A Pathogenetic Model Of Type 1 Diabetes
In parallel to celiac disease, about one-fifth of Caucasians carry HLA-defined susceptibility to type 1 diabetes, whereas the lifetime cumulative incidence of clinical disease can be estimated to be close to 1%, indicating that only 5% of individuals with HLA-conferred predisposition progress to overt type 1 diabetes. Our hypothesis holds that progression to clinical diabetes requires the combination of genetic disease susceptibility, a critically timed trigger, and high subsequent exposure to a driving antigen. If any of these determinants is missing or any of the exogenous factors are inappropriately timed, the risk of type 1 diabetes would be minimal even in the presence of the other predisposing elements. Such a model could explain why only a small minority of individuals with HLA-conferred genetic susceptibility to type 1 diabetes do present with overt disease. In addition to the trigger and the driving antigen, there are most likely a series of environmental factors modifying the fate and pace of the -cell destructive process, some having protective and other predisposing effects.
Zygosity And Type 1 Diabetes Status
Eighty-eight pairs and one triplet entered this study: 34 were MZ , 54 were DZ , and the triplet was trizygotic. Enrolled pairs were not different from nonparticipating ones with respect to gender , geographic origin , and proportions of same-gender vs. opposite-gender pairs . Participating twins are significantly younger than nonparticipants as a consequence of our ascertainment procedure involving only pediatric centers that lose diabetic patients as they become adults. Possible differences in zygosity or concordance between the two groups could not be tested because information on these two variables was not available for nonparticipants.
Overall, there were 104 affected twins, almost equally distributed between genders . Mean age at enrollment was 15.8 yr . Type 1 diabetes was diagnosed at a mean age of 8.1 yr with no gender differences . Median age at onset was 6.9 yr in index twins, 9 yr in cotwins, and 7.6 yr in all affected twins . Ninety-four percent of index twins were diagnosed at a pediatric age . The test for heterogeneity of mean age at diagnosis in index twins by zygosity, gender, and type 1 diabetes concordance did not detect any significant difference.
More Information On Genetics
If you would like to learn more about the genetics of all forms of diabetes, the National Institutes of Health has published The Genetic Landscape of Diabetes. This free online book provides an overview of the current knowledge about the genetics of type 1 and type 2 diabetes, as well other less common forms of diabetes. The book is written for health care professionals and for people with diabetes interested in learning more about the disease.
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Other Defined Loci Gwa And Microarrays
Besides these well-established non-HLA loci, a number of other associations with T1D have been reported for IL2RA/CD25 , SUMO4 and IFIH1 . Of these 3 genes, the clearest confirmation is for IL2RA , with the finding of more than 1 SNP associated with T1D. The IL2RA/CD25 locus is implicated in a number of autoimmune disorders including multiple sclerosis, but in that case a different SNP is associated with increased risk. The IL2RA/CD25 SNPs associated with risk for T1D have been shown to have different circulating concentrations of CD25 despite extensive overlap between concentrations, this variation in concentration is highly significant when a large number of individuals are studied . The mechanism by which the SNPs contribute to diabetes risk is currently unknown, and may be complex given 2 associated SNPs in the same locus, neither of which alters the coding sequence.
Several GWA studies of T1D have now been performed and reported . A GWA study for T1D was completed in 2007 by the Wellcome Trust Case Control Consortium, which reported signals at known loci and also described signals at several novel loci . The associations at 12q24, 12q13, 16p13, and 18p11 were confirmed in other recent independent studies . Additional follow-up studies and metaanalyses of GWA have increased the list of new T1D loci to more than 40.
Deep Sleep Diabetes Remedy
When Scott Hansen was faced with the raw possibility of losing his better half to Type 2 Diabetes, he was desperate to locate a solution for her. He located a possible service when he met an old good friend Tom, that had apparently reversed his Type 2 Diabetes, shed 40lbs and currently looked like he was 10 years younger, and much healthier. is type 1 diabetes hereditary or acquired
Tom directed Scott towards a neighborhood doctor he had fulfilled in Thailand. It was additionally this physician that patiently clarified to Scott concerning the real root cause of type 2 diabetes mellitus and how to address it using an unique tea formula.
After verifying the info versus readily available research study, Scott quickly got down to providing his partner this specific tea formula. To his pleasure, he saw her problem improve. It was additionally then, that they agreed even more people needed this solution. They worked with a clinical study and also nourishment specialist and fine-tuned the service into a program: The Deep Sleep Diabetes Remedy. is type 1 diabetes hereditary or acquired
This value-packed program includes these sections as well as a lot more:
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Genetic Markers In Prediction Of T1d
A number of large population-based studies have been carried out stratifying individuals at birth by HLA genotype and insulin gene polymorphisms. Children born in Denver with the highest risk genotype DR3/4-DQ8 comprise 2.4% of newborns and almost 50% of children developing antiislet autoimmunity by age 5 . The BabyDiab study of offspring of patients with T1D in Germany and the Diabetes Prediction and Prevention study from Finland provide similar information concerning the risk associated with specific HLA genotypes and insulin gene polymorphisms . Risk can be further stratified by selection of children with susceptible genotypes at other diabetes genes , by selection of children with a multiple family history of diabetes , and by selection of relatives that are HLA identical to the proband . In the DAISY cohort, siblings of children with T1D who have the highest risk HLA DR3/DR4-DQ8 and are identical by descent for both HLA haplotypes with their diabetic proband sibling were found to have a 65% risk for developing islet autoantibodies by age 7 years and a 50% risk of developing diabetes by age 10 years . These findings suggest that additional MHC-linked genes determine T1D risk.
HLA DR3/DR4-DQB1*0302 siblings progression to islet autoimmunity and T1D grouped by the number of MHC haplotypes shared with proband siblings
Can You Reduce Your Risk
While family history does increase your risk, simply having a genetic predisposition doesn’t ensure you will develop diabetes. If you have a family history of gestational diabetes or type 2 diabetes, there are ways to reduce your risk of developing the disease.
Maintain a healthy weight or losing weight if you are overweight, particularly in the abdominal area, to reduce risk. Even modest weight reduction, about 5% to 10% weight loss, can reduce your risk. For people who are pregnant, gaining weight slowly rather than excessively can help to prevent gestational diabetes.
Stay active. Aim to exercise at least 150 minutes per week and avoid sitting for extending periods of time.
Eat more plants,such as fruits, vegetables, legumes, nuts, seeds, and whole grains. This has also been associated with a reduced risk of developing type 2 diabetes.
Health maintenance and regular checkups are important. If you’ve recently gained weight or are feeling very sluggish and tired, you may be experiencing high blood sugar, which is characterized by insulin resistance.
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How Type 1 Is Different From Type 2
Although type 1 diabetes and type 2 diabetes may seem similar, they are .
- With type 1 diabetes, the body cant produce insulin properly due to the destruction of the insulin-producing cells in the pancreas. This condition is an autoimmune disorder caused primarily by genetic factors.
- With type 2 diabetes, the body cant use insulin properly and, in some cases, may not be able to produce enough insulin either. This condition is caused by lifestyle factors and genetics.
While type 1 diabetes is the condition that has the strongest genetic risk factors, there are also certain genetic risk factors for type 2 diabetes as well, including family history, age, and race.
Potential Driving Antigens In Preclinical Type 1 Diabetes
There is no direct evidence of an exogenous antigen driving the type 1 diabetes disease process from initial -cell autoimmunity to clinical disease. Accordingly, this idea is based on indirect data and parallels with celiac disease, and it has to be critically considered. In general terms, one may argue that the driving antigen must represent a relatively common exposure among the population in most developed countries, and one can also assume that there must be some variability in the exposure within and across populations. In addition, one may hypothesize that the candidate antigen must comprise original or processed structural motifs bound by HLA molecules encoded by major histocompatibility complex class II susceptibility genes and presented effectively to T-cells by antigen-presenting cells.
From a theoretical point of view, a dietary antigen would fit well into the role as the factor driving the disease process toward clinical type 1 diabetes, since the exposure to most dietary factors tends to be frequent, and still there is some variation in the exposure both within and across populations. Bovine insulin is an attractive candidate, since an immune response initially induced by bovine insulin will cross-react and may target human insulin in the -cell.
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Is Diabetes Genetic Or Acquired
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What Happens To The Pancreas
In type 1 diabetes, the pancreas, a large gland behind the stomach, stops making insulin because the cells that make the insulin have been destroyed by the bodys immune system. Without insulin, the bodys cells cannot turn glucose , into energy.
The onset of type 1 diabetes occurs most frequently in people under 30 years, however new research suggests almost half of all people who develop the condition are diagnosed over the age of 30. About 10-15 per cent of all cases of diabetes are type 1.
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These Are Some Of The Statistics:
- 80-90% of people with Type 2 diabetes have other family members with diabetes.
- 10-15% of children of a diabetic parent will develop diabetes.
- If one identical twin has type 2 diabetes, there is up to a 75% chance that the other will also be diabetic.
- There are many genetic or molecular causes of type 2 diabetes, all of which result in a high blood sugar.
- As yet, there is no single genetic test to determine who is at risk for type 2 diabetes.
- To develop type 2 diabetes, you must be born with the genetic traits for diabetes.
- Because there is a wide range of genetic causes, there is also a wide range in how you will respond to treatment. You may be easily treated with just a change in diet or you may need multiple types of medication.
The hallmark of type 2 diabetes is resistance to the action of insulin and insufficient insulin to overcome that resistance
Is Type 2 Diabetes Increasing
Type 2 diabetes is increasing at an epidemic rate, and is being diagnosed at younger and younger ages. The most likely reason for this increase is that individuals with a genetic susceptibility to type 2 diabetes are developing the disease due to lifestyle changes namely less physical activity, weight gain, and longer life span.
The good news is that scientific research confirms that by eating healthy foods, exercising regularly and maintaining an ideal body weight, you can delay or prevent the onset of type 2 diabetes.
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Genes And Family History
As in type 1 diabetes, certain genes may make you more likely to develop type 2 diabetes. The disease tends to run in families and occurs more often in these racial/ethnic groups:
- African Americans
- Native Hawaiians
- Pacific Islanders
Genes also can increase the risk of type 2 diabetes by increasing a persons tendency to become overweight or obese.
Why Is The Incidence Of Type 1 Diabetes Rising Among Children In Developed Countries
There has definitely been an increase in the incidence of childhood type 1 diabetes in most industrialized countries after World War II . Whether this reflects a population-wide increase or is a consequence of decreasing average age at disease presentation is controversial. A recent Swedish study reported that there was no significant change in the overall incidence of type 1 diabetes over a 16-year period in the Swedish population below the age of 35 years, but there was a shift toward a younger age at diagnosis both among males and females . In contrast, there seems to be a concomitant increase in incidence as well as a decrease in average age at diagnosis among the population below the age of 30 years according to preliminary Finnish data .
Reducing The Risk Of Passing On Diabetes
Researchers have yet to discover all the genetic risk factors for diabetes, and it is not yet possible for everyone to have genetic testing to determine their risk.
However, people who know that they are more likely to develop the condition can often take steps to reduce their risk.
Genetic testing can predict type 1 diabetes and distinguish between types 1 and 2 in some people.
Researchers are still working on genetic tests that can predict type 1 and type 2 diabetes.
Anyone who is interested should ask their doctor about these tests.
Genes Ethnicity And Geography May All Play A Role
There are several risk factors that may make it more likely that youll develop type 1 diabetesif you have the genetic marker that makes you susceptible to diabetes. That genetic marker is located on chromosome 6, and its an HLA complex. Several HLA complexes have been connected to type 1 diabetes, and if you have one or more of those, you may develop type 1. actually develop type 1.)
Other risk factors for type 1 diabetes include:
Viral infections: Researchers have found that certain viruses may trigger the development of type 1 diabetes by causing the immune system to turn against the bodyinstead of helping it fight infection and sickness. Viruses that are believed to trigger type 1 include: German measles, coxsackie, and mumps.
- American Diabetes Association. Standards of Medical Care in Diabetes2009. Diabetes Care. 2009 32:S13-61.
Members Of The Type 1 Diabetes Genetics Consortium
Asia-Pacific Network: Eesh Bhatia, Francois Bonnici, Pik To Cheung, Peter Colman, Andrew Cotterill, Jenny Couper, Ric Cutfield, Elizabeth Davis, Tim Davis, Paul Dixon, Kim Donaghue, Paul Drury, Mark Harris, Len Harrison, Tim Jones, Uma Kanga, Alok Kanungo, Betty Kek, Jeremy Krebs, Yann-Jinn Lee, Margaret Lloyd, Amanda Loth, Narinder Mehra, Grant Morahan, C.B. Sanjeevi, Brian Tait, Mike Varney, Jinny Willis, Loke Kah Yin, Goh Siok Ying.
North American Network: Alan Aldrich, Mark Anderson, Christophe Benoist, Noureddine Berka, Patrick Concannon, Mark Daly, Jayne Danska, Larry Dolan, David Donaldson, Alessandro Doria, Janice Dorman, George Eisenbarth, Henry Erlich, Pamela Fain, Rosanna Fiallo-Scharer, Kenneth Gabbay, Daniel Geraghty, Soumitra Ghosh, Steven Gitelman, Nat Goodman, Gregory Goodwin, Carla Greenbaum, William Hagopian, John Hansen, Joel Hirschhorn, Leroy Hood, Kevin Kaiserman, Jean Lawrence, Victoria Magnuson, Jennifer Marks, John Mayberry, Elizabeth Mayer-Davis, Richard McIndoe, Brad McNeney, Eric Mickelson, Antoinette Moran, Gerald Nepom, Janelle Noble, Jill Norris, Tihamer Orban, David Owerbach, Andrew Paterson, Catherine Pihoker, Constantin Polychronakos, Alberto Pugliese, Philip Raskin, Marian Rewers, Henry Rodriquez, Jerry Rotter, Monique Roy, Desmond Schatz, Gary Schoch, Jin-Xiong She, Richard Spielman, Andrea Steck, Kent Taylor, Jay Tischfield, Ellen Toth, Diane Wherrett, Stephen Willi, Darrell Wilson, Lue Ping Zhao.