**19. Conclusion**

Conjugated bile acids (bile salts) can form micelles that solubilise and transport lipids across biological membranes. Bile acids as absorption promoters have the potential to aid intestinal, ocular, nasal, pulmonary and rectal absorption of insulin. Bile acids are hypoglycemic agents on their own and thus can be used as adjunct therapy in treating T1D. However, in high concentrations, bile acids may damage tissue, so it is important to examine their safety profile thoroughly before application e.g. in buccal formulations as there is conflicting evidence on the morphological changes that occur in the buccal epithelium upon contact with bile acids. However, such an improvement in insulin absorption is still insufficient and subcutaneous injection remains the commonly used method. Nasal administration has certain advantages such as ease of use and high bioavailability. However, it does not allow transport of high molecular weight proteins and peptides. Bile acids have demonstrated the ability to enhance the nasal absorption of insulin and other drugs. One of the main disadvantages of the applications of bile acids as permeation enhancers is that the greater the bile acid is at promoting permeation of through mucosa, the more toxic it becomes. Accordingly, it is important to determine the mechanism of action by which bile acids enhance absorption in order to design absorption promoting agents that are not toxic or irritant. In addition, knowledge of the mechanism of action may allow prediction of the exact amount of a therapeutic substance that will reach the systemic circulation. The metabolism and deconjugation of bile acids are brought about by the gut microflora. Interestingly, gut microflora plays a major rule in energy balance and gut inflammation. Probiotics have shown hypoglycemic effect, when administered alone, thus, their use in T1D should be studied further.

Type 1 diabetes and its complications cannot be cured by the best most intensive insulin therapy (Shamoon et al. 1993). This clearly emphasizes the fact that the disease is more complex, interdependent, and challenging to treat than being a simple hyperglycemia. That is why, in our opinion, multidrug approach which integrates a comprehensive, targeted, and tailored treatment should guarantee the best outcome for diabetic patients.
