We derived nationally representative data from the CHARLS and found an independent and positive relationship between the simple surrogate of IR (TyG index) and risk of new-onset diabetes in middle-aged and elderly Chinese adults. Additionally, the effects of TyG index on diabetes were not interacted by age, gender, BMI and glycemic status. The associations between TyG index and incident diabetes were more pronounced in the elderly, women, individuals with obesity, and prediabetic subjects.
Our results were consistent with previous studies that indicated a linear relationship between TyG index and risk of diabetes. A recent study involving 4,285 middle-aged and elderly Korean adults with BMI < 25 kg/m2 found a positive association of TyG index and diabetes after 12 years of follow-up. Similarly, in lean Chinese individuals, Zhang et al. suggested that TyG index was predictive of incident diabetes. The authors claimed that lean people were more likely to be comorbid with hypertriglyceridemia because of lacking subcutaneous fat, leading to subsequent IR and β-cell dysfunction . In a White European population, Navarro-Gonzalez et al. reported that the risk of developing diabetes was increased by 54% for per SD increase of TyG index, and the authors also suggested that TyG index was a better predictor of diabetes than TG or FBG separately .
In the subgroup analyses, we found that the positive relationship between TyG index and diabetes was more evident in elderly, women, obese or prediabetic individuals. The reasons could be explained as follows. Visceral adiposity tissue increases with age and may lead to the higher incidence and risk of diabetes . In addition, the higher hepatocellular lipids in women may contribute to the increased risk of diabetes . Moreover, a recent study showed that TyG was an important mediator in the BMI-related diabetes development in both obese and non-obese individuals . Another retrospective study of 2,900 Korean adults reported that TyG index of 8.8 or higher significantly increased the risk of type 2 diabetes regardless of BMI range . Finally, prediabetes is more likely related to IR than normoglycemia, which explains the more pronounced risk of developing diabetes in this population [24–26].
Several mechanisms have been reported to explain the predictive value of TyG index for the development of diabetes. On the one hand, increased TG level in the blood contributes to the inhibitory insulin activity, production of inflammatory cytokines, and muscle catabolism while overloaded TG in the pancreatic islet cells disrupts the β-cell function . On the other hand, elevated glucose concentrations exert toxic effects on β-cells by raising reactive oxygen species . These mechanisms have been confirmed in an intervention study indicating that the capacity of insulin secretion and IR status were improved by reduce TG and FBG level . As the product of TG and FBG, high TyG index reveals both seriously decreased β-cells and increased IR, which are considered to be the major events of incident diabetes . Despite this, more mechanistic researches need to be conducted in different ethnic populations to reveal the difference and consistency of the role of TyG in the development of diabetes in order to better guide clinical practice.
Our findings have a few clinical implications. First, TyG index was recently reported to be superior to traditional predictors of IR and diabetes such as TG/HDL-C and HMOA-IR . Second, several studies have shown that TyG index improved prediction of diabetes compared with FBG or TG itself, as well as single other lipid markers such as TC, LDL-C, and HDL-C cross different ethnic groups [12, 32, 33]. Third, TyG index is a simple, inexpensive and routine indicator and is suitable for clinical practice. Finally, and most importantly, monitoring the TyG index can help identify people at high risk of developing diabetes, even though their FBG or TG is not high or is at a borderline high level. For this group of people, timely lifestyle and diet adjustments are crucial .
The strength of the current research was to include a nationally representative sampling design, rigorous and standard protocol for data collection and follow-up, which made our results of prospective relationship more reliable. However, some limitations should be considered for cautious interpretation. First, despite we have fully adjusted for many risk factors, residual confounding might exist due to unrecognized confounders such as physical activity and family history of diabetes. Second, 2 h oral glucose tolerance test was not included to detect cases of diabetes, which might underestimate the incidence of diabetes. Third, the follow-up time was relatively short. Longer duration of follow-up is needed to further verify our results. Finally, all participants were Chinese people aged 45 years or older, caution should be made when interpreting our findings in younger individuals and in other ethnic populations.