Cardiovascular disease is strongly associated with diabetes. Compared with nondiabetic patients, patients with T2DM have a double risk of developing cardiovascular diseases[11]. The FPG level is increased by 1 mmol/L (18 mg/dL), and the risk of a cardiovascular event or death increases by 17%[12]. There are some common risk factors for diabetic vascular change and arteriosclerosis, which is caused by other reasons, such as aging, gender, obesity, hyperlipidaemia and hypertension. Diabetes is pathophysiologically characterised by insulin resistance, hyposecretion and hyperglycaemia; diabetic vascular changes are also closely related to it.
The population in the present study comprised patients screened for T2DM and prediabetic patients. The results of the study showed statistically significant differences between the new-onset T2DM and prediabetic groups and the NGT group in terms of age, SBP, FPG, 2hPG, 2hINS and HOMA-IR. However, 2hINS showed an increasing trend, suggesting that the older the age, the higher the incidence of diabetes. The insulin resistance of patients with new-onset diabetes was higher than that of prediabetic patients. The 2hINS was the highest in prediabetic patients, indicating that the delayed insulin secretion in prediabetic patients might be more significant than that in patients with diabetes.
This study used the recognised non-invasive indicators of baPWV and ABI and the cell biological marker FGF21 to reflect early arteriosclerosis. The baPWV was higher in the new-onset diabetic group compared with the prediabetic group, and in the prediabetic group compared with the NGT group. Statistically significant differences in the FGF21 were observed among the three groups: it was higher in the new-onset diabetic group compared with the NGT group, but no significant differences were noted between the prediabetic group and the other two groups. Moreover, no significant difference in the ABI was found among the three groups. Further correlation and regression analyses showed that besides age, the blood glucose and HOMA-IR were closely related to the baPWV and the ABI. The baPWV, as a method for detecting arterial stiffness, has been widely used in the early assessment and prediction of arteriosclerotic diseases. It is a specific and sensitive indicator reflecting vascular aging. Some previous studies have confirmed a significant increase in the baPWV in patients with T2DM, but related studies on baPWV in prediabetic and new-onset diabetes populations are few. Some studies reported baPWV in patients with impaired fasting glucose (IFG). A study by Ohnish et al.[13] on the Japanese population found an increase in baPWV in IFG populations compared with individuals with the ideal blood glucose level. Lukich et al.[14] analysed the effect of IFG on carotid and radial arterial PWV in the Caucasus population and found an increase in PWV in the IFG group compared with the group with the ideal blood glucose level.
In this study, the insulin resistance index and the baPWV in prediabetic patients increased significantly, suggesting that diabetic vascular disease might occur in prediabetes. Besides the progression to diabetes at a rate of 5–10% per year for the prediabetic population, an abnormal glucose metabolism can increase the risk of macrovascular complications, such as coronary heart disease and stroke[11]; it also increases total mortality and cardiovascular disease mortality[15, 16]. Prediabetic patients have a significantly increased risk of macrovascular complications. The mechanism is related to hyperinsulinaemia, insulin resistance, dyslipidaemia, abnormal blood pressure, vascular endothelial dysfunction, oxidative stress and an inflammatory response in this population.
Insulin resistance is considered to be the common pathophysiological basis of metabolic disorders and cardiovascular diseases. It is also an important cause of atherosclerosis. Furthermore, atherosclerosis is the pathological basis for patients with diabetes and nondiabetic patients, including those with multiple cardiovascular and cerebrovascular diseases, such as myocardial infarction and stroke. Animal experiments and clinical studies have demonstrated that vascular calcification and arteriosclerosis are associated with insulin resistance, which promotes vascular calcification[17–19]. The mechanism of insulin resistance is that the metabolic signalling pathway of IRS/PI3K/Akt is impaired, while the growth signalling pathway of Shc/Ras/MAPK is compensatorily enhanced. The metabolic signalling pathway has an anti-atherosclerotic effect, while the growth signalling pathway has an atherogenic effect. The impaired metabolic signalling pathway is the initial factor during insulin resistance, which promotes the compensatory enhancement of the growth signalling pathway. Both have synergistic effects and comprise a self-enhanced vicious cycle process. This study showed that HOMA-IR positively correlated with the ABI and was an independent risk factor for the ABI and the baPWV, suggesting that insulin resistance was closely related to arteriosclerosis.
Previous studies have shown that the serum FGF21 levels are significantly elevated in patients with T2DM[20, 21]. This study found that the FGF21 levels were elevated in patients with prediabetes and new-onset diabetes. Recent studies have revealed that FGF21 protects against lipotoxicity-induced pancreatic β-cell dysfunction by regulating AMP-activated protein kinase (AMPK) signal transduction and lipid metabolism[22]. Therefore, it is considered that an increase in the FGF21 levels in patients with diabetes is a compensatory increase. FGF21 is preferentially produced in the liver but has been identified as an endocrine and metabolic hormone due to its effects on lipids, glucose metabolism, insulin sensitivity and energy balance[23]. Studies have found that the serum FGF21 levels are significantly elevated in patients with carotid atherosclerotic plaques[24]. Chow et al.[25] proposed that FGF21 was independent of known cardiovascular risk factors, and its serum level positively correlated with carotid atherosclerosis. In animal and in vitro studies, FGF21 has been shown to improve lipid distribution and inhibit key processes of the pathogenesis of atherosclerosis. It acts on the cardiovascular system through adiponectin-dependent and adiponectin-independent mechanisms[26]. Yan et al.[9] found that FGF21 protected cells from premature aging induced by H2O2 by delaying the replicative senescence of the endothelial cells. This study suggested that FGF21 positively correlated with baPWV and was an independent risk factor for baPWV.
This study found no significant differences in the ABI levels among the three groups. This was probably because the study population comprised individuals screened for prediabetes and new-onset diabetes. The age range was 30–70 years for the study population.
It is estimated that 45.8% (174.8 million) of patients with adult-onset diabetes are undiagnosed worldwide, and the proportion is 24.1–75.1% in different countries[27]. Multiple studies have shown that combining the early detection of undiagnosed diabetes with effective prevention, health examinations or opportunistic screening methods, early identification of patients with abnormal glucose metabolism and timely interventions can help prevent and delay diabetic complications[28, 29].