A Closer Look At New Developments In Diabetes
The prevalence of diabetes is increasing rapidly and is expected to reach epidemic proportion over the next decade. Recent research estimates that the number of people diagnosed with diabetes will rise from 23.7 million to 44.1 million between 2009 and 2034.1 The Centers for Disease Control and Prevention (CDC) further predict that up to one-third of U.S. adults could have diabetes by 2050 if Americans continue to gain weight and avoid exercise.2
Diabetes is associated with a myriad of complications with foot ulcerations being the most common. An estimated 15 percent of all patients with diabetes will develop foot ulcers.3 About half of these ulcers become infected and 20 percent of those patients will end up with some form of lower extremity amputation.3 With the prevalence of diabetes dramatically increasing, billions of dollars are spent in the field of diabetes research for the early diagnosis, prevention and management of this disease.
With that said, here is a closer look at current research in the field of diabetes and emerging methods of disease management.
What You Should Know About Biomarkers For Diabetes
Researchers are constantly studying biomarkers to help predict the possibility of developing certain diseases. Biomarkers can indicate a change in the expression or state of a protein that correlates with the risk or progression of a disease, or with the susceptibility of the disease to a given treatment.
Recently, researchers from the United Kingdom have reported that microRNA (MiR) can help identify people who are likely to develop type 2 diabetes even before the onset of symptoms.4 MicroRNAs are classes of approximately 22 non-coding nucleotide regulatory ribonucleic acid (RNA) molecules that play important roles in controlling the developmental and physiological processes.5 Specifically, microRNAs regulate gene expression including differentiation and development by either inhibiting translation or inducing target degradation. MicroRNAs can also help serve as diagnostic markers to identify those who are at high risk of developing coronary and peripheral arterial disease.
In a study of 822 people, researchers identified five specific microRNA molecules with an abnormally low concentration in blood in people with diabetes and in those who subsequently went on to develop the disorder.6 One molecule in particular, microRNA 126 (MiR-126), was among the most reliable predictors of current and future diabetes. MiR-126 is known to help with angiogenesis and regulate the maintenance of vasculature. Healthy blood vessel cells are able to release substantial quantities of MiR-126 into the bloodstream.
However, when endothelial damage occurs, the cells retain MiR-126 and subsequently release less MiR-126 into the bloodstream. A decrease in plasma MiR-126 can therefore be an indicator of blood vessel damage and cardiovascular disease. Researchers also found that levels of MiR were lower when they gave large amounts of sugar to mice with a genetic propensity to develop diabetes.6 The MiR test can directly assess vascular endothelial damage secondary to diabetes and has a fairly low cost at around $3 per test. Clinicians may possibly be able to use this in conjunction with conventional tests in the near future.
Plasma thrombin activatable fibrinolysis inhibitor (TAFI) antigen is another biomarker that may participate in arterial thrombosis in cardiovascular diseases and may be involved in the mechanism of vascular endothelial damage in patients with diabetes.
Erdogan and colleagues investigated the association of plasma TAFI antigen level in the development of diabetic foot ulcers in people with type 2 diabetes.7 Specifically, researchers determined TAFI antigen levels in plasma samples in 50 patients with diabetic foot ulcers, 34 patients with diabetes but without diabetic foot ulcers, and 25 healthy individuals. The diabetic foot ulcer group and the diabetic non-ulcer group were similar in terms of mean age and sex distribution.
The researchers found TAFI levels to be significantly elevated in patients with diabetes with or without foot ulcers in comparison to the healthy controls. However, there was no difference in TAFI levels between the diabetic foot ulcer group and diabetic non-ulcer group, or between diabetic foot ulcer stages.
As research in this arena continues, a new class of blood markers may give additional insight to screen people who are at a higher risk of developing diabetes and intervene before the symptoms and the broad spectrum of associated complications occur.
Can An Artificial Pancreas System Enhance Glucose Control?
The artificial pancreas is a technology that is best described as a closed loop glucose management system that is intended to afford patients with diabetes better glucose control while averting the hypoglycemic state.8 With the advancement of technologies, newer artificial pancreas systems consist of a real-time continuous glucose monitoring (CGM) system. This system transmits information every one to five minutes from an under the skin sensor to a handheld receiver that can be integrated into a pump. The device also has an insulin pump with a pre-programmed algorithm that calculates appropriate insulin dosages based on the glucose ratings.
A potential imperfection to this CGM system is that the system reads glucose levels from the patient’s interstitial fluid as opposed to the actual blood glucose levels. The interstitial compartment has a lag time of eight to ten minutes and can affect the glucose readings, especially postprandial readings.
The insulin pump is a beeper-sized device that is flexibly attached via a tube in the tissue just under the skin and will release as per patient requirement. Some partial “half-loop” solutions are available in Europe and the FDA has recently approved three of the closed loop systems. Meticulous testing is still needed before the system can go on the market.9
Emerging Insights On Stem Cell Advances
With islet cell transplantation research quickly on the rise to help regenerate the disordered islet cells of the pancreas, we have seen much promise in stem cell research. Ideally, the in vitro generation of insulin-producing cells from stem or progenitor cells presents a promising approach to overcome the scarcity of donor pancreases for cell replacement therapy in people with diabetes.10
In an ongoing study, researchers at the Diabetes Research Institute are assessing the effects of biohybrid devices, also known as “scaffolds,” to house and protect the transplanted insulin producing cells.11 These “scaffolds” are designed to mimic the pancreatic environment and are being tested in different areas of the body that include the abdominal pouch, muscle tissue or subcutaneously. Furthermore, the “scaffolds” are also being tested to deliver favorable agents that may help promote the growth and viability of the transplanted islet cells.
Current studies are very optimistic in showing that these “scaffolds” co-transplanted with mesenchymal stem cell regenerative islet cells can help accelerate angiogenesis, which prolongs the longevity and functionality of islet cell regeneration.12
Encouraging Patient Adherence: What Recent Studies Reveal
Patient adherence is one of the many challenges in the treatment and management of diabetes. For years, physicians have been researching new methods in tracking patient adherence to glucose monitoring and management, and to pressure mitigation devices.
In an article published in the Annals of Family Medicine, researchers looked at the participation levels of patients with type 2 diabetes in their primary care check-up visits.13 Several offices sent questionnaires to these patients regarding their treatment goals and plans at the initial visit as well as follow-up visits. Researchers found that the more patients participated in their treatment decisions and management, the better they adhered to the prescribed medications and treatment. This resulted in better control of their diabetes.
Another study compared the efficacy of a reciprocal peer support program with that of nurse care management in 244 men with diabetes in two Veterans Affairs healthcare facilities.14 Researchers matched patients in the reciprocal peer support group with another age-matched peer patient and were encouraged to talk via telephone and participate in optional group sessions. Patients in the nurse care management group attended a 1.5-hour educational session and were assigned to a nurse care manager.
After six months, the mean hemoglobin A1C level for patients in the peer support program decreased from 8.02% to 7.73% while it increased from 7.93% to 8.22% in the nurse care management group.14 This was statistically significant.
Both studies support the notion that some patient empowerment in their treatment decisions and management may translate into better long-term outcomes.
Diabetes is estimated to impose more than $174 billion dollars per year on United States healthcare. This astounding financial toll is expected to continue to rise as more and more people are diagnosed with this debilitating disease.2 In addition to being aware of the plethora of current research, patient education and preventative care are important strategies to emphasize. It is through innovative research, teamwork and preventative strategies that we continue to gain successful outcomes and improvement in the prevention and management of diabetes and its complications.
Mr. Farnen is a third-year podiatric medical student at the Dr. William M. Scholl College of Podiatric Medicine.
Dr. Wu is an Associate Professor of Surgery at the Dr. William M. Scholl College of Podiatric Medicine and Associate Professor of Stem Cell and Regenerative Medicine at the School of Graduate Medical Sciences at Rosalind Franklin University of Medicine and Science in Chicago. She is also the Director for Educational Affairs and Outreach at the Center for Lower Extremity Ambulatory Research (CLEAR) in Chicago.
Dr. Steinberg is an Associate Professor in the Department of Plastic Surgery at the Georgetown University School of Medicine in Washington, D.C. He is a Fellow of the American College of Foot and Ankle Surgeons.
1. Huang ES, Basu A, O’Grady M, Capretta JC. Projecting the future diabetes population size and related costs for the U.S. Diabetes Care 2009; 32(12):2225-9.
2. Boyle JP, Thompson TJ, Gregg EW, et al. Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence. Popul Health Metr. 2010;8(1):29.
3. Wu SC, Driver VR, Wrobel JS, Armstrong DG. Foot ulcers in the diabetic patient, prevention and treatment. Vasc Health Risk Manag. 2007; 3(1):65-76.
4. Regazzi R. Diabetes mellitus reveals its micro-signature. Circ Res. 2010; 107(6):686-688.
5. Chen C, Tan R, Wong L, et al. Quantitation of MicroRNAs by real-time RT-qPCR. Methods Mol Biol. 2011; 687:113-134.
6. Zampetaki A, Kiechl S, Drozdov I, et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010; 107(6):810-817.
7. Erdogan M, Solmaz S, Canataroglu A, et al. Plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen levels in diabetic foot ulcers. Endocrine. 2010; 37(3):449-454.
8. Dassau E, Atlas E, Phillip M. Closing the loop. Int J Clin Pract Suppl. 2010; 166:20-25.
9. Harvey RA, Wang Y, Grosman B, et al. Quest for the artificial pancreas: combining technology with treatment. IEEE Eng Med Biol Mag. 2010; 29(2):53-62.
10. Joglekar MV, Hardikar AA. Epithelial-to-mesenchymal transition in pancreatic islet beta cells. Cell Cycle. 2010; 9(20):4077-9.
11. Badylak S OJ, Gilbert T. Functional tissue reconstruction with the use of biologic scaffolds, stem cell therapy for diabetes. Stem Cell Biology Regen Med. 2010; Part 3:223-239.
12. Bensaid W, Triffitt JT, Blanchat C, et al. A biodegradable fibrin scaffold for mesenchymal stem cell transplantation. Biomaterials 2003; 24(14):2497-2502.
13. Parchman ML, Zeber JE, Palmer RF. Participatory decision making, patient activation, medication adherence, and intermediate clinical outcomes in type 2 diabetes: a STARNet study. Ann Fam Med. 2010; 8(5):410-417.
14. Heisler M, Vijan S, Makki F, Piette JD. Diabetes control with reciprocal peer support versus nurse care management: a randomized trial. Ann Intern Med. 2010; 153(8):507-515.