The powerful link between obesity and multimorbidities is a critical target for disease prevention that avoids the burden of multi-target preventive measures.

Obesity is a shared risk factor for many common diseases, explains Mika Kivimäki, PhD. “Obesity has been linked to increased risk for numerous diseases,” Dr. Kivimäki says, adding that previous research has shown that complex multimorbidity, defined as four or more obesity-related diseases, makes prevention challenging if each disparate disease state is treated separately.

For a study published in The Lancet Diabetes & Endocrinology, Dr. Kivimäki and colleagues developed an observational study to explore the role obesity plays in the development of complex multimorbidity.

“We wanted to know whether these diseases are distributed across all people with obesity, or whether they cluster in smaller groups of individuals with obesity-related multimorbidity, Dr. Kivimäki says. “In the first scenario, for example, one person with obesity has diabetes, another has musculoskeletal problems, and a third has respiratory problems, depending on their individual vulnerabilities,” he explains. “In the latter scenario, different diseases cluster in the same people with high BMI. We found more support for the latter.”

BMI Categorized from Obesity to Underweight

For an observational study, Dr. Kivimäki and team cultivated pooled prospective data from two Finnish cohort studies comprising 114,657 adults aged 16-78 and the UK Biobank with a cohort of 499,357 adults aged 38-73, which served as replication in an independent population.

Participants’ BMI and clinical characteristics were assessed at baseline and were categorized as obesity (≥30.0 kg/m2), overweight (25.0-29.9 kg/m2), healthy weight (18.5-24.9 kg/m2), and underweight (<18.5 kg/m2). These designations were then further categorized into class 1 (BMI 30.0-34.9 kg/m2), class 2 (35.0-39.9 kg/m2), and class 3 (≥40.0 kg/m2).

Using Cox proportional hazards regression in the cohorts drawn from the Finnish databases, the study team examined links between obesity and 78 health outcomes in separate models. Obesity-disease associations were only considered if they yielded an HR ≥1.50, were meaningful at a Bonferroni corrected α level, and had a P-value of less than 6.3×10-4.

Participants With Obesity Are at Higher Risk for Multimorbidity

Analysis of the data showed that participants with obesity were at a higher risk for developing simple multimorbidity (defined as two or more obesity-related diseases) or complex multimorbidity when compared with participants with a healthy weight (Figure). Age was an additional factor for risk.

Participants with obesity who reached age 75 had an estimated occurrence of simple multimorbidity of 53.3% (95% CI, 50.1-56.3) and complex multimorbidity of 8.3% (95% CI, 6.0-10.4). Among participants with a healthy weight, these occurrences were less likely with simple multimorbidity occurrence of 8.3% (95% CI, 6.0-10.4) and complex multimorbidity of 1.0% (95% CI, 0.6-1.4).

Obesity before age 50 was noted as being more strongly related to the incidence of complex multimorbidity (HR 22.11, 95% CI, 13.68-35.74) than obesity at older ages (HR 7.90, 5.48-11.41; P=0.0091).

Obesity Exposes People to Increased Burden of Multimorbidities

 “We found that obesity exposes people to increasing burdens of heterogeneous multimorbidities, including cardiometabolic, digestive, respiratory, neurological, musculoskeletal, infectious, and malignant diseases,” Dr. Kivimäki says. “No specific combination of obesity-related diseases was particularly common. In contrast, the first four diseases formed as many as 140 different combinations. For this reason, we use the term ‘heterogeneous multimorbidity.’”

These findings suggest that obesity is an important target for disease prevention, to avoid the burden of a multi-target regimen. “The creation of healthy living environments with less factors that predispose to obesity presents a parsimonious approach to reduce multimorbidity at the population level, while obesity treatments, such as lifestyle interventions, pharmacotherapy, and bariatric surgery could prevent multimorbidity among those who receive them,” the study authors wrote.