This was a study to investigate the association of various non-traditional lipid parameters with pre-DM and T2DM in Chinese CHD patients. This study found that among non-traditional lipid parameters, elevated TG/HDL-C was the risk factor with the strongest correlation with the risk of pre-DM and T2DM. The TG/HDL-C was significantly correlated with glucose metabolism-related indicators (FBG, HbA1c) in different diabetic states. We also found that TG/HDL-C, among the non-traditional lipid parameters, had the highest predictive value for pre-DM and T2DM.
T2DM is a chronic metabolic disorder characterized by insufficient insulin production or IR caused by other factors . Pre-DM is the intermediate stage between NG and DM, all people with T2DM pass the pre-DM stage, and about 5–10% of pre-DM will progress to T2DM each year . Pre-DM and T2DM has been reported to be associated with the increased risk of CVD including CHD [22, 24]. Therefore, management of risk factors for pre-DM and T2DM is necessary. Glucose metabolism is closely related to lipid metabolism [25–26]. Previous studies have demonstrated the correlation of lipid parameters including TG, TC, HDL-C, LDL-C, LDL-C/HDL-C, non-HDL-C, TC/HDL-C with pre-DM and DM [27–30]. Among them, TG and HDL-C have been considered as important risk factors for the development of cardiovascular disease (CVD) in Asians [31–32]. As a product of these two, the potential clinical significance of TG/HDL-C has been widely explored. Recent study pointed out that TG/HDL-C was associated with insulin resistance, suggesting that it may be a potential tool for identifying patients with diabetes . Then, it has been demonstrated that TG/HDL-C is a good predictor of lipid metabolism in DM compared to other lipid parameters in the study by Z Bai et al. . However, data on the association between TG/HDL-C and pre-DM are limited. Our study found that TG/HDL-C is not only a good predictor of T2DM, but also had a significant association with pre-DM.
The association of TG/HDL-C with pre-DM and T2DM may be explained by the following reasons: TG elevated results in increased free fatty acids (FFA) reduce insulin sensitivity , continued exposure to free fatty acids due to TG may reduce AMP-activated kinase protein activity and increase TG accumulation, leading to changes in pancreatic α-cell insulin signaling and hypersecretion of glucagon , thereby creating a vicious cycle between TG levels and insulin resistance. It leads to impaired glucose tolerance and the development of pre-DM and T2DM. At the same time, HDL protected β cells from cytokine- or glucose-induced apoptosis through two components including ApoA1 (the major protein component of HDL) and S1P. Decreased HDL-C levels affect beta-cell function or survival, which has a regulatory role in the pathogenesis of T2DM [37–39]. What’s more, the combination of high TG and low HDL-C, known as atherogenic dyslipidemia, is also a strong risk factor for CHD. Therefore, as a ratio of the two (TG and HDL-C), the TG/HDL-C ratio was considered as a potential predictive marker of insulin resistance and β-cell dysfunction. It is closely associated with pre-DM and T2DM as well as the development of CVD [40–42]. This study also examined the association of TG/HDL-C with pre-DM and T2DM for sex, age and lifestyles including smoking and drinking, as IR changes with these factors [17, 43–44]. Unlike our finding that TG/HDL-C was associated with pre-DM and T2DM at different ages and in both sexes but stronger in women and in CHD people over 60, Ji Xiao-Wei et al.  found no correlation between TG/HDL-C and DM in women. Studies pointed out that in men, the increase in TG/HDL-C ratio was more pronounced in DM in middle-aged patients . The key factors contributing to this gender and age difference may be hormone levels and risk factors such as smoking, alcohol consumption, physical activity [47–48]. Also, the anabolism is significantly lower in the elderly compared with middle-aged-onset patients. Elderly-onset T2DM patients have relatively preserved β-cell function and higher IR . Furthermore, while previous studies have demonstrated a high prevalence of IR and T2DM in smokers and drinker , the univariate analysis in this study found that smoking was only associated with pre-DM but not T2DM, and that drinking was not associated with pre-DM and T2DM. The present study also found that the association of TG/HDL-C with pre-DM and T2DM was not affected by smoking and drinking status. The reason for this difference may be the effect of the level of smoking and alcohol consumption e.g., light, moderate, heavy, which indicates that further longitudinal studies may be required as a validation.
FBG and HbA1c are important indicators of glycemic control status and diagnosis of T2DM , and the UK Prospective Diabetes Study has shown that effective control of blood FBG and HbA1c is beneficial to the long-term prognosis of patients with DM including T2DM . Therefore, we confirmed the association of TG/HDL-C with FBG and HbA1c and examined this association in NG, pre-DM and T2DM populations, which indicated that TG/HDL-C may be a viable biochemical predictor of glycemic control and be used to aid in the definitive diagnosis of diabetes in the future.
Based on these results, we believe that early identification of non-traditional lipid parameters, including TG/HDL-C, is essential to guide the accurate prevention of pre-DM and T2DM, so we finally tested the predictive value of non-traditional lipid parameters for pre-DM and T2DM and demonstrated that TG/HDL-C was a better predictor of pre-DM and T2DM than other parameters, and was an indicator that can effectively predict DM, with an AUC greater than 0.60.
This present study has some strengths. First, it used a large sample size to comprehensively analyze lipid parameters that may affect diabetic status, strong association of TG/HDL-C with pre-DM and T2DM was confirmed. It was also verified at different ages, genders and lifestyles in order to exclude the influence of potential factors on this association. Secondly, possible confounders were also included in the analysis to rule out their interference with the results. Nonetheless, this study still has some limitations. Above all, as an observational study, this study is not suitable to examine the causal relationship between non-traditional lipid parameters and pre-DM and T2DM. Next, current use of hypoglycemic agents and BMI, as important confounders, was not included in the regression model due to the missing data. We will conduct prospective cohort studies in the future to investigate causality and collect as comprehensive data as possible. Finally, as a multicenter study, there may be some unavoidable bias between centers.