## 2 Physiological Methods of Insulin Delivery
### Hyperglycemia and Hypoglycemia  
Insulin cannot be infused until the BG level exceeds 180-200 mg/dL. This condition is referred as hyperglycemia [38]. The condition of hyperglycemia is found to be common in intensive care units (ICU) [37]. According to existing surveys presented by [PERSON] et al. [39], even a small level of hyperglycemia can lead to an increased rate of hospital mortality in ICUs [39]. Sugar level control with insulin infusion has a risk of hypoglycaemia. Sugar level which is \(<\)50 mg/dL is the called hypoglycemia. The hypoglycemia can be diagnosed by the Whipple's triad, with three steps. (i) neuroglycemia symptoms, (ii) immediate glucose of \(<\)40 mg/dL, and (iii) symptoms of the relief after glucose intake [40]. Biological Perspective on How \(\beta\)-Cell Achieves Glucose Control and Energy Metabolism in Type 1 Diabetes Mellitus (T1 DM)  
The biological perspective on how a \(\beta\)-cell achieves glucose control can be summarized in four steps as: (i) after a person takes a meal, the small intestine absorbs glucose from the digested food. Consequently, the BG levels rise; (ii) increase in BG levels stimulate the \(\beta\)-cells in the pancreas to produce insulin; (iii) after that, insulin triggers liver, muscle, and fat tissue cells to absorb the glucose, where it is stored. As glucose is absorbed in the related parts, the BG levels fall; (iv) Once the glucose levels drop below a certain threshold, there is no longer a sufficient stimulus for insulin release, and the \(\beta\)-cells stop releasing further insulin. The conceptual overview of the whole process is shown in Figure 2. Due to the synchronization of the insulin release with the \(\beta\)-cells, basal insulin concentration oscillates in the blood following a meal. The oscillations are clinically important, since they are believed to help maintain sensitivity of insulin receptors in the target cells. The key role of the \(\beta\)-cells is to sense the BG levels, and regulate insulin accordingly. For example, when the BG increases following food intake, \(\beta\)-cells sense this change in concentration, and subsequently secrete insulin into the blood. On the other hand, when blood glucose levels are low, such as following a prolonged fasting period, the release of insulin from \(\beta\)-cells is inhibited [41]. Doctors have tried to help patients of T1 DM to maintain their glucose values as close to the normal range as possible to delay the onset and slow the progression of long-term diabetes complications such as renal disease, retinopathy, neuropathy, and heart disease. Monitoring glucose levels is vital for achieving desirable glycemia and avoiding hypoglycemia. Continuous Glucose Monitoring (CGM) is a recent glucose monitoring device that assists to achieve these aims. CGM has been shown to improve glycemia without an increase in the hypoglycemia for adults with T1 DM who wear it most days [42; 43; 44]. Furthermore, studies have reported the positive psychosocial changes such as decreased partners' anxiety, vigilance and negative experiences surrounding hypoglycemia, and improved patients' mood and general quality of life [45; 46]. Currently, flash glucose monitoring is emerging  
Figure 2: Conceptual overview of the biological perspective on how a \(\beta\)-cell achieves glucose control. as an innovative technology, it enables self-monitoring of blood glucose [47]. With the help of CGM and other related technologies, doctors and clinicians are able to gain more insight into the glucose variability, temporarily improved sense of control, reduced distress and reduced dependency on the others physical devices. However, some participants experienced confrontation with the CGM output as intrusive, whereas others reported frustration due to the technical failures and difficulty in trusting the devices. Active and passive self-management behaviours were reported by the participants, mirroring individual differences in attitudes and coping styles [48].