Study Finds First-Degree Family History of Diabetes Linked With NAFLD

Using the fatty liver index (FLI) to identify nonalcoholic fatty liver disease (NAFLD), researchers sought to understand the association between first-degree family members of patients with diabetes and NAFLD.

A recent study examined the association between a first-degree family history of diabetes and nonalcoholic fatty liver disease (NAFLD) and the influence of glucose metabolic status, given that insulin resistance is recognized as a common contributor to both diseases.

NAFLD prevalence in Western countries ranges from 24% to 46%, but the authors said it is now a new public health crisis in China as well. NAFLD and type 2 diabetes (T2D) have a bidirectional relationship, with T2D influencing a worsening of NAFLD progression, including liver cancer, severe steatohepatitis, and advanced fibrosis. NAFLD is linked with an increase in T2D risk. However, reversal or improvement of NAFLD contributes to a reduction of T2D risk.

The first-degree relatives of patients with diabetes have a predisposition to insulin problems, but few studies have explored possible relationships between NAFLD and families with a history of diabetes. Clarifying any associations between NAFLD and a family history with diabetes can assist with NAFLD prevention efforts in high-risk populations, the authors said.

Using the fatty liver index (FLI) to identify NAFLD, researchers sought to understand the association between first-degree family members of patients with diabetes and NAFLD.

The dataset for this research came from the previous reported REACTION study, which was conducted between 2011 and 2012 among 259,657 adults in 25 communities across mainland China to examine the relationship between diabetes and cancer.

Researchers of the current study enrolled a total of 11,162 participants with an average age of 55.57 (9.66), including 9870 individuals without diabetes in their family history and 1292 first-degree relatives of people with diabetes.

First-degree family history was defined as at least 1 patient with diabetes among parents, siblings or children, and first-degree relatives were defined as those having first-degree family

The fatty liver index (FLI) was calculated to identify NAFLD, and FLI was one of the metabolic factors independently associated with first-degree family history of diabetes (P = .006). Glucose metabolic status was determined the standards set by the American Diabetes Association in 2020 normal, prediabetes, and diabetes.

In addition, first-degree relatives were more susceptible to NAFLD, regardless of glucose metabolism status, and having a family history of diabetes was an independent risk factor for NAFLD. They were also more likely to have a high FLI.

The proportions of subjects without NAFLD, with intermediate FLI, and with NAFLD differed significantly between those without first-degree relatives without diabetes and those with diabetes (P < .001).

Multivariate variance analysis showed positive associations of first-degree FHD and glucose metabolic status (both P < .001) with FLI, which were independent of each other (P for interaction = .182) and of age, gender, metabolic health conditions, and current smoking.

Multiple stepwise linear regression analysis showed that first-degree family was independently and positively associated with FLI in men, premenopausal women, and postmenopausal women (all P < .05).

The study had some limitations. NAFLD was not diagnosed with a liver biopsy, which is the gold standard, as FLI, as a noninvasive and inexpensive test, is more suitable for a large community-based study, the authors noted.

Also, the cross-sectional study design meant that the chronological link between the occurrence and development of NAFLD and metabolic alterations could not be known.

Even if they do not have diabetes, first-degree relatives of patients with diabetes should be screened for NAFLD, the authors concluded.


Hu X, Yu W, Yang L, et al. First-degree family history of diabetes is associated with nonalcoholic fatty liver disease independent of glucose metabolic status. J Diabetes Complications. Published online November 4, 2021. doi: 10.1016/j.jdiacomp.2021.108083.