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Archive - 06 - 2007
June 29, 2007 (EurekAlert) - Researchers at the University of Warwicks Warwick Medical School have uncovered a process that locks the bodys metabolism in a diabetic state after only relatively limited exposure to high glucose levels.Researchers were already aware that there seems to be a point of no return in the onset of diabetes. This was apparent in the Diabetes Complications and Control Trial (DCCT) in the 1990s when Type 1 diabetic patients were either placed on standard or intensive treatment regimens to normalize their glucose levels. Because complications were so profoundly reduced in patients with tight glucose control, all the remaining DCCT patients were switched early onto intensive therapy. However a follow-up study found that several years after switching to intensive therapy the patients who started the trial on only the standard treatment regimen continued to have more complications than those who received intensive therapy throughout the trial.Research since has speculated that exposure to high glucose levels quickly creates a metabolic memory in which diabetes persists long after glucose levels have been corrected. Research to date suggested that oxidation played a role but the exact mechanism was unknown.The Warwick research team, led by Dr Antonio Ceriello, have now proven that the damage seems to be done in a process called glycation when early on in a period of high glucose levels glucose sugar molecules are able to bind to proteins in the mitochondria of cells (the parts of cells governing the production and regulation of energy). This persists even if glucose levels later fall to normal. This inhibits and distorts the mitochondrias normal function and results in an overabundance of the production of free radicals (or Reactive Oxygen Species ROS) which cause oxidation and thus continued diabetic complications.The Warwick Medical School researchers proved their hypothesis by taking tissue and exposing it to 2 weeks of high levels of glucose, followed by one week of normal glucose however for half the tissue they also applied several antioxidants at the end of the two weeks of high glucose. The tissue without antioxidants levels of glucose stress remained high but where antioxidants had been applied there was a dramatic fall in the incidence of free radicals and there was also a significant drop in 5 of the 6 key markers for high glucose stress.The Warwick Medical School research confirms the need for very early tight control of glucose levels to avoid diabetic complication and that that control must be supplemented with the use of antioxidant agents to mitigate the progression of complications.However long term use of antioxidants can in itself produce health problems so in a further research published this month the Warwick Medical School team have tested the use of the AT-1 receptor blocker Telmisartan and found it can be used in exactly the same way to suppress the build up of free radicals without the side affects that long term use of antioxidants would cause.Dr Ceriello is now beginning to look at how to move beyond simply suppressing the problematic production of free radicals and actually finding ways of reversing the glycation process itself thus erasing the harmful "metabolic memory".
June 29, 2007 (Newswise) Approximately 15,000 children and adolescents in the United States are diagnosed with type 1 diabetes, and about 3,700 youth are diagnosed with type 2 diabetes annually, according to estimates from a major national study called SEARCH for Diabetes in Youth. SEARCH, a multi-center study of childhood diabetes in racially and ethnically diverse populations, is the largest surveillance effort of diabetes among youth under the age of 20 conducted in the United States to date. The study covers 10 locations across the country where about 5.5 million children live. In a report in the June 26, 2007, issue of the Journal of the American Medical Association (JAMA), study investigators identified 2,435 youth who were diagnosed with type 1 and type 2 diabetes in 2002 and 2003. The estimated overall incidence of diabetes in youth is 24.3 per 100,000 per year. The number of youth with newly diagnosed diabetes varies across major U.S. racial and ethnic groups as well as across age groups, said lead author Dana Dabelea, MD, PhD, an associate professor of preventive medicine at the University of Colorado at Denver and Health Sciences Centers School of Medicine, and SEARCH principal investigator (PI) for the Colorado site. In children under the age of 10, most had type 1 diabetes, previously known as insulin-dependent diabetes, regardless of their race or ethnicity. Even among older youth ages 10-14, type 1 diabetes was frequent among non-Hispanic white (32.0 per 100,000 per year), African-American (19.2 per 100,000) and Hispanic adolescents (19.2 per 100,000 per year), but was much less common among Asian Pacific Islander (8.3 per 100, 000 per year) and American Indian youth (7.1 per 100,000 per year). In all age groups, the highest rates of type 1 diabetes were observed in non-Hispanic white boys and girls. SEARCH estimates of type 1 diabetes incidence are higher than the incidence of insulin-dependent diabetes mellitus reported by previous U.S. childhood diabetes registries. Type 1 diabetes is an autoimmune disease in which a persons own immune cells attack and destroy the beta cells of the pancreas, which produce the hormone insulin needed for survival. Researchers believe that the disease arises from a combination of susceptibility genes and an environmental trigger or triggers, such as an infectious agent or dietary component, that have not yet been identified. The study also found that newly diagnosed type 2 diabetes was extremely rare in children under age 10 and gradually increased with age. Among minority adolescents and young adults 15-19 years of age high rates were documented among American Indian (49.4 per 100,000 per year), Asian-Pacific Islander (22.7 per 100,000 per years), African American (19.4 per 100,000 per year) and Hispanic (17.0 per 100,000 per year) youth. Although still relatively infrequent, type 2 diabetes was, nevertheless, present among non-Hispanic white youth 15-19 years of age (5.6 per 100,000 per year). The incidence of type 2 diabetes in youth is consistent with the increasing rates of type 2 diabetes in adults. In both adults and children, this form of diabetes is closely linked to obesity, physical inactivity and a family history of type 2 diabetes. Reports of increasing incidence of both type 1 and type 2 diabetes in youth have been among the most concerning aspects of the evolving diabetes epidemic, said Ann Albright, PhD, and director of the CDCs Division of Diabetes Translation. The SEARCH study has provided a clear picture of diabetes burden among youth of all US major racial/ethnic groups. These estimates are essential to ultimately design and implement public health efforts to prevent type 1 diabetes, once prevention strategies are identified, and type 2 diabetes, and to reduce the risk for both acute and chronic complications of diabetes in youth.Information on the rates of diabetes in children is critical to developing policies to keep todays and tomorrows youth healthy, said Barbara Linder, MD, PhD, of the NIDDK. The control, and ultimately the cure and prevention, of diabetes are particularly important in children because the risk of complications increases with disease duration. Fortunately, new therapies are allowing children with diabetes to have improved outcomes. The study investigators will continue to track the incidence of diabetes in youth in all of the various population groups through 2009. Continuing this surveillance effort is essential to document temporal trends in the incidence of diabetes among various racial and ethnic groups and accurately assess the future health care burden of diabetes and its complications in the U.S. pediatric and young adult population, said Dabelea.The study was funded by the Division of Diabetes Translation at the Centers for Disease Control and Prevention (CDC) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), a part of the National Institutes of Health (NIH). It involves six clinical centers in the states of California (Jean Lawrence, ScD; PI), Colorado (Dana Dabelea, MD, PhD, PI, study vice-chairperson), Hawaii (Beatriz Rodriguez, MD, PI), Ohio (Lawrence Dolan, MD, PI), South Carolina (Elizabeth Mayer-Davis, PhD, PI, study chairperson) and Washington (Catherine Pihoker, MD, PI). The central laboratory for the study is the Northwest Lipid Research Laboratories in Seattle, Wash. (Santica Marcovina, PhD, PI). The coordinating center is at the Division of Public Health Sciences at Wake Forest University School of Medicine (Ronny Bell, PhD, PI).The School of Medicine faculty work to advance science and improve care as the physicians, educators and scientists at University of Colorado Hospital, The Childrens Hospital, Denver Health, National Jewish Medical and Research Center and the Veterans Administration Medical Center. The School is part of the University of Colorado at Denver and Health Sciences Center, one of three universities in the University of Colorado system.
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