albuminuria. Similarly, a 2024 Pakistani study involving 218 patients demonstrated a positive relationship between the TyG index and UACR, supporting its potential relevance in identifying diabetic renal involvement.[12, 13]

Although there have been improvements in screening for DKD, there are still many clinical challenges in identifying patients who develop albuminuria while maintaining normal BP and preserved eGFR. These patients might exhibit early microvascular and metabolic alterations that are not detected by standard measures of BP and serum creatinine. In this relatively early stage of the disease, the relationship between the TyG and albuminuria could be of interest in understanding the link between insulin resistance and subclinical renal injury. In addition, the TyG index is a simple test that is routinely assessed in patients with T2DM, and thus could be an accessible marker for identifying patients who may benefit from reduced renal monitoring. This population of patients is of special interest for early risk stratification, and the evidence presented here may have implications for the significance of the inclusion of metabolic indices in the standard care of diabetics. Therefore, this study aimed to determine the association of the triglyceride-glucose index with albuminuria in normotensive patients with type 2 diabetes mellitus and preserved renal function.

The study comprised 280 patients with type 2 diabetes mellitus. The participants' mean age was 49.6 ± 9.2 years, with the majority being male. The mean duration of diabetes was 7.4 ± 4.1 years. Table 1 shows the demographic and clinical features of the study group.

The biochemical evaluation revealed a mean fasting plasma glucose of 158.7 ± 42.6 mg/dL and mean HbA1c of 7.8 ± 1.3%. The mean triglyceride-glucose (TyG) index was 9.08 ± 0.62, and the estimated glomerular filtration rate (eGFR) was 103.6 ± 11.2 mL/min/1.73 m². Other biochemical and renal parameters are summarized in Table 2.

The prevalence of albuminuria and normoalbuminuria was 84(30.0%) and 196(70.0%), respectively. Among patients with albuminuria, 80 (28.6%) had moderately increased albuminuria, and 4 (1.4%) had severely increased albuminuria (Table 3).

Patients with albuminuria had significantly higher TyG index, fasting plasma glucose, triglyceride levels, HbA1c, and urinary albumin-to-creatinine ratio than those without albuminuria. Other clinical and renal parameters did not differ significantly between the groups, except for increased diabetes duration and age. The comparison of clinical and biochemical characteristics according to albuminuria status is shown in Table 4.

There was a strong positive correlation between TyG index and urinary albumin-to-creatinine ratio (r = 0.421, p < 0.001) in all patients, as revealed by correlation analysis. The TyG index was also positively correlated with fasting plasma glucose, triglycerides, HbA1c, diabetes duration, and BMI (Table 5).

In multivariable logistic regression analysis, a higher TyG index remained significantly associated with albuminuria after adjustment for age, sex, diabetes duration, BMI, and HbA1c (adjusted OR = 2.48, 95% CI: 1.55–3.97; p < 0.001). The area under the curve for the ROC curve analysis was 0.78 (95% CI: 0.72-0.84), with a cut-off value of 9.12, a sensitivity of 71.4%, and a specificity of 72.4% in identifying albuminuria (Table 6).

Table 1. Sociodemographic and clinical characteristics of participants (n=280)

Table 2. Biochemical and renal parameters of participants (n=280)

Table 3. Distribution of albuminuria among study participants (n=280)

Table 4. Comparison of demographic, clinical, and biochemical characteristics according to albuminuria status

Table 5. Correlation of TyG index with urinary albumin-to-creatinine ratio and selected clinical variables

Table 6. Multivariable logistic regression and ROC analysis for albuminuria

In the present study, 30% of normotensive patients with type 2 diabetes mellitus and preserved renal function had albuminuria. Among individuals with albuminuria, the TyG index was significantly elevated and moderately positively correlated with urinary albumin-to-creatinine ratio (UACR). Furthermore, the association remained statistically significant after adjustment for age, sex, diabetes duration, BMI, and HbA1c. The ROC analysis showed moderate discriminatory ability. In conclusion, these results indicate that the TyG index is a potential marker of insulin resistance and may be related to albuminuria in this selected population.

In a cohort of 2446 Chinese adults by Gao et al. 2021, the highest TyG tertile group was found to be 1.71-fold more likely to develop albuminuria than the lowest TyG tertile group during a median follow-up period of 3.9 years. While their study did not focus on patients with diabetes, it offers longitudinal evidence for the association of an elevated TyG index with albuminuria.[15] Moreover, a 2022 study of hypertensive patients revealed a positive correlation between TyG index and albuminuria, with the highest TyG quartile having a higher likelihood of albuminuria than the lowest quartile. The positive association found in our study was directionally similar to the findings of these studies, but the clinical characteristics of the populations were different.[16]

Nabipoorashrafi et al. (2023) have conducted a cross-sectional study of 2,934 patients with type 2 diabetes and have found that the TyG index is independently associated with albuminuria and has an AUC of 0.62 and an optimal cut-off of 9.39.[17] Our analysis, in contrast, yielded an AUC of 0.78 for a cut-off of 9.12. The discrepancy in discriminatory performance may be attributed to differences in study population, inclusion/exclusion criteria, the prevalence of albuminuria, and the statistical techniques. Nevertheless, both studies indicate that the TyG index may help distinguish patients with and without albuminuria.

The prevalence of albuminuria also increased in the higher TyG quartiles, and there was an independent relationship between higher TyG index and albuminuria, reported by Wang et al. (2023) on 9,872 adults in the United States. This study did not include only normotensive patients with type 2 diabetes, but the results are also in line with the link between metabolic disorders and albumin excretion in the urine. The association between TyG and UACR in this study was modest, with a correlation coefficient of 0.421. This means that an increase in TyG index was associated with increased urinary albumin excretion.[18]

Another cross-sectional study of 218 type 2 diabetic patients from Rawalpindi, Pakistan, was reported by Khan et al. (2024) and confirmed the above findings. The investigators compared the TyG index with insulin resistance and UACR and found that insulin resistance and UACR were associated with diabetic nephropathy. They are especially pertinent as their study was carried out in a clinical environment in Pakistan.[19] Similarly, Li and Wang (2024) studied the relationship between TyG and albuminuria and chronic kidney disease in patients with type 2 diabetes and found that the highest quartile of TyG was associated with the highest odds for albuminuria and chronic kidney disease compared to the lowest quartile, after accounting for potential confounding factors (TyG, adjusted OR = 2.241, 95% CI: 1.245–4.034). These observations are comparable to our adjusted association between TyG index and albuminuria (OR = 2.48, 95% CI: 1.55–3.97).[20]

In 2025, Yilmaz and Erinc compared 570 patients with type 2 diabetes and reported that median TyG was higher in the albuminuria group compared to the non-albuminuria group (10.0 vs. 9.1; p<0.001). They also reported an increase in TyG values with increasing albuminuria severity and identified the TyG index as an independent factor associated with albuminuria. They reported that the cut-off value was 9.6 and the AUC was 0.870. They have shown discriminatory performance greater than what was seen in our analysis, but have shown a positive association between the TyG index and albuminuria. The variation in diagnostic performance may partly be attributed to differences in renal function, patient selection, and distribution of albuminuria.[21]

The AUC of 0.78 indicates there is moderate discrimination, but a cut-off of 9.12 was determined using the same sample, so it has not been validated externally. Moreover, the correlation of the TyG index with UACR does not prove that the TyG index can be used in place of UACR or eGFR in the routine assessment of diabetic kidney disease. Its potential use would be as an additional metabolic marker to existing renal investigations.

Limitations

There were some limitations of the study. First, it has a cross-sectional design and cannot establish temporal/causal relationships between the TyG index and albuminuria. Second, ‘albuminuria' was determined by a single spot urine UACR measurement, which may not reflect persistent albuminuria and can be affected by transient factors. Third, the study was carried out at a single centre, which might reduce the extent to which its findings can be generalized. Moreover, in the regression analysis, potential confounding factors were controlled for, but unmeasured metabolic, lifestyle and treatment-related factors may have exerted a residual confounding effect. Lastly, the ROC-derived TyG cut-off was computed from the study population and should be validated in independent populations.

A higher triglyceride-glucose index was significantly associated with albuminuria among normotensive patients with type 2 diabetes mellitus and preserved renal function. The TyG also performed quite well in discriminating for albuminuria. These results indicate that the TyG index could be a new metabolic marker to evaluate patients in need of a more detailed renal examination. However, prospective studies with repeated UACR measurements are required to validate this association and determine its clinical usefulness.

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