Early Adulthood Weight Gain in Women Identified as Potential NAFLD Risk Factor

fatty liver
fatty liver
Investigators studied the impact of changes in adiposity over patients’ life courses on the midlife development of nonalcoholic fatty liver disease.

Early adulthood weight gain and lifetime body shape trajectory in women were found to be significantly and independently associated with an excess risk of developing nonalcoholic fatty liver disease (NAFLD) midlife, according to findings from a study published in Metabolism Clinical and Experimental.

The researchers analyzed data from 110,054 women enrolled in the Nurses’ Health Study II trial, an ongoing, prospective US cohort study that began in 1989 and enrolled 116,430 female registered nurses, aged 25 to 42 years. Early adulthood weight change was defined as the difference in kg between early adulthood weight (age 18 years) and the weight reported in the current questionnaire cycle.

These data were updated prospectively every 2 years and classified by 1 of the 6 following categories: weight loss of 2.0 kg or more, weight loss or weight gain within 2.0 kg, weight gain between 2.0 and 5.9 kg, weight gain between 6.0 and 9.9 kg, weight gain between 10.0 and 19.9 kg, and weight gain of 20.0 kg or greater.

The study authors documented 3798 cases of NAFLD over 20 years of follow-up. Women with the highest categorical weight gain (≥20.0 kg) had the most elevated risk for developing NAFLD. Compared with women who maintained stable weight (± 2kg), women with adulthood weight gain of 20.0 kg or more had a multivariable adjusted hazard ratio (aHR) of 6.96 (95% CI, 5.27-9.18; P <.0001). This trend remained significant after further adjusting for early adulthood body mass index (BMI) and updated BMI (both P <.0001).

When adjusted for smoking status, total calories, menopausal hormone therapy, and other variables, the aHRs were 1.26 (95% CI, 0.91-1.74), 1.59 (1.17-2.16), 2.99 (2.26-3.97), and 6.96 (5.27-9.18) for women with weight gain of 2.0 to 5.9 kg, 6.0 to 9.9 kg, 10.0 to 19.9 kg, and 20.0 kg or more, respectively.

The investigators also calculated the risk for NAFLD development according to body shape trajectory. Compared with women who had a medium-stable body shape trajectory, the multivariable aHRs for NAFLD were 2.84 (95% CI, 2.50-3.22) for lean-marked increase, 2.60 (95% CI, 2.27-2.98) for medium-moderate increase, and 3.39 (95% CI, 2.95-3.89) for medium-marked increase.

“Both excess adiposity and weight gain since early adulthood were associated with a significantly higher risk of developing incident NAFLD in midlife,” the researchers stated. “The significant, positive association between early adulthood weight gain and NAFLD risk was independent of attained BMI, and it was evident even with as little as 6 kg of weight gain since early adulthood.”

The study authors went on to identify 5 patient subgroups based on participants’ body-shape evolution. They found that women who had a medium body shape in early life and subsequently gained “marked weight” between 5 and 50 years had the highest NAFLD risk. Conversely, those who maintained a medium body shape throughout life had the lowest overall risk.

“Importantly, being lean in early life did not counteract the adverse effects of subsequent weight gain,” the researchers wrote. “Compared [with] adults who maintained a medium body shape throughout life, those who were initially lean in early life but subsequently gained substantial weight had a 2.8-fold higher risk of developing NAFLD later in life.”

The investigators noted several limitations to their study, including the all-women patient population, which comprised mostly White participants. Further, although the study authors validated the NAFLD diagnoses, they acknowledged that misclassification was possible because NAFLD was based on self-reported and patient-recalled information.

“Given the increasing prevalence of NAFLD, our findings support the development of public health strategies to maintain a healthy weight and body shape throughout life for the prevention of NAFLD,” the investigators concluded.

Disclosures: One of the study authors reported an affiliation with the pharmaceutical industry. Please see the original reference for the author’s disclosure.


Kim MN, Lo C-H, Corey KE, et al. Weight gain during early adulthood, trajectory of body shape and the risk of nonalcoholic fatty liver disease: a prospective cohort study among women. Metabolism. Published online October 12, 2020. doi: 10.1016/j.metabol.2020.154398