Can Weight Loss Induce Remission of Prediabetes and Prevent Type 2 Diabetes?

In their study, Sandforth and colleagues investigate the mechanisms behind weight loss-induced remission in individuals with prediabetes, finding that those who achieved a minimum weight loss of 5% had significant improvements in insulin sensitivity and reductions in visceral fat. These results suggest that returning to normal glucose regulation can potentially prevent the progression to type 2 diabetes.

The remission of type 2 diabetes has been linked to weight loss, which is associated with reductions in liver fat and pancreas fat, as well as improved insulin secretion. Understanding these mechanisms is crucial, particularly in the context of prediabetes, a condition that often precedes type 2 diabetes. There is a pressing need for effective strategies to reverse prediabetes, as early intervention can halt its progression to diabetes. Sandforth and colleagues attempt to fill this gap in our knowledge by determining how weight loss can lead to the remission of prediabetes and whether similar mechanisms are at play as those observed in type 2 diabetes.

The study is a prespecified post-hoc analysis of data from the Prediabetes Lifestyle Intervention Study (PLIS), which ran from March 2012 to August 2016, involving eight clinical study centers in Germany. Participants were randomly assigned to receive either a control intervention, a standard lifestyle intervention, or an intensified lifestyle intervention for 12 months. To validate the findings, the researchers compared results against the Diabetes Prevention Program (DPP) study, conducted between 1996 and 1999 in the United States. Only participants who lost at least 5% of their body weight and were assigned to a lifestyle intervention or placebo were included in the analysis. Responders were defined as those who returned to normal fasting plasma glucose and glycosylated hemoglobin (HbA1c) levels, while non-responders did not meet these criteria. Key outcomes assessed included insulin sensitivity, insulin secretion, visceral adipose tissue (VAT), and intrahepatic lipid content (IHL), evaluated using linear mixed models.

Of the 1160 participants recruited to the PLIS, 298 (25.7%) achieved the weight loss target. Among these, 128 (43%) were categorized as responders, while 170 (57%) were non-responders. Notably, responders were younger than non-responders, with a mean age of 55.6 years compared with 60.4 years. In the DPP validation cohort, which included 683 participants who lost at least 5% of their body weight, only 132 (19%) were responders. Interestingly, both groups experienced similar reductions in BMI. However, responders demonstrated a greater increase in whole-body insulin sensitivity during the 12 months, with a significant difference in baseline and post-intervention measurements. While IHL decreased in both groups, the reduction in VAT was more pronounced in responders. Furthermore, responders had a 73% lower risk of developing type 2 diabetes compared with non-responders within two years following the intervention.

Despite the valuable insights gained, the study has limitations. The sample size for responders was relatively small. Additionally, the study design does not account for long-term maintenance of weight loss or sustained lifestyle changes beyond the intervention period, potentially impacting the durability of the results.

The study concludes that “return to normal glucose regulation (NGR) prevents development of type 2 diabetes,” advocating for the concept of remission of prediabetes as a primary therapeutic goal. By framing the remission of prediabetes in a similar context to type 2 diabetes, the research underscores the importance of early intervention in reversing prediabetes and preventing the progression to more severe metabolic disorders.

Reference

Sandforth A, von Schwartzenberg RJ, Arreola EV, et al. Mechanisms of weight loss-induced remission in people with prediabetes: a post-hoc analysis of the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS). Lancet Diabetes Endocrinol. 2023; 11(11):798-810. doi:10.1016/S2213-8587(23)00235-8.