Study Proposes Remission as a Promising Treatment Objective for Prediabetes

People with type 2 diabetes are at increased risk of kidney disease, heart attack or stroke and face higher mortality. Until a few years ago, type 2 diabetes was considered an irreversible disease. It is now known that type 2 diabetes can be brought into a state of remission in some of those affected by significant weight loss, although this is rarely permanent: most patients develop type 2 diabetes again after five years. Diabetes.

“We have therefore set ourselves the goal of starting earlier and investigating whether it is possible to take preventive action in the preliminary stage of type 2 diabetes, prediabetes, and to reverse it,” explains senior author Prof .Dr. Andreas Birkenfeld, Medical Director of the Medical Clinic IV of the University Hospital of Tübingen and Head of the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Munich at the University of Tübingen. This would be of great importance for patients with prediabetes, as they have an increased risk of complications of the heart, kidneys and eyes.

But what mechanisms lead to remission in prediabetes? DZD scientists from the Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich in Tübingen and the Clinic for Diabetology, Endocrinology and Nephrology at the University Hospital of Tübingen investigated this in a post-hoc analysis of participants with prediabetes from the Prediabetes Lifestyle Intervention Study (PLIS).

As part of this randomized-controlled multicenter study by the DZD, 1,105 prediabetes patients took part in a lifestyle intervention consisting of a healthy diet and more physical exercise for over a year. The researchers evaluated the 298 participants who had lost at least five percent of weight as part of this intervention. Participants whose fasting blood sugar, 2-hour glucose and HbA1c levels had normalized within the twelve months, i.e. had gone into remission, were considered responders. Those who did not achieve remission despite weight loss and continued to have prediabetes were considered nonresponders.

Contrary to the researchers’ initial assumptions, it was not weight loss that distinguished the people who went into remission and those who did not, because there was no difference in relative weight loss between responders and non-responders. However, those who achieved remission were characterized by the fact that they were able to improve their insulin sensitivity more than non-responders. They were able to increase their sensitivity to the blood sugar-lowering hormone insulin significantly more than the non-responders. The amount of insulin secreted remained unchanged in both groups. This represents an important difference from remission of type 2 diabetes, which is mediated in particular by an improvement in insulin secretion.

Reduction in visceral abdominal fat could contribute to remission in prediabetes
In order to find out why insulin sensitivity had improved more in the responders, the researchers looked for further differences between the two groups – and found them in the middle of the body: Despite losing the same weight, the responders had lost more visceral abdominal fat than the non-responders. Visceral belly fat lies directly in the abdominal cavity and surrounds the intestines. It can affect insulin sensitivity, including through an inflammatory reaction in fatty tissue.

The participants who went into remission actually also had fewer inflammatory proteins in their blood. “Since responders particularly showed a reduction in visceral abdominal fat, it is important to identify the factors that promote the loss of visceral abdominal fat in the future,” emphasizes Arvid Sandforth, one of the two first authors. However, when it came to reducing liver fat – also an important risk factor for the development of diabetes – there were surprisingly no differences between the two groups.

The participants who achieved remission still had a 73 percent reduced risk of developing type 2 diabetes two years after the end of the lifestyle intervention. They also showed reduced markers of kidney damage and better condition of their blood vessels. The participants in the PLIS study will also be further monitored by the scientists in order to determine how long this advantage will continue in the future.

Currently, the treatment of prediabetes consists of weight loss and lifestyle improvements in order to delay the onset of type 2 diabetes – although there are no glucose-based target values ​​available to guide the treatment process. The new analysis from the DZD closes this gap: “Based on the new data, remission should be the new therapeutic goal in people with prediabetes. This has the potential to change treatment practice and minimize the complication rate for our patients,” says co-first author Prof. Dr. Reiner Jumpertz-von Schwartzenberg.

According to the study, remission in prediabetes can be assumed if the fasting blood sugar is below 100mg/dl (5.6 mmol/l), the 2-hour glucose below 140mg/dl (7.8 mmol/l) and the HbA1c value falls below 5.7 percent. According to the new results, the likelihood of remission increases the more body weight is reduced and the abdominal circumference is reduced by at least around 4 cm in women and around 7 cm in men. According to the researchers, medical staff and patients could now use this as a guide. In the further course, they want to investigate whether this strategy is cost-saving in order to ensure the support of the payers for appropriate therapy.