Cardiovascular

Non-lean versus lean MASLD: associations with advanced cardiovascular-kidney-metabolic syndrome in adults with type 2 diabetes mellitus, a cross-sectional study.

TL;DR

In patients with T2DM and MASLD, non-lean MASLD exhibits an independent positive correlation with severe CKM syndrome when compared to lean MASLD (OR = 2.674, P < 0.001).

Key Findings

Non-lean MASLD was independently associated with a higher prevalence of advanced cardiovascular-kidney-metabolic (CKM) syndrome stage compared to lean MASLD in patients with type 2 diabetes.

  • Binary logistic regression analysis showed OR = 2.674, P < 0.001 for non-lean MASLD vs. lean MASLD
  • Study population comprised 705 hospitalized patients with T2DM and MASLD
  • BMI cutoff of 23 kg/m² was used to distinguish lean from non-lean categories
  • Analysis accounted for age, gender, and diabetes duration as covariates
  • Cross-sectional study design was used

Among 705 hospitalized patients with T2DM and MASLD, 26.7% had the lean MASLD phenotype.

  • This means approximately 188 patients were classified as lean MASLD and 517 as non-lean MASLD
  • Classification was based on a BMI cutoff of 23 kg/m²
  • Data collected included clinical characteristics, fat distribution, liver and kidney function, and metabolic markers

Non-lean MASLD patients had significantly higher rates of cardiovascular events compared to lean MASLD patients.

  • Cardiovascular event prevalence was 21.3% in non-lean vs. 10.1% in lean MASLD (P < 0.05)
  • This difference was observed after accounting for age, gender, and diabetes duration
  • The finding reflects nearly a twofold higher rate in the non-lean group

Non-lean MASLD patients had significantly higher rates of cerebrovascular events compared to lean MASLD patients.

  • Cerebrovascular event prevalence was 18.0% in non-lean vs. 12.2% in lean MASLD (P < 0.05)
  • Difference was statistically significant after adjustment for age, gender, and diabetes duration

CKM stage 4 prevalence was significantly higher in non-lean MASLD patients than in lean MASLD patients.

  • CKM stage 4 prevalence was 33.5% in non-lean vs. 18.6% in lean MASLD (P < 0.05)
  • No significant difference was observed in CKM stage 3 prevalence (61.9% vs. 56.9%, P = 0.148)
  • CKM stage 4 represents the most advanced category of cardiovascular-kidney-metabolic syndrome

Non-lean MASLD patients showed higher levels of visceral fat area, insulin resistance, and C-peptide compared to lean MASLD patients.

  • All differences in visceral fat area, insulin resistance, and C-peptide were statistically significant (all P < 0.05)
  • Liver fibrosis indices were similar between lean and non-lean groups
  • These metabolic differences may contribute mechanistically to the higher CKM syndrome burden in non-lean patients

What This Means

This research examined whether body weight status among people who have both type 2 diabetes and a liver condition called metabolic dysfunction-associated steatotic liver disease (MASLD) affects their risk of developing severe cardiovascular-kidney-metabolic (CKM) syndrome — a condition involving interconnected problems with the heart, kidneys, and metabolism. The study divided 705 hospitalized patients into two groups based on BMI: 'lean' (lower body weight) and 'non-lean' (higher body weight), and found that about 1 in 4 patients fell into the lean category. The non-lean group had notably higher rates of heart events (21.3% vs. 10.1%), brain-related vascular events (18.0% vs. 12.2%), and the most severe stage of CKM syndrome (33.5% vs. 18.6%). Statistical analysis showed that being in the non-lean group was associated with more than 2.5 times the odds of having advanced CKM syndrome. This research suggests that among people with type 2 diabetes and fatty liver disease, those who are overweight or obese face a substantially greater burden of severe, multi-organ disease affecting the heart, blood vessels, and kidneys. The non-lean group also had more visceral (abdominal) fat and greater insulin resistance, which may help explain why this group fares worse. Interestingly, both groups had similar levels of liver scarring (fibrosis), suggesting that excess body weight adds disease risk beyond what liver disease alone can account for. The findings highlight that body weight classification in people with type 2 diabetes and fatty liver disease may be clinically meaningful when assessing overall cardiometabolic risk. This research suggests that the combination of excess weight, fatty liver, and diabetes may create a particularly high-risk profile for severe multi-system disease, though the cross-sectional design of the study means it cannot establish that non-lean status directly causes worse outcomes.

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Citation

Wang J, Jiang L, Gao L, Ren J, Zhao S, Qiao Y, et al.. (2026). Non-lean versus lean MASLD: associations with advanced cardiovascular-kidney-metabolic syndrome in adults with type 2 diabetes mellitus, a cross-sectional study.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1910398