Storing fat at the waist may NOT up diabetes risk, surprise findings indicate

Recent research from the University of Virginia School of Medicine challenges the conventional wisdom regarding fat storage and its association with type 2 diabetes. While it has been widely believed that storing fat around the belly increases the risk of diabetes, the surprising new findings indicate that natural genetic variations can influence fat distribution and simultaneously provide protection against diabetes.

This unexpected discovery offers a more nuanced understanding of the relationship between obesity and diabetes, as well as other related health conditions. Moreover, it opens the possibility for advancing personalized medicine, where treatments can be tailored to individual genetic profiles. For instance, healthcare professionals may prioritize weight loss interventions for patients with genetic predispositions to diabetes, while placing less emphasis on it for those with protective gene variants, according to the researchers. This breakthrough could lead to more targeted and effective approaches in managing diabetes and improving overall health outcomes.

According to Mete Civelek, PhD, from UVA's Center for Public Health Genomics, there is an increasing body of evidence supporting the concept of "metabolically healthy obesity." This intriguing condition suggests that certain individuals, despite being obese, are shielded from the typical cardiovascular and diabetes risks associated with obesity. In their research, they have identified a genetic connection that may clarify how this protection occurs in these specific individuals. Understanding the various forms of obesity becomes crucial in tailoring effective treatments for individuals at high risk of obesity-related health problems.

As medical knowledge advances, the significance of naturally occurring gene variations in providing personalized treatments becomes increasingly apparent. Civelek and his team's recent work demonstrates how certain genetic variants can predispose some individuals to store abdominal fat, potentially putting them at risk for metabolic syndrome-a cluster of health issues-while simultaneously safeguarding them from type 2 diabetes. As metabolic syndrome is linked to an elevated risk of diabetes, stroke, and other serious health complications, comprehending these genetic connections holds promise for more targeted and tailored healthcare approaches.

Doctors currently rely on abdominal obesity as one of the metrics to diagnose metabolic syndrome in patients, often determined by comparing waist and hip measurements. However, Civelek's research suggests that this approach may not be sufficient for all patients. Instead, a more sophisticated method involving genetic analysis might be necessary to effectively guide individuals towards better health outcomes.

The study's lead author, Yonathan Aberra, a PhD candidate at UVA's Department of Biomedical Engineering, which is a joint program of the School of Medicine and School of Engineering, stated that among the numerous regions in our genomes that contribute to excess abdominal fat accumulation, five regions surprisingly play a different role. These five regions, rather than increasing the risk of type 2 diabetes, actually decrease an individual's susceptibility to the disease.

In the future, doctors may incorporate genetic analysis to identify these specific gene variations, enabling a more personalized approach to managing health and reducing the risk of type 2 diabetes for certain patients. This breakthrough could revolutionize the way metabolic syndrome is understood and managed, leading to more targeted and effective interventions.

Civelek's research not only reveals surprising findings but also offers significant advancements in understanding the complexities of gene variations. The sophisticated approach devised by Civelek and his collaborators to identify relevant genetic variants and their potential impacts presents valuable tools for future research on metabolic syndrome and related conditions.

Furthermore, these tools hold immense promise in the development of improved treatments for metabolic syndrome, as highlighted by the scientists involved in the study.

Moving forward, Civelek emphasizes the need to broaden their investigations by including more women and individuals from diverse genetic backgrounds. This expansion aims to identify additional genes contributing to the phenomenon of metabolically healthy obesity. With this knowledge, the researchers plan to conduct further experiments to potentially pinpoint a therapeutic target for managing metabolic syndrome effectively.

Reference:

Yonathan Tamrat AberraLijiang MaJohan LM BjörkegrenMete Civelek (2023) Predicting mechanisms of action at genetic loci associated with discordant effects on type 2 diabetes and abdominal fat accumulation eLife 12:e79834, https://doi.org/10.7554/eLife.79834.