Metabolic health affects risk of diabetes, but not of incident CVD in obese

Hinnouho GM, Czernichow S, Dugravot A et al.
Eur Heart J. 2014 Mar 26

Background

Recent studies have identified a subgroup of obese individuals who can be considered ‘metabolically healthy obese’ (MHO), because they have a low burden of adiposity-related metabolic abnormalities as compared with individuals with metabolic syndrome (MetS) who are at risk of adverse health outcomes [1-5]. The good metabolic profile in MHO is characterised by high levels of insulin sensitivity, low prevalence of hypertension and a favourable fasting glucose, lipid and inflammation profile [6].
Contradicting results have been published about the extent to which the MHO phenotype is associated with a decreased risk of adverse health outcomes. Findings may differ depending on the chosen definition of metabolic health, as well as the studied health outcome.
This study investigated the association of the MHO phenotype with incident cardiovascular disease (CVD) and type 2 diabetes (T2DM), in 7122 individuals over a 17-year follow-up period. The Adult Treatment Panel-III (ATP-III) criteria were used to define MHO.

Main results

• The MHO phenotype represented 3.9% (n=279) of the total sample and 42.5% of the obese population. Triglycerides, LDL-c, fasting glucose and blood pressure were higher in metabolically unhealthy obese (MUO) than in MHO, while HDL-c was higher in MHO.
• 828 incident CVDs were observed during a median follow-up of 17.4 years, of which 4.5% was seen in the MHO and 8% in the MUO. 798 incident type 2 diabetes events were seen, 6.0% in the MHO and 16.0% in the MUO.
• Compared with metabolically healthy individuals (irrespective of obesity), metabolically unhealthy individuals had an increased risk of incident CVD (HR: 1.97, 95% CI: 1.72-2.27)  and T2DM (HR: 3.22, 95% CI: 2.79-3.73).
• Compared with the MH-normal weight, all five other groups (based on metabolic status and overweight or obese) had an increased risk of incident CVD and type 2 diabetes. Associations for T2DM were consistently stronger.
• In normal weight and overweight individuals, the metabolically unhealthy had an increased risk of incident CVD and T2DM. In obese individuals, however, being metabolically unhealthy did not give an increased risk of incident CVD, while it did increase risk of T2DM.
• Overweight/obese individuals who became metabolically healthy between 1991-1993 and 1997-1999 (n=45) did not have a lower risk of CVD than those who remained MUO (n=89) over this period (HR: 0.89, 95%CI: 0.62-1.28), while their risk of T2DM decreased (HR: 0.39, 95%CI: 0.26-0.58).

Conclusion

Metabolically healthy obese persons had a higher risk of CVD and T2DM than metabolically healthy individuals with normal weight. MHO individuals did not have a lower risk of incident CVD than MUO, while risk of T2DM was lower in the metabolically healthy. Thus, the prognosis of MHO is not the same for all outcomes. The current findings suggest that obesity outweighs the impact of metabolic status for risk of CVD. Metabolic health is, however, important for the risk of T2DM, since MHO had a lower risk than MUO.

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