Metabolic dysfunction-associated steatotic liver disease (MASLD) carries an increased risk of type 2 diabetes (T2D), with the risk increase disproportionately higher for individuals with earlier-onset MASLD, as shown in a study.
In China’s Kailuan Study cohort, the risk of T2D was highest among patients whose MASLD was diagnosed before age 40 years, with a sixfold risk increase relative to MASLD-free participants (hazard ratio [HR], 6.18, 95 percent confidence interval [CI], 4.28–8.93). [Clin Gastroenterol Hepatol 2026;doi:10.1016/j.cgh.2026.06.028]
T2D risk progressively decreased but remained significantly elevated among patients whose MASLD was diagnosed at an older age: 40 to <50 years (HR, 3.29, 95 percent CI, 2.70–4.00), 50 to <60 years (HR, 3.14, 95 percent CI, 2.69–3.66), 60 to <70 years (HR, 2.94, 95 percent CI, 2.39–3.62), and ≥70 years (HR, 2.17, 95 percent CI, 1.56–3.01).
“To the best of our knowledge, this is the first prospective study to examine how MASLD onset age influences the risk of developing T2D,” said first study author Dr Zhenyu Huo from Beijing Friendship Hospital, Capital Medical University in Beijing, China, and colleagues.
“As the central metabolic organ, the liver plays an important role in glucose homeostasis. Individuals with younger-onset MASLD may have a longer duration of metabolic dysfunction, thereby conferring a higher risk of T2D,” they explained.
Huo and colleagues added that unhealthy lifestyle habits such as smoking, alcohol drinking, and physical inactivity and family history of T2D among patients with younger-onset MASLD could factor into their increased T2D susceptibility.
“Our findings highlight the importance of lifelong MASLD management, coupled with early screening and prompt intervention, with particular attention to patients with early-onset MASLD … to prevent or delay T2D onset,” the authors said.
“Clinicians should also maintain vigilance for T2D development in older MASLD patients. Community-level interventions, including promotion of healthy diets, regular physical activity, and weight management, remain critical to reducing the metabolic burden across the entire MASLD population,” they added.
The study included 38,861 participants (mean age 53.84 years, 76.25 percent male), of which 19,378 had new-onset MASLD and 19,483 were MASLD-free.
Over a median follow-up of 11.82 years, 2,301 incident T2D events were recorded. The incident rate of T2D was 8.36 per 1,000 person-years among participants with new-onset MASLD vs 2.58 per 1,000 person-years among MASLD-free controls.
When stratified by age at MASLD onset, the incidence rates of T2D per 1,000 person-years were 6.33, 8.79, 8.80, 9.41, and 6.69 among those with age at disease onset of <40 years, 40 to <50 years, 50 to <60 years, 60 to <70 years, and ≥70 years.
Additional analyses revealed notable effect modifications by sex, smoking, and alcohol consumption on the association between MASLD and T2D risk. This association was more pronounced among female participants aged 40–50 years, likely driven by hormonal transitions and increased insulin resistance during the perimenopausal period, Huo and colleagues noted.
“Interestingly, both smoking and alcohol showed age-dependent interaction patterns,” such that the association between MASLD and T2D was stronger for non-smokers and non-drinkers among younger participants, as well as for current smokers and drinkers among older participants, the authors said.
“These findings suggest that in younger individuals, MASLD-related insulin resistance and hepatic lipid accumulation may dominate over lifestyle-related oxidative stress, while in older adults, cumulative toxic exposures from smoking and alcohol may further deteriorate metabolic homeostasis, magnifying diabetes risk,” they explained.
No significant interactions were detected for BMI across any age strata, indicating that lean individuals with MASLD may also represent a subgroup at elevated risk of T2D, according to Huo and colleagues.