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Lifestyle-Induced Visceral Fat Loss as a Key Target for Durable Cardiometabolic Health: MRI-Assessed 5- and 10-Year Follow-Up After 2 Clinical Trials
Key result
Visceral fat loss linked to ~28% lower risk of incident type 2 diabetes.
- HR 0.72
- 95% CI 0.54-0.94
- P=0.02
- n=366
Figures
Why the study?
Although participants achieved reductions in abdominal and ectopic fat during two lifestyle trials, the long-term postintervention cardiometabolic profile associated with these changes remained to be examined.
Does visceral fat loss achieved during a lifestyle intervention improve long-term cardiometabolic measures and reduce the risk of incident type 2 diabetes in adults with abdominal obesity or dyslipidemia?
Key Points
- To examine the 5- and 10-year postintervention cardiometabolic profile associated with lifestyle-induced reductions in abdominal and ectopic fat depots.
- Follow-up study evaluating 366 of 381 eligible participants (96%) from two 18-month randomized controlled trials (CENTRAL [NCT01530724] and DIRECT-PLUS [NCT03020186]).
- Interventions evaluated dietary patterns (low-fat, healthy dietary guidelines, and Mediterranean diet variants including polyphenol-enriched 'green' Mediterranean diets) with structured physical activity.
- Abdominal depots (visceral adipose tissue, deep subcutaneous adipose tissue, superficial subcutaneous adipose tissue) and ectopic fat (intrahepatic and intrapancreatic fat) were quantified using 3T magnetic resonance imaging at 5 and 10 years post-trial.
- Despite complete body weight regain, waist circumference, visceral adipose tissue, deep subcutaneous adipose tissue, and superficial subcutaneous adipose tissue partially preserved postintervention reductions (false discovery rate ≤0.01 for all).
- Postintervention reductions of intrahepatic fat and intrapancreatic fat were fully and excessively regained during follow-up, respectively (false discovery rate ≤0.01 for both).
- Each 10% intervention-induced reduction in visceral adipose tissue was independently associated with a 28% lower risk of incident type 2 diabetes (hazard ratio, 0.72 [95% CI, 0.54–0.94]; multivariable model) during follow-up.
Study Design
Type
Cohort (n=366)
Blinding
Single-blind
Multicenter
No
Structured PICO
Does visceral fat loss achieved during a lifestyle intervention improve long-term cardiometabolic measures and reduce the risk of incident type 2 diabetes in adults with abdominal obesity or dyslipidemia?
P
Population
366 predominantly male adults with abdominal obesity or dyslipidemia who completed an 18-month lifestyle intervention, followed observationally for 5 to 10 years to assess long-term cardiometabolic health.
E
Exposure
18-month lifestyle interventions consisting of dietary patterns (low-fat, healthy dietary guidelines, Mediterranean, low-carbohydrate, or polyphenol-enriched 'green' Mediterranean diet) combined with structured physical activity.
O
Outcome
5 MRI-assessed abdominal adipose tissue depots and ectopic fat deposits (visceral adipose tissue [VAT], deep subcutaneous adipose tissue [SAT], superficial SAT, intrahepatic fat [IHF], and intrapancreatic fat [IPF]) measured at baseline, 18 months, and 5 and 10 years postintervention.surrogate
Main Result
Hazard Ratio: 0.72 (95% CI 0.54–0.94)
p-value: p=0.02
A 10% reduction in visceral fat during an 18-month lifestyle intervention predicts durable long-term improvements in cardiometabolic health and a nearly 30% lower risk of incident type 2 diabetes, independent of subsequent weight regain.
Limitations
- Predominantly male cohort (>90%), limiting generalizability to women.
- Perivascular adipose tissue and epicardial adipose tissue were not assessed in the imaging protocol.
- Participants were followed at 2 different posttrial timepoints (5 or 10 years) based on their original trial.
- Predominantly male cohort
Discussion
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Repeated participation in a lifestyle program for weight loss, even after a perceived 'failure,' may lead to significant health benefits over the years, especially in reducing dangerous abdominal fat.”
“Weight alone does not accurately reflect abdominal fat or blood parameters. Therefore, even if the weight comes back, it is very possible that health is still improved, and the success of a process cannot be defined solely by a number on the scale.”
Implication
May support diabetes prevention via visceral fat loss despite weight regain; extends RCT follow-up but remains hypothesis-generating and should not yet change practice.
Abstract
BACKGROUND: During the 18-month CENTRAL (Effect of Weight-Loss Diet Strategies and Exercise on Dynamics of Body Fat Depots and Metabolic Rate) and DIRECT-PLUS (Effects of Green-Mediterranean Diet via the Gut-Fat-Brain Axis) randomized controlled trials, participants achieved considerable reductions in abdominal and ectopic fat. We examined the long-term postintervention cardiometabolic profile associated with these changes. METHODS: We invited participants from CENTRAL (2012–2014) and DIRECT-PLUS (2017–2018), which evaluated dietary patterns (low-fat, healthy dietary guidelines and Mediterranean diet variants, including standard, low-carbohydrate, and polyphenol-enriched “green” Mediterranean diets) combined with structured physical activity. Participants underwent additional magnetic resonance imaging of visceral adipose tissue, deep subcutaneous adipose tissue (SAT), superficial SAT, intrahepatic fat, and intrapancreatic fat, along with clinical follow-up measurements, 5 and 10 years after completion of the trials. RESULTS: We reached 366 out of 381 eligible participants (96%) for follow-up. Despite complete weight regain, waist circumference and abdominal fat depots, including visceral adipose tissue, deep SAT, and superficial SAT, partially preserved their intervention-induced achievements at long-term follow-up (false discovery rate ≤0.01 for all). In contrast, postintervention reductions of intrahepatic fat and intrapancreatic fat were fully and excessively gained during follow-up, respectively (false discovery rate ≤0.01 for both). Each 10% intervention-induced loss of visceral adipose tissue, superficial SAT, and intrapancreatic fat were associated with long-term postintervention improvements in Metabolic Score for Insulin Resistance, composite risk score, and Metabolic Syndrome Severity Score (meta-analysis models adjusted to weight change, Mediterranean diet adherence, and physical activity scores at follow-up, and further measures; all P <0.05). Only 10% visceral adipose tissue loss, however, was independently associated with a 28% lower risk of incident type 2 diabetes (hazard ratio, 0.72 [95% CI, 0.54–0.94]; multivariable model) during follow-up. CONCLUSIONS: This 5- and 10-year follow-up of 18-month clinical trials suggests that diet and physical activity lifestyle interventions may yield long-term improvements in cardiometabolic measures despite weight regain. A 10% reduction in visceral fat due to lifestyle interventions may reduce future type 2 diabetes risk by nearly 30%. Visceral fat loss rather than weight loss emerges as a key target for durable cardiometabolic health. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01530724; URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03020186.
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Cite This Study
Klein et al. (2026) conducted a cohort in Abdominal obesity or dyslipidemia (n=366). 10% visceral adipose tissue (VAT) loss achieved during an 18-month lifestyle intervention was evaluated on Incident type 2 diabetes (HR 0.72, 95% CI 0.54-0.94, p=0.02). A 10% reduction in visceral adipose tissue during an 18-month lifestyle intervention was independently associated with a 28% lower risk of incident type 2 diabetes over a 5- to 10-year follow-up.