Zhejiang University index - connecting type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: Clinical utility and future horizons

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the main comorbidity of type 2 diabetes mellitus, yet often under-recognized in daily clinical practice. Although liver biopsy is still considered to be the standard method for MASLD diagnosis, it is too invasive to be widely adopted in mass screenings. Recently, the Zhejiang University index using simple anthropometric and biochemical parameters was assessed in type 2 diabetes mellitus patients and found strongly associated with both the presence and severity of MASLD. These new findings illustrate that some metabolic composite scores may help complement current diagnostic strategies. In this editorial, we contextualize them, review existing ones and contrast these results, and finally explore possible research areas or directions in clinical applications.

Key Words: Type 2 diabetes mellitus; Metabolic dysfunction-associated steatotic liver disease; Non-invasive biomarker; Zhejiang University index; Cardiometabolic risk

Core Tip: Zhejiang University index provides a convenient way to estimate metabolic dysfunction-associated steatotic liver disease risk in type 2 diabetes mellitus without resorting to imaging or biopsy, relying only on basic clinical data. This simplicity makes it suitable for settings with limited medical infrastructure. However, questions remain about its validity in varied populations and whether it can reliably anticipate future liver and heart complications.

TO THE EDITOR

The coexistence of type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) is not just the incidence of two more common illnesses, it represents a confluence of interrelated pathophysiological states with major clinical relevance. MASLD represents the hepatic manifestation of systemic metabolic dysfunction[1,2]. In diabetic populations, MASLD incidence exceeds 70%, with a sizeable fraction of patients developing advanced fibrosis or cirrhosis[3,4]. Beyond liver damage, MASLD increases the already high cardiovascular risk that represents most diabetes related deaths[5].

Despite these concerns, there remains a noticeable silence around diagnosis. Common diagnostic tools, such as ultrasound or magnetic resonance imaging, are either too sensitive in initial stages to be clinically relevant or too costly for general screening. Biopsy, although conclusive, represents an invasive procedure rarely feasible to perform with asymptomatic patients[6]. This gap has created an appetite for non-invasive scores that might, at least partially, close the gulf between current demand and future feasibility.

THE ZHEJIANG UNIVERSITY INDEX AND ITS VALIDATION IN DIABETIC POPULATIONS

The index was developed in the Chinese population with components of body mass index (BMI), fasting glucose, triglycerides and alanine aminotransferase/aspartate aminotransferase[7-9]. On the surface, one finds a simple combination of available variables - one that seems trivial until realizing that each is a correlate of the same triad: Adiposity, dysglycemia and liver stress.

The recent study re-examined this index specifically in T2DM patients, confirming that higher Zhejiang University (ZJU) scores paralleled both the prevalence and severity of MASLD[10]. This observation is more than a technical validation - it reaffirms that easily measurable clinical parameters retain diagnostic power even in an era dominated by advanced imaging. Recent research revisits this particular set, testing the ZJU index only among the diabetic cohorts. It reaffirms that the higher the score, the greater the incidence and severity of MASLD - a finding more than mere verification: An assertion that easy metrics retain utility in the world of advanced imaging. Still, one cannot take this study at face value. While the findings are certainly notable, they remain unproven in two respects; could the ZJU index truly forewarn disease progression, and were their criteria equally valid outside East Asian populations? These are all questions to address before ZJU is put into universal usage.

COMPARISON WITH EXISTING NON-INVASIVE SCORES

It is not the only one, over the last decade indices - fatty liver index (FLI), hepatic steatosis index (HSI), non-alcoholic fatty liver disease (NAFLD) liver fat score - proposed to help identify fatty liver in general population[11-13]. Most, were not developed considering specifically diabetes - what if any would underperform in major cohort showing features of dyslipidemia or particularly dysglycemia and related complications?

Yet comparing in Chinese patients with T2DM saw ZJU performs best among these of fibrosis cirrhosis index’s (FLI and HSI) comparison studies[14], likely due to having glycemic and enzymatic ratios tied to factors intrinsic to the metabolic abnormalities seen in diabetic pathology. “Multiple Chinese-population studies have shown that the ZJU index exhibits superior discriminative performance compared with established indices such as the FLI and HSI. For example, one paper reported an area under the curve (AUC) of 0.822 for the ZJU index in 9602 Chinese adults, compared to lower values for FLI and HSI[7]. In an American obese female cohort found the ZJU index achieved an AUC of 0.742, higher than HSI (AUC 0.728) and lipid accumulation product index (AUC = 0.682)[15]. These data support the claim of superior performance. But it’s impossible to tell if such performance would also exist for individuals carrying different profiles like body mass, routine diet or inherited traits[16]. The absence of multinational validation keeps us cautious on this one.

CLINICAL AND PUBLIC HEALTH IMPLICATIONS

As for day-to-day practice, what can we say? It’s quite possible that the ZJU index may function as an early detection triage - something easily deployed by first time clinicians - an initial flagging of a patient from a larger group at higher probability of needing further examination before fibrotic damage occurs. Additionally, the same triage may serve to flag a person already identified to be at high risk, referring them through radiological or medical hepatology for a full-scale investigation and management optimizing usage for potentially expensive diagnostic imaging devices. At this point stratification might be essential for someone with potential disease severity that could otherwise prevent access in populations where modern methods might be reserved only for highly select candidates. Lastly the issue of MASLD should be looked at with much higher levels of caution. MASLD has been studied as being an independent cardiovascular concern even accounting for extent of fibrosis[17]. If future major registries back these claims, then one of our main aims for ZJU index remains to serve as proxy markers that help predict some kind of cardiac complications or help identify other damage not yet considered. At the same time let us not over stretch its relevance - we aren’t claiming that ZJU index will replace fibrosis-4 since when considering factors determining prognostic value MAFLD concerns progression rather than damage stages themselves - that grading of fibrosis doesn’t mean stage - ZJU therefore serves to compliment not compete[18]. Although ultrasound and routine biochemical indicators remain widely used in T2DM follow-up and offer practical early-warning potential, their sensitivity for early MASLD remains variable. The ZJU index should therefore be considered a complementary tool rather than a replacement, helping to flag patients who may benefit from more focused hepatic evaluation.

Because the ZJU index was originally developed in Chinese cohorts, its performance may differ in non-East Asian populations due to several ethnic-specific metabolic and anthropometric characteristics. Western and African populations generally have higher lean mass and different visceral adiposity patterns at the same BMI, which may influence the contribution of BMI to the index. Metabolic phenotypes also vary, as East Asians tend to develop insulin resistance at lower BMI, whereas African populations often present with more favorable lipid profiles but higher BMI. In addition, the background prevalence of dyslipidemia, hypertension, and metabolic syndrome differs substantially across ethnic groups, potentially altering baseline alanine aminotransferase and aspartate aminotransferase levels. Furthermore, lifestyle and dietary patterns (e.g., saturated fat intake, carbohydrate load, alcohol use) may influence hepatic fat accumulation independent of ZJU components. These factors suggest that population-specific recalibration and validation across Western, African, and South Asian cohorts are necessary before adopting a universal cut-off value for the ZJU index.

FUTURE DIRECTIONS

Several avenues for research emerge: (1) Longitudinal studies are needed to determine whether ZJU predicts progression to fibrosis, cirrhosis, or hepatocellular carcinoma, not merely steatosis; (2) Integration with fibrosis markers such as fibrosis-4 or NAFLD fibrosis score could yield a two-step algorithm, balancing sensitivity and specificity[19]; (3) Cardiovascular implications warrant exploration: If ZJU correlates with cardiovascular outcomes, it could provide a holistic risk marker in T2DM[20]; (4) Digital health integration may amplify impact. Embedding ZJU into electronic records could enable automatic alerts, nudging clinicians toward timely intervention[21]; and (5) Cross-population validation remains essential. The heterogeneity of MASLD across ethnicities argues against a “one-size-fits-all” cutoff. Replication in Western and African cohorts should precede global endorsement[22].

CONCLUSION

Although only providing proof-of-concept, the current study offers one new thing for anyone interested in metabolic care. Namely, there exists a real need for such simple, readily applicable methods of risk screening as they could help T2DM patients access options for better health management that would benefit them most. Claiming the ZJU heralds a brand new wave with not even room for any preliminary medical investigations is premature. The best it could offer are complementary tools by offering screening applications within primary care and referral clues within secondary clinics or, perhaps at an even greater level, serving as indirect predictors for cardiometabolic comorbidities, not only the liver itself. To substantiate what appeared here earlier on in this group of patients, further rigorous validations for different population groups are needed as well as correct calibration toward its place in clinical staging for an ever-growing array of diabetes mellitus screening indexes.