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<h1>Welcome to the University of Virginia iGEM 2015 Wiki</h1>
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<p id="above-nav">University of Virginia iGEM 2015</p>
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<p id="above-nav">University of Virginia iGEM 2015</p>
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<p> General Questions?</p><p> Contact us by email <a href="mailto:virginia.igem@gmail.com">Virginia.iGEM@gmail.com</a> </p>
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<p> Wiki Questions?</p><p>Contact Dominic Ritchey by email at <a href="mailto:dmr5bq@virginia.edu">dominicritchey@email.virginia.edu</a></p>
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House of Carbs
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<p>A Novel Solution to Minimizing Postprandial Hyperglycemic Spikes</p>
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<h1>Project Overview</h1>
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<h3 id="h3-1">The Problem: Diabetes Mellitus and Hyperglycemia</h3>
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<p>From diabetes mellitus a number of devastating complications, such as amputations, blindness, crippling neuropathies, and many others, can arise from increased blood sugar levels on a regular basis, but many of
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the major complications of diabetes arise from drastic fluctuations in the blood glucose
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level (Ceriello et al., 2012). Up to two-thirds of people with diabetes die of
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cardiovascular disease (CVD) brought about by diabetes-related macrovascular diseases
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(Deshpande et al. 2008). In fact, the risk for cardiovascular disease mortality is 2 to 4
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times higher in people with diabetes than in people who do not have diabetes.
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Additionally, diabetic retinopathy is the most common microvascular complication
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among people with diabetes and results in more than 10,000 new cases of blindness per
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year. Retinopathy is associated with prolonged hyperglycemia; it is slow to develop, and
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there is some evidence that it can begin to develop as early as 7 years before clinical
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diagnosis of diabetes (Deshpande et al., 2008).
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</p>
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<p>Postprandial (post-meal) blood sugar spikes specifically are one of the most
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damaging complications of diabetes (Parkin et al., 2002). Many diabetics are able to
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effectively manage post-meal glycemic spikes with self-administered doses of insulin,
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but these hyperglycemic incidents still kill more Americans per year than any other
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diabetes-related complications (Parkin et al., 2002). Arguably, the gravest consequence of
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glycemic spikes in diabetes patients is the development of progressive macrovascular
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disease (MVD), which affects the large blood vessels of the body, hardening and
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blocking these vessels (Ceriello et al., 2012). MVD is the leading cause of death among
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T2DM patients in the United States, causing up to 65% of diabetes-related deaths, making it a huge target for diabetes treatments research (Deshpande et al., 2008). MVD
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also frequently leads to other severe complications such as ischemia in the extremities
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and blindness (Haffner et al., 1998).
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<h3 id="h3-2">Controlling Hyperglycemic Spikes</h3><div id="des2">
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<p>For many T1DM and T2DM patients, it has been shown that the regular
 
control and management of blood glucose levels prevents many of the vascular
 
complications of the disease, but most of the time control over glucose is difficult to
 
attain because the self-dosing insulin treatment system that a lot of moderately to
 
severely sick diabetes patients use is often hard to calibrate and use (Parkin et al., 2002).
 
</p>
 
<p>Compared to sucrose-rich food, starch-rich food has been found to create less
 
fluctuation in blood glucose levels, and thus is beneficial to diabetes patients and
 
hyperglycemia patients. There is evidence that this flatter response caused by a starch
 
rich meal is associated with the slower rate of digestion of complex sugars versus simple
 
sugars (Jenkins, Wolever, & Jenkins, 1988). Thus, if some of the simple sugars are first
 
converted into complex saccharides inside the E. coli and then released back into small
 
intestine, a similar flatter glycemic response will take place, which will be beneficial to
 
the patients.
 
</p></div>
 
<h3 id="h3-3">Our Devices</h3><div id="des3">
 
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<p style="margin-bottom:30px;"> We have assembled one plasmid with genes that dictate a controllable level of simple sugars uptake and one plasmid to produce glucan and fructan from simple sugars and then lyse to release the complex sugars back into the environment. In essence, this microbial device runs on two genetic devices -- an uptake circuit and a polymerization circuit. </p></div>
 
<p style="font-style:italic; border-top:1px dotted #007bb6"> In order to learn more details, please visit the <a href="/Team:Virginia/Project">Project page.</a> </p>
 
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<p>Show References</p>
 
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<h3>References</h3>
 
<p>A. Ceriello, S. Colagiuri, (2011). Guideline for management of postmeal glucose in
 
diabetes. International Diabetes Federation Guideline Development Group,
 
http://www.idf.org/sites/default/files/postmeal%20glucose%20guidelines.pdf ,
 
Accessed May. 6th, 2015
 
</p>
 
<p>American Diabetes Association (2014). National Diabetes Statistics Report.
 
http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf
 
Accessed May. 5th, 2015
 
</p>
 
<p>Anal, A. K., & Singh, H. (2007). Recent advances in microencapsulation of probiotics for
 
industrial applications and targeted delivery. Trends in Food Science &
 
Technology, 18(5), 240–251. http://doi.org/10.1016/j.tifs.2007.01.004
 
</p>
 
<p>Anan, F., Masaki, T., Eto, T., Fukunaga, N., Iwao, T., Kaneda, K., ... Yoshimatsu, H.
 
(2008). Postchallenge Plasma Glucose and Glycemic Spikes Are Associated with
 
Pulse Pressure in Patients with Impaired Glucose Tolerance and Essential
 
Hypertension. Hypertension Research, 31(8), 1565–1571.
 
http://doi.org/10.1291/hypres.31.1565
 
</p>
 
<p>AHFS Consumer Medication Information [Internet]. Bethesda (MD): American Society
 
of Health-System Pharmacists, Inc.; ©2008. Acarbose; [revised 2015 Feb. 15;
 
reviewed 2015 Apr. 28; cited 2015 May. 3]; Available from:
 
http://www.nlm.nih.gov/medlineplus/druginfo/meds/ a696015.html
 
</p>
 
<p>AHFS Consumer Medication Information [Internet]. Bethesda (MD): American Society
 
of Health-System Pharmacists, Inc.; ©2008. Pramlintide; [revised 2015 Feb. 15;
 
reviewed 2015 Apr. 28; cited 2015 May. 3]; Available from:
 
http://www.nlm.nih.gov/medlineplus/druginfo/meds/a605031.html
 
</p>
 
<p>Banguela, A., Arrieta, J. G., Rodríguez, R., Trujillo, L. E., Menéndez, C., & Hernández,
 
L. (2011). High levan accumulation in transgenic tobacco plants expressing the
 
Gluconacetobacter diazotrophicus levansucrase gene. Journal of Biotechnology,
 
154(1), 93–98. http://doi.org/10.1016/j.jbiotec.2011.04.007
 
</p>
 
<p>Barr EL, Zimmet PZ, Welborn TA et al. (2007). "Risk of cardiovascular and all-cause
 
mortality in individuals with diabetes mellitus, impaired fasting glucose, and
 
impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study
 
(AusDiab)". Circulation 116 (2): 151–7.
 
</p>
 
<p>Bernard, A. M., Anderson, L., Cook, C. B., & Phillips, L. S. (1999). What do internal
 
medicine residents need to enhance their diabetes care? Diabetes Care, 22(5),
 
661–666. http://doi.org/10.2337/diacare.22.5.661
 
</p>
 
<p>Boada C, Martínez-Moreno J. Pathophysiology of diabetes mellitus type 2: beyond the
 
duo "insulin resistance-secretion deficit.". Nutricion Hospitalaria [serial online].
 
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</p>
 
<p>B. Göke, H. F. (1995). Voglibose (AO128) Is an Efficient α-Glucosidase Inhibitor and
 
Mobilizes the Endogenous GLP-1 Reserve. Digestion, 56(6), 493–501.
 
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</p>
 
<p>Brown, J. B., Harris, S. B., Webster-Bogaert, S., Wetmore, S., Faulds, C., & Stewart, M.
 
(2002). The role of patient, physician and systemic factors in the management of
 
type 2 diabetes mellitus. Family Practice, 19(4), 344–349.
 
http://doi.org/10.1093/fampra/19.4.344
 
</p>
 
<p>Butterworth, P. J., Warren, F. J., & Ellis, P. R. (2011). Human α-amylase and starch
 
digestion: An interesting marriage. Starch - Stärke, 63(7), 395–405.
 
http://doi.org/10.1002/star.201000150
 
</p>
 
<p>Centers for Disease Control and Prevention. (2014). National Diabetes Statistics Report.</p>
 
<p>Chiasson, J.-L., Josse, R. G., Gomis, R., Hanefeld, M., Karasik, A., & Laakso, M. (2002).
 
Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM
 
randomised trial. The Lancet, 359(9323), 2072–2077.
 
http://doi.org/10.1016/S0140-6736(02)08905-5
 
</p>
 
<p>Chiasson, J.-L., Josse, R. G., Hunt, J. A., Palmason, C., Rodger, N. W., Ross, S. A., ...
 
Wolever*, T. M. S. (1994). The Efficacy of Acarbose in the Treatment of Patients
 
with Non–Insulin-Dependent Diabetes Mellitus: A Multicenter, Controlled
 
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http://doi.org/10.7326/0003-4819-121-12-199412150-00004
 
Crude and Age-Adjusted Rate per 100 of Civilian, Noninstitutionalized Population with
 
Diagnosed Diabetes, United States, 1980–2011. (2014, September 5). Retrieved
 
April 24, 2015, from
 
http://www.cdc.gov/diabetes/statistics/prev/national/figage.htm
 
</p>
 
<p>Dedonder, R. 1966. Levansucrase from Bacillus subtilis. Methods Enzymol. 8:500–505.</p>
 
<p>Deshpande, A. D., Harris-Hayes, M., & Schootman, M. (2008). Epidemiology of diabetes
 
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</p>
 
<p>D.M. Nathan, P.A. Cleary, J.Y. Backlund, S.M. Genuth, J.M. Lachin, T.J. Orchard, et al.,
 
Intensive diabetes treatment and cardiovascular disease in patients with type 1
 
diabetes, N Engl J Med, 353 (2005), pp. 2643–2653
 
</p>
 
<p>D.R. Whiting, L. Guariguata, C. Weil, J. Shaw, IDF diabetes atlas: global estimates of the
 
prevalence of diabetes for 2011 and 2030 Diabetes Res Clin Pract, 94 (2011), pp.
 
311–321
 
</p>
 
<p>Duncan, A. E. (2012). Hyperglycemia and Perioperative Glucose Management.Current
 
Pharmaceutical Design, 18(38), 6195–6203.
 
</p>
 
<p>Edelman, P. S., Maier, H., & Wilhelm, K. (2012). Pramlintide in the Treatment of
 
Diabetes Mellitus. BioDrugs, 22(6), 375–386. http://doi.org/10.2165/0063030-
 
200822060-00004
 
</p>
 
<p>Ferraris, R. P., Yasharpour, S. A. S. A. N., Lloyd, K. C., Mirzayan, R. A. F. F. Y., &
 
Diamond, J. M. (1990). Luminal glucose concentrations in the gut under normal
 
conditions. American Journal of Physiology-Gastrointestinal and Liver
 
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</p>
 
<p>Gay, P., Le Coq, D., Steinmetz, M., Ferrari, E., & Hoch, J. A. (1983). Cloning structural
 
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1431.
 
</p>
 
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Medicine, 164(10), 1134–1139. http://doi.org/10.1001/archinte.164.10.1134
 
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<p>Hoffmann, J., & Spengler, M. (1997). Efficacy of 24-Week Monotherapy With Acarbose,
 
Metformin, or Placebo in Dietary-Treated NIDDM Patients: The Essen-II Study.
 
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</p>
 
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</p>
 
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International Dairy Journal, 11(1–2), 1–17. http://doi.org/10.1016/S0958-
 
6946(01)00036-X
 
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</p>
 
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Absorption: Validation on Gold Standard Data. IEEE Transactions on Biomedical
 
Engineering, 53(12), 2472–2478. http://doi.org/10.1109/TBME.2006.883792
 
</p>
 
<p>Meigs, J. B., Nathan, D. M., Wilson, P. W., Cupples, L. A., & Singer, D. E. (1998).
 
Metabolic risk factors worsen continuously across the spectrum of nondiabetic
 
glucose tolerance. The Framingham Offspring Study. Annals of Internal Medicine,
 
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</p>
 
<p>Narimasa, S., Tatsuo, H., Mitsutaka, Y., & Toshio, I. (1979). Action of human pancreatic
 
and salivary α-amylases on maltooligosaccharides: Evaluation of kinetic
 
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</p>
 
<p>National Diabetes Data Group. (1979). Classification and Diagnosis of Diabetes Mellitus
 
and Other Categories of Glucose Intolerance. Diabetes, 28(12), 1039–1057.
 
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</p>
 
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<p>Parkin, C. G., & Brooks, N. (2002). Is postprandial glucose control important? Is it
 
practical in primary care settings?. Clinical Diabetes, 20(2), 71-76.
 
</p>
 
<p>Patterson, Joan (2013). Many Schools Cutting Back on Physical Education. Las Vegas
 
Review - Journal.
 
Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S.
 
adults. The Third National Health and Nutrition Examination Survey, 1988-1994.
 
</p>
 
<p>Peng, C.-K., Buldyrev, S. V., Havlin, S., Simons, M., Stanley, H. E., & Goldberger, A. L.
 
(1994). Mosaic organization of DNA nucleotides. Physical Review E, 49(2),
 
1685–1689. http://doi.org/10.1103/PhysRevE.49.1685
 
</p>
 
<p>Rathmann, W., & Giani, G. (2004). Global Prevalence of Diabetes: Estimates for the
 
Year 2000 and Projections for 2030: Response to Wild et al. Diabetes Care, 2568-
 
2569.
 
</p>
 
<p>Recorbet, G. H. I. S. L. A. I. N. E., Robert, C., Givaudan, A., Kudla, B., Normand, P., &
 
Faurie, G. (1993). Conditional suicide system of Escherichia coli released into
 
soil that uses the Bacillus subtilis sacB gene. Applied and environmental
 
microbiology, 59(5), 1361-1366.
 
</p>
 
<p>Ried, J. L., and A. Collmer. 1987. An nptI-sacB-sacR cartridge for constructing directed,
 
unmarked mutations in Gram-negative bacteria by marker exchange-eviction
 
mutagenesis. Gene 57:239–246.
 
</p>
 
<p>Riddle, M., Frias, J., Zhang, B., Maier, H., Brown, C., Lutz, K., & Kolterman, O. (2007).
 
Pramlintide Improved Glycemic Control and Reduced Weight in Patients With
 
Type 2 Diabetes Using Basal Insulin. Diabetes Care, 30(11), 2794–2799.
 
http://doi.org/10.2337/dc07-0589
 
</p>
 
<p>Saydah, S. H., Miret, M., Sung, J., Varas, C., Gause, D., & Brancati, F. L. (2001).
 
Postchallenge Hyperglycemia and Mortality in a National Sample of U.S. Adults.
 
Diabetes Care, 24(8), 1397–1402. http://doi.org/10.2337/diacare.24.8.1397
 
</p>
 
<p>Snelling, Anatasia; Korba, Casey; Burkey, Alyvia (2007). The National School Lunch
 
and Competitive Food Offerings and Purchasing Behaviors of High School
 
Students, 77(10), 701-705.
 
</p>
 
<p>Sonnenborn, Ulrich; Schulze, Jurgen. 2009. The Non-Pathogenic Escherichia coli strain
 
Nissle 1917 - Features of a Versatile Probiotic. Microbial Ecology in Health and
 
Disease, (21), 122-158.
 
</p>
 
<p>S.M. Haffner, S. Lehto, T. Ronnemaa, K. Pyorala, M. Laakso, Mortality from coronary
 
heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and
 
without prior myocardial infarction, N Engl J Med, 339 (1998), pp. 229–234
 
</p>
 
<p>Schultz, M. (2008). Clinical use of E. coli Nissle 1917 in inflammatory bowel disease.
 
Inflammatory Bowel Diseases, 14(7), 1012–1018.
 
http://doi.org/10.1002/ibd.20377
 
</p>
 
<p>Seifter, S., & Dayton, S. (1950). The estimation of glycogen with the anthrone reagent.
 
Archives of Biochemistry, 25(1), 191–200.
 
</p>
 
<p>Shulman, N. B., Martinez, B., Brogan, D., Carr, A. A., & Miles, C. G. (1986). Financial
 
cost as an obstacle to hypertension therapy. American Journal of Public Health,
 
76(9), 1105–1108.
 
</p>
 
<p>Suwattee, P., Lynch, J. C., & Pendergrass, M. L. (2003). Quality of Care for Diabetic
 
Patients in a Large Urban Public Hospital. Diabetes Care, 26(3), 563–568.
 
http://doi.org/10.2337/diacare.26.3.563
 
</p>
 
<p>Temelkova-Kurktschiev, T. S., Koehler, C., Henkel, E., Leonhardt, W., Fuecker, K., &
 
Hanefeld, M. (2000). Postchallenge plasma glucose and glycemic spikes are more
 
strongly associated with atherosclerosis than fasting glucose or HbA1c level.
 
</p>
 
<p>Diabetes Care, 23(12), 1830–1834. http://doi.org/10.2337/diacare.23.12.1830
 
What are normal blood glucose levels? Retrieved from Virginia Mason Medical Center
 
website: https://www.virginiamason.org/whatarenormalbloodglucoselevels.
 
Accessed: May. 5th ,2015
 
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