Diabetes: biological mechanisms and clinical overview

Diabetes is one of the most pervasive chronic diseases of this century, already affecting more than 180 million people around the world. As per WHO statistics, by the year 2030 there will be more than 300 million diabetics. The fact that 15 years ago the number of diabetics were only 30 million indicates the pandemic nature of diabetes and the serious healthcare implications in the control and management of the disease. [Katarina Hjelm et.al, 2003] There are three types of diabetes namely type 1 (DM1), type 2 (DM2) and gestational diabetes. Type1 diabetes is an autoimmune disorder characterized by the degeneration of islet of langerhans and consequent inhibition of insulin synthesis. There is also a rare subtype of type1 diabetes known as idiopathic type1, which has no known cause. Type 2 diabetes is a condition of insulin resistance where the body does not respond properly to insulin. Both genetic and environmental factors are implicated in the onset of diabetes. Though there is no known cure, significant strides have been achieved in better control and management of the disease. Let us have a brief overview of Type 1 diabetes, its treatment and the recent developments in the management of this chronic condition.

Type 1 Diabetes

As mentioned above type 1 diabetes is due to insulin deficiency caused by deterioration of the pancreatic ss cells by the body's immune cells. Several studies over the last decade have identified the role of T. lymphocytes in the attack on the pancreatic ss cells. It is reported that in severe diabetic patients the ss cell mass is decreased to as low as 1% of the size in a normal human being. [George S. Eisenbarth, 2007] A study by Kent et.al (2005) that analyzed the pancreatic lymph nodes from patients with type 1 diabetes revealed T cell receptors and activity of T cells with insulin A chain peptides. [Kent et.al (2005)] A Recent study by McGill University has indicated that the misfiring of the immune system controlling CD4+Treg cells maybe responsible for the auto immune reaction and insulitis. Dr. Piccirillo, the chief researcher of the study said, "We have been able to demonstrate this in mice with type 1 diabetes, and other genetic studies have shown that this same mechanism is applicable to humans [McGill University].

Genetics of Type 1 Diabetes

Statistics show that direct relatives of D1 (type 1) patients have a much greater (6%) risk for developing diabetes when compared to the general population (

Environmental Risk Factors

The most important environmental risk factors attributed to D1 are enteroviruses and infant nutrition. It is known now that several viruses cause damage to the pancreatic islet cells. Enteroviruses such as Coxsackie virus B, cytomegalovirus, rotavirus, Mumps have been studied and postulated in the etiology of Diabetes. Other factors such as early introduction to cow's milk and lesser period of breast-feeding are also thought to increase the risk for diabetes. [WHO] Some nutritional studies have attested that vitamin D deficiency during childhood increases the risk factor for diabetes. [Mathieu, 2005]

Diabetes Treatment -- New developments

Daily intake of insulin through injections or orally constitutes the main therapeutic approach. However, advancements in pharmacogenetics promises new and better ways of managing diabetes. Studies have shown that Lisofylline, an anti-inflammatory compound is very effective in suppressing the autoimmune activity and in improving the islet secretion of insulin. Mice studies showed significant difference (25% vs. 91.6%) in the onset of diabetes among Lisofylline treated mice compared to placebo mice. Reduction of inflammatory cytokines IFN-? And TNF-? levels correlated with reduction in ss cell apoptosis. [Yang et.al, 2003] Recent study by Lipsett et.al (2007) has shown that Islet Neogenesis-Associated Protein (INGAP) is useful as a pancreatic regeneration agent. Successful tests in mice and regeneration of cultured human pancreatic cells have encouraged the researchers to seriously consider INGAP as an effective agent for improving insulin synthesis. [Lipsett et.al, (2007)]

A recent Cornell University study focused on an entirely different approach to diabetes management. The researchers examined the possibility of recombinant Commensal bacteria engineered to secrete insulinotropic proteins GLP-1 and PDX-1. The study revealed that the GLP-1 and PDX-1 proteins secreted in the gut bacteria were able to stimulate the intestinal epithelial cells to secrete insulin in response to glucose. This method has the added advantage that commensal bacteria are well tolerated and therefore cause no adverse reactions. [Faping Duan]