Steatotic liver disease in pediatric obesity and increased risk for youth-onset type 2 diabetes

Objective

To assess (i) the association between metabolic dysfunction associated steatotic liver disease (MASLD) in pediatric obesity and youth-onset type 2 diabetes, (ii) the joint effect of MASLD and intermediate hyperglycemia on type 2 diabetes risk, and (iii) the effect of obesity treatment on type 2 diabetes risk.

Research Design and Methods

A cohort study using the Swedish Childhood Obesity Treatment Register (BORIS) (1999–2020) linked with national registers was conducted. We included 10346 children with overweight or obesity and 59336 matched controls. MASLD was defined by transaminases and diagnosis code, separately. Type 2 diabetes was ascertained from national registers.

Results

In the obesity cohort, median age at type 2 diabetes diagnosis was 16.9 (Q1, Q3: 14.7, 21.4) years, median follow-up was 8.1 (Q1, Q3: 5.1, 11.7) years. Cumulative incidence of type 2 diabetes at age 30 was 22.7% (obesity and MASLD), 9.9% (obesity alone), and 0.7% (controls). MASLD was associated with risk for type 2 diabetes, HR: 2.71 (95% CI 2.14–3.43), independently of age, sex, degree of obesity, intermediate hyperglycemia, and parental type 2 diabetes. Joint effect of MASLD and intermediate hyperglycemia increased type 2 diabetes risk, HR: 9.04 (6.38–12.79). Optimal response in obesity treatment reduced the risk, HR: 0.23 (0.09– 0.57).

Conclusions

MASLD, defined by transaminases or diagnosis code, in pediatric obesity is associated with increased risk for youth-onset type 2 diabetes. MASLD interacts synergistically with intermediate hyperglycemia to dramatically increase the risk. Optimal response in obesity treatment reduces type 2 diabetes risk, despite MASLD.