The quest for better diabetes control

Insulin administered in the right amount at the right time can compensate for the effects of diabetes. Although over-simplified, this statement is the basis for research into a closed-loop system that would provide insulin in response to blood glucose readings—a so-called artificial pancreas. Rather than periodic testing, continuous blood glucose monitoring will be part of this system because it promises tighter, more immediately responsive control.

As the authors of a research paper commented, continuous monitoring is a “critical step toward development of an artificial pancreas.” A very small sensor is inserted just under the skin to monitor glucose levels. However, in addition to a sensor remaining operational for a long period of time, problems such as inflammation at the insertion site must be addressed.

The paper described refinements to the basic glucose oxidase (GO_x) chemistry to improve selectivity, sensitivity, and response time as well as a means of releasing medication at the insertion site. “The working electrode … is sequentially coated with five layers containing: (1) electropolymerized polyphenol (PPh), (2) glutaraldehyde-immobilized GO_x enzyme, (3) dip-coated polyurethane (PU), (4) glutaraldehyde-immobilized catalase enzyme, and (5) a physically cross-linked polyvinyl alcohol (PVA) hydrogel membrane …. The inner membrane improved sensor selectivity via elimination of electrochemical interferences, while the third PU layer afforded high linearity by decreasing the glucose-to-O₂ ratio. The fourth catalase layer improved sensor response time and eliminated hysteresis through active withdrawal of GO_x-generated H₂O₂ from the inner sensory compartments. The outer PVA hydrogel provided mechanical support and a continuous pathway for diffusion of various participating species while acting as a host matrix for drug-eluting microspheres.”¹

The FDA-approved Dexcom SHARE device provides remote mobile communications capability for the company’s G4 PLATINUM continuous glucose monitoring system. The Dexcom website quotes Lori Laffel, M.D., M.P.H., chief of the pediatric, adolescent, and young adult section, Joslin Diabetes Center, Boston, as saying, “Continuous glucose monitoring offers a unique opportunity for patients with diabetes to aim for glucose levels close to the reference range found in persons without diabetes.” She said that the ability for up to five people to monitor the patient’s glucose level on their smartphones was important in helping to improve diabetes control both in the short term and long term. The website concluded, “Continuous glucose monitoring is important because, in addition to providing the glucose level, it provides the direction and rate of glucose change with the push of a button and alerts users when glucose is too low or too high.”

Also commenting in an article on the necessity of continuous monitoring was Randall Jean, associate professor of electrical and computer engineering at Baylor University. “Jean says that the sensor he and his colleagues are developing will be ‘truly noninvasive’ and will not require that any fluid—blood or otherwise—pass through the skin. The sensor itself is a small, spiral-shaped microwave circuit, which acts as a transmission line and emits electromagnetic waves. When a person places a thumb on the spiral, the electrical properties of the thumb change how energy passes through the circuit. Jean and his colleagues measure this change, and they seem to have found patterns in early trials that correspond to variations in glucose levels.

“The energy does not specifically respond to glucose; it responds to the aggregate effect of blood, muscle, fat, skin, and glucose,” says Jean. ‘What we’re hoping is that over a broad enough frequency range the individual components have unique signatures that allow us to extract the glucose.”²

This research did not result in a commercial product. Other approaches to bloodless glucose monitoring that sense a change in skin or blood color have been more successful. Late in 2013, Israeli start-up Cnoga Medical reported that a noninvasive glucose meter, the TensorTip CoG Combo-Glucometer (Figure 1), had been developed based on skin color. According to the report, the device was being sold in Europe but had not been approved by the FDA in the United States.

Figure 1. Noninvasive blood glucose meter
Courtesy of Cnoga Medical

Comments attached to the article included a May 14, 2015 response from Cnoga to a reader’s question about availability: “Sales are restricted to countries that have cleared the Combo-Gluconmeter for sale. The restriction includes the United States where the FDA clearance is in the process. Currently, we are restricting the sales to diabetics type 2 only. Sales to individuals only.” Further comments from a number of readers questioned the meter’s accuracy.³ More initiatives using ultrasound, lasers, and electromagnetic waves are underway, but to date, the FDA has not approved a bloodless, noninvasive glucose meter.

As reported in an Abbott Diabetes Care news release, the company’s FreeStyle Libre Glucose Monitoring System has received the CE mark. The product is a continuous monitoring device that requires the patient to wear a small patch to sense glucose levels. Actually, the patch is attached to a very tiny sensor implanted just under the skin—the sensor is the glucose measuring part. The monitor removes the need for periodic calibration via finger-stick measurements. It also provides a wireless link between the patch and meter that eliminates the usual hard-wired connection to a sensor. A sensor is implanted for 14 days.

Diabetes apps

Entering data into a personal log book is an important part of a diabetic’s self-monitoring. Writing your glucose levels in the log book, possibly along with notes about food consumed and exercise taken, makes you more aware of trends, especially if your diabetes isn’t well controlled. Smartphone apps can provide a similar log book function but also allow that data to be transmitted to healthcare providers or to a program in the cloud, making the data more widely accessible.

According to a recent article, more than 1,000 diabetes-related apps are available, although “only 1.2% of people with diabetes who own a smartphone or tablet use apps to manage their condition.” Also, the article explained, the market is very fragmented with 14 companies accounting for 65% of the market with shares ranging from 17.8% to less than 5%.⁴

Diabetes-related apps have a wide range of capabilities. For example, Diabetes Buddy includes a food database that supports identification of a specific meal together with its level of carbohydrates, calories, protein, sugar, and fiber. LogFrog DB (Figure 2) extends diabetes logging to include data from several types of medical exams but does not offer a food database. In contrast, TRACK3 features a comprehensive food database and has a separate section where users can email questions to a product support team.

Figure 2. Typical LogFrog DB display of glucose level vs. time
Courtesy of Amphistyle

Figure 3. iBGStar blood glucose monitoring device
Courtesy of Sanofi-Aventis

The iBGStar Diabetes Manager from Sanofi Diabetes is an app that runs on an iPhone or iPad Touch. It syncs with output from the directly connected iBGStar glucose meter (Figure 3)that also can be used separately. When combined with a wireless device, the meter and app make it possible to easily display, manage, and communicate diabetes information.

Diabetes management trends

If the patient requires frequent contact with a healthcare provider, then a cloud-based, readily accessible system can be a good solution. Similarly, closed-loop glucose measurement/insulin pump communication is a major improvement for people using insulin pumps.

While app usage is forecast to increase, apps are only one part of an overall diabetes management program. Meters that require no coding and meters that communicate wirelessly have eliminated significant error sources but they haven’t reduced the amount of lifestyle-related information the user must provide for an app to be truly helpful.

To form a complete picture of a patient’s condition, information about meals, exercise, and medications is required in addition to glucose level. For a user to take the time to enter this data into an app, the app must offer benefits beyond the level of management that a traditional log book would provide. A food database is a good example of a feature that reduces the patient’s involvement in analyzing the effects of meals. And, some apps help quantify how exercise may affect glucose level and suggest appropriate insulin dosage.

References