Novel and Emerging Therapies
Implantable Continuous Glucose Monitoring Devices
Many type 1 diabetics who use insulin have made the transition from self-injections and adjustable glucose infusion pumps to continuous glucose monitoring systems, also known as “closed-loops,” in which an implantable device measures blood glucose and constantly adjusts the insulin infusion rate. These systems allow for continual monitoring and adjustment of the insulin infusion rate without the need for patient predictions (Hovorka 2011).
In one study, type 1 diabetics on implantable insulin pumps were randomly assigned in crossover fashion to their standard therapy or a closed-loop system. The closed-loop system achieved better overnight control of insulin and reduced the risk of hypoglycemia (Hovorka 2011).
The use of integrated closed-loop control has been shown to reduce hypoglycemic episodes 2.7-fold over traditional insulin therapy. Moreover, it provided a 6-fold reduction in overnight hypoglycemia. This represents an important step toward improving patient safety and decreasing the risk of complications (Breton 2012). In another study, a closed-loop delivery system combining glucose monitoring with insulin and glucagon infusions dramatically reduced the number of participants who developed at least one hypoglycemic episode from 53% to 7% (Haidar 2013).
Improving Hypoglycemia Awareness
A major problem in the treatment of type 1 diabetes is patient unawareness of hypoglycemia. This occurs due to defects in the neural response that normally accompanies low blood glucose levels. The result is that individuals with type 1 diabetes may not be aware their glucose levels are falling too low (Cryer 2008). This phenomenon is called hypoglycemia-associated autonomic failure (Vele 2011).
Some evidence suggests that naltrexone (Revia®), a drug used in the management of addictive disorders, may help improve hypoglycemia awareness (Feeney 2001; Blasio 2013). It works by blocking opioid receptor signaling. Studies show that blocking opioid receptor signaling helps improve the perceptibility of hypoglycemia (Vele 2011). As of the time of this writing, naltrexone, at a 25-50 mg/day dose, is being tested in type 1 diabetics to determine whether it can prevent hypoglycemia unawareness (Kumar 2012).
Fluoxetine (Prozac®), the selective serotonin reuptake inhibitor used as an antidepressant, may also be useful for increasing hypoglycemia awareness. In one study, 20 healthy patients were subjected to an experimentally controlled bout of hypoglycemia, treated with 40-80 mg/day fluoxetine for 6 weeks, and then re-tested. The study found that this treatment increased several categories of counter-regulatory responses to hypoglycemia and resulted in an increase in endogenous glucose production (Briscoe 2008). The increased counter-regulatory response may allow patients to be more aware of an impending hypoglycemic episode.
The Overlooked Potential of Acarbose in the Management of Reactive Hypoglycemia
Individuals who suffer from reactive hypoglycemia may not realize that glucose levels going too high after a meal may be the culprit driving their symptoms. This seemingly counterintuitive phenomenon is the result of ingesting large amounts of carbohydrate, which are then quickly broken down to glucose by enzymes in the gastrointestinal tract before being absorbed. The subsequent spike in blood glucose levels triggers an exaggerated release of insulin from the pancreas, which then causes glucose levels to plummet to a hypoglycemic state (Brun 2000).
One way of avoiding post-meal hypoglycemia is reducing carbohydrate consumption. However, this can be difficult in modern society where so many starchy foods are readily available. Fortunately, there is another method that most people who suffer from hypoglycemia are probably unaware of, and which is overlooked by many physicians: the anti-diabetic drug acarbose (Bavenholm 2006; Hanefeld 2007; Gerard 1984; Hasegawa 1998; Ozgen 1998; Derosa 2012).
One of the key enzymes that break down carbohydrate into glucose is alpha-glucosidase. Acarbose inhibits alpha-glucosidase, thereby slowing the rate of glucose absorption into the bloodstream. This drug is typically used to help type 2 diabetics keep their blood sugar from going too high, but it may also benefit those who suffer from reactive hypoglycemia by suppressing the post-meal glucose surge that triggers excess insulin release and subsequent hypoglycemia (Bavenholm 2006; Hanefeld 2007; Derosa 2012).
Several studies have investigated the efficacy of acarbose in managing reactive hypoglycemia. In one study, 21 subjects with reactive hypoglycemia were treated for 3 months with acarbose. Before the treatment, the subjects’ lowest glucose level 3 hours after an oral glucose challenge was 39 mg/dL. After 3 months of treatment with acarbose, the lowest glucose level 3 hours after the glucose load was 67 mg/dL. Moreover, the subjects’ insulin levels were reduced within the first few hours following a meal after treatment with acarbose. The researchers concluded “These results confirm that acarbose may be of value in preventing reactive hypoglycemia by reducing the early hyperglycemic stimulus to insulin secretion…” (Ozgen 1998).
Another study demonstrated the immediate benefit of acarbose. Twenty-four subjects with postprandial hypoglycemia symptoms were given an oral sucrose challenge. Along with the sucrose solution, participants were given either 100 mg acarbose or a placebo. Compared to subjects who received placebo, those who took acarbose experienced significantly less reactive hypoglycemia after the sucrose challenge. Also, in some of the subjects who took acarbose, the post-challenge glucose level variance was attenuated: both the highest and lowest glucose levels were closer to baseline than in those who took the placebo. This indicates that acarbose blunted the post-challenge spike in glucose levels and the subsequent drop that characterizes reactive hypoglycemia. Insulin levels were also reduced in subjects who took acarbose (Gerard 1984).
Additional evidence comes from a small study in which subjects with type 2 diabetes and symptoms of reactive hypoglycemia were treated with acarbose for one month. In this study, each subject took either 50 or 100 mg of acarbose 3 times daily before meals. Before treatment, all the subjects in the study experienced symptoms such as weakness, palpitation, and dizziness after meals. After one month of treatment with acarbose, these symptoms subsided and subjects’ post-meal glucose and insulin levels stabilized (Hasegawa 1998).
For those who want to avoid prescription drugs, there are nutrients described later in this chapter that suppress alpha-glucosidase and other functions in the digestive tract that can cause too much glucose to be rapidly absorbed.