The main finding of the present study is the high prevalence of MetS in a Taiwan indigenous population, and there was an association between serum ALT levels and MetS. Higher serum ALT levels, especially over 36 U/L, were associated with an increased risk of MetS.
The results were consistent with the findings of several previous studies. A hospital-based study showed that more than half of the indigenous adults in southeastern Taiwan had MetS [6], and two community-based studies revealed that the prevalence of MetS in indigenous populations in northern Taiwan was over 48% [7, 17]. In contrast, without regard to regional difference, the data from the Taiwan Health Promotion Administration revealed that the overall prevalence of MetS in Taiwanese adults above the age of 20 was 19.7% in 2007 [15]. According to a cross-sectional survey, the MetS prevalence in a Taiwan metropolitan area was 33.32% among adults aged over 40 years in 2007 [18]. Therefore, it seems that the prevalence of MetS is higher in the Atayal tribe than in the metropolitan or overall population in Taiwan. This inference was in line with the results of the 2005–2008 NAHSIT, which revealed that the highest prevalence of MetS was found in the indigenous area (mountains) compared to the prevalence in other places in Taiwan [4]. Additionally, this idea was supported by a cross-sectional study illustrating that indigenous groups in Taiwan had a markedly higher prevalence of MetS than the Taiwanese and Hakka groups [19].
The reasons for the above phenomenon could be multifactorial. First, there were some health disparities between indigenous individuals and the general population in Taiwan [20]. For example, the lifetime prevalence of alcoholism according to ICD or DSM in four Taiwanese indigenous groups was 40–60% [21], and a large prospective cohort study revealed that heavy alcohol consumption is associated with an increased risk of the MetS [22]. In addition, a study suggested that 6% of inhabitants in Kaohsiung, the second-largest city of Taiwan, were current betel chewers, whereas 42% of the indigenous individuals aged over 15 years in southern Taiwan were current chewers [23]. Although areca nut chewing is deeply rooted in indigenous culture and symbolizes social belonging in Taiwan [24], chronic areca nut chewing is one of the independent risk factors for MetS and contributes to metabolic derangements via the involvement of tumor necrosis factor-𝛼, leptin, and leukocyte count [25].
Second, there is a socioeconomic gap between the indigenous people and the general public in Taiwan. According to the economic status survey from the Council of Indigenous Peoples in Taiwan, the indigenous household income was approximately 61% of the average household income of Taiwan in 2014, and only 6.58% of primary income earners had a university education or above [26]. However, a study suggested that good socioeconomic status could protect against MetS [27], and a study with a large sample size also implied that a higher education level was related to a lower risk of MetS [28]. In other words, low socioeconomic status could negatively impact the health of indigenous people. Third, the indigenous population in our study was located in the mountains without adequate healthcare resources, and the lack of medical accessibility caused them to delay seeking care to improve their health outcomes. In summary, differences in health behaviors, low socioeconomic status and limited access to healthcare in remote areas all impacted the health inequality between the Atayal tribe and individuals from metropolitan areas.
In the present study, the second major finding was that baseline serum ALT level and MetS were positively associated with the cut-off point of 20.50 U/L based on the AUC, and the adjusted OR of abnormal ALT levels (> 36U/L) for MetS was 2.58 after correction for age, sex, hypertension, diabetes, hyperlipidemia, and BMI. These results corroborate the findings from a large-population, community-based study conducted in China, which verified a positive correlation between normal serum ALT levels and the morbidity rate of MetS after age and BMI correction. The optimal ALT boundary value based on the ROC curve was 24.5 for men and 14.5 U/L for women [29]. In short, an elevated ALT level, even at a level still within the reference interval, may reflect early metabolic changes.
On the other hand, our study also implied that an abnormal ALT level (> 36U/L) was associated with a tendency towards a higher prevalence of MetS compared to the prevalence associated with normal ALT levels (≤ 36 U/L). The finding was similar to the results of prior studies. A systematic review and meta-analysis revealed that the baseline circulating ALT level is associated with the risk of MetS and exhibits a linear dose-response relationship [14], which was identical to the results of a cross-sectional study including over 15000 adults and a longitudinal study with 7 years of follow-up from China [12] [13]. Taken together, these research studies have indicated that people with higher ALT levels have a higher risk of MetS.
In addition, a Korean study also confirmed that serum ALT levels were positively associated with MetS and its components (FPG, TGs, BP, and WC) [11], and we also found weak positive linear relationships between serum ALT levels and cardiometabolic risk factors (BMI, SBP, DBP, WC, FPG, HS-CRP) in our study. Although the present study only included adults aged over 18, a nationwide study conducted in Iran indicated that MetS and some cardiometabolic risk factors were significantly associated with ALT levels in children and adolescents aged 7–18 years [30].
Although the mechanisms underlying the association between serum ALT levels and MetS are not entirely understood, a study from the Netherlands shed light on a possible mechanism. Insulin resistance acts as a major mediator of the association between the MetS and ALT level, while inflammatory adipokines, endothelial dysfunction, and nonesterified fatty acids also play minor roles but to a lesser extent [31]. ALT is a catalyzer that is involved in the transfer of the amino group of alanine to α-ketoglutarate [32], and a study from Argentina proposed that abnormal ALT levels are related to a dysregulation of normal amino acid metabolism in the liver, and aberrant liver metabolism could lead to MetS and insulin resistance [33]. Further studies are required to better clarify the pathophysiology.
Strengths and limitations
A key strength of this study is that it was a community-based study targeting the Taiwan indigenous population and demonstrating the positive association between baseline serum ALT levels and MetS in the Taiwan Atayal tribe. There were also three limitations in this study. First, the cross-sectional design resulted in the inability to effectively determine the causal relationship between MetS and serum ALT levels. Second, serum ALT is a sensitive marker for liver dysfunction and is affected by heavy alcohol consumption [34] and some medications [35]. However, there was a lack of information on drug history, such as nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, and lipid-lowering drugs in this study. There was also no clear personal history for viral hepatitis, NAFLD, or alcohol consumption. Third, there were more female subjects than male subjects. The participants in the study were from three remote villages of Taoyuan County and had lived in these villages for over 6 months. The shift from rural low-wage labor to metropolitan higher-paying jobs reduced the available number of indigenous men in the mountain region. Therefore, more comprehensive and meticulous consideration should be used in future studies.