Our findings add to the evidence that early events of continuums of diabetes and cardiovascular disease are already present in adolescents, showing an association between the Insulin Resistance Phenotype and the Vascular Risk Phenotype in both sexes. The Insulin Resistance Phenotype was also an indirect association pathway between higher values of fat mass index and the Vascular Risk Phenotype. Harmful use of alcohol was directly associated with the Insulin Resistance Phenotype and indirectly associated with the Vascular Risk Phenotype through the pathway of increased values of the Insulin Resistance Phenotype.
The Insulin Resistance Phenotype showed high convergent validity (standardized coefficient SC > 0.7) for the indicators TG-HDL ratio, TyG index and VLDL concentrations in both sexes. The increase in triglycerides is the crucial event in the alteration of insulin sensitivity, already observed in white adipose tissue  and the liver . The TG-HDL ratio has been identified as an early marker of insulin resistance, capable of predicting Type 2 Diabetes . Furthermore, the TG-HDL ratio is more efficient than HOMA-IR for diagnosing insulin resistance in obese young people . The TyG index is also a marker of insulin resistance based on the increase in the flow of free fatty acids from adipose tissue to the liver and increase in hepatic triglycerides, which are strong determinants of hepatic insulin resistance . Concurrently, hepatic synthesis of triglycerides results in increased production of VLDL cholesterol .
All indicators (SBP, DBP and PWV) of the latent variable Vascular Risk Phenotype had convergent validity for both sexes. These results confirm previous findings; however, using a population-based sample that was 3.85 times larger than our anterior study (n = 653) . Advantageously, the Vascular Risk Phenotype represents incipient vascular alterations linked to vascular risk in young people while not requiring the adoption of a cut-off point to address vascular risk in this population.
Higher values of fat mass index were directly associated with the Insulin Resistance Phenotype. This phenotype was an indirect pathway in the association between higher values of fat mass index with the Vascular Risk Phenotype. The increase in adipocytes results in hypoxia and consequently the accumulation of macrophages in adipose tissue, which is the primary source of inflammatory mediators that can induce insulin resistance . Oxidative stress in obesity can culminate in mitochondrial dysfunction and consequently lipid accumulation, accelerating both insulin resistance  and atherosclerosis . Insulin resistance has been explained from the lipocentric view. The collection of intramuscular lipids from the entry of fatty acids into cells inhibits the translocation of GLUT-4 to the plasma membrane, leading to the loss of insulin-dependent glucose uptake .
Higher values of fat mass index were also directly associated with the Vascular Risk Phenotype, which could be due to excess fat, leading to increased blood pressure via elevated sympathetic activity, subsequent sodium reabsorption, and peripheral vascular resistance .
The Insulin Resistance Phenotype and the Vascular Risk Phenotype were also directly associated. As a possible explanation, excessive dietary carbohydrate intake induces insulin resistance in skeletal muscle, which can promote atherogenic dyslipidemia by diverting carbohydrates used in muscle glycogen storage to de novo lipogenesis (Fig. 2), resulting in elevated plasma triglyceride, decreased HDL, elevated small and dense LDL and reduced hepatic triglyceride synthesis, and consequently, increasing VLDL . Added sugars activate hepatic lipogenesis pathways from glucose  and fructose  by increasing plasma triglyceride levels and result in dyslipidemia , insulin resistance  and type 2 diabetes  regardless of fat. Fructose induces the faster formation of fatty acids compared to glucose since it lacks hepatic feedback regulatory mechanisms , increasing de novo lipogenesis and liver fat, decreasing insulin sensitivity, regardless of weight gain , contributing to the greater secretion of VLDL .
VLDL was the indicator of the Insulin Resistance Phenotype showing the highest factor loading in both sexes, emerging in our study as an insulin resistance marker linked to cardiovascular risk in young people. Research using VLDL as a biological marker is scarcer, even though VLDL is associated with insulin resistance  and CVD . Elevated plasma triglyceride and VLDL determine greater insulin secretion in obese adolescents, regardless of initial insulin sensitivity . Insulin resistance plays an essential role in VLDL metabolism by increasing the availability of apolipoprotein B (ApoB), the primary lipoprotein of VLDL, leading to the increased hepatic synthesis of VLDL . At the same time, VLDL concentration is essential in the initiation and progression of atherosclerosis  and can manifest in young people .
Harmful use of alcohol was directly associated with the Insulin Resistance Phenotype. In addition, the harmful use of alcohol in young people was indirectly associated with the Vascular Risk Phenotype through increased Insulin Resistance Phenotype in both sexes. Excessive alcohol consumption is linked to oxidative stress, inflammatory responses  and hypertension .
More distally, higher values of Family Socioeconomic Status were associated with lower values of the Insulin Resistance Phenotype in both sexes. Higher values of Family Socioeconomic Status were also associated with lower values of the Vascular Risk Phenotype, but only in females, confirming a previous study that shows the highest cardiovascular risk and incredibly high disease burden for low-income groups . Low socioeconomic status groups have a higher risk of developing cardiovascular disease . People with lower socioeconomic status may be more vulnerable to CVD and diabetes due to material deprivation, unsanitary living conditions, limited access to high-quality health care, reduced opportunities to prevent complications, inappropriate, risky behavior such as tobacco use, unhealthy foods habits, a sedentary lifestyle and being overweight or obese . A possible explanation for this difference between the sexes in our study is that higher values of Family Socioeconomic Status were associated with higher values of fat mass index in boys. In addition, cardiovascular risk is also higher for males , which could be explained by hormonal differences, possibly linked to estrogen activities or factors associated with the X chromosome that protect vascular walls in females .
The main limitation is that the cross-sectional design did not allow us to assume a temporal link among the exploratory variables, Insulin Resistance Phenotype, and the vascular outcome. Furthermore, we cannot rule out reverse causality in shown associations, for example, the inverse pathway of the Insulin Resistance Phenotype increasing the fat mass index. Some bias may arise from losing participants from the original Cohort from birth and the necessity to open the sample at 18–19 follow-up to survey representativeness. In this respect, to guarantee the sample power fellow was opened using official Brazilian data (SINASC). In this respect, we compared some characteristics between the original cohort and new participants from SINASC (retrospective cohort) related to head of the family, economic class, monthly family income, alcohol consumption, and fat mass index; however, we did not find statistically significant differences between these populations.
The study’s strengths lie in the construction of the latent variable Insulin Resistance Phenotype aimed at reducing the measurement error of early markers of insulin resistance and test the validity of the Vascular Risk Phenotype in a population sample stratified by sex to estimate incipient vascular changes in adolescents.