TOPLINE:

Prediabetes may leave a molecular “footprint” on fat tissue that makes maintaining weight loss after bariatric surgery difficult, new research showed.

METHODOLOGY:

• Researchers divided 78 women with severe obesity (BMI, 39-49) into two groups: normal glucose tolerance (NGT; n = 43) and prediabetes (preDM; n = 35); the NGT group had fasting glucose less than 100 mg/dL and A1c less than 5.7%, whereas the prediabetes group had fasting glucose between 100 and 125 mg/dL and/or A1c between 5.7% and 6.4%.
• Subcutaneous fat tissue samples were collected at the time of surgery and 1 year later, and gene expression was analyzed via microarray in a subgroup of 11 women from each group.
• The metabolic workup included fasting glucose, insulin response, lipid profile, DEXA body composition, and liver fat by ultrasound, plus a mixed-meal test to examine the metabolic response to food.
• Weight changes were tracked for up to 3 years post-surgery, and analyses were adjusted for age, body weight, hepatic steatosis, and menopause status.

TAKEAWAY:

• Before surgery, women with prediabetes had higher glucose and insulin responses during the mixed-meal test; a higher prevalence of hepatic steatosis (88% vs 57%); and a less favorable lipid profile, including higher cholesterol and triglyceride levels than women with normal glucose tolerance.
• At 1 year post-surgery, blood sugar and metabolic markers normalized in both groups, and short-term weight loss was similar, but fat tissue gene activity remained markedly different.
• In women with prediabetes, genes involved in lipid metabolism remained less active than in women without prediabetes, including key regulators such as SREBF1 and FADS2, suggesting a persistent impairment in the ability of adipose tissue to handle fats efficiently after surgery.
• Despite similar early weight loss, by 3 years post-surgery, women with prediabetes had higher cholesterol levels and had regained significantly greater weight (5-6 kg in the preDM group vs 1-2 kg in the NGT group).

IN PRACTICE:

“Our study shows that prediabetes is associated with persistent changes in fat tissue that are not fully reversed by bariatric surgery…. Importantly, these changes may not be permanent and could potentially be modified through targeted interventions such as diet, pharmacological treatments, or lifestyle strategies aimed at improving adipose tissue function,” the principal author said in a press release.

SOURCE:

The study led by Ana de Hollanda, Hospital Clínic de Barcelona, Barcelona, Spain, will be presented at the 33rd European Congress on Obesity (ECO) 2026, Istanbul, on May 12-15.

LIMITATIONS:

This study had certain limitations. It was observational and could not establish a causal relationship between the molecular changes and weight regain because behavioral factors such as diet may have contributed. The generalizability of the findings may be limited because the study population was small and included only women, mainly of European origin.

DISCLOSURES:

No funding information was provided. The authors declared having no conflicts of interest.

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.