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{{Virginia}}
 
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<p>iGEM 2015</p>
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<p>Welcome the University of Virginia iGEM 2015 Wiki! Use the navigation bar at the top of every page to move between pages. Please let us know if you have any comments or questions about our project by visiting the “Contact Us” page.</p>
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<p>(click to close)</p>
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<p id="above-nav">University of Virginia iGEM 2015</p>
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<li><a href="/Team:Virginia/Team">Team</a></li>
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<li><a href="/Team:Virginia/Project">Project</a></li>
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<li><a href="/Team:Virginia/Practices">Policy and Practices</a></li>
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<li><a href="/Team:Virginia/Attributions">Attributions</a></li>
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<li><a href="/Team:Virginia/Contact_us">Contact Us</a></li>
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<h2>
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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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</h2>
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</div>
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<div id="description-wrapper">
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<div id="description-text-wrapper">
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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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<div id="des1">
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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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</p></div>
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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
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control and management of blood glucose levels prevents many of the vascular
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complications of the disease, but most of the time control over glucose is difficult to
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attain because the self-dosing insulin treatment system that a lot of moderately to
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severely sick diabetes patients use is often hard to calibrate and use (Parkin et al., 2002).
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</p>
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        <ul class = "pull-left">
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<p>Compared to sucrose-rich food, starch-rich food has been found to create less
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          <li><a href="2015.igem.org/Team:Virginia">Home</a></li>
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fluctuation in blood glucose levels, and thus is beneficial to diabetes patients and
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hyperglycemia patients. There is evidence that this flatter response caused by a starch
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rich meal is associated with the slower rate of digestion of complex sugars versus simple
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<li><a href="2015.igem.org/Team:Virginia/Team">Team</a></li>
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sugars (Jenkins, Wolever, & Jenkins, 1988). Thus, if some of the simple sugars are first
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          <li><a href="2015.igem.org/Team:Virginia/Project_main">Project</a></li>
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converted into complex saccharides inside the E. coli and then released back into small
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          <li><a href="2015.igem.org/Team:Virginia/Policy_and_practices">Policy and Practices</a></li>
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intestine, a similar flatter glycemic response will take place, which will be beneficial to
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          <li><a href="2015.igem.org/Team:Virginia/Support_and_sponsors">Support and Sponsors</a></li>
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the patients.
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<li><a href="2015.igem.org/Team:Virginia/Contact_us">Contact Us</a></li>
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</p></div>
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<h3 id="h3-3">Our Devices</h3><div id="des3">
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        <h1>University of Virginia iGEM 2015</h1>
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<p><a href="#">About the 2015 U.Va. iGEM team. </a></p>  
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</script>
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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>
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<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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<a href="javascript:void(0);"><div id="ref-button">
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<h3>Policy and Practices</h3>
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<p>Show References</p>
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<p><a href="#">Explore our policy and practices.</a></p>
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</div></a>
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<h3>References</h3>
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<h3>Sponsors and Support</h3>
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<p>A. Ceriello, S. Colagiuri, (2011). Guideline for management of postmeal glucose in
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<p><a href="#">Learn more about our sponsors.</a></p>  
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diabetes. International Diabetes Federation Guideline Development Group,
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<img src="https://encrypted-tbn3.gstatic.com/images?q=tbn:ANd9GcQUA5CF2C_kOVnWjyl62TA17VNs6RSsPIkrCejlLbtZ7rAVgzQxOQ">
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http://www.idf.org/sites/default/files/postmeal%20glucose%20guidelines.pdf ,
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      </div>
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Accessed May. 6th, 2015
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  <div class = "col-md-4">
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</p>
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<h3>Contact us</h3>
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<p>American Diabetes Association (2014). National Diabetes Statistics Report.
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<p><a href="#">Contact the 2015 U.Va. team.</a></p>
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http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf
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            <img src="https://encrypted-tbn3.gstatic.com/images?q=tbn:ANd9GcQUA5CF2C_kOVnWjyl62TA17VNs6RSsPIkrCejlLbtZ7rAVgzQxOQ">
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Accessed May. 5th, 2015
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  </div>
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</p>
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  <div class = "col-md-4">
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<p>Anal, A. K., & Singh, H. (2007). Recent advances in microencapsulation of probiotics for
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<h3>About iGEM</h3>
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industrial applications and targeted delivery. Trends in Food Science &
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<p><a href="#">Learn more about iGEM</a></p>
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Technology, 18(5), 240–251. http://doi.org/10.1016/j.tifs.2007.01.004
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<img src="https://encrypted-tbn3.gstatic.com/images?q=tbn:ANd9GcQUA5CF2C_kOVnWjyl62TA17VNs6RSsPIkrCejlLbtZ7rAVgzQxOQ">
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</p>
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<p>Anan, F., Masaki, T., Eto, T., Fukunaga, N., Iwao, T., Kaneda, K., ... Yoshimatsu, H.
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    </div>
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(2008). Postchallenge Plasma Glucose and Glycemic Spikes Are Associated with
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Pulse Pressure in Patients with Impaired Glucose Tolerance and Essential
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</div>
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Hypertension. Hypertension Research, 31(8), 1565–1571.
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http://doi.org/10.1291/hypres.31.1565
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</p>
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<p>AHFS Consumer Medication Information [Internet]. Bethesda (MD): American Society
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of Health-System Pharmacists, Inc.; ©2008. Acarbose; [revised 2015 Feb. 15;
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+
reviewed 2015 Apr. 28; cited 2015 May. 3]; Available from:
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http://www.nlm.nih.gov/medlineplus/druginfo/meds/ a696015.html
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height: 500px;
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</p>
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background-repeat: no-repeat;
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<p>AHFS Consumer Medication Information [Internet]. Bethesda (MD): American Society
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background-size: 100%;
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of Health-System Pharmacists, Inc.; ©2008. Pramlintide; [revised 2015 Feb. 15;
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background: url('https://encrypted-tbn3.gstatic.com/images?q=tbn:ANd9GcQUA5CF2C_kOVnWjyl62TA17VNs6RSsPIkrCejlLbtZ7rAVgzQxOQ');
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reviewed 2015 Apr. 28; cited 2015 May. 3]; Available from:
 +
http://www.nlm.nih.gov/medlineplus/druginfo/meds/a605031.html
 +
</p>
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<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].
 +
March 2, 2013;28:78-87. Available from: Fuente Académica, Ipswich, MA.
 +
Accessed April 16, 2015.
 +
</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.
 +
http://doi.org/10.1159/000201282
 +
</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
 +
Clinical Trial. Annals of Internal Medicine, 121(12), 928–935.
 +
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
 +
and diabetes-related complications. Physical therapy, 88(11), 1254-1264.
 +
</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
 +
Physiology, 259(5), G822-G837.
 +
</p>
 +
<p>Gay, P., Le Coq, D., Steinmetz, M., Ferrari, E., & Hoch, J. A. (1983). Cloning structural
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gene sacB, which codes for exoenzyme levansucrase of Bacillus subtilis:
 +
expression of the gene in Escherichia coli. Journal of bacteriology,153(3), 1424-
 +
1431.
 +
</p>
 +
<p>Gray, G. M., & Ingelfinger, F. J. (1966). Intestinal absorption of sucrose in man:
 +
interrelation of hydrolysis and monosaccharide product absorption. Journal of
 +
Clinical Investigation, 45(3), 388.
 +
</p>
 +
<p>Grant, R. W., Buse, J. B., & Meigs, J. B. (2005). Quality of Diabetes Care in U.S.
 +
Academic Medical Centers Low rates of medical regimen change. Diabetes Care,
 +
28(2), 337–442. http://doi.org/10.2337/diacare.28.2.337
 +
</p>
 +
<p>Grant, R. W., Pirraglia, P. A., Meigs, J. B., & Singer, D. E. (2004). Trends in complexity
 +
of diabetes care in the United States from 1991 to 2000. Archives of Internal
 +
Medicine, 164(10), 1134–1139. http://doi.org/10.1001/archinte.164.10.1134
 +
</p>
 +
<p>Halschou, K., Bukhave, K., & Rikardt, J. (2012). Intestinal Disaccharidase Activity and
 +
Uptake of Glucose from Sucrose. In S. Chackrewarthy (Ed.), Glucose Tolerance.
 +
InTech. Retrieved from http://www.intechopen.com/books/glucose-
 +
tolerance/intestinal-disaccharidase-activity-and-uptake-of-glucose-from-sucrose
 +
</p>
 +
<p>Hanahan, D. (1983). Studies on transformation of Escherichia coli with plasmids. Journal
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of Molecular Biology, 166(4), 557–580.
 +
</p>
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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.
 +
The American Journal of Medicine, 103(6), 483–490.
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Latest revision as of 14:29, 18 September 2015

iGEM 2015

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University of Virginia iGEM 2015

House of Carbs

A Novel Solution to Minimizing Postprandial Hyperglycemic Spikes

Project Overview

The Problem: Diabetes Mellitus and Hyperglycemia

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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 the major complications of diabetes arise from drastic fluctuations in the blood glucose level (Ceriello et al., 2012). Up to two-thirds of people with diabetes die of cardiovascular disease (CVD) brought about by diabetes-related macrovascular diseases (Deshpande et al. 2008). In fact, the risk for cardiovascular disease mortality is 2 to 4 times higher in people with diabetes than in people who do not have diabetes. Additionally, diabetic retinopathy is the most common microvascular complication among people with diabetes and results in more than 10,000 new cases of blindness per year. Retinopathy is associated with prolonged hyperglycemia; it is slow to develop, and there is some evidence that it can begin to develop as early as 7 years before clinical diagnosis of diabetes (Deshpande et al., 2008).

Postprandial (post-meal) blood sugar spikes specifically are one of the most damaging complications of diabetes (Parkin et al., 2002). Many diabetics are able to effectively manage post-meal glycemic spikes with self-administered doses of insulin, but these hyperglycemic incidents still kill more Americans per year than any other diabetes-related complications (Parkin et al., 2002). Arguably, the gravest consequence of glycemic spikes in diabetes patients is the development of progressive macrovascular disease (MVD), which affects the large blood vessels of the body, hardening and blocking these vessels (Ceriello et al., 2012). MVD is the leading cause of death among 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 also frequently leads to other severe complications such as ischemia in the extremities and blindness (Haffner et al., 1998).

Controlling Hyperglycemic Spikes

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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).

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.

Our Devices

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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.

In order to learn more details, please visit the Project page.

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References

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American Diabetes Association (2014). National Diabetes Statistics Report. http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf Accessed May. 5th, 2015

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

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