Non-alcoholic Fatty Liver Disease in Low Birth Weight Individuals

Steno Diabetes Centers

Status: Not yet enrolling

Conditions: NAFLD

Treatments: Behavioral: Caloric restriction intervention; Other: No intervention

Study type: Interventional

Funder types: Other

Identifiers

NCT05842850

NAFLD reversibility

Details and patient eligibility

About

The investigators will conduct a proof-of-principle deep phenotyping 4-weeks caloric restriction intervention study in low birth weight (LBW) subjects with NAFLD and normal birth weight (NBW) controls. Furthermore, the investigators will provide extended in-depth mechanistic insight into the role of impaired subcutaneous adipose tissue (SAT) expandability in ectopic fat deposition in LBW subjects in LBW individuals with and without NAFLD.

Full description

An adverse fetal environment characterized by low birth weight (LBW) plays a key role in the development of type 2 diabetes (T2D). The investigators recently demonstrated a 3-fold increase in liver fat in 26 early middle-aged LBW compared to 22 normal birth weight (NBW) men, and 20% of the LBW - but none of the normal birth weight (NBW) - men had previously unknown non-alcoholic fatty liver disease (NAFLD). The investigators hypothesize that ectopic fat deposition and NAFLD is among the earliest disease manifestations and on the critical path to the development of more severe cardiometabolic disease in LBW. The investigators furthermore hypothesize, that LBW individuals exhibit ectopic liver fat due to reduced capacity to store fat in the subcutaneous adipose tissue (SAT) depot, and that early detection and subsequent intensive caloric restriction, in middle-aged LBW individuals with overt NAFLD, may represent a targeted and highly efficient way forward to prevent more severe cardiometabolic disease manifestations in LBW subjects. To further explore the recent findings, the investigators aim to perform an extended nested case-control screening study for NAFLD in 250 early middle-aged non-obese LBW men and women, and subsequently to conduct a deep-phenotyping, proof-of-principle 4 week time-restricted eating (TRE) intervention study in 12 LBW subjects with NAFLD including measures of hepatic fat content, glucose, insulin and lipid metabolism, as well as 24h metabolic profiles using respiratory chambers. Finally, the investigators will provide extended in-depth mechanistic insight into transcriptional, epigenetic as well as functional SAT and preadipocyte perturbations underlying impaired SAT expandability in LBW individuals with and without NAFLD and NBW controls studied before and after different dietary interventions including TRE and high carbohydrate overfeeding.

Enrollment: 24 estimated patients

Sex: All

Ages: 35 to 40 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• LBW subjects with NAFLD (liver fat content ≥5% liver fat content verified on MRS)
• Gender- and body mass index-matched NBW controls without NAFLD
• Born at term (weeks 39-41)

Exclusion criteria

• BMI<18.5 and BMI>30 kg/m2
• Family history of diabetes (siblings, parent, and grandparents)
• Disease/medication known to affect primary outcome
• Self-reported high physical activity level
• Alcohol intake above general recommendations.
• Metabolic/liver disease
• Weight gain/loss of >3 kg within the past 6 months

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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24 participants in 2 patient groups, including a placebo group

LBW individuals with NAFLD

Experimental group

Description:

LBW individuals with NAFLD

Treatment:

Behavioral: Caloric restriction intervention

NBW controls without NAFLD

Placebo Comparator group

Description:

Age-, gender- and body mass index-matched NBW controls without NAFLD

Treatment:

Other: No intervention