Excess weight may function not simply as a static risk factor but as a cumulative exposure that shapes metabolic health across the lifespan, according to new findings from a decades-long study.

Investigators conducted a prospective study following nearly 2500 individuals for 36 years. Using cumulative BMI exposure, they examined the association between elevated BMI early in life and later metabolic multimorbidity, including combinations of hypertension, diabetes, dyslipidemia, and kidney and liver dysfunction.

Higher BMI burden, measured as both total and incremental area under the curve (AUC), was strongly associated with metabolic multimorbidity. Rapid BMI accumulation during childhood appeared to confer especially high risk for long-term cardiometabolic complications.

“These findings highlight the importance of life stage-specific strategies: curbing rapid BMI gain in childhood and maintaining long-term weight control through adulthood,” wrote Tongshuai Guo, MD, of the Department of Cardiology, First Affiliated Hospital of Medical School, Xi’an Jiaotong University in Xi’an, China, and colleagues.

The findings were published in Diabetes Care.

An Innovative, Decades-Long Analysis

Metabolic disorders, such as hypertension, diabetes, dyslipidemia, and impaired kidney or liver function, are increasingly common worldwide and frequently occur together. This clustering of conditions, known as metabolic multimorbidity, contributes substantially to patients’ overall health burden. 

Childhood obesity is already recognized as a major risk factor for adult metabolic disease. However, the investigators noted that single BMI measurements may not adequately capture long-term metabolic risk because BMI trajectories established early in life often persist into adulthood.

To better understand cumulative risk, the researchers used AUC analysis to quantify long-term BMI exposure over time. Unlike prior studies that focused on individual metabolic diseases, the investigators evaluated how cumulative BMI burden across childhood and adulthood influenced the later development of multiple coexisting metabolic conditions. 

The researchers analyzed data from the Hanzhong Adolescent Hypertension Study, a prospective population-based cohort study conducted in China. The study began in 1987, with follow-up assessments conducted in 1989, 1992, 1995, 2013, 2017, and 2023. 

The current analysis included 2446 participants who had at least two BMI measurements during childhood (ages 6-18 years) and at least two during adulthood (ages 19-52 years). Primary analyses included 1524 participants with complete data available.

Greater BMI Accumulation Linked to Higher Risk

Higher total and incremental BMI AUC during childhood, adulthood, and across the life course were consistently associated with an increased risk for adult metabolic multimorbidity.

However, the pattern of risk differed by life stage. During childhood, rapid increases in BMI appeared especially important. Among participants with at least two metabolic conditions, childhood incremental BMI AUC — which reflected accelerated BMI gain over time — was associated with higher odds of metabolic multimorbidity (odds ratio [OR], 4.33) than was childhood total BMI AUC (OR, 1.51). 

In adulthood, however, sustained long-term BMI burden appeared more influential than rapid BMI increases. Adult total BMI AUC was associated with an OR of 2.51 compared with 1.94 for adulthood incremental BMI AUC.

Across the full life course, both cumulative BMI burden and accelerated BMI accumulation remained strongly associated with metabolic multimorbidity, with ORs of 2.59 for total AUC and 3.97 for incremental AUC.

Risk estimates became even stronger among participants with more severe disease burden. Among those with at least three metabolic diseases, childhood incremental BMI AUC was associated with nearly a sixfold higher risk (OR, 5.96), while life-course incremental BMI AUC was associated with a fivefold higher risk (OR, 5.11). Adult total BMI burden also remained strongly associated with severe multimorbidity (OR, 3.06).

Associations were generally stronger in males than females, particularly during adulthood and across the life course. Among participants with at least three metabolic diseases, life-course total BMI AUC was associated with an OR of 5.78 in men vs 2.09 in women, whereas life-course incremental BMI AUC showed ORs of 7.50 and 3.75, respectively.

All associations were statistically significant (P < .05).

Childhood total BMI burden was not significantly associated with metabolic multimorbidity in women, although childhood incremental AUC remained strongly predictive in both sexes. The authors suggested that differences in adipose tissue distribution, sex hormones, and lifestyle factors such as smoking and alcohol use may partly explain the greater susceptibility observed in males.

The authors acknowledged that the study’s generalizability may be limited because all participants were recruited from a single province in China. Early study visits also lacked detailed data on factors such as childhood lifestyle, nutrition, pubertal stage, and estrogen exposure.

Expert Perspectives

Commenting for Medscape Medical News, Dace Trence, MD, professor emeritus of medicine in the Division of Metabolism, Endocrinology, and Nutrition at the University of Washington, Seattle, described the study as “impressive” due to its 36-year duration and robust cohort size.

She said the findings also open important avenues for future research, particularly regarding the observed sex differences. 

“The sex differential, especially in the young cohort, is curious and begs further exploration,” she said.

Trence, president of the American Association of Clinical Endocrinology, noted that although BMI is a commonly used metric for defining obesity, interest is increasing in measures such as waist circumference to more accurately assess weight-related risk in adults. Whether such measures may also prove useful in children remains unclear, she added.

Nevertheless, she emphasized the study’s clinical relevance.

“Weight control is important, even during ages 6 to 18 — typically an age range in which we don’t focus on weight unless obesity or morbid obesity is present,” Trence said. “But taste preferences are developed very early, so the impact of food choices on weight would be a beneficial conversation, even as early as preschool time.”

This work was supported by the National Natural Science Foundation of China, the Key Research and Development Program of Shaanxi, Distinguished Professor of the Changjiang Scholars Program, the Clinical Research Award of the First Affiliated Hospital of Xi’an Jiaotong University, and the International Joint Research Center for Cardiovascular Precision Medicine of Shaanxi Province. The authors and Trence reported having no relevant financial relationships.

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).