Background Most observational studies suggest that blood glucose (BG) decreases in diabetics undergoing.

Hyperbaric oxygen therapy (HBOT) (Kakhnovskii, Longoni, Spinger, Takahashi, Blackburn, OMalley, Pontani). This decreasa in BG has been a consistent finding in nearly all observational studies, usually on the order of 50 mg/dl. However, it is still not clear whether this drop is causally related to the hyperbaric therapy itself, or merely an effect of the timing of teatmentwith feeding and medications. Blood glucose does not apper to be signifiantly affected in non-diabetic patients. How might hyperbaric therapy affect blood glucose in the diabetic patient? Why is this question so hard to answer? The practitioner must first have a basic understanding of glucose metabolism of glucose metabolism and the role of insulin. Glucose metabolism The major hormone regulating glucose metabolism is insulin, a hoemone synthesized in the beta cells of the pancreas. It stimulates glucose uptake in fat and muscle cells and the conversion in the liver of glucose to glycogen. As blood glucose levels fall in response to insulin, glucagon release from the alpha cells of the pancreas is stimulated. Glucagon stimulates the liver to break down glycogen and amino acid so that glucose is released into the blood. Glucagon also inhibits the uptake of glucose y muscle and fat cells. In nondiabetics the level of blood glucose controls secretion of glucagon and insulin via negative feedback system. Low blood glucose level stimulates the release of glucagon whereas high blood glucose level stimulates secretion of insulin. Diabetes mellitus is a group of disorders that all lead to an elevation of glucose in the blood. The two major types of diabetes are insulin-dependent diabetes mellitus (IDDM), and non-insulin-dependent diabetes mellitus (NIDDM). Typically, juvenile onset diabetes is insulin dependent, but some patients with adult onset diabetes also become insulin, and injections are required to prevent death. The cellular metabolism of an untreated patient with IDDM is similiar to that of a starving person. Since insulin is not available to aid the entry of glucose into body cells, most cells use fatty acids to produce ATP. Ketones are byproducts of fatty acid catabolism, which causes a from of acidosis called ketoacidosis. The catabolism of strored triglycerides and proteins also causes weight loss. In non-insulin-dependent diabetes mellitus, the symptoms are generally less severe, and diet, exercise, weight loss, and oral medications may control the high glucose levels in the blood, at least initially. Many patients with NIDDM have a sufficient amount or even a surplusof insulin in the blood. For these patients, the cause of the diabetes is not from a shortage of insulin, but because target cells become less sensitive to it. For most patients, medication is the key to regulation of the blood glucose levels. In the past, medical therapy for IDDM and NIDDM were quite different. A complete review of diabetes management is beyond the scope of this chapter. However, it is now apparent that, rather than two different diseases, diabetes represents more of a continuum which blurs the categories of insulin dependence and non-insulin-dependence. Many physicians are now

prescribing oral medications to supplement a patients insulin regime, and vice versa. Some patient with adult onset diabetes do require insulin. Clearly, this combined therapy complicates the interpretation of studies done to evaluate the effect of HBOT on blood glucose. A further complication in the interpretation of studies is the issue of timing of medication (whether insulin or oral agents) and hyperbaryc oxygen therapy. The goal of diabetic management is a relatively even control of blood sugar troughout the day, and this is usually achieved by using combinations of different types of insulin and / or oral medications. Regular insulin is usually considered to reach its peak activity in the blood about 2 to 4 hours after administration. In contrast, other forms of insulin take longer to peak, but may last longer in the blood stream, thus affecting blood glucose levels for several hours. For example, NPH is usually considerec to reach its peak activity in 10 to 16 hours. Oral agents also differ in the timing of their peak effect on blood glucose, and in general have even longer lasting effects than the various forms of insuluin. For this reason, the timing of the administrationnof insulin and the administration of HBOT are crucial. A patient undergoing HBOT just as their hypoglicemic agent peaks will obviously be more likely to have a drop in blood glucose than a patient whose medication is past its peak, or has not yet reached its peak (see figure 2). Add to this the timing of food consumption, which may be altered from the patients normal schedule as a result of the time required to travel to the chamber and undergo treatment with HBOT. The result is an incredibly complex equation involving several variables including: the amount of insulin, the type of insulin, the amount of food eaten, the time that food is eaten, the type of oral agent used, and the timing and duration of hyperbaric therapy. Furthermore, results of studies can be affected by theway in which blood glucose is measured which will be discussed below.

Measuring blood glucose In monoplace chamber, blood glucose is usually measured prior to entering the chamber or after exiting. However, in multiplace chambers, it is possible for attendants to measure blood glucose during HBOT, either by sending samples out of the chamber to be analyzed at sea level, or by compressing a glucometer inside the chamber to measure blood glucose at depth. The hyperbaric environment may affect the function of glucose monitoring equipment if measurements are done in the hyperbaric chamber. In a study by Shafer, it was noted that the One Touch System was the most accurate overall when exposed to treatment depth of 2.4 ATA. It appears that the high oxygen levels in the chamber affected all the systems available for use at the time, because they all used some form of the glucose oxidase reaction. An important consideration for the researcher would be to note the location of the glucose monitor during testing (in the chamber versus topside). The current One Touch II system ring testing (in the chamber versus topside). The current One Touch II system does not require the monitor to be placed into the multiplace chamber, but the test strips may be locked in and out for testing during treatment. Unfortunately, many studies involving the

effect of HBOT on blood glucose fail to report either the equipment used in testing, or th conditions under which testing occurred.

OBSERVATIONAL AND EXPERIMENTAL DATA Clinical Studies Most clinicians agree that there is no siqnificant effect on blood glucose levels in the non-diabetic. The effect of HBOT may also be less on non-insulin dependent diabetes melitus patient (Zivkovic and Mandic). A study by springer noted that in a random selection of 25 IDDM patient, an average drop of 51 mg/dl was detected post treatment. Takahasi determined that 5 severe diabetic patient monitored continuously during hyperbaric oxygen therapy showed decrease in glucose of 51 mg/dl after 75 minutes of HBOT at 2 ATA with gradual return to pretreatment levels after decompression. In contrast, four well-controlled diabetics and non-diabetics showed a glucose change of less than 50 mg/dl or no change. One furthur observation was that plasma glucose levels decreased markedly in diabetic patient while it sometimes increased in healthy controls. Longoni observed that insulin requirements were decreased in eleven of fifteen diabetic patient undergoing a series of 15 HBOT at 2.8 ATA, suggesting that blood glucose levels were reduced during the course of HBOT. Insulin requirements retruned to normal values when the course of HBOT was completed. Pontani reported a retrospecttive analysis in which the patients underwent blood glucose screening before, during, and after routine HBOT at 2.4 ATA. Non-diabetic had a small but siqnificant decrease in blood glucose levels. For the eighteen patients eith IDDM, glucose levels. For the eighteen patients with IDDM, glucose drop on average was 60 mg/dl and was unchanged one hour later. We retrospectively evaluated pre and post HBOT blood glucose levels of ninety-one consecutive diabetics. We defined low blood sugar (LBS) as any blood glucosa below 100, regardless of wherher the patient was symptomatic. In this analysis, blood glucose dropped below 100 after HBOT in 26,4% of all patients. However, since patients were treated multiple times, this represented only 1.92% of the total HBOT treatments. All patients were asymptomatic. Regression analysis on fifty-two patients with LBS showed that the lower the initial glucose level, the greater the likeli-hood of adrop in BG after HBOT. Also, insulindependent diabetics were more likely to drop. However, the percent drop in blood glucose was medicated by the number of kilo-calories fed prior to HBOT, and the age of the patient (older patients drpped less). Not surprisingly, the risk of patients experiencing LBS increased with the number of treatments they received.