How do changes in weight (weight loss or weight gain) affect cardiovascular (CV) risk in type 2 diabetes

So, what is the “obesity paradox”? Well, this term has been used to describe that overweight or obese adults have demonstrated a survival advantage compared with leaner adults in several population-based samples. This counterintuitive association has been termed the obesity paradox. There is also evidence that this obesity paradox has been demonstrated in patients with type 2 diabetes.

How do changes in weight affect cardiovascular risk in diabetes mellitus

• there is evidence of a survival benefit with overweight and mild obesity in patients at risk or with established CV disease (1)
  • weight reduction in the LOOKAHEAD trial in overweight T2DM patients did not improve outcomes of mortality or morbidity (2)
    • a reduction of body weight and of subsequent surrogate markers of the metabolic syndrome was indeed achieved
    • the study showed that this weight reduction did not improve any of the outcome variables on mortality or morbidity
  • weight loss was an independent risk factor for all-cause mortality after 19-year follow-up of the DCGP trial (3)
    • showed that weight loss in obese patients regardless of intention did not improve outcome but was an independent risk factor for increased all-cause mortality
• the ORIGIN trial investigated 12 537 patients with type 2 DM or pre-diabetes with 100% prevalent CV risk factors
  • aim of this analysis from the ORIGIN trial data is to assess the relationship between body weight, weight change, and CV outcome in this cohort at high risk of CV events (4)
  • showed that in patients with type 2 DM and prevalent CV risk profile overweight and mild obesity are associated with lower all-cause mortality and CV mortality compared to patients with normal body weight (BMI 22 - <25 kg/m2)
    • weight loss was related to higher all-cause and CV mortality compared to no weight loss while weight gain was not
  • note thought that (5):
    • there may be non-causal potential mechanisms include residual confounding could lead to study results e.g. those in the lowest BMI were older and had longest duration of diabetes, while those in the highest BMI group had the lowest prevalence of prior CVD
    • also the study may reveal some reverse causality e.g. generally the sickest patients lose weight between 3-10 years before they die due to reduced appetite, and less physical activity
    • trials are needed to settle whether intentional weight loss is beneficial or harmful in patients with existing CVD

Reference:

1. Costanzo P, Cleland JG, Pellicori P, Clark AL, Hepburn D, Kilpatrick ES, Perrone-Filardi P, Zhang J, Atkin SL. The obesity paradox in type 2 diabetes mellitus: relationship of body mass index to prognosis: a cohort study. Ann Intern Med 2015;162:610–618.
2. Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013;369:145–154.
3. Koster-Rasmussen R, Simonsen MK, Siersma V, Henriksen JE, Heitmann BL, de Fine Olivarius N. Intentional weight loss and longevity in overweight patients with type 2 diabetes: a population-based cohort study. PLoS One 2016;11:e0146889.
4. Doehner W, Gerstein HC, Ried J, et al. Obesity and weight loss are inversely related to mortality and cardiovascular outcome in prediabetes and type 2 diabetes: data from the ORIGIN trial. Eur Heart J 2020 41, 2668–2677, doi:10.1093/eurheartj/ehaa293
5. Sattar N, Welsh P. The obesity paradox in secondary prevention: a weighty intervention or a wait for more evidence? Eur Heart J. 2020 Jul 21;41(28):2678-2680. doi: 10.1093/eurheartj/ehaa398.