Does metabolic health in overweight and obesity persist? – Individual variation and cardiovascular mortality over two decades

Abstract

Objective: Overweight and obese individuals may be metabolically healthy, but attention needs to be given to long-term persistence of this trait and any associated variation in cardiovascular risk. Design: Cross-sectional and longitudinal variation in metabolic health and associated cardiovascular mortality were analysed in 1099 white European-origin normal-weight and overweight or obese males followed for 20 years. Methods: Definitions of metabolic health were based on LDL and HDL cholesterol, triglycerides, blood pressure, fasting glucose and cardiovascular risk. Insulin resistance (e.g. HOMA-IR) and sub-clinical inflammation (ESR and white blood cell count) were explored. Cardiovascular mortality risks and persistence of metabolic health status were evaluated. Results: There were 87 cardiovascular deaths. Insulin resistance was increased in metabolically healthy overweight or obese participants (median HOMA-IR 2.63, 95% CI: 1.79-3.65, P < 0.001) relative to normal-weight participants (median HOMA-IR 1.67, 95% CI: 1.08-2.67, P < 0.001) as was sub-clinical inflammation but metabolically healthy overweight or obese individuals were not at increased risk of cardiovascular mortality compared with the metabolically healthy normal-weight individuals (hazard ratio 1.13, 95% CI: 0.34-3.72, P = 0.8). The proportions of initially metabolically healthy overweight or obese who remained metabolically healthy for visits 2, 3 and 4 were 54, 48 and 39% respectively, and for initially normal-weight individuals, 68, 51 and 41%. A lower proportion of metabolically healthy overweight or obese individuals remained metabolically healthy at visit 2 compared with normal-weight individuals (P = 0.007), but proportions converged thereafter. Conclusions: Despite being insulin resistant and having greater sub-clinical inflammation, and despite instability in metabolic health status, metabolically healthy overweight or obese individuals were at no greater risk of cardiovascular mortality than their normal-weight equivalents.

Genes that make you fat, but keep you healthy

“…The disease risks associated with MHO and MONW vary across studies and across disease outcomes studied. Some studies found that the disease risk for MHO individuals is similar to that of normal‐weight individuals (at least for cardiovascular disease , stroke , peripheral vascular disease , dyslipidemia , type 2 diabetes ) and mortality ), even after many years of follow‐up. However, cumulating evidence from several large‐scale prospective studies suggests that MHO individuals have a higher risk than healthy normal‐weight individuals for many cardiometabolic outcomes (cardiovascular disease , cerebrovascular disease , hypertension , insulin resistance and type 2 diabetes ), yet their risk is lower than that of metabolically unhealthy obese individuals.…”

“…Lifestyle and demographic factors have been shown to explain at least part of the difference between metabolically healthy and metabolically unhealthy obese individuals. MHO individuals are generally younger, female, more often of African ancestry, have a relatively lower BMI and waist circumference, tend to live a healthier lifestyle (smoke less, more physically active, healthier diet) and have less often a family history of cardiometabolic disease compared to their unhealthy obese peers . Similar factors partially explain why some normal‐weight individuals are metabolically unhealthy; that is, MONW individuals are often older, male, less likely of African ancestry, have a higher BMI and larger waist circumference, live a less healthy lifestyle and have more often a family history of cardiometabolic disease compared to healthy normal‐weight individuals .…”

“…Nevertheless, even after accounting for these demographic and environmental correlates, MHO individuals continue to have a more favourable cardiometabolic risk profile than the unhealthy obese individuals, and MONW individuals continue to be at greater risk than the healthy normal‐weight individuals . This suggests that innate, biological mechanisms also contribute to the cardiometabolic differences amongst obese and normal‐weight individuals.…”

“…An estimated 15–45% of obese individuals are considered to be metabolically healthy, despite excess adiposity (the so‐called metabolically healthy obese, MHO) . Conversely, not all normal‐weight individuals (18.5 kg m −2 ≤ BMI < 25 kg.m −2 ) are protected from metabolic disease; that is, an estimated 6–30% of normal‐weight people demonstrate cardiometabolic abnormalities that are typically seen in obese individuals (the so‐called metabolically obese normal weight, MONW) . These subgroups of obese and normal‐weight individuals were first described in the early 1980's , but in the past decade, research into their aetiology, correlates and future disease risk has increased exponentially.…”

Obesity is bad regardless of the obesity paradox for hypertension and heart disease

“…Thus, MHO adults are at an increased risk for developing T2DM than NWMH adults. In another study, Kaur and colleagues investigated whether metabolic health persists in overweight and obese individuals long term. They studied 1099 NW, overweight, or obese male individuals (mean age 46.4 years) for 20 years.…”