Impact of intentional weight loss in cardiometabolic disease: what we know about timing of benefits on differing outcomes?

[Eddy Edson]

Impact of intentional weight loss in cardiometabolic disease: what we know about timing of benefits on differing outcomes?

There is a widening appreciation that excess adiposity may be a more important risk factor for multiple cardiometabolic outcomes than previously imagined. Gains

academic.oup.com

A nice survey of current knowledge & future directions.

There is a widening appreciation that excess adiposity may be a more important risk factor for multiple cardiometabolic outcomes than previously imagined. Gains in knowledge from well-conducted epidemiological studies, genetics, and follow-ups of bariatric surgery studies have stimulated more interest in the role of intentional weight loss in preventing or treating cardiometabolic disease. However, it is less well appreciated that the timing of such benefits may vary dependent on the disease process considered (Figure 1). Such issues are important as the results of several outcome trials (e.g. SELECT,1 SURPASS-CVOT2) testing the benefits and safety of agents that cause considerable weight loss, often 10 kg or more, will report over the next several years.3,4 As the relevant drugs also likely deliver direct tissue benefits, the pattern and timing of any outcome benefits in these trials will be eagerly scrutinized to try to decipher the relative contributions of direct drug effects vs. impacts of their large-scale weight loss.

Figure 1

Table 1
Summary of metabolic and vascular changes with weight loss, potential mechanisms, and area of need for future research

	Speed and patterns of change	Potential Mechanisms	More research needed
Diabetes and lipids	Rapid (within days) reductions in HbA1c, liver fat, triglyceride levels	Rapid reduction in calories leading to reductions in ectopic fat stores in various compartments including liver, circulation and pancreas, and elsewhere?	Some evidence for favourable pancreatic remodelling from weight loss but needs repeated
Systolic blood pressure	Rapid (within weeks) dependent on degree of weight loss	Reduction in salt intake? Haemodynamic changes? Other mechanisms e.g. modulation of sympathetic drive?	More trials in resistant hypertension and more mechanistic studies
ASCVD	Slower (after few years)	Changes in upstream risk factors take time to impact or slow atherosclerosis process sufficient to see reductions in hard outcomes	The pattern of outcome benefits in ongoing outcome trials will be informative though it may be difficult to decipher direct effects of drugs vs. their impacts due to weight loss.
HFpEF	Intermediate (perhaps a few months). Some evidence for reduction in LV mass with weight loss within 3–6 months	Haemodynamic changes leading to reductions in cardiac output and systemic resistance? Improvements in myocardial blood flow? Cellular mechanisms to be more clearly elaborated?	Larger weight loss trials needed with low-calorie diets to determine to what extent remodelling related to weight loss per se More frequent imaging would also help determine speed of benefits
Chronic Kidney Disease	Likely intermediate (perhaps a few months) but more data needed	Haemodynamic changes? Other cellular mechanisms?	Well-designed RCTs of weight loss with more modern methods and techniques needed in patients with CKD to look at changes in eGFR slopes and in albuminuria over time and, if present, to investigate potential mechanisms

 

[Deleted member 21371]

Rapid weight loss is specifically mentioned just once.

"rapid weight loss begets prompt reductions in liver fat and circulating triglycerides levels"

I wonder if that's because it's the only method that has been proven, or if the implication is other methods of weight loss don't?

"Additional studies would usefully extend these findings."

 

[Eddy Edson]

I wonder if that's because it's the only method that has been proven, or if the implication is other methods of weight loss don't?

I'd say the former. The references are to the major DiRECT papers; leaves the question of slower weight loss open.

 

[AndBreathe]

Rapid weight loss is specifically mentioned just once.

"rapid weight loss begets prompt reductions in liver fat and circulating triglycerides levels"

I wonder if that's because it's the only method that has been proven, or if the implication is other methods of weight loss don't?

"Additional studies would usefully extend these findings."

The other thing about the more usually recommended pace of weight loss is it is easier to accurately track and measure over shorter period. Over longer period, other factors can come into play.

Whichever it is, I think it a positive outcome to identify potential benefits and recognise the need for more work.