Weight Cycling Linked to Fat-Free Mass Loss in People At Risk of Diabetes

Tom Yates, PhD

Credit: University of Leicester

Weight cycling, defined as weight loss, followed by weight regain, was associated with a progressive loss in fat-free mass, despite a rebound to baseline levels in fat mass, among people with overweight and obesity at high risk of type 2 diabetes (T2D).¹

The prospective cohort analysis, using data from the Walking Away from T2D trial, showed this loss of fat-free mass was greater than those who maintained their weight during each 24-month period. Weight loss after an initial 12-month period of gain, meanwhile, showed an overall increase in fat mass, despite fat-free mass returning to baseline levels.

“Those that maintained weight loss or weight gain following established patterns of body composition change, with fat-free mass contributing ~30% of overall weight change,” wrote the investigative team, led by Tom Yates, PhD, of the diabetes research center at the University of Leicester, Leicester General Hospital. “This suggests that weight cycling may lead to a progressive loss in fat-free mass or gain in fat-mass in those with overweight and obesity.”

Global rates of overweight and obesity are expected to surpass 50% by 2035, and the high related costs have led to an evolution in evidence-based dietary interventions and pharmacological weight loss therapies.² Agents like semaglutide, a glucagon-like peptide-1 receptor agonist, have been shown to induce weight loss of 15% and have been approved by multiple global regulatory agencies. However, despite the growing number of obesity management options, sustaining weight loss maintenance in clinical practice is expected to be challenging.¹

Once an obesity therapy is withdrawn, weight gain has been shown to be common, and the increased prescription of these agents may lead to an increased prevalence of weight cycling. Weight cycling itself has been linked to negative impacts on body composition, in which fat mass is preferentially accumulated at the expense of fat-free mass.¹

In this analysis, Yates and colleagues evaluated the impact of different weight loss and weight gain change trajectories on fat mass and fat-free mass in those at risk of T2D.¹ The Walking Away from T2D trial collected data at baseline, as well as 12, 24, and 23 months after baseline. Adults at risk of T2D were recruited from 2009 to 2010 through 10 primary care centers across the United Kingdom.

For the purpose of analysis, investigators used cohort data from two repeated 24-month periods, either baseline to 24 months or 12 to 36 months. Weight loss was defined as ≥5% reduction in body weight, while weight gain was defined as ≥5% increase in body weight, and weight maintenance was categorized as a change in body weight no more or less than 5%.

A total of 622 individuals were included for analysis, with an average age of 63.6 years and body mass index (BMI) of 32.0 kg/m2, contributing 1163 observations. The weight maintenance group contributed 805 (69.2%) observations, showing no overall change to body weight, fat mass, or fat-free mass after 24 months.

Upon analysis, investigators found a minority of observations (4.6%) lost over 5% of body weight between baseline and 12 months, which was subsequently regained between 12 and 24 months. In the analysis adjusted for confounders, including age, sex, and ethnicity, those that experienced weight loss followed by regain lost 1.50 kg (95% CI, 0.66 - 2.35) fat-free mass over 24 months with no change to fat mass.

On the other hand, individuals who experienced weight gain followed by weight loss gained 1.70 kg (95% CI, 0.27 - 3.12) in fat mass with no change to fat-free mass. These differences were statistically significant compared with the reference group showing weight maintenance.

Yates and colleagues indicated those living with obesity and chronic disease, including T2D, often have an increased risk of poor physical function which manifests far earlier than in healthy populations. The effect of weight cycling on the loss of fat-free mass could thus implicate other manifestations of aging, including a progression to frailty.

“Given the increase in licensed weight loss therapies, which may be used for limited time periods and data from dietary interventions showing weight regain after initial weight loss, there is some urgency in investigating whether these results are replicated with different therapies used to achieve initial weight loss and, if replicated, the wider implications on longer-term aging-related health risks, including frailty,” investigators wrote.

References

1. _{Yates T, Biddle GJH, Henson J, et al. Impact of weight loss and weight gain trajectories on body composition in a population at high risk of type 2 diabetes: A prospective cohort analysis. Diabetes Obes Metab. Published online December 14, 2023. doi:10.1111/dom.15400}
2. _{Okunogbe A, Nugent R, Spencer G, Powis J, Ralston J, Wilding J. Economic impacts of overweight and obesity: current and future estimates for 161 countries. BMJ Glob Health. 2022;7(9):e009773.}