## 3 Open Loop Administration of an Insulin
### Multiple Daily Insulin Therapy  
The most renowned method of insulin therapy consists of the regular periodic injection of basal (baseline) insulin multiple times in a day--known as multiple daily insulin injections (MDI)--supported by the additional insulin doses (boluses), and oral glucose or glucagon as required to maintain normoglycemic conditions (e.g., at mealtimes) [84]. While calculating the required basal and bolus  
Figure 5: Comparison of the inhaled insulin with the subcutaneous (SC) injection [45].  
insulin doses, practical guidelines need to be followed. Due to the significant complications, there is now an array of options/factors that allow for the personalization and situational evaluation of the treatments [84]. MDI using short- and long-acting doses are currently the main strategies of the insulin administration in this population. Depending upon the scenarios, some injections are developed as a mix of rapid acting (i.e., quick onset and peak times with short duration) and long acting (i.e., delayed onset time, low or no peak, and long duration) insulin to provide both basal and bolus action from a single injection, thereby reducing the number of injections required per day [85,86]. In addition, in some cases, it may be helpful to perform islet transplantation or that of the pancreas, in place of insulin therapy to significantly lower the treatment costs [85].  
Generally, MDI comprise of three or more injections per day. It contains one injection of long-acting (LA) insulin in the evening, and an injection of the short-acting (SA) insulin ahead of every meal. LA insulin is drafted in such a way that it delivers insulin steadily and remains in the body for around 24 h. Meanwhile, the SA insulin needs to be adjusted to match the meal using the insulin-to-carbohydrate ratio [87]. The presentation of MDI and its use in diabetes control and complications trials (DCCT) study has been the ideal case to protect the patients with T1 DM. The recent evolution of automated bolus calculations for the MDI is available to help patients to perform complex calculations that are required for functional insulin therapy (FIT) [88,89]. But there are some limitations of MDI to be considered: those patients who use very small amount of insulin doses or are insulin-sensitive may conflict with the MDI as it comes up with the limitations and accuracy's issues. Similarly, for patients who require large doses, the use of continuous subcutaneous insulin infusion (CSII) may be very helpful from the pharmacodynamics aspect. Continuous infusion works better on delivery of basal insulin rather than using a large subcutaneous depot. MDI is not very effective on those who eat frequently or living soft lifestyle, demanding a large number of injections of the SA insulin, and it becomes difficult to manage through MDI [88]. The Hypo-Ana research study shows that using an analogue-based regimen decreases the severe hypoglycemia in patients with impaired knowledge of hypoglycemia [88,89]. Data also suggests it is being taught already as a way of adjusting the insulin, but many patients ignore the fact and underestimate the insulin doses face difficulty while calculating appropriate amount of insulin adjustments and which acts like a barrier. In early study, the use of bolus calculator recommended reduced errors of insulin and fear hypoglycemia [90,91]. The use of a bolus automated calculator is linked with revised HbA1c and reduced glycemic fluctuations even in the younger patients with T1 DM on MDI [92]. The list of distinct categories of the insulin available in medicine (adopted from [93]) is summarized in Table 1.