New study sheds light on how to reverse prediabetes

Prediabetes, a condition preceding type 2 diabetes, heightens the risk of heart attacks, kidney issues, eye diseases, and various cancers. Currently, there are no approved drug therapies for prediabetes. However, researchers at the German Center for Diabetes Research (DZD) have unveiled a promising path toward remission, where blood glucose levels return to normal, safeguarding against type 2 diabetes and improving long-term kidney and vascular health.

This groundbreaking study reveals distinct mechanisms at play in prediabetes remission compared to type 2 diabetes. Type 2 diabetes was once considered irreversible, but recent findings have shown that substantial weight loss can induce remission. Yet, this remission often proves fleeting, with individuals frequently relapsing into type 2 diabetes within a few years.

The research led by Prof. Dr. Andreas Birkenfeld sought to explore preventive measures at an earlier stage, targeting prediabetes with the aim of reversing it. This approach holds potential significance for those with prediabetes, as they face an elevated risk of developing type 2 diabetes, along with associated complications like heart issues, kidney problems, and eye disorders.

The key question addressed by scientists from the Institute of Diabetes Research and Metabolic Diseases at Helmholtz Munich and the Department of Diabetology, Endocrinology, and Nephrology at the University Hospital of Tübingen was: What triggers prediabetes to go into remission?

In a randomized-controlled multicenter study known as the Prediabetes Lifestyle Intervention Study (PLIS), involving 1,105 prediabetic individuals, participants underwent a year-long lifestyle intervention involving a healthy diet and increased physical activity. The focus was on the 298 participants who achieved a minimum weight loss of 5% due to the intervention.

The responders were those participants whose fasting blood glucose, 2-hour glucose, and HbA1c levels normalized within twelve months, indicating they had entered remission. On the other hand, non-responders did not achieve remission despite losing weight and still had prediabetes.

Interestingly, contrary to initial assumptions, weight loss alone didn’t distinguish responders from non-responders, as there was no significant difference in relative weight loss between the two groups. Instead, those who achieved remission demonstrated a marked improvement in insulin sensitivity compared to non-responders. Essentially, they enhanced their responsiveness to insulin, a hormone that lowers blood glucose levels, significantly more than those who didn’t respond.

Remarkably, the quantity of insulin secreted remained unchanged in both groups. This distinction is crucial compared to type 2 diabetes remission, which typically relies on improved insulin secretion.

Reducing abdominal fat mass may help reverse prediabetes

To uncover the reason behind the heightened insulin sensitivity seen in responders, the researchers delved into a comparative analysis of the two groups. They found that responders, despite losing the same amount of overall body weight, had shed more abdominal fat than non-responders. Notably, this abdominal fat, specifically visceral abdominal fat nestled within the abdominal cavity, has a notable impact on insulin sensitivity due in part to its association with an inflammatory response in adipose tissue.

Furthermore, participants who entered remission exhibited lower levels of inflammatory proteins in their blood. Arvid Sandforth, one of the lead authors, emphasized the importance of identifying factors promoting the loss of this abdominal fat depot in the future. Surprisingly, there were no discernible differences between the two groups in the reduction of liver fat, which also plays a critical role as a risk factor for diabetes development.

The benefits of achieving remission were substantial, with participants showing a remarkable 73% reduced risk of developing type 2 diabetes even two years after concluding the lifestyle intervention. Additionally, they displayed reduced indicators of kidney damage and improved vascular health.

Presently, prediabetes treatment primarily focuses on weight reduction and lifestyle enhancements to delay the onset of type 2 diabetes, lacking specific glucose-based targets. The analysis conducted by the DZD bridges this gap. Co-first author Prof. Dr. Reiner Jumpertz-von Schwartzenberg asserts that, based on this new data, remission should become the new therapeutic objective for individuals with prediabetes. This paradigm shift holds the potential to reshape treatment approaches and minimize complication rates for patients.

According to the study’s findings, remission in prediabetes can be defined when fasting blood glucose falls below 100 mg/dl (5.6 mmol/l), 2-hour glucose drops below 140 mg/dl (7.8 mmol/l), and HbA1c falls below 5.7%. The likelihood of achieving remission increases when body weight is reduced, and waist circumference decreases by approximately 4 cm in women and about 7 cm in men. These criteria can now serve as valuable biomarkers for tracking and targeting remission in prediabetes.

Source: German Center for Diabetes Research

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