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Type 2 Diabetes Mellitis (T2DM), also known as adult-inset diabetes, is the most common form of diabetes, and is characterized by hyperglycemia due to relative deficiency of insulin, known as insulin resistance. Researchers at McGill University in Montreal tested 392,935 single-nucleotide polymorphisms in a French case-control cohort. In total, T2DM association was tested for 100,764 (human1) and 309,163 (Hap300) SNPs representing 392,935 unique loci (Figure 1). Markers were selected for assessment in the second cohort using significance thresholds on the basis of the divergence between the observed and expected P-values. The stage 1 results included the known association with the TCF7L2 SNP rs7903146 and several other SNPs at that locus also illustrated Genome-wide significance after correcting for 392,935 tests. Of the 57 SNPs tested in stage 2, 8 SNPs representing 5 unique loci showed significant association based on P-values calculated using 10 million permutations of the disease state labels (Table 1). Fast-track stage 2 genotyping confirmed the reported association for TCF7L2 (rs7903146) on chromosome 10, and in addition identified significant associations for 7 SNPs representing 4 novel loci (table 1, above). SNPs rs1111875 and rs7923837 are located near the telomeric end of a 270-kb linkage disequilibrium block on chromosome 10 (Figure 2B). To do this, the population attributable risk (PAR) was calculated for each marker (Table 1). The T2DM risk loci that were identified by this study involve genes implicated in pancreatic development and the control of insulin secretion. Consumption of low-fat dairy lowers the odds of developing type 2 diabetes by about 10% for each additional serving per day. High-fat dairy products, as a group, show no significant association with type 2 diabetes, although some studies suggest that cheese may be preventative. Type 2 diabetes describes a condition where cells that would normally respond to insulin by absorbing glucose from the blood stop doing so, allowing blood glucose to rise to unhealthy levels. Typically during the development of type 2 diabetes, the number of functional insulin receptors sitting on the surface of fat and muscle cells decreases over time. Experiments with both mice [1] and people [2] show that eating whey protein stimulates the insulin-producing cells in the pancreas to work harder than they normally would. One study [3] on type 2 diabetics reported that when whey protein is added to a meal of easy-to-digest carbohydrates, blood insulin levels are hiked by 57%. Whey’s benefits are also implied by studies that link the consumption of dairy products to an overall lower likelihood of developing diabetes. A meta-analysis [4] conducted in 2011 by researchers at Soochow University in Suzhou, China, brought the results of seven cohort studies together. Perhaps the most instructive individual cohort study is the one that followed its participants for the longest time. Eight European countries, 340,000 people in total, are taking part in EPIC InterAct, a study that aims to unpick the genetic and lifestyle factors that contribute to type 2 diabetes risk. Although many questions remain unanswered, this research is heartening, particularly for people with a family history of type 2 diabetes.
The genome of patients with type 2 diabetes (DT2) has been elucidated, for the first time, thanks to the use of new DNA chip technologies allowing 400,000 DNA mutations to be studied simultaneously. There are more than 200 million diabetics worldwide, and it has been predicted that this number will double by 2030. Initially, DNA from non-obese patients with type 2 diabetes and a family history of the disease was compared with DNA from 669 non-diabetic subjects from the DESIR study, a prospective study run by INSERM and directed by Beverly Balkau. TCF7L2 and HHEX encode transcription factors (molecules regulating the activity of other genes) controlling the Wnt signalling pathway essential for cell survival. EXT2 encodes an enzyme involved in the foetal development of several organs, including the pancreas. This work has predictive value and has potential implications for DT2 prevention and treatment. These results from the analysis of very high-density DNA chips — the first in the world for a common disease like DT2 — demonstrate the validity of this approach. Millions of cases of diabetes in 2000 and projections for 2030, with projected percent changes. Notes: 1) The continuation of this work will require DNA samples from a larger number of French subjects. Robert Sladek, Ghislain Rocheleau, Johan Rung, Christian Dina, Lishuang Shen, David Serre, Philippe Boutin, Daniel Vincent, Alexandre Belisle, Samy Hadjadj, Beverley Balkau, Barbara Heude, Guillaume Charpentier, Thomas J. The next EGID International Symposium will be held on 29 and 30 November in Lille Grand Palais. Markers with the most significant difference in genotype frequencies between cases of type 2 diabetes control were then tested in a second cohort, identifying 4 loci containing variants that confer type 2 diabetes risk. In the first stage, they obtained genotypes from 392,935 single-nucleotide polymorphisms in 1,363 T2DM cases and controls. Because there were unequal numbers of males and females in the study, 12,666 sex-chromosome SNPs were analyzed separately for each gender. 59 SNPs were then prioritized from stage 1 due to significant T2DM association, including one of the eight significant TCF7L2 markers.


The first involves 3 SNPs within introns of exostatin2 (EXT2) at the telomeric end of a linkage disequilibrium block on chromosome 11q (Figure 2C).
Stepwise logistic regression showed that one SNP per locus explains the entire effect of the locus and that there was no significant epistaxis between loci.
Also, these loci may also affect the peripheral response to insulin, suggesting a more complex combination of multiple genes associated with characteristics common in T2DM. Therefore, the signal these cells receive for any given amount of circulating insulin slowly wanes. More importantly, the blood glucose levels of the diabetics in the study were 21% lower than they were after they ate a control meal.
They report a 14% reduction in the risk of type 2 diabetes in people with high dairy consumption compared to people with very low diary consumption. They confirm that consuming dairy products as an adult offers modest protection against type 2 diabetes. Another component was brought into the spotlight by a closer analysis of the particular kinds of dairy products that are good for diabetics. The researchers running EPIC InterAct have not found any statistically significant anti-diabetic benefit to drinking lots of milk [6].
Like obesity, diabetes can have devastating medical consequences over time—indeed, it is the primary non-traumatic cause of blindness and kidney failure in developed countries.
Researchers James Doidge and colleagues [8] asked how much increasing the consumption of dairy in Australia could cut the national healthcare bill. This increase in the number of diabetics is linked to the obesity epidemic, which currently affects 1.1 thousand million people, including 150 million children. This method is based on the use of DNA chips, with a surface of only a few square centimetres, carrying almost half a million DNA mutations.
The key results of this first screening were then confirmed in more than 5500 French diabetic patients treated at Corbeil-Essonnes Hospital (Guillaume Charpentier) and Poitiers University Hospital (Samy Hadjadj) and in additional control subjects. At a time when the number of diabetics is soaring due to the increasing frequency of early, severe obesity, we need to be able to establish the profile of the young adults most at risk; this would allow personalised preventive strategies to be implemented. The method will be made available in France in March 2007, through the CNRS genotyping platform at Lille, largely funded by the Nord-pas-de-Calais Regional Council. He is also a Marie Sklodowska-Curie Individual Fellow supported by the European Commission (2016-2018). Within his PhD programme, he received one year’s training in the Nutrition and Genomics Lab at Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in the USA, where he worked on the project of gene-nutrient interaction on diabetes traits. Pre-conceptional intake of folic acid supplements is inversely associated with risk of preterm birth and small-for-gestational-age birth: a prospective cohort study.
Circulating 25-hydroxyvitamin D, IRS1 variant rs2943641 and insulin resistance: replication of a gene-nutrient interaction in four populations of different ancestries.
Modulation by dietary fat and carbohydrate of IRS1 association with type 2 diabetes traits in two populations of different ancestries. Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies.
Common symptoms associated with Type 2 Diabetes include excess thirst, frequent urination, and constant hunger. The first loci was the known associative TCF7L2 gene, which has already been implicated in association with type 2 diabetes in multiple populations.
Genotypes for each subject were obtained using two platforms: Illumina Infinium Human1 Bead Arrays (assay 109,365 SNPs chosen using a gene-centered design) and Human Hap300 BeadArrays (assay 317,503 SNPs chosen to tag haplotype blocks identified by the Phase I HapMap). Genotypes for the 57 SNPs were obtained from 2,617 cases and 2,894 controls, and the SNPs were analyzed in the same way as they were in stage 1.
Confirmed association results association, the Wald Test (3 ) was used to assess the effects of age, sex, and BMI on the association between the markers and T2DM.
SLC30A8 encodes a zinc transporter expressed only in the secretory vesicles of beta-cells of the pancreas, and has involvment in the final stages of insulin biosynthesis, in which co-crystallization with zinc occurs. EXT2 modulates hedgehog signalling, a pathway involved in early pancreatic development and the regulation of insulin synthesis.
Various studies link the regular consumption of low-fat dairy products to reduced odds of developing type 2 diabetes.
In other words, the body’s internal message relaying that it’s time to remove glucose from the blood gets communicated more loudly. This dose-dependent effect implies a 10% reduction in the odds of getting type 2 diabetes with each additional daily serving of low-fat dairy.
They began enrolling in the study in 1989 and have filled in biennial lifestyle questionnaires ever since. The place to study such a topic is Europe, where high dairy consumption is combined with strong national preferences.
But, after statistically correcting for all sorts of risk factors, including obesity, they have reported that a diet rich in fermented dairy products, including cheese, is protective.
They include the zinc transporter of pancreatic insulin-secreting cells (ZnT8), which is a potential target for treatment.


These results demonstrate very strong associations between DT2 and at least four genes encoding proteins playing major roles in the development of the pancreas and of insulin-producing cells: TCF7L2, HHEX, EXT2 and SLC30A8. Some of the genes identified in this study, including the ZnT8 zinc transporter gene in particular, may be good targets for treatments to combat DT2. These advances should make it possible to unravel genetic predisposition to vascular complications of diabetes and to solve the mysteries shrouding childhood obesity and certain cancers linked to obesity(1).
The major interests of his current research are 1) genetic and dietary determinants of nutritional biomarkers, such as plasma fatty acids, circulating 25(OH)D, vitamin C and carotinoids; and the associations of the nutritional biomarkers with metabolic markers and type 2 diabetes.
The main cause of type 2 diabetes is obesity in those who are genetically predisposed to the disase.
A wald test is used when a relationship exists within or between data items and is used to test the true value of the parameter based on the sample estimate. Another study illustrated that overexpression of SLC30A8 in insulinoma cells resulted in increased glucose-stimulated insulin secretion.
This block also was found to contain ALX4, a homeodomain protein with possible involvement in the Wnt signalling pathway. And this counteracts the lessened ‘listening’ ability of those cells whose job it is to pick up blood sugar. This suggests the mixed results from other cohorts might boil down to when and for how long the researchers tracked the participants.
The French, for example, eat a lot of cheese, meanwhile the Swedes and Dutch get through large quantities of yogurt. Whether they are correct or not, the ballpark their calculation landed in is surely worthy of attention.
This study of the French population was carried out as a French-British-Canadian collaboration between the teams directed by Philippe Froguel (CNRS, University of Lille 2, Pasteur Institute, Imperial College London) and Rob Sladek (McGill University, Montreal, Canada).
Froguel and Mellitech, a biotech company from Grenoble, ZnT8 is the only molecule apart from insulin produced exclusively in the insulin-secreting beta cells of the pancreas. The work of this French-British-Canadian team was financed principally by the Canadian government and by the province of Quebec.
It is causally linked to a number of the leading causes of mortality and morbidity in the UK, including type 2 diabetes, cardiovascular disease and some cancers. 2) prenatal risk factors and early infant feeding practice with growth pattern and adiposity in Chinese children. Most can manage type 2 diabetes by making dietary changes and increasing the amount of exercise that they engage in.
About 70% of the genetic risk of DT2 is accounted for by these new discoveries, published online in Nature on February 11 2007.
These individuals become hyperglycaemic when they put on weight and are resistant to the insulin they produce. Zinc is a  trace element present in very small amounts in the body, but essential for survival. It also has a significant economic impact, with high costs to the health service and to the wider economy.
If these changes do not adequately lower blood glucose, medications metformin or insulin may be necessary.
The team of Philippe Froguel was the first to identify a gene associated with DT2 — that encoding glucokinase — in 1992. Zinc deficiency is common in developing countries and has been associated with many diseases, including diabetes.
In England today, more than two-thirds of men and more than half of women are overweight or obese. Several other such genes have since been discovered, but together these genes account for only a small proportion of DT2 cases. Insufficient knowledge of the human genome and the absence of cheap, simple-to-use, rapid analytical techniques hampered progress in medical research for many years. Obesity is also occurring earlier in life and more than one-third of children in England are overweight or obese by the time they start secondary school. The recent sequencing of the human genome and the establishment of a complete map of DNA variations in the human species have finally made it possible to explore genetic predisposition to DT2 in its entirety.
UK guidelines and policies for the prevention and management of obesity focus on the environmental causes, and current care guidelines make little mention of the role of genetics, other than in particularly severe or complicated cases.
The PHG Foundation report, a€?The genomics of obesitya€?, identifies a typical four-tier system of obesity services and care pathways in the NHS and proposes where and under what circumstances genetic testing for obesity could benefit patient care.



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