Previous studies have shown that the HOMA-β value of patients newly diagnosed with T2DM was only half of the normal value, and it decreased progressively at a rate of 4.5% annually and deteriorated with the course of the disease19. Therefore, the HOMA-β value of CHB patients under NGT condition was lower than that of non-HBV patients who were newly diagnosed with T2DM.
A new staging method for NGT, IGR, and DM was proposed according to the function of β cells: normal phase of β cell function, compensatory phase of β cell function, decompensated phase of β cell function, and failure phase of β cell function in the general population. The compensatory secretion of β cell function occurs in individuals with NGT and IR and reaches the peak of compensatory secretion. The decompensation of β cell function has occurred in individuals with prediabetes20. In recent years, most studies have confirmed that not all individuals with NGT were healthy and that some presented with IR21. The risk of developing prediabetes and/or T2DM significantly increased in individuals with NGT, but not in those with IR and dysfunction of β cell secretion22.
However, the βcell function of the CHB population will directly go to decompensated and failure phases, without undergoing normal and compensatory phases, even under NGT condition, and this phenomenon leads to higher FPG levels and high prevalence of IGR and DM in the CHB population. The evident increase in the FPG level in CHB patients was associated with worsening β cell function compared with non-HBV patients but with similar glycometabolism status.
Generally, in patients with CHB, the HOMA-β value gradually decreased and the FPG levelgradually increased along with the deterioration of glucose metabolism. Therefore, the comparisonof HOMA-β value between CHB and non-HBV patients was conducted under similar glucose metabolism conditions.
Previous studies have found that chronic liver inflammation and fibrosis caused by HBV infection are associated with some indicators of glycometabolism: CHB patients with mild liver dysfunction had high serum insulin levels and HOMA-IR values. A correlation analysis has shown that ALT was positively correlated to IR. However, HBV DNA load was not correlated to IR. A regression analysis has indicated that ALT wasan independent risk factor of IR in patients with mild liver dysfunction23,24. A pathological study has found that the FINS level and HOMA-IR value of CHB patients with G3 grade inflammation are higher than those of patients with G2 grade inflammation, and the FINS level and HOMA-IR value of CHB patients with S3 grade fibrosisare higher than those of patients with S2 grade fibrosis. Moreover, HOMA-IR was positively correlated to ALT25. When the duration of HBV is longer, patients aremore likely to develop IR and abnormal glucose metabolism10,11. When glutamic transpeptidase(GGT) is less than the 1.5-fold upper limit of the normal value, IR is not observed. When the value is 1.5–2 fold than the upper limit of the normal value, IR is most significant. However, it decreases with the increase in GGT level26. The secretory function of islet β cells in patients with hepatitis B cirrhosis is normal, and IGT to a certain extent is observed. In CHB patients, the secretory function of islet β cells decreased significantly9. In particular, when the GGT level is 1.5–2 times higher than the normal value26, the steady-state model had the lowest HOMA-β value, with an average of only 20.34mIU/mmol. With the increase in GGT level, the HOMA-β value was more likely to increase26.
Fundamental studies have found that HBV infection can increase the production of tumor necrosis factor(TNF). The over production of TNF can decrease the phosphorylation of insulin receptor substrates 1 and 2, inhibit phosphoinositol 3-kinase and protein kinase B, block the phosphorylation of glucose transporter 4, and preventthecell uptake of glucose27,28 and increase in blood glucose level. Prostate six-transmembrane protein 2(STAMP2) is a factor associated with inflammation and dietary adipocyte function and system metabolism. It can be induced by nutrition, feeding, and cytokines, such as TNF alpha, interleukin (IL)-1β, and IL-6, which can inhibit IR in rats. IR and visceral and hepatic insulin signaling disorders were observed in mice lacking STAMP2. In the presence of inflammation and obesity, the increased expression of STAMP2 has protective effects against insulin signaling in the liver29. Moreover, HBV X protein induces liver fat accumulation and IR by reducing the expression of STAMP2. STAMP2 down-regulates the insulin-induced phosphorylation of P3K p85 subunit and protein kinase and the expression of insulin receptor substrate 1, and the post-transcriptional level of insulin receptor substrate 1 plays a role30, which leads to the increase in blood glucose levels.
Although basic studies have confirmed that HBV infection can lead to increased hepatic glucose output and IR, it cannot explain the decrease in HOMA-β value and FINS level. Further basic studies have indicated that HBV infection affects the function of islet cells in CHB patients.
This case-control study first compared the differences in HOMA-β value and FPG level between CHB patients and non-HBV patients matched according to gender, age and BMI. Results showed that the HOMA-β value of CHB patients was significantly lower than that of non-HBV patients under NGT and the normal value, and was lower than that of non-hepatitis B patients under the same glycometabolism condition. However, the FPG level of CHB patients was significantly higher than that of non-hepatitis B patients.
The present study had some limitations. The sample size was small, and a single-center and retrospective study, rather than a multicenter and prospective study, was conducted.