Diabetes currently affects 366 million people worldwide and is expected to affect 552 million by 2030. It is a disease characterized by high levels of sugars in the blood, often resulting in cardiovascular disease, kidney disease and nerve damage, and can lead to the loss of limbs. It also linked to an increased risk of developing cancer. Its prevention has become a key focus area for the drug development market. During the period few drug has been halted due to concerns that while medication it may raises the risk for fractures, kidney problems and heart failure.
Reasons for getting diabetes
Various theories been forwarded, Normally the pancreas produces insulin in its beta cells to shuttle sugars or simple carbohydrates, from the foods which we eat to the various muscles and organs in the body, to acts as fuel for smooth function. In the people with diabetes, either the pancreas will not produce insulin ( type-1) or the insulin which produced isn't effectively shuttling sugar to the organs( type-2). In the type-1 normally pancreas beta cells die with no reason. While type-2 usually develops during adulthood and is strongly associated with obesity or a diet high in sugars and processed foods, due to sedentary lifestyles and sometime hereditary factors.
In recent discovery the protein TXNIP, short for thioredoxin-interacting protein activated by sugars also found to kill insulin-producing cells through one mechanism, but also damages the cells to produce type-2 diabetes. TXNIP triggers the beta cells to make a snippet of genetic material, called microRNA-204. This mechanism releases a wave of molecules called free radicals that tell the beta cells to commit cellular suicide in a process called apoptosis. In the event even small increases in blood sugar levels can lead to accumulation of TXNIP and the associated beta cell dysfunction and death. TXNIP is a key player in a host of diseases related to ER stress, such as Alzheimer's disease, Parkinson's disease, and Wolfram Syndrome, Urano's specialty, a rare genetic disorder whose symptoms include type 1 diabetes, blindness and deafness. It recognized that a key event leading to development of type 2 diabetes is uncontrolled glucose production from the liver, identified aP2 as a novel hormone released from fat cells that controls this critical function. The communication system between adipose tissue and liver may have evolved to help fat cells command the liver to supply the body with glucose in times of nutrient deprivation and aP2 harmone plays a key role. However, when the engorged fat cells lose control over this signal in obesity, the blood levels of aP2 rise, glucose is poured into the bloodstream and cannot be cleared by other tissues Diabetes and obesity are also associated with the over production of mitochondrial reactive oxygen species (ROS), leading to mitochondrial and cellular oxidative damage. This, in turn, contributes to the development and progression of diabetic complications and to worsening of the diabetic state. One path by which mitochondrial dysfunction can lead to diabetes is insulin resistance, characterized by a weakened ability to respond to insulin and to process glucose. Elderly individuals can gradually lose mitochondrial function due to accumulation of DNA defects commonly associated with the aging process. Insulin-resistant individuals are more efficient at processing glucose and need less energy; therefore, they have fewer mitochondria in their cells show more blood sugar.
Diet and diabetese control
A diet rich in fiber and complex carbohydrates found in leafy green vegetables, legumes and whole grains can help prevent type 2 diabetes. A study to be reported in the September 2013 issue of The Journal of Nutrition shows a surprising connection between Diabetes, omega 3 and physical activity. who had regular physical activity had more omega 3 in their blood and were therefore at less of a risk of diabetes and heart disease than those who didn’t exercise. A hearty breakfast that includes protein and fat may actually help people with type 2 diabetes better control both their hunger and their blood sugar levels. Patients who ate a big breakfast for three months experienced lower blood sugar (glucose) levels, and nearly one-third were able to reduce the amount of diabetic medication they took.
The researchers based their new study on previous investigations that found that people who regularly eat breakfast tend to have a lower body mass index (BMI) than those who skip the meal. Breakfast eaters also enjoy lower blood sugar levels and are able to use insulin more efficiently. Doctors found that after 13 weeks, blood sugar levels and blood pressure dropped dramatically in people who ate a big breakfast every day.
Medication
Once diabetes progresses, however, repairing damaged beta cells remains difficult to impossible. Currently available immune suppressants have not been perfected yet and can have adverse effects ranging from gastrointestinal problems to increased blood cholesterol levels, hypertension, anemia, fatigue, decreased white blood cell counts, decreased kidney function, increased susceptibility to bacterial and viral infections, and increased risk of tumors and cancer. There are 86 drugs in the diabetes pipelines of major pharmaceutical companies worldwide, which make it the third largest therapeutic area (after CNS and oncology/hematology) for drug development activity. The vast majority of these agents treat only the symptoms of diabetes rather than stopping the progression or preventing the condition altogether. Regenerative medicine is another area being explored for treatment of diabetes. Beta cell regeneration and beta cell development from stem cells have been touted as a means of replacing lost beta cells and restore insulin production within diabetic cells companies such as Evotec have been actively pursuing the development of beta cell regeneration drugs for more than ten years. LY2405319 is a new drug being developed by Eli Lilly. The drug is in a new class of treatments known as FGF21 analogues. FGF21 stands for fibroblast growth factor 21, which is a hormone in the body that stimulates glucose uptake of adipose cells (fat cells). Albiglutide is a GLP-1 agonist, and therefore in the same class of drugs as the medications exenatide (Byetta), liraglutide (Victoza) and lixisenatide (Lyxumia) DiaPep277 is being developed by Teva/Andromeda biotech and is currently at phase 3 clinical trial stage. DiaPep277 falls into the class of injectable synthetic peptides, and is made up of 24 amino acids MGA031/hOKT3?1/teplizumab (Ala-Ala) GAD-alum/rhGAD65 is being developed by Diamyd Medical/Ortho-McNeil Janssen Pharmaceutical. This vaccine helps to preserve beta cell function amongst recent-onset type 1 diabetes mellitus and has also reached phase 3 clinical trial.This drug is being developed by Eli Lilly/MacroGenic. It is currently at phase 3 and is an intravenously humanised anti-CD3 MAb which could help to inhibit autoimmune response that damages pancreatic beta cells. According to researchers, dapagliflozin, a diabetes drug developed jointly by two pharmaceutical companies has shown significant benefits when teamed with metformin and sulfonylurea. The drug, already available in Europe, is produced by Bristol-Myers and AstraZeneca. It has been shown to improve blood sugar levels, help reduce body weight, and lead to lower A1c levels when used in tandem with the two other diabetes drugs.
(The author is Research scientist, Astrazeneca)