Introduction: Challenging the Conventional Wisdom on Diabetes Prevention
For decades, the global message for preventing type 2 diabetes (T2D) has been crystal clear: lose weight. This advice reflects the stark reality—over 460 million people worldwide currently have T2D, and millions more live in the prediabetic state, teetering on the edge. Prediabetes, characterized by blood sugar levels higher than normal but not high enough to be diagnosed as diabetes, carries a significant risk: an annual progression rate to T2D of 5% to 10%, and a lifetime risk reaching as high as 74%. Clinicians and health guidelines have long emphasized weight reduction as the key to lowering this risk.
But is weight loss the only path to remission from prediabetes? A landmark study published in Nature Medicine in 2025 shakes this long-held belief, revealing that improved blood sugar control and a dramatically reduced risk of progression to T2D can be achieved without losing weight—sometimes even when weight slightly increases—through targeted lifestyle interventions.
What Does the Evidence Show? Insights From the PLIS Study
This new perspective comes from the German Diabetes Center’s large-scale “Prediabetes Lifestyle Intervention Study” (PLIS). Unlike typical research focusing on participants who successfully shed pounds during interventions, this study zoomed in on an intriguing subgroup: individuals whose weight stayed the same or increased despite faithfully following lifestyle changes over one year.
Among 234 such participants, 22% (51 individuals) achieved complete remission of prediabetes, returning to normal glucose regulation as defined by stringent clinical markers: fasting blood glucose below 5.6 mmol/L, 2-hour post-glucose challenge below 7.8 mmol/L, and hemoglobin A1c under 39 mmol/mol. This group, termed “responders” (R), contrasted sharply with the “non-responders” (NR), who remained in the prediabetic category.
Interestingly, there was no significant difference in weight or Body Mass Index (BMI) changes between these two groups. This paradoxical finding begged the question: what biological mechanisms distinguished those who improved their blood sugar control without weight loss?
Fat Distribution: The Hidden Factor Beyond the Scale
The answer lies in how and where the body stores fat. Using advanced magnetic resonance imaging (MRI), researchers measured participants’ visceral adipose tissue (VAT)—the fat surrounding internal organs—and subcutaneous adipose tissue (SCAT), which lies just beneath the skin.
The responders managed to shift fat storage toward the subcutaneous depot, with significant increases in SCAT but no increase in VAT. Non-responders, however, experienced increases in VAT with stable SCAT. The ratio of SCAT to VAT improved markedly in the responders but worsened or stayed the same in the non-responders.
Why does this matter? Visceral fat is metabolically active and releases inflammatory molecules and free fatty acids that contribute to insulin resistance in the liver and muscles—key drivers of diabetes. Subcutaneous fat acts more like a benign reservoir, safely storing excess lipids and helping to insulate the body from metabolic harm.
This subtle redistribution of fat—not the total amount on the scale—emerges as a crucial factor in improving glucose metabolism and reducing diabetes risk.
The Double Win: Improved Insulin Sensitivity and Secretion
Beyond fat distribution, the responders demonstrated significant improvements in insulin function at the cellular and systemic levels. Over the intervention period:
- Blood glucose levels steadily decreased.
- Post-glucose challenge insulin concentrations rose, indicating better beta-cell responsiveness—the cells in the pancreas that produce insulin.
- Measures of insulin sensitivity, such as the Oral Glucose Insulin Sensitivity (OGIS) and Matsuda indices, improved, reflecting enhanced effectiveness of insulin in controlling blood sugar.
- Markers related to early-phase insulin secretion, including the ratio of C-peptide to glucose in the first 30 minutes post-glucose load, also rose significantly.
These dual improvements—both enhanced insulin secretion and insulin sensitivity—illustrate a comprehensive restoration of glucose regulation mechanisms in the responders. In contrast, the non-responders’ insulin function remained largely unchanged, even with no weight loss.
Long-term Impact: A Remarkable 71% Reduction in Diabetes Risk
The most compelling aspect of the PLIS study is the nearly decade-long follow-up data. Participants who achieved prediabetes remission without weight loss saw their risk of progressing to type 2 diabetes drop by 71%, a reduction nearly identical to the 73% risk reduction observed in previous studies where weight loss was the primary driver of remission.
This finding fundamentally shifts how risk reduction strategies might be approached. It highlights that metabolic health improvement—even absent weight loss—is both achievable and highly impactful in preventing diabetes.
Reframing Misconceptions: It’s Not Just About the Scale
Many patients and health practitioners have long equated better metabolic health with lower numbers on the scale. This study prompts a re-examination of such assumptions:
- Misconception: Weight loss is required to reverse prediabetes.
- Clarification: While weight loss is beneficial, remission can also occur via improved fat distribution and insulin function without weight reduction.
- Misconception: All fat is equally harmful.
- Clarification: Visceral fat contributes significantly more to metabolic risk than subcutaneous fat, making fat distribution critical.
- Misconception: Monitoring weight alone is sufficient to assess diabetes risk.
- Clarification: Blood glucose, insulin sensitivity, and body fat distribution assessments provide a more complete risk profile.
Practical Takeaways: Lifestyle Changes That Matter
The PLIS study confirms lifestyle interventions remain fundamental to diabetes prevention. However, the focus should expand beyond weight loss to include strategies that improve fat distribution and insulin function. These may encompass:
- Dietary Approaches: Emphasizing nutrient-rich whole foods, low glycemic loads, and healthy fats can modulate fat storage patterns and insulin sensitivity.
- Physical Activity: Both aerobic exercise and resistance training promote insulin sensitivity and help shift fat away from visceral depots.
- Stress Management and Sleep: These impact hormonal regulation and metabolic health.
Importantly, patients should be reassured that even if the scale doesn’t budge, significant health gains are possible.
An Illustrative Patient Scenario: Meet Susan
Susan, a 52-year-old school teacher, was diagnosed with prediabetes during a routine check-up. Though initially discouraged by a lack of weight loss over six months of dietary and exercise changes, her recent follow-up labs showed normal blood sugar and improved insulin markers. Susan’s fat distribution shifted toward more subcutaneous storage, as revealed by advanced imaging at a clinical research center. Her physician celebrated her metabolic success, emphasizing that her risk for diabetes had dramatically dropped despite no change in her weight. Susan’s story exemplifies the paradigm shift this study encourages.
Expert Insights and Recommendations
Dr. Maria Sandforth, lead author of the PLIS study, notes, “Our findings compel clinicians to look beyond weight as the sole indicator of metabolic health. Achieving normal blood sugar and improving insulin function through lifestyle is just as critical—even if weight remains unchanged.”
Clinical guidelines may soon evolve to incorporate metrics of fat distribution and emphasize remission of prediabetes, not just prevention through weight loss.
Conclusions: Toward a More Nuanced Understanding of Diabetes Prevention
This pioneering research challenges the ingrained dogma linking prediabetes remission strictly with weight loss. Instead, it unveils a more complex but hopeful picture: by improving fat storage patterns and restoring insulin dynamics, people can reverse prediabetes and sharply cut diabetes risk without losing weight.
For clinicians, patients, and public health strategies, this emphasizes the need for personalized approaches, comprehensive metabolic assessments, and a compassionate focus on meaningful health improvements beyond the scale.
Continued research will refine these insights, but for now, the message is clear: Waistlines are not destiny, and blood sugar control is the true goal.
Funding and Clinical Trials
The PLIS study was funded by the German Diabetes Center and supported by the European Union’s Horizon 2020 research program. Detailed trial information is available at ClinicalTrials.gov under identifier NCT02757952.
References
[1] Sandforth, A., Arreola, E.V., Hanson, R.L. et al. Prevention of type 2 diabetes through prediabetes remission without weight loss. Nat Med 31, 3330–3340 (2025). https://doi.org/10.1038/s41591-025-03944-9
[2] American Diabetes Association. Standards of Medical Care in Diabetes—2024. Diabetes Care. 2024;47(Suppl 1):S1-S249.
[3] Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006 Dec 14;444(7121):840-6.
