This report explored the relationship between TG/HDLC and T2DM. The correlation between TG/HLD-C and T2DM has been investigated in several studies on populations in different regions of China, and their studies[12, 13] showed a non-linear connection between TG/HDL-C and diabetes events. This is consistent with our finding. Unexpectedly, in this study, T2DM showed a J-shaped relationship with baseline TG/HDL-C after adjusting for confounders gender, age, exercise habits, BMI, fatty liver, total cholesterol, FPG, HbA1c, alcohol consumption, and smoking status (Table 4 and Fig. 1). In addition, we calculated a threshold value of 0.35 for TG/HDL-C by threshold effect analysis. It's worth noticing that the link between TG/HDL-C and T2DM had the opposite effect on different sides of threshold value. Participants had the lowest risk of T2DM when TG/HDL-C was approximately 0.35, and when TG/HDL-C was lower than 0.35, TG/HDL-C was negatively linked with T2DM. However, the risk was not statistically significant (HR 0.27, 95%CI 0.01–6.55, P-value 0.4234). When TG/HDL-C > 0.35, there was a positive association between TG/HDL-C and the risk of diabetes, suggesting that the risk of diabetes is increased with either a high or low TG/HDL-C. However, the J-shaped association between TG/HDL-C and T2DM and the mechanisms behind the threshold value are unclear. The issue has significant physiological and clinical implications based on the impact of dyslipidemia on diabetes.
According to studies, disorders of lipid metabolism have a major role in the development of T2DM, and the impact of dyslipidemia on developing type 2 diabetes cannot be ignored [5, 26–28]. Elevated triglycerides decrease insulin sensitivity and increase the risk of developing diabetes[29–31], while high-density lipoprotein cholesterol plays a protective role[32]. Elevated plasma triglycerides and decreased HDL-C are danger markers and predictors of diabetic events and insulin resistance in the population[33]. It was shown that elevated triglycerides, TG/HDL-C and decreased HDL-C can contribute to the onset and progression of diabetes[34]. The ratio of TG/HDL-C is a relatively easy, convenient, and low-cost indicator obtained during routine clinical care or physical examination and is considered by some authors to be a highly sensitive and specific predictive indicator of diabetes.[27, 34]. TG/HDL-C is better than TG or HDL-C alone on predicting diabetes risk[34]. Therefore, it is more than recommended to use TG/HDL-C for predicting impaired beta-cell and insulin resistance[35–39]. Studies have reported that the predictive function of TG/HDL-C for diabetes is race-specific, and it has been suggested that TG/HDL-C could be a useful predictive indicator for diabetes in Chinese Singaporean, Hispanic, and African American, as well as Chinese populations[16, 17, 37, 40]. We reviewed the relevant literature and found several studies that associated TG/HDL-C with T2DM. Liu's research team and Kim's research team noted a close connection between the TG/HDL-C and T2DM [13, 19]. A cohort study of 114,787 Chinese participants showed a positive relationship between TG/HDL-C and diabetes risk, using subjects in the lowest quartile of TG/HDL-C as a reference, subjects in the highest quartile of TG/HDL-C were more susceptible to acquiring T2DM[13]. Similar results were found by Uruska et al. for the study of the TG/HDL-C ratio to assess IR in patients with type 1 diabetes[41]. Our results also show that TG/HDL-C is positively associated with the risk of T2DM by a proportional hazards model, and their relationship remains positive after adjusting for different confounders, and the results suggest an independent relationship between them.
Glucose and lipid metabolism are influenced by various factors, and it remains controversial whether TG/HDL-C was correlation with diabetes differs between genders.Liu et al. showed that the results of subgroup analysis indicated that the correlation of TG/HDL-C ratio on the incidence of T2DM was not significantly different between genders, with a P-value of 0.53 for their interaction[12]. Similarly, a cohort study by Chen et al. showed the same results for gender-specific subgroups, with P = 0.058 for their interaction[13]. To investigate the differences between Japanese men and Japanese women in the association of TG/HDL-C withT2DM, we performed a subgroup analysis in this study (Table 5). Our study showed a non-significant difference in TG/HDL-C and T2DM between genders, female (HR = 1.26, P = 0.06) vs. male (HR = 1.19, P < 0.01), with a P-value of 0.65 for the interaction.
Our findings show there was no significant difference in the risk of diabetes with increased TG/HDL-C by gender in the Japanese population. And the finding indicated with increased TG/HDL-C that the risk of diabetes was consistent between genders in the Japanese population. However, other studies have obtained different results: for example, some studies in Iranian, Chinese, Chinese Singaporeans, and Japanese populations suggest that the correlation between TG/HDL-C and T2DM as significantly higher in females than in males[17, 19, 20, 42]. Another study concluded that high TG/HDL-C was an influential factor in incident diabetes in men participants and that TG/HDL-C was available to infer the risk of T2DM in male, but their study did not include female participants[43]. Qin et al. investigated the effect of TG/HDL-C on diabetes in Chinese adults and whether there were differences between genders and discovered that the correlation between TG/HDL-C and diabetes was independent[40]. This association was significant only in Chinese adult males.[40]. Similarly, Zhang et al. reported that the trajectory of TG/HDL-C was only observed to be correlated with the progression of diabetes in men, but not in women[16]. Whether gender affects the relationship between lipid metabolism and diabetes can be further investigated
Our study has several strengths. First, this investigation is the first to show a J-shaped correlated between baseline TG/HDL-C and T2DM risk. Second, this is a large cohort study, involving a relatively large number of people, and is highly representative of the Japanese population. Third, to improve the stability of the results, we analyzed TG/HDL-C as categorical and continuous variables, respectively. Fourth, to explore the impact of baseline TG/HDL-C on T2DM in different populations, a subgroup analysis was conducted in this study.
Despite its strengths, the study has some limitations. First, some covariates were not available in the study due to the limitations of the original study data; therefore, residual confounding may be present in this study. Second, this investigation did not distinguish between types of diabetes mellitus. But, type 1 diabetes is not extremely common in the Japanese population[44]. Therefore, we inferred that almost all new-onset diabetes in this study was T2DM. Third, in this investigation, oral glucose tolerance tests were not used to screen for T2DM, so the findings may have underestimated the risk of developing T2DM. Fourth, given that T2DM prevalence is associated with race and region, and the study population in this study was Japanese, this result is not necessarily generalizable to populations outside of Japan.