INTRODUCTION

The increasing prevalence of diabetes worldwide is cause for concern both in terms of associated morbidity and increasing health costs. Diabetes is a defect in the body’s ability to convert glucose (sugar) to energy. Glucose is the main source of fuel for our body. When food is digested it is changed into fats, protein, or carbohydrates. Foods that affect blood sugars are called carbohydrates. Carbohydrates, when digested, change to glucose. Examples of some carbohydrates are: bread, rice, pasta, potatoes, corn, fruit, and milk products. Individuals with diabetes should eat carbohydrates but must do so in moderation. Glucose is then transferred to the blood and is used by the cells for energy.

In order for glucose to be transferred from the blood into the cells, the hormone - insulin is needed. Insulin is produced by the beta cells in the pancreas (the organ that produces insulin). In individuals with diabetes, this process is impaired. Diabetes develops when the pancreas fails to produce sufficient quantities of insulin – Type 1 diabetes or the insulin produced is defective and cannot move glucose into the cells – Type 2 diabetes.

Either insulin is not produced in sufficient quantities or the insulin produced is defective and cannot move the glucose into the cells. Diabetes mellitus refers to a number of disorders that share the cardinal characteristic feature of elevated blood glucose levels. The 2 most common general categories of this disease are termed type 1 and type 2diabetes.[1].Research has enormously increased our understanding of type 1 and type 2 diabetes, but much more remains to be done.

Type 1 Diabetes

Type 1 diabetes occurs most frequently in children and young adults, although it can occur at any age. Type 1 diabetes accounts for 5-10% of all diabetes in the United States. There does appear to be a genetic component to Type 1 diabetes, but the cause has yet to be identified. Management of type 1 diabetes is best undertaken in the context of a multidisciplinary health team and requires continuing attention to many aspects, including insulin administration, blood glucose monitoring, meal planning, and screening for comorbid conditions and diabetes-related complications. [2]. Type 1 diabetes is a condition in which pancreatic -cell destruction usually leads to absolute insulin deficiency.[3,4]Two forms are identified: type 1A results from a cell-mediated autoimmune attack on cells,[5]whereas type 1B is far less frequent, has no known cause, and occurs mostly in individuals of Asian or African descent, who have varying degrees of insulin deficiency between sporadic episodes of ketoacidosis.[6].Type 1 diabetes has transformed from a disease with certain death in the era before the discovery of insulin to one with substantial risk of long-term morbidity and mortality [7].A fundamental shift in the management of type 1 diabetes seems unlikely until we are able to close the loop through either artificial endocrine pancreas implantation, or islet replacement by transplantation or stem cell engineering. In the meantime, individuals with type 1 diabetes and their health providers need to focus their energies on the therapeutic approaches best capable of maximum risk reduction, including the risks of hypoglycaemia and diabetic ketoacidosis in the short term, and microvascular and macrovascular disease and psychological distress in the longer term.

TYPE 2 DIABETES:

Type 2 diabetes is much more common and accounts for 90-95% of all diabetes. Type 2 diabetes primarily affects adults, however recently Type 2 has begun developing in children. There is a strong correlation between Type 2 diabetes, physical inactivity and obesity. Lifestyle choices can contribute to the development of type 2 diabetes. People with type 2 diabetes are usually insulin resistant. This means that their pancreas is making insulin but the insulin is not working as well as it should. The pancreas responds by working harder to make more insulin. [8] Eventually it can’t make enough to keep the glucose balance right and blood glucose levels rise. Adopting a healthy lifestyle may delay the need for tablets and/or insulin. However it is important to know that if you do need tablets and/or insulin, this is just the natural progression of the condition. By taking tablets and/or insulin as soon as they are needed, the risk of developing complications caused by diabetes can be reduced.

Ilets Transplantation in Patients with Type 1 Diabetes:

Previously, research toward a cure was focused on transplantation of the cells in the pancreas that produce insulin, the islet cells or parts of the pancreas. In type 1 diabetes, the body’s immune system turns on itself and destroys these islet cells. As a result, the body can’t produce the insulin required to escort glucose from the food we eat to where it is needed—into the cells of the body’s muscles and other organs. We are now focusing on ways to understand this immune attack to find safe ways to block it. There are several ongoing studies using our knowledge of immunology to try to intervene and prevent type 1 diabetes[9].

Another important effort is directed to regenerating islet cells—to produce insulin again—either through the use of stem cells, embryonic or adult, or other ways of engineering these cells. We are now hopeful that a large number of people with type 1 diabetes still have surviving islet cells left to regrow [10]. This optimism has been raised by the findings that many type 1 diabetes patients may still have residual islets that have retained some function to make insulin. Type 1 diabetes remains a therapeutic challenge.[11] However, for islet transplants to become a widespread clinical reality, additional advances are still needed. In particular, restoration of insulin independence must be achieved with a single donor, as is also the case with pancreas transplants, to reduce the risks and costs and increase the availability of islet transplantation [12].

Recent Advances in Pancreatic Transplantation:

Pancreatic transplantation has progressed in the past 25 years since its initial stages, proving to be highly promising for those with diabetes and its resultant multiorgan disorders. [13]Some patients with type 1 diabetes have experienced positive results from pancreas transplants. Typically, part or all of a new pancreas is surgically implanted. The old pancreas is left alone; it still makes digestive enzymes, even though it doesn’t make insulin. Most organs are obtained from someone who has died but has decided to be an organ donor. Several studies have shown that patients who receive transplants have better glycemic control, blood pressure control, lipid control, and show reversal of microscopic diabetic changes including neuropathy and improved cardiovascular risks. [13] the goals of transplantation are to restore glucose-regulated endogenous insulin secretion arrest the progression of the complications of diabetes, and improve the quality of life. Both pancreas and islet transplantation require lifelong immune-suppression to prevent rejection of the graft and recurrence of the autoimmune process. The advantages of islet cell transplantation are that it requires only local anaesthesia and is a minor radiological procedure having minimal risk to the patient. Unfortunately the merits of both pancreas and islet cell transplantation have to be weighed against the need for immune suppression and for those patients having a pancreas transplant the risk of the surgical procedure.[14]. In cases of advanced neuropathy a pancreas transplant will have no benefit. In less severe cases, a pancreas transplant can improve peripheral and autonomic neuropathy [15,16].

Benefits of Pancreas Transplants:

You may be able to maintain a normal blood glucose level without taking insulin. Many of the diabetes-related side effects are prevented or delayed. Most people with nerve damage who receive a pancreas transplant do not get worse and sometimes show improvement.

Downsides to Pancreas Transplants :

The body treats the new pancreas as foreign and the immune system attacks the transplanted pancreas. Transplant patients must take powerful immune-suppressant drugs to prevent rejection of the new pancreas. Drugs that suppress the immune system can lower resistance to other diseases, such as cancer, and to bacterial and viral infections.

Engineered Pancreatic Beta Cell:

Pancreatic β cells are highly specialized endocrine cells that produce, store, and secrete insulin, the only physiological hypoglycemic hormone in the body. Clusters of such cells, which make up about 1% of the total pancreatic cells, form the islets of Langerhans, the micro-organs that lie scattered throughout the exocrine pancreas. In addition to β cells, these micro-organs have other cell types, such as α, δ, and PP cells, which produce glucagon (GCG), somatostatin (SST), and pancreatic polypeptide, respectively. Due to their scattered distribution in the exocrine pancreas, the isolation of a homogeneous population of pancreatic β cells remains challenging. Furthermore, the use of growth factors to promote the expansion of adult human β cells induced their dedifferentiation in vitro [17,18] Human embryonic stem cells (hESCs) have also been recently tested as an unlimited β cell source; however, the procedures for generating functional β cells from hESCs have not been fully developed [19].Thus, alternate strategies for the mass production of functional human β cells still need to be developed.

CONCLUSION:

Curing diabetes has been an elusive dream. A huge body of research has been aimed at effecting a cure. However, the greatest success in diabetes research has been in the treatment of diabetes, with little progress toward a cure. Current therapies aimed at curing diabetes fall into 5 categories: (1) pancreatic transplantation, (2) islet transplantation, (3) engineered pancreatic beta cells, (4) the virtual pancreas, and (5) islet regeneration. More advances in diabetes research is still under process, which leads way that diabetes can be cured very fast at low cost and time.

REFERENCES:

1. Unger RH, Foster DW. Diabetes Mellitus: Williams Textbook of Endocrinology. 9th ed. Philadelphia, Pa: WB Saunders Co; 1998:973-1059

2. Division of Endocrinology, Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada M5G 1X8 (Prof D Daneman FRCPC),Lancet 2006; 367: 847–58.

3. American Diabetes Association. Clinical practice recommendations. Diabetes Care 2005; 28 (suppl 1): S1–79.  

4. Devendra D, Liu E, Eisenbarth GS. Type 1 diabetes: recent developments. BMJ 2004; 328: 750–54.  

5. Redondo MJ, Fain PR, Eisenbarth GS. Genetics of type 1A diabetes. Recent Prog Horm Res 2001; 56: 69–89.

6. Abiru N, Kawasaki E, Eguch K. Current knowledge of Japanese type 1 diabetic syndrome. Diabetes Metab Res Rev 2002; 18: 357–66.  

7. Feudtner C. A disease in motion: diabetes history and the new paradigm of transmuted disease. Perspect Biol Med 1996; 39: 158–70.

8. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet.1998;352:837-853.

9. Shapiro AM, Lakey JR, Ryan EA. et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343:230-23.

10. Goss JA, Schock AP, Brunicardi FC. et al. Achievement of insulin independence in three consecutive type-1 diabetic patients via pancreatic islet transplantation using islets isolated at a remote islet isolation center. Transplantation. 2002; 74:1761-1766

11. Kaufman DB, Baker MS, Chen X, Leventhal JR, Stuart FP. Sequential kidney/islet transplantation using prednisone-free immunosuppression. Am J Transplant. 2002;2:674-677

12. Markmann JF, Deng S, Huang X. et al. Insulin independence following isolated islet transplantation and single islet infusions. Ann Surg. 2003 ; 237:741-749 

13. Advances in pancreatic transplantation. Iacovidou A1, Hakim N. Imperial College London - Department of Surgery and Cancer, St Mary's Hospital, Praed Street London, London W2 1NY, United Kingdom.

14. White SA, Nicholson ML, London NJM (1998) Vascularised pancreas transplantation—clinical indications and outcome. Diabet Med, pp 533 –543

15. Transplantation on diabetic neuropathy. N Engl J Med 322:1031–1037.

16. Müller-Felber W, Landgraf R, Scheuer R, et al. (1993) Diabetic neuropathy 3 years after successful pancreas and kidney transplantation. Diabetologia 42:1482–1486.

17. Beattie GM, et al. Sustained proliferation of PDX-1+ cells derived from human islets. Diabetes. 1999;48(5):1013–1019. 

18. Russ HA, Bar Y, Ravassard P, Efrat S. In vitro proliferation of cells derived from adult human beta-cells revealed by cell-lineage tracing. Diabetes. 2008;57(6):1575–1583. 

19. Kroon E, et al. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol. 2008;26(4):443–452.

Received on 16.06.2016 Modified on 06.07.2016

Research J. Pharm. and Tech 2016; 9(10):1806-1808.

DOI: 10.5958/0974-360X.2016.00366.8