# Non-Centrifugal Sugar (NCS) and Health: A Review on Functional Components and Health Benefits
## 6 Biological Properties of NCS
### Non-Centrifugal Sugar and Metabolic Syndrome
#### 6.3.2 Antidiabetic Effect  
Type 2 diabetes mellitus (T2 DM) has become an epidemic of non-communicable diseases, with 415 million people presently suffering from diabetes around the world. According to the International Diabetes Federation, around 5 million persons died from DM in 2015, and the survey predicts that there will be about 642 million diabetic patients by 2040 [55]. A core characteristic of T2 DM is hyperglyaemia due to high liver glucose levels, insulin resistance, and abnormal production of pancreatic insulin [55]. Present control of T2 DM in the clinical environment includes a large-scale examination of the overall population, change of habits and weight management, and pharmacological attention as the final option [56]. Since a long time ago, researchers have been conducting several clinical and preclinical studies to investigate the beneficial effects of natural sweeteners on diabetes management [57; 58; 59]. Indeed, RS is readily absorbed in the blood, and high amounts of energy are released rapidly. Therefore, it is not recommended for diabetic people. While NCS is digested slowly and the energy release is also slow, it is a better and healthier alternative for a diabetic [50]. Several attempts have been made to understand the role of NCS in glucose metabolism and insulin resistance. In 1984, [PERSON] et al. [60] revealed that the non-sugar fraction of kokuto prevented the rise of insulin secretion in rats fed a high refined sugar diet for two months and with no increased blood glucose level. Moreover, it was reported that this non-sugar fraction prevented the adsorption of glucose and fructose from the small intestine of rats. These benefits were attributed to the presence of 3,4-dimethyl-phenyl-O-D-glucose and 3,4,6-trimethoxy-phenyl-O-D-glucose (BS-1). Recently, [PERSON] et al. [54] investigated the effect of 15% RS or BS solution on insulin resistance, weight gain and serum levelof brain-derived neurotrophic factor (BDNF) in healthy Wistar rats for 42 days. It was found that the adverse effects of BS on these factors were less than those of RS. The serum level of BDNF was less in the RS group due to higher insulin resistance and weight gain observed in the RS group compared to that of the BS group. The effectiveness of BS on insulin resistance and consequently, higher BDNF levels were attributed to chromium and antioxidant compounds. BDNF helps to develop and maintain the nervous system health and synaptic plasticity. BDNF has an additional role in metabolic control, especially in glucose metabolism and insulin resistance [61]. The blood level of BDNF was lower in individuals with insulin resistance and hyperglyaemia [60]. Future research is required to investigate the impacts of various dosages of RS and BS on biochemical profiles in healthy and diabetic subjects. Histology of different organs and immunohistochemistry also were not examined. In another investigation, 10% feeding of BS for rats, maintained glucose tolerance similar to the control group, in spite of the intake of an HFD. In contrast, the group fed RS showed glucose intolerance [52]. Likewise, long-term consumption of 10% BS for 4 months maintains almost normal glucose and insulin levels while RS produces hyperglynia and hyperinsulinemia [50]. The authors also reported that rats fed with RS promoted the expression of GLUT 2 in the enterocytes, increasing the glucose transport and the most elevated blood glucose levels compared to rats fed with BS. A surge in GLUT2 has been reported in obese subjects linked to low insulin sensitivity and hyperglyemia [62]. Rats fed on BS showed a better insulin sensitivity by controlling the phosphorylation level of IRS\({}_{\text{tyr}}\) and Akt and increased white adipose GLUT 4 expression compared to rats fed on RS that showed insulin resistance [50]. Transgenic rodents lack GLUT 4 to reduce overall-body insulin sensitivity [63]. Another recent study reported that administering 1 g/kg of jaggery to alloxan-induced diabetic rats did not show any significant benefits over metabolic health [64].