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. 2024 Dec 1;47(12):2196-2204.
doi: 10.2337/dc24-1236.

Steatotic Liver Disease in Pediatric Obesity and Increased Risk for Youth-Onset Type 2 Diabetes

Resthie R Putri  1 , Thomas Casswall  1 , Pernilla Danielsson  1 , Claude Marcus  1 , Emilia Hagman  1
Affiliations

Steatotic Liver Disease in Pediatric Obesity and Increased Risk for Youth-Onset Type 2 Diabetes

Resthie R Putri et al. Diabetes Care. .

Abstract

Objective: To assess 1) the association between metabolic dysfunction-associated steatotic liver disease (MASLD) in pediatric obesity and youth-onset type 2 diabetes, 2) the joint effect of MASLD and intermediate hyperglycemia on type 2 diabetes risk, and 3) the effect of obesity treatment on type 2 diabetes risk.

Research design and methods: A cohort study using the Swedish Childhood Obesity Treatment Register (Barnobesitas Registret i Sverige [BORIS]) (1999-2020) linked with national registers was conducted. We included 10,346 children with overweight or obesity and 59,336 matched control individuals. 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 (quartile 1 [Q1], quartile 3 [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% (control individuals). MASLD was associated with risk for type 2 diabetes (hazard ratio [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.

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Conflict of interest statement

Duality of Interest. P.D. reports a leadership or fiduciary role on scientific/medical committee: Member of the steering committee for the Swedish Childhood Obesity Treatment Register, chairman of a working group developing the Swedish national guidelines for pediatric obesity treatment, and secretary of the Swedish Childhood Obesity Association. C.M. reports consulting fees from Novo Nordisk, Rhythm, Oriflame Wellness, DeFaire Medical, and Evira AB; honoraria for lectures from Novo Nordisk, Oriflame Wellness, and AstraZeneca; payment for expert testimony from Novo Nordic Foundation and Rhythm; leadership or fiduciary role on scientific/medical committee: board member of European Society for Paediatric Endocrinology (ESPE) Obesity working group, board member of the Swedish Pediatric Obesity Society, and Register holder for the Swedish Childhood Obesity Treatment Register. E.H. reports commissioned research for Novo Nordisk (2023), but not for the current study; honoraria for lectures from Novo Nordisk; a leadership or fiduciary role on scientific/medical committee: Member of the steering committee for the Swedish Childhood Obesity Treatment Register and secretary of Obesity COBWEB (COllaBoration in health economic modelling of OverWEight and oBesity). No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
A: Cumulative incidence of type 2 diabetes by MASLD and intermediate hyperglycemia (IH). The shaded areas indicate the 95% CI of the cumulative incidence. B: Joint effect MASLD and IH for developing type 2 diabetes in the obesity cohort.
See this image and copyright information in PMC

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