Oral Delivery of Insulin

T.A. Sonia, Chandra P. Sharma, Chandra P Sharma

• Publisher: Woodhead Publishing
• Year: 2014
• Print ISBN: 9781907568473
• eBook ISBN: 9781908818683
• Topic: Medicine
• Subtopic: Endocrinology & Metabolism

Diabetes Mellitus, a syndrome of disordered metabolism, characterised by abnormal elevation in blood glucose level, has become a life-threatening condition for many people. Current means of therapy for Diabetes Mellitus do not mimic the normal physiological pattern of insulin release. Oral delivery is the preferred route of administration due to its non-invasive nature. Oral delivery of insulin presents an overview of Diabetes Mellitus, and discusses the strategies and techniques adopted for oral delivery of insulin. This title begins with an introductory chapter on symptoms, complications and therapy for Diabetes Mellitus. Subsequent chapters cover the various routes for administering insulin; the challenges and strategies of oral delivery; experimental techniques in the development of an oral insulin carrier; lipids; inorganic nanoparticles and polymers in oral insulin delivery; and a summary and presentation of future perspectives on oral delivery of insulin. - Presents an overview of Diabetes Mellitus - Includes a discussion of various strategies and techniques adopted for oral delivery of insulin - Presents an update of research in the field

1

Diabetes mellitus – an overview

Abstract

The prevalence of diabetes mellitus, a chronic metabolic disorder, has increased dramatically over the years, and the trend is continuing at an alarming rate. The development of acute and chronic complications adds greatly to the morbidity and mortality associated with this silent disease, making it a major health concern. This chapter presents an overview of diabetes mellitus, its symptoms and complications. Furthermore, conventional treatment options, such as the use of oral hypoglycaemic agents and insulin therapy, and innovative approaches like incretin therapy, gene therapy and stem cell therapy are also briefly discussed.

Key words

type 1 diabetes

type 2 diabetes

gestational diabetes

antidiabetic drugs

insulin

incretin

1.1 Diabetes mellitus – an introduction

Diabetes mellitus (DM), a chronic metabolic disorder of the pancreas often referred to simply as diabetes, is characterized by highly elevated blood glucose levels with disturbances in carbohydrate, fat and protein metabolism [1]. It occurs either due to defective insulin secretion by the pancreas (i.e. the pancreas does not produce enough insulin) or due to ineffective response by the cells to the insulin that is produced. This diseased state may also be due to overproduction of hormones which are antagonistic to insulin – e.g. glucagon, hormones of the pituitary, adrenaline and thyroid – or to improved production of insulinase and insulin antagonists present in plasma, substances which inactivate insulin [2]. DM, if left undiagnosed or untreated, can lead to serious complications affecting major organs in the body, which can ultimately lead to death.

1.1.1 Statistical epidemiology of diabetes

The World Health Statistics Report 2012 states that DM is one of the most common non-communicable diseases globally and is increasing dramatically in both developed and developing nations [3]. The International Diabetes Federation estimates that 382 million people have diabetes in 2013, and this is expected to rise to 592 million by 2035 [4]. So, DM has become one of the most challenging health problems in the twenty-first century [4]. China is host to the largest diabetic population in the world, with an estimated 35 million people, amounting to 10% of the adult population, followed by India and the US. The greatest burden of diabetes is faced by low and middle-income countries.

The increasing prevalence of diabetes may be due to:

■ population growth;

■ ageing, i.e. increased life expectancy resulting in a higher ratio of aged population more prone to diabetes;

■ urbanization;

■ increasing frequency of obesity and physical inactivity;

■ unhealthy diets and sedentary lifestyles.

The majority of the people affected with diabetes are undiagnosed. This silent disease, if left undiagnosed or untreated, can lead to serious complications affecting major organs in the body such as eyes, kidneys, peripheral nerves and heart, resulting in blindness, nephropathy, neuropathy and cardiovascular complications. DM has become a life-threatening condition in human society. Annually, around 3.8 million deaths are attributed to complications arising from diabetes, making it the fourth most common cause of death in humans. It is estimated that DM caused 4.6 million deaths in 2011 [5]. Increased morbidity arising from complications of diabetes augments the direct and indirect medical costs associated with the disease. Various governments and healthcare institutions around the world are investing in health education, diagnosis and treatments for this chronic ailment. In terms of market value, diabetes has now become one of the largest sectors in the global healthcare industry [5]. The International Diabetes Federation (2011) estimates that diabetes caused healthcare expenditures of at least 465 billion US dollars in 2011 [5]. In the United States alone, it is estimated that healthcare expenditures for diabetes exceed 200 billion dollars per year. The World Health Organization's (WHO) World Health Statistics 2012 reports that women are at higher risk for developing diabetes than men as they are more likely than men to be obese [3].

Diabetes has now become a lifestyle disease afflicting people of all ages. As the number of patients is increasing at an alarming rate across the globe, there has never been a stronger and more urgent need for therapeutic measures to slow the growth of the disease and alleviate its secondary manifestations. Therefore, there is an urgent need to undertake proper corrective measures, including scrutiny, raising standards of diagnosis and treatment that can afford rapid detection, counselling and proper medications that control blood glucose levels. These steps can ensure that the disease is prevented, or at least delayed, in people with diabetes, which is critical to this process of controlling diabetes.

1.2 Glucose homeostasis

Insulin is needed by most cells to allow entry of glucose molecules. In healthy individuals, insulin is secreted into the bloodstream by the islet β cells of the pancreas in response to elevated blood glucose levels. After food intake, carbohydrates in food are broken down into glucose molecules in the gut. The amount of glucose available from breakdown of carbohydrates often exceeds the cellular need for glucose. These glucose molecules are absorbed into the bloodstream, leading to increased blood glucose levels, which stimulates the insulin secretion from the β cells of the pancreas. The excess glucose molecules are stored in the liver in the form of glycogen. As and when energy is required, glycogen stored in the liver is converted into glucose via glycogenolysis, elevating blood glucose levels and providing the needed cellular energy source. Glucose is also produced by liver from fat (fatty acids) and proteins (amino acids) through a process known as gluconeogenesis. Glycogenolysis and gluconeogenesis both serve to increase blood glucose levels (Figure 1.1). For the function and survival of all organs, a continuous supply of the correct amounts of glucose is essential. Insulin binds to insulin receptors in the cell and promotes entry of glucose into the cell, which uses the glucose for production of energy. The increased insulin secretion from the pancreas and the utilization of glucose by cells result in lowering of blood glucose levels. When there is not enough insulin produced or when the cells no longer recognize the insulin, glucose stays in the blood rather than entering the cells. This decreased insulin production inhibits glucose entry into cells such as muscle cells, resulting in hyperglycaemia, i.e. elevated blood glucose...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright page
• List of figures and tables
• About the authors
• 1: Diabetes mellitus – an overview
• 2: Routes of administration of insulin
• 3: Oral insulin delivery – challenges and strategies
• 4: Experimental techniques involved in the development of oral insulin carriers
• 5: Lipids and inorganic nanoparticles in oral insulin delivery
• 6: Polymers in oral insulin delivery
• 7: Summary and future perspectives for oral insulin delivery
• Index