Ebbs and flows in weight influence CVD risk in T2D patients
31 Mar 2022
byAudrey Abella
In individuals with type 2 diabetes (T2D), greater variability in adiposity indices (BMI and waist circumference [WC]) was tied to increased risk of cardiovascular disease (CVD) outcomes and death – but an intensive weight loss programme mitigated this risk, a study suggests.
On quartile (Q) analyses, among participants receiving standard care*, those in the highest quartile (Q4) of BMI had significantly increased risk for all-cause mortality (hazard ratio [HR], 4.06; ptrend<0.001), CV death** (HR, 15.28; ptrend<0.001), and CV events*** (HR, 2.16; ptrend=0.03) compared with those in Q1. Whereas for those receiving an intensive lifestyle intervention (ILI#) programme, the corresponding HRs for the said outcomes were lower at 0.99, 1.14, and 0.77.
For WC, the corresponding HRs in the standard-care arm were 1.84, 6.46, and 1.28 which, as with BMI, were higher than those in the ILI arm (1.23, 0.55, and 0.70). [JAMA Network Open 2022;5:e220055]
The stronger associations with BMI suggest that weight fluctuations may have a stronger effect on BMI than WC, the researchers noted. “This may be because BMI measures not only fat mass but lean mass, including muscle mass. The peripheral muscle is a metabolic organ and thus has an influence on outcomes. Lifestyle changes are likely to affect muscular mass, hence BMI and outcomes.”
Taken together, the data depict how higher variabilities in BMI and WC correlate independently with elevated risk of CVD outcomes, and how an intensive weight loss programme can help in keeping this risk at bay.
The researchers pointed to the exercise component of ILI as a potential contributor to the programme’s benefit. “[B]ody weight variability associated with higher intensity exercise in the ILI group would be expected to be associated with a reduction in abdominal adiposity; indeed, exercise training has been shown to be very effective at reducing total abdominal and visceral fat.”
What could be the culprit?
Although lifestyle interventions often lead to weight loss, the effect is mostly transient, as interruptions typically lead to weight fluctuations – a process referred to as weight cycling. [Obes Rev 2015;16:7-18]
“[These] fluctuations have been associated with the development of all the components of metabolic syndrome,” said the researchers. In a preclinical study, a high number of CD4+ and CD8+ T cells were seen in the adipose tissue of weight-cycled mice, with increased cytokine production that could contribute to metabolic dysfunction and adverse outcomes tied to weight cycling. [Diabetes 2013;62:3180-3188]
Weight regain following repeated attempts at weight loss from dieting might also explain for the association between increased variability of obesity measures and adverse outcomes in this patient cohort. [Clin Nutr 2011;30:718-723] “Weight gain results in rapid expansion and hyperplasia of adipose tissue [owing to] metabolic shifts that tend to favour lipid accumulation. Metabolically active adipose tissue then produces an array of adipokines (leptin and others) leading to adverse outcomes,” said the researchers. “[This] likely mediated the increased risk of CVD outcomes in the [standard-care] arm.”
Clinical implications
The study involved 3,604 individuals (mean age 58.4 years, 62 percent female) from the Look AHEAD## trial who had no CVD at baseline. Of these, 1,829 went through the ILI programme, while the rest received standard care.
Although the main Look AHEAD study did not show beneficial effects of ILI on CVD outcomes, [N Engl J Med 2013;369:145-154] “the research and public health implications of this study are manifold,” said the researchers. “Our findings imply that weight fluctuations during weight loss attempts among individuals with T2D may lead to deleterious health outcomes.”
“While it is premature to make any specific recommendation for change in clinical practice based on our study, our findings suggest that strategies involving ILI, including exercise, and those geared toward maintaining weight loss and preventing weight regain should constitute a major focus of weight loss prescriptions for individuals with overweight or obesity and T2D,” they concluded.