Our study found that a significant positive linear dose-response association between FBG and SSBP in 2051 Chinese adults from the EpiSS study. The associations of FBG with SS prevalence or all BP changes were significantly in saline loading period but non-significantly in diuretic shrinkage period. For every IQR increase in FBG, the SS prevalence was increased by 14%, and ΔMAP1, ΔSBP1 and ΔDBP1 increased by 0.421 mmHg, 0.589 mmHg and 0.340 mmHg, respectively. Meanwhile, we detected that the ΔMAP1 increased by 0.973 mmHg and 1.449 mmHg in IFG and diabetic patients compare to NFG individuals. Furthermore, in stratified analyses, we found that the above associations were stronger in youngers (age < 60 years old), females, hypertensives, non-diabetics, non-current smokers and non-current drinkers than those in the corresponding subgroups. Our results supported that blood glucose could be an independent risk factor of SSBP.
Although the exact mechanisms underlying the relationship of the blood glucose with SSBP is unclear, several researches suggested it may be linked to insulin resistance. Insulin resistance is associated with hyperinsulinemia and hyperglycemia, under insulin resistance, the target cells fail to respond to ordinary levels of circulating insulin thus higher concentrations of insulin are required for a normal response . Meanwhile, the impairment of blood glucose uptake in muscle and an increased gluconeogenesis by the liver resulting in hyperglycemia . Hyperglycemia stimulates the reabsorption of sodium. In general, kidneys reabsorb the same amount of blood glucose as they filter each day as to prevent valuable energy from being lost in the urine. Most of the capacity for renal glucose reabsorption is provided by sodium glucose cotransporter (SGLT) 2 in proximal tubule. However, hyperglycemia could enhance the glucose filtration and increase capacity of glucose/sodium reabsorption . SGLT2 inhibitors, a kind of hypoglycemic drugs, could suppress the cotransport of glucose coupled with sodium and significantly attenuated the high salt-induced elevation of BP . Therefore, many studies performed a series of analyses to uncover the relationships between blood glucose and/or insulin resistance with SSBP.
Studies of the associations between salt sensitivity and insulin resistance have yielded contradictory results. Maaten et al.  and Dengel et al.  supported that insulin resistance was negatively correlated with salt sensitivity, but Bigazzi et al.  and Giner et al.  observed contrary results. The reasons for these apparent discrepancies are not exactly known but may be related to differences in study populations and study methods. Previous studies focusing on the association between FBG and SSBP obtained consistent results. In animal study, high sucrose diets could increase BP of SS rats , and the moderate fructose-enriched diet also stimulates salt-sensitive hypertension in rats . Somova et al. observed Dahl salt-sensitive rats significantly decreased blood glucose utilization and clearance . Ilhami et al. clarified that basal blood glucose level was significantly higher in SS than in SR rats . In human, Sharma et al. [16, 19], Egan et al.  and Galletti et al.  uncovered that the FBG was higher in SS individuals than in SR group. This study included adequate samples (n = 2051) and found that the FBG level in SS patients was significantly higher than that in SR individuals. Our analysis supported the previous findings and provided clues to the positive correlation between blood glucose and SSBP.
SSBP is also reported to be elevated in patients with diabetes . The current study observed the prevalence of diabetes in SS patients significantly higher than that in SR individuals. However, we considered that using blood glucose as a risk factor of SSBP and as the basic of preventive strategies for SS is of greater clinical significance than diabetes, since hyperglycemia plays key role in the genesis of SS in patients with type 2 diabetes . And, we found evidence of significant positive associations between FBG with prevalence of SS (OR = 1.140) or with ΔBP1 (β for ΔMAP1, ΔSBP1 and ΔDBP1 = 0.421, 0.589 and 0.340). Our results are consistent with previous reports [40, 46] and clarified that blood glucose level could be an independent risk factor for SS.
The present study further demonstrated that there were positive dose-response associations between blood glucose with SS prevalence or with ΔBP1 in 2051 participants. For every IQR increase in FBG, the SS prevalence and ΔBP1 significantly increased for a trend. It was worth noting that compared to participants with FBG < 5.00 mmol/L (Q1), both the SS prevalence and the ΔBP1 showed significantly elevated in the subjects with 5.44 ≤ FBG < 6.19 mmol/L (Q3) and FBG > 6.19 mmol/L(Q4). And the value of 5.44 mmol/L is even slightly below the diagnostic criteria for IFG of 6.11 mmol/L. Consistently, the ΔBP1 of IFG participants also significantly increased when compared with NFG individuals. These results suggested that relatively higher glucose, though not diagnosed as diabetic, could also increase the SSBP. We highlighted that controlling the elevation of blood glucose in the early stage might be much more important for preventing SS. Our results need to be validated in more larger population association studies.
We further analyzed the associations between FBG with SSBP after stratified participants according to variables including sex, age, obesity, hypertension, diabetes, smoking and drinking to determine the sensitive population. Our results suggested that the effects of blood glucose on SSBP were a little different in population with different characters. The associations of FBG with SSBP in youngers (age < 60 years old), females, hypertensives, non-diabetics, non-current smokers and non-current drinkers were more significant than the corresponding subgroups, which suggested that these sensitive population should pay more attention to the effect of blood glucose on SS.
Some strengths and limitations of the current study should be acknowledged. This is the first epidemiologic study based on general population to focus on the associations between blood glucose with the SS or with the BP changes during acute salt load period and diuresis shrinkage period. This study included a large sample size and meticulously controlled conditions, which made the result of statistical analysis more persuasive. Our results uncovered the positive dose-response association between blood glucose and SSBP in population and highlighted that controlling the elevation of blood glucose in the early stage might be much more important for preventing SS. Furthermore, we performed stratified analysis and found the role of blood glucose as an independent risk factor for SS, especially in youngers, females, hypertensives, non-diabetics, non-current smokers and non-current drinkers. Some scholars claimed that acute salt loading has adverse cardiovascular effects , therefore we developed a set of strict inclusion criteria for study subjects, and there was no side effect occurred during saline loading. The limitations are as follows, although the methods for determining SSBP are not uniform at present, the dietary intervention methods are more accurate than the acute saline load test methods; this is a cross-sectional study and lack of the ability for causal inference analyses like prospective cohort studies, so the causal association between blood glucose and salt sensitivity is not yet available; blood glucose could affect by renal function and insulin resistance, but we didn’t take them into concern due to lack of data; participants were all from two cities in northern China, which may affect the extrapolation of results.