Body Weight Fluctuation Linked to CV Events in Diabetes

Liam Davenport

May 10, 2018

LISBON, Portugal — Patients with type 2 diabetes whose weight fluctuates appear to be at increased risk for cardiovascular (CV) events, such as stroke, myocardial infarction (MI), and death, compared with those whose weight remains stable, an analysis of previously published trial data suggests.

Looking at outcomes in over 6000 patients with type 2 diabetes, the researchers found that each standard deviation (SD) increase in body weight variability was associated with a significantly increased risk for any coronary event, major coronary events, and death.

Moreover, the results, presented here at the European Atherosclerosis Society (EAS) 2018 meeting, suggested that individuals with the highest body weight variability had a 59% increased risk for any coronary event, a 99% increased risk for MI, a 92% increased stroke risk, and an 82% increase in the risk for death.

David Waters, MD, professor emeritus, University of California San Francisco, who presented the study, said that it is not clear from the data whether the weight fluctuations were intentional, such as due to dieting, and "we don't know if people are able to influence their weight fluctuations."

Speaking to | Medscape Cardiology, he said that there is a "long history of other physiological variables that fluctuate a lot being risk factors. For example, if you have high blood pressure variability, it's a big risk factor for stroke and cardiovascular events; if you have high heart rate variability, that's not good for you," and previous studies have shown that high variability in lipids is also a risk factor.

However, "we don't know what any of the mechanisms are, except maybe for blood pressure," although he believes that it a common underlying mechanism is unlikely, particularly because there seems to be poor correlation between variations in variables.

Waters said that one study they carried out showed that people whose blood pressure fluctuated weren't the same ones necessarily with fluctuations in cholesterol.

"It seems that if you aren't able to keep yourself stable for a lot of different variables, it's a bad thing, but we don't know exactly why."

Fluctuations in Weight

Most patients with type 2 diabetes are overweight or obese, and weight loss is recommended as part of their management, Waters said in his presentation.

However, weight loss associated with lifestyle interventions is typically temporary, and repeated attempts to diet and exercise may lead to fluctuations in weight.

Having previously shown that body weight variability is a risk factor for CV events in patients with coronary artery disease (CAD), they examined the relationship between body weight variability and CV events in patients with diabetes.

They gathered data on intraindividual variations in body weight in 6408 patients with type 2 diabetes from the CARDS, ASPEN, and TNT trials, who were followed up at 3, 6, and 12 months after randomization and then every 6 months.

The primary endpoint was any coronary event, a composite of coronary heart disease (CHD) death, MI, resuscitated cardiac arrest (apart from CARDS), coronary revascularization, and unstable or new-onset angina.

A major coronary event was defined as CHD death, MI, and resuscitated cardiac arrest (again, except for the CARDS trial), and any CV event was defined as any coronary event plus fatal or nonfatal stroke, transient ischemic attack, peripheral vascular disease, or heart failure.

The overall average patient age was 61.7 ± 8.1 years, 31.7% of patients were female, and the mean body mass index was 29.2 ± 4.1 kg/m2.

There were some notable differences in baseline characteristics between the trials, at least in part due to TNT participants having taken atorvastatin 10 mg/day for 8 weeks at baseline.

The mean weight change during the course of follow-up was 0.9 ± 52 kg, with patients in the CARDS and ASPEN trials recording a 1.3 ± 5.6-kg and 1.1 ± 5.8-kg increase in weight, respectively, and TNT patients having a 0.2 ± 2.8-kg decrease.

Calculating the average successive variability (ASV) in weight between follow-up visits, the researcher found that the median ASV was 1.72 kg.

Defining low and high body weight variability as an ASV below or above the median, the researchers found the 3205 study participants with high variability in body weight were, compared with the 3203 patients with low weight variability, significantly younger (P < .0001); were more likely to be current smokers (P = .017); and were more likely to have a higher body mass index, body weight, and weight change (P < .0001 for all three).

They also had significantly lower high-density lipoprotein cholesterol levels (P < .0001) and lower triglycerides (P = .0009) and were more likely to experience a CV event during follow-up, at 22.4% vs 15.7% (P < .0001).

Taking into account treatment, mean body weight, and weight change, as well as clinical and risk factors and lipid measurements, the researchers determined that each 1-SD increase in body weight variability was associated with a significantly increased risk for any coronary event, at a hazard ratio (HR) of 1.08 (95% CI, 1.01 - 1.14; P = .017).

Each SD increase in weight variability was also associated with significantly increased risks for a major coronary event, at an HR of 1.12 (95% CI, 1.04 - 1.20; P = .002); for any CV event, at an HR of 1.08 (95% CI, 1.03 - 1.14; P = .0015); and for death, at an HR of 1.16 (95% CI, 1.10 - 1.22; P < .0001).

The risks were even higher when the team compared the highest and lower quintile of body weight variability, at an HR for any coronary event of 1.59 (95% CI, 1.26 - 2.00; P < .0001), an HR for a major coronary event of 1.82 (95% CI, 1.29 - 2.56; P = .0006), an HR for any CV event of 1.75 (95% CI, 1.44- 2.13; P < .0001), and an HR for death of 1.82 (95% CI, 1.31 - 2.53; P = .0003).

In addition, being in the highest quintile of body weight variability vs the lowest quintile was associated with an increased risk for stroke, at an HR of 1.92 (95% CI, 1.15 - 3.20; P = .012), and an increased risk for MI, at an HR of 1.99 (95% CI, 1.33- 2.97; P = .0008).

The impact of body weight variability was greatest in overweight and obese people. For example, 17.48% of obese patients with a variability greater than the median experienced any coronary event vs 11.44% of those with a lower body weight variability (P < .0001).

Among overweight people, the rates were 15.31% and 10.98%, respectively (P = .014), while the difference all but disappeared among normal-weight individuals, at 11.16% vs 10.72, respectively (P = .8470).

A similar pattern was seen for any CV event.

Waters concluded that among patients with type 2 diabetes, "fluctuation in body weight was associated with higher mortality and a higher rate of cardiovascular events, independent of traditional cardiovascular risk factors."

He added: "The magnitude of this risk increased with greater body weight variability and among those who were overweight or obese at baseline."

Incomplete Picture

Session chair Emilio Ros, MD, PhD, director of the Lipid Clinic and senior consultant, endocrinology and nutrition service, Hospital Clínic, Barcelona, Spain, told | Medscape Cardiology that the current results fit with what was seen with the previous analysis in patients with CAD.

He said that CAD and type 2 diabetes "are closely interrelated, so I think it makes sense." However, to explain "why that happens, we need mechanistic studies and, also, as Dr Waters mentioned, there are limitations to the study."

"They don't know if these weight fluctuations were on purpose or were associated with illness or were due to social interactions that enable people to say, 'You're too fat, you should lose weight,' and so on," Ros, who was not involved in the study, added.

"The picture is not complete, but we know that what he showed for diabetes and what he showed for coronary artery disease is very interesting."

Waters report remuneration for clinical trial committee participation from CSL Ltd, Pfizer, Regeneron, Resverlogix, and Sanofi and honoraria for lectures and consulting fees from Pfizer. Ros reports grants/research support from the California Walnut Commission, Alexion, Amgen, Pfizer, and Sanofi-Aventis and consulting fees/honoraria from the California Walnut Commission, Aegerion, Alexion, Akcea, Merck, Sanofi-Aventis, Ferrer International, and Danone.

European Atherosclerosis Society (EAS) 2018. Presented May 8, 2018.

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