3.1 Baseline characteristics of the study population
116855 participants without diabetes at baseline were included, with an average age of 44.08 ± 12.93. Among these subjects, 62868 (53.8%) were males, during a median follow-up year of 2.98, 2685 (2.30%) developed incident diabetes. The baseline characteristics of the population were compared and presented in Table 1. In comparison with nondiabetic subjects, diabetic subjects tended to be older, had higher levels of SBP, DBP, FPG, TG, TC, LDL-c, ALT, AST, BUN, Sc, and lower HDL-c levels at baseline levels. Furthermore, participants with diabetes were more likely to have smoking and drinking behavior, and a diabetes family history (p < 0.05). In addition, TG/HDL-c, TyG, and TyG-BMI were all higher in the diabetes group (p < 0.001) (Table 2).
Table 1
Baseline and laboratory characteristics of participants with and without diabetes
Variables | Total (n = 116855) | Diabetes (n = 2685) | Non-diabetes (n = 114170) | p value |
Age, years | 44.08 ± 12.93 | 56.63 ± 16.62 | 43.78 ± 12.79 | < 0.001 |
Male, n (%) | 62868 (53.8%) | 1890 (70.4%) | 60978 (53.4%) | < 0.001 |
BMI, kg/m2 | 23.35 ± 3.30 | 26.03 ± 3.43 | 23.28 ± 3.27 | < 0.001 |
Current smoker, n (%) | 547 (0.5%) | 22 (0.8%) | 525 (0.5%) | 0.007 |
Current drinker, n (%) | 878 (0.8%) | 31 (1.2%) | 847 (0.7%) | 0.014 |
Family history of diabetes, n (%) | 2640 (2.3%) | 99 (3.7%) | 2541 (2.2%) | < 0.001 |
SBP, mmHg | 119.43 ± 16.67 | 131.95 ± 18.76 | 119.13 ± 16.51 | < 0.001 |
DBP, mmHg | 74.45 ± 10.97 | 80.57 ± 11.92 | 74.29 ± 10.91 | < 0.001 |
FPG, mg/dl | 4.95 ± 0.61 | 5.92 ± 0.71 | 4.92 ± 0.58 | < 0.001 |
TG, mmol/L | 1.10 (0.76–1.66) | 1.70 (1.17–2.50) | 1.10 (0.76–1.64) | < 0.001 |
TC, mmol/L | 4.79 ± 0.90 | 5.07 ± 0.95 | 4.78 ± 0.89 | < 0.001 |
HDL-c, mmol/L | 1.37 ± 0.30 | 1.29 ± 0.34 | 1.38 ± 0.30 | < 0.001 |
LDL-c, mmol/L | 2.77 ± 0.68 | 2.90 ± 0.70 | 2.77 ± 0.68 | < 0.001 |
ALT, U/L | 18.10 (13.00-27.60) | 25.00 (17.00–38.00) | 18.00 (13.00-27.20) | < 0.001 |
AST, U/L | 22.00 (18.60–26.80) | 25.00 (21.00-31.70) | 22.00 (18.60–26.60) | < 0.001 |
BUN, mmol/L | 4.69 ± 1.12 | 5.01 ± 1.29 | 4.68 ± 1.17 | < 0.001 |
Scr, µmol/L | 70.34 ± 15.81 | 73.08 ± 16.43 | 70.27 ± 15.80 | < 0.001 |
Data were presented as mean ± SE or median (IQR) for continuous variables or numbers (percentages) for categorical variables. BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; TG, triglyceride; TC, total cholesterol; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; Scr, serum creatinine. |
Table 2
Insulin resistance indices of participants with and without diabetes
Variables | Total (n = 116855) | Diabetes (n = 2685) | Non-diabetes(n = 114170) | p value |
TG/HDL-c | 0.82 (0.52–1.34) | 1.36 (0.87–2.18) | 0.81 (0.52–1.32) | < 0.001 |
TyG | 8.41 ± 0.61 | 9.01 ± 0.61 | 8.40 ± 0.61 | < 0.001 |
TyG-BMI | 197.29 ± 36.96 | 234.98 ± 37.72 | 196.41 ± 36.48 | < 0.001 |
TG/HDL: triglyceride to high-density lipoprotein ratio, TyG: triglyceride-glucose, TyG-BMI: triglyceride glucose-body mass index. |
3.2 The T2DM incidence rate in subjects with different levels of IR parameters
2685 of 116855 subjects developed T2DM during the follow-up of 362268.4 person-years, the overall incidence rate of T2DM was 7.41 cases/1000 person-years. Participants were then divided into four quartiles based on the baseline value of TG/HDL-c, TyG, and TyG-BMI. Notably, T2DM incidence rate dramatically increased with the quartiles of these IR indicators increasing. The T2DM incidence rate had reached 14.85, 18.79, and 19.15 per 1000 person-years in the 4th quartile (Table 3, Fig. 2).
Table 3
Incidence rate for the development of T2DM by TG/HDL-c, TyG and TyG-BMI
Variables | | | | |
TG/HDL-c | Q1 | Q2 | Q3 | Q4 |
No. of cases | 193 | 413 | 715 | 1364 |
No. of person-years | 90472.84 | 89761.55 | 90173.71 | 91860.34 |
Incidence rate* | 2.13 | 4.60 | 7.93 | 14.85 |
TyG | Q1 | Q2 | Q3 | Q4 |
No. of cases | 107 | 266 | 634 | 1678 |
No. of person-years | 93157.98 | 90491.09 | 89339.53 | 89279.84 |
Incidence rate* | 1.15 | 2.94 | 7.10 | 18.79 |
TyG-BMI | Q1 | Q2 | Q3 | Q4 |
No. of cases | 99 | 232 | 630 | 1724 |
No. of person-years | 91430.24 | 90761.2 | 90300.48 | 90008.52 |
Incidence rate* | 1.08 | 2.56 | 6.98 | 19.15 |
* per 1000 person-years. TG/HDL: triglyceride to high-density lipoprotein ratio, TyG: triglyceride-glucose, TyG-BMI: triglyceride glucose-body mass index. |
3.3 Univariate analysis of incident T2DM
Univariate analysis of risk factors for T2DM are displayed in Table 4. Positive associations were found between age, male, BMI, smoking, drinking, diabetes family history, SBP, DBP, FPG, TG, TC, LDL-c, ALT, AST, BUN, Scr, and T2DM (p < 0.05), while negative correlation was found between HDL-c and T2DM risk (HR = 0.575, 95% CI: 0.506–0.654, p < 0.001). Of note, these three IR parameters were all positively correlated with T2DM.
Table 4
Univariate analysis of incident T2DM
Variables | HR | 95% CI | P value |
Age | 1.064 | 1.062–1.067 | < 0.001 |
Male | 2.017 | 1.856–2.191 | < 0.001 |
BMI | 2.222 | 2.212–2.233 | < 0.001 |
Smoking | 1.659 | 1.090–2.524 | 0.018 |
Drinking | 1.738 | 1.220–2.476 | 0.002 |
Family history of diabetes | 1.403 | 1.148–1.715 | 0.001 |
SBP | 1.037 | 1.035–1.039 | < 0.001 |
DBP | 1.042 | 1.039–1.045 | < 0.001 |
FPG | 9.982 | 9.452–10.542 | < 0.001 |
TG | 1.260 | 1.245–1.275 | < 0.001 |
TC | 1.338 | 1.239–1.390 | < 0.001 |
HDL-c | 0.575 | 0.506–0.654 | < 0.001 |
LDL-c | 1.348 | 1.281–1.419 | < 0.001 |
ALT | 1.004 | 1.004–1.004 | < 0.001 |
AST | 1.006 | 1.005–1.007 | < 0.001 |
BUN | 1.213 | 1.182–1.244 | < 0.001 |
Scr | 1.007 | 1.006–1.008 | < 0.001 |
TG/HDL-c | 1.245 | 1.229–1.262 | < 0.001 |
TyG | 3.851 | 3.662–4.050 | < 0.001 |
TyG-BMI | 1.022 | 1.022–1.023 | < 0.001 |
HR: hazard ratio; CI: confidence interval; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; TG, triglyceride; TC, total cholesterol; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; Scr, serum creatinine; TG/HDL: Triglyceride to high-density lipoprotein ratio, TyG: triglyceride-glucose, TyG-BMI: triglyceride glucose-body mass index. |
3.4 The association between IR indicators and T2DM
Cox regression analyses were conducted to assess the impact of three IR parameters on the incidence of T2DM (Table 5). Three models (crude model, partially and fully-adjusted model) were constructed to evaluate the effect of IR indicators on T2DM. The covariates in fully-adjusted model 3 were selected from the results of univariate analysis, which included age, sex, BMI, smoking and drinking history, diabetes family history, SBP, DBP, ALT, AST, BUN, and Scr. 1.177 (95% CI: 1.140–1.216, p < 0.001), 2.776 (95% CI: 2.551–3.020, p < 0.001), and 1.108 (95% CI: 1.016–1.019, p < 0.001) fold risk for developing T2DM were found in subjects with one-unit increase of TG/HDL-c, TyG, and TyG-BMI in model 3.
Table 5
Multivariate-adjusted hazard ratios of TG/HDL-c, TyG, and TyG-BMI for incident T2DM during follow-up.
Variables | Model 1 | | Model 2 | | Model 3 | |
| HR (95% CI ) | P value | HR (95% CI ) | P value | HR (95% CI ) | P value |
TG/HDL-c | 1.245(1.229–1.262) | < 0.001 | 1.218(1.197–1.238) | < 0.001 | 1.177 (1.140–1.216) | < 0.001 |
TyG | 3.851(3.662–4.050) | < 0.001 | 3.213 (3.038–3.399) | < 0.001 | 2.776 (2.551–3.020) | < 0.001 |
TyG-BMI | 1.022(1.022–1.023) | < 0.001 | 1.020 (1.020–1.021) | < 0.001 | 1.018 (1.016–1.019) | < 0.001 |
HR: hazard ratio; CI: confidence interval. Model 1: unadjusted. Model 2: adjusted for age, sex, smoking history, drinking history, and family history of diabetes. Model 3: adjusted for age, sex, BMI, SBP, DBP, smoking history, drinking history, family history of diabetes, ALT, AST, BUN, and Scr. |
TG/HDL-c, TyG, and TyG-BMI values were categorized into 4 quartiles as follows: TG/HDL-c: Q1 (≤ 0.52), Q2 (0.52–0.82), Q3 (0.82–1.34), and Q4 (> 1.34); TyG: Q1 (≤ 7.97), Q2 (7.97–8.37), Q3 (8.37–8.81), and Q4 (> 8.81); TyG-BMI: Q1 (≤ 169.19), Q2 (169.19-193.88), Q3 (193.88-221.19), and Q4 (> 221.19). The risk for T2DM increased dramatically with the increasing quartiles of these IR parameters (Fig. 3). Compared with the 1st quartile, participants in the 4th quartile of TG/HDL-c, TyG, and TyG-BMI had 3.298 (95% CI: 2.615–4.610), 8.402 (95% CI: 6.176–11.429), and 8.468 (95% CI: 6.157–11.646) fold risk for incident T2DM, respectively (p < 0.001). The cumulative T2DM incidence in participants with different levels of IR was compared using Kaplan-Meier curves. As shown in Fig. 4, the cumulative incidences of T2DM were remarkably different among these quartiles (Log-rank test, p < 0.001). The nonlinear association between these three IR indicators and T2DM was evaluated by RCS and presented in Fig. 5 (p for overall < 0.001, p for nonlinear < 0.001).
3.5 Stratification analysis
Subgroup stratification analyses by age and gender was then performed to assess the effect of age and sex on the relationship between IR and diabetes. As displayed in Fig. 6, significant interactions between TyG and T2DM risk were observed between sex subgroups (p for interaction = 0.043). In addition, The association between IR and T2DM differs between age ≥ 40 and age < 40 group. The correlations between these three IR parameters and T2DM were more pronounced in subjects aged less than 40. One-unit increase of TG/HDL-c, TyG, and TyG-BMI were associated with 1.165, 4.207, and 1.025 fold risk for T2DM, respectively.
3.6 ROC
Predictive value of IR indicators in the identification of T2DM
ROC curves were constructed to assess the predictive value of these three IR-associated parameters for T2DM, respectively. The area of the curve (AUC) and 95% confidence interval, cut-off value, corresponding sensitivity, and specificity are listed in Table 6 and Fig. 7. Among these three IR parameters, TyG-BMI had the highest AUC for predicting T2DM, with a cut-off value of 213.289.
Table 6
ROC curve analysis of the insulin resistance parameters in predicting T2DM
Variables | AUC | 95%CI | Cut-off value | Sensitivity | Specificity |
TG/HDL | 0.699 | 0.696–0.702 | 1.009 | 0.678 | 0.624 |
TyG | 0.765 | 0.763–0.768 | 8.567 | 0.777 | 0.631 |
TyG-BMI | 0.774 | 0.772–0.777 | 213.289 | 0.726 | 0.695 |
TG/HDL: triglyceride to high-density lipoprotein ratio, TyG: triglyceride-glucose, TyG-BMI: triglyceride glucose-body mass index. |