The HLA region There are at least two genes in the HLA region that account for 40 to 50 percent of the diabetes risk that people inherit from their parents. Different versions (or alleles) of these genes can put a person at risk for — or prevent them from — developing Type 1 diabetes. One gene in the HLA regionthat plays an important role in diabetes is called DR. Peoplecan inherit one form of DR from their mother and one form of DR from their father. Its the combination of these two forms of the gene that determine a persons overall risk.Two forms of DR, designated DR3 and DR4, are present in 95 percent of Type 1 diabetics, and 30 percent have inherited both DR3 and DR4. This is in contrast with the general population, where only 50 percent of people have DR3 or DR4 and 1 to 3 percent have both.
• HLA allele Risk level DR 1 Slight DR 2 Protective DR 3 Significant DR 4 Significant DR 5 Slight DR 6 Neutral DR 7 Protective with risk in Africans DR 8 Neutral DR 9 Risk in Chinese and Japanese
Insulin gene• If a person inherits two short VNTR regions, they are two to five times more likely to develop Type 1 diabetes than a person with at least one long VNTR.• The longer (protective) VNTR region seems to decrease the amount of insulin produced in the pancreas. This finding may seem contradictory, because the longer VNTR also protects a person from developing diabetes. However, researchers have found that insulin is produced in the thymus during development. (The thymus is also where many cells in the immune system develop). During this time, the longer VNTR causes more insulin to be produced. Researchers think that when developing immune cells are exposed to high levels of insulin, they learn to identify insulin and are less likely to react against it and cause diabetes later in life.
Metabolic syndrome• Definition:• Its a group of metabolic condition that occurs together in one person increasing the risk of heart disease, stroke & D.M.Role in diabetes:the driving force behind the insulin resistance that ultimately leads to •.hypertension, dyslipidemia, hypercoagulability and inflammationEven normal-weight individuals with increased visceral fat can become •insulin resistant. The take-home message was that nutrient excess, obesity, and visceral adiposity are the primary contributors, and the pathophysiologic consequences that follow are a direct result of increased .plasma free fatty acids and insulin resistanceHyperglycemia is one of the metabolic syndrome criteria •There is increasing evidence that coronary heart disease associated with •the metabolic syndrome and type 2 diabetes is in large part as result of vascular inflammationVisceral adiposity is also associated with reduced adiponectin, which is an •"insulin-sensitizing protein" with vascular protective effects
Prevention of type 1 Diabetes• Since type 1 diabetes is an idiopathic disease or may occur due to genetic abnormalities. So its control is somehow difficult.• Lots of trials have been done to prevent the occurrence of diabetes,BUT these trials were proved to be useless• But other techniques have been suggested and its results have not yet been proven.
The first trial done to prevent type 1 diabetes in 2002• Preventing Type 1 diabetes is an active area of research. Some of the techniques that researchers are looking into are:• Vaccines to prevent the immune system from destroying the pancreas cells. This technique has been effective in mice, but has not yet been tested in humans.• Giving people with a family history of diabetes injected or oral insulin before they develop diabetes. This approach has been effective in mice,but it proved its failure with human beings
Studies done as a trial for prevention of diabetes type 1
Prevention of type 2 diabetes Before people develop type 2 diabetes, they almost always have "pre-diabetes" -- blood glucose levels that are higher than normal but not yet high enough to be diagnosed as diabetes Take our diabetes risk test to see if you are at risk for developing diabetes. Diabetes is more common in African Americans, Latinos, Native Americans, Asian Americans and Pacific Islanders. is a powerful new risk assessment tool. It can be used to explore the effects of a wide variety of health care interventions, including losing weight, stopping smoking, and taking certain medications. Diabetes Prevention Program study conclusively showed that people with pre-diabetes can prevent the development of type 2 diabetes by making changes in their diet and increasing their level of physical activity. Keeping an eye on these risk factors -- keeping them "in check" Keeping an eye on these risk factors -- keeping them "in check" -- can help you prevent diabetes and heart disease . . -- can help you prevent diabetes and heart disease
• During measurement of diabetic risk factors,other factors should be considered:
DietGo for Get restrictionwhole plenty ofgrain fibers Lose extra weight Tips for Physical prevention activity of type 2 diabetes Skip fat diets and make healthier choice
When we discuss methods of prevention of diabetes we have also to discuss methods of preventionof its complications
What is the diabetes prevention program (DPP)?• was a major multicenter clinical research study aimed at discovering whether modest weight loss through dietary changes and increased physical activity or treatment with the oral diabetes drug metformin (Glucophage) could prevent or delay the onset of type 2 diabetes in study participants.
Method Theaddition ofmetformin alsoproduced a dramatic effect
AIM• The DPP contributed to a better understanding of how diabetes develops in people at risk and how they can prevent or delay the development of diabetes by making behavioral changes leading to weight loss.• DPP researchers continue to examine the roles of lifestyle and metformin and other diabetes medications in preventing type 2 diabetes.• They also continue to monitor participants to learn more about the study’s long-term effects through the Diabetes prevention Program Outcomes Study (DPPOS).• DPPOS is examining the impact of long-term risk reduction on diabetes-related health problems, such as nerve damage and heart, kidney, and eye disease.• The National Institute of Diabetes and Digestive and kidney Diseases supports a wide range of research related to the DPP, such as studies that assess cost-effective methods of delivering lifestyle modifications in group settings and over the internet, as well as methods to sustain behavior change and weight loss
How??• Weight gain is a common side effect for people who take insulin — a hormone that regulates the absorption of sugar (glucose). The more insulin you use to control your blood sugar level, the more glucose that gets into your cells and the less glucose thats wasted in your urine. Glucose that your cells dont use accumulates as fat. If you continue to eat as you did before, youll likely gain weight when you start taking insulin.• Think about it this way: Before starting insulin, you could eat more food than you needed without gaining weight because your body didnt use the food properly. But with insulin, your body uses food properly, and you may need less food than you think.
Pancreas transplants are generally performedtogether with or some time after a kidney transplant?• but why with kidney?• 1-new kidney requires taking immunosuppressive drugs such as ciclosporin. Nevertheless this allows the introduction of a new, functioning pancreas to a patient with diabetes without any additional immunosuppressive therapy• 2-pancreas transplants alone can be wise in patients with extremely labile type 1 diabetes mellitus
insulin-producing cells are transplanted into body organs• where is residence of cells ?• in liver• advantages:• 1-less invasive• 2-higher rates of success• Recent studies have shown that islet cell transplants have progressed to the point that 58% of the patients in one study were insulin independent one year after islet cell transplant.(1)• 2-disadvantage:• 1- immunosuppressant drugs must be given to prevent the body from rejecting the transplanted cells.• 2-failure of transplant• solution:• but scientists in New Zealand are also looking into placing them within a protective housing derived of seaweed which enables insulin to flow out and nutrients to flow in while protecting the islets from immune system attack via white blood cells
BCG research• role of TNF alpha :is part of the immune system. It helps the immune system distinguish self from non-self tissue. People with type 1 diabetes are deficient in this substance•• theory:• Dr. Denise Faustman theorizes that giving Bacillus Calmette-Guérin (BCG) which stimulates TNF-α production. TNF-α kills the white blood cells responsible for destroying beta cells,• efficacy• prevents, or reverses diabetes. She has reversed diabetes in laboratory mice with this technique.
a vaccine has been proposed• a-Diamyd:(2)• clinical trial :GAD65, an autoantigen involved in type 1 diabetes, has in clinical trials delayed the destruction of beta cells for at least 30 months• efficacy:• 1-Phase III trials are under way in the USA and in Europe• 2- Two prevention studiehere the vaccine is given to persons who have not yet developed diabetes, will start in 2009(3)
Stem cells approach• a-South Korea• In January 2006, a team of South Korean scientists has grown pancreatic beta cells, which can help treat diabetes, from stem cells taken from the umbilical cord blood of newborn babies.• b-University of North Carolina• In September 2008, scientists from the University of North Carolina at Chapel Hill School of Medicine have announced their success in transforming cells from human skin into cells that produce insulin• BUT HOW ?• The skin cells were first transformed into stem cells and then had been differentiated into insulin-secreting cells.
Gene therapy approach• A-viral vector method :• 1-oral medication, consisting of viral vectors containing the insulin sequence, is digested and delivers its genes to the upper intestines• 2-Those intestinal cells will then behave like any viral infected cell, and will reproduce the insulin protein• 3-The virus can be controlled to infect only the cells which respond to the presence of glucose, such that insulin is produced only in the presence of high glucose levels.• 4-BUT Due to the limited numbers of vectors delivered, very few intestinal cells would actually be impacted and would die off naturally in a few days• 5-BUT SOLVED -----------amount of oral medication used again and so on (4)• B-cure the cause of beta cell destruction (5)• C-turn duodenum cells and duodenum adult stem cells into beta cells (6)• not well understood but this what happens• 1-By delivering beta cell DNA to the intestine cells in the duodenum, a few intestine cells will turn into beta cells• 2-adult stem cells will develop into beta cells• 3-This makes the supply of beta cells in the duodenum self replenishing, and the beta cells will produce insulin in proportional response to carbohydrates consumed
Insulin pump• future developments:• A-When insulin pump technology is combined with a continuous blood glucose monitoring system, the technology seems promising for real-time control of the blood sugar level. Currently there are no mature algorithms to automatically control the insulin delivery based on feedback of the blood glucose level.the system may function as an artificial pancreas• B-Insulin pumps are being used for infusing pramlintide (brand name Symlin, or synthetic amylin) with insulin for improved postprandial glycemic control compared to insulin alone.• C-bolus calculators: Pump software helps by calculating the dose for the next insulin bolus. The user enters the grams of carbohydrates to be consumed, and the bolus "wizard" calculates the units of insulin needed• D-custom alarms: The pump can monitor for activities during specific times of day and alarm the user if an expected activity did not occur. Examples include a missed lunch bolus, a missed blood glucose test