**21. References**

388 Type 1 Diabetes – Complications, Pathogenesis, and Alternative Treatments

hepatotoxicity and can damage the gastric mucosa. Cholylsarcosine (CS) is a stable bile salt derivative of deoxycholic acid. It resists bacterial activation to the more toxic bile acid, deoxycholic acid, and thus has a good safety profile. It is commonly used as an absorption enhancer in the treatment of primary biliary cirrhosis (Ricci et al. 1998). Deoxycholic acid salt is also used in the formulation of Amphotericin B, which is commonly used for treating fungal infections of the eyes (Samiy et al. 1996). However, due to its limited safety profile, Amphotericin B in doses as low as 1 µg has been shown to cause retinal damage despite the fact that the recommended dose is 5-10 µg (Souri & Green 1974). The administration of Amphotericin B deoxycholate may also result in cataract formation,

When it comes to predicting the toxicity of bile salts, it seems that toxicity increases with their permeation ability. The more capable bile salts are to solubilizing membrane proteins, the more toxic they are (Shao et al. 1992a). In one study (Hersey & Jackson 1987b), bile acids damaged nasal epithelium causing nasal irritation, congestion and bleeding. The authors concluded that nasal applications of bile salts should be limited

Formulation of bile salts in inhalations can cause pulmonary oedema, when inhaled in large quantities. This is due to the solubilization and dissolution of the pulmonary membranes and pulmonary hemorrhage (Kaneko et al. 1990). However, such side effects are only caused

Probiotic administration has shown good safety profile in individuals with overall good health status, and may be suffering from mild infections or GI disorders (Luoto et al. 2010). Probiotic safety stems from the fact that many strains are of human origin and present in large numbers in human GIT (Rozanova & Voevodin 2008). Accordingly, the reported incidences of probiotics inducing bacterial infection and bacteremia are very low (Snydman 2008). The only major concern with probiotic administration is the potential of bacterial translocation resulting in the induction of antibiotic-resistance strains that may lead to pathogenesis and haemodyscrasia (Liong 2008; Snydman 2008). Having said that risks of infections caused by probiotic treatment is expected to be significant in

If the use of probiotics and bile acids is to become part of T1D therapy, their safety concerns may be overcome by thoroughly studying appropriate dosing and frequency, their short and long term effect on mucosal membranes and the variation of their effect in

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

opacity, retinal necrosis and retinal ganglion cell loss (Cannon et al. 2003).

immunocompromised patients (Marteau & Shanahan 2003; Rayes et al. 2005).

with infrequent dosing regimen.

by largely inhaled doses.

different populations.

**19. Conclusion** 


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**19** 

*U.S.A.* 

**Role of Vitamin D in the Pathogenesis and** 

This chapter will review the role of vitamin D in the pathogenesis and treatment of type 1

We will discuss the mechanisms through which vitamin D might affect pancreatic function. We will summarize the results of in-vitro and animal studies and will conclude with a

Type 1 diabetes mellitus is an autoimmune disease in which the pancreas is unable to respond to secretagogue stimulation with appropriate insulin secretion. Hyperglycemia develops when more than 70-90% of the insulin-producing beta cells are destroyed. An autoimmune destructive process, which plays a central role in the development of type 1 diabetes mellitus, is facilitated by the subject's own genetic susceptibility and by non-genetic factors. Non-genetic factors include viral infections, toxic chemicals, and others. Vitamin D deficiency is a non-genetic factor that appears to be associated with an increased risk of

Type 1 diabetes mellitus complications are classified into acute and chronic. The acute complications include life-threatening conditions like severe hypoglycemia or diabetic ketoacidosis (DKA). Chronic diabetic complications can be divided into microvascular complications (retinopathy, neuropathy and nephropathy) and macrovascular complications (cardiovascular, cerebrovascular and peripheral vascular disease). Severe microvascular and macrovascular complications can lead to renal failure (the most common

Overall, uncontrolled diabetes mellitus in patients over 50 years of age reduces life expectancy in males and females by 7.5 and 8.2 years respectively (Franco et al.,2007).

In 2010, about 215,000 people younger than 20 years of age had diabetes (type 1 or type 2) in the United States. A 2011 Centers for Disease Control and Prevention (CDC) report estimates that nearly 26 million Americans have diabetes. Diabetes affects 8.3% of

cause of hemodialysis in the US), blindness or lower extremity amputations.

**1. Introduction** 

diabetes mellitus.

**2. Definition** 

**3. Epidemiology** 

review of the relevant clinical trials.

developing type 1 diabetes mellitus.

**Therapy of Type 1 Diabetes Mellitus** 

Agustin Busta, Bianca Alfonso and Leonid Poretsky

*Albert Einstein College of Medicine, Beth Israel* 

*Medical Center New York* 

