The Diabetic Traveler
May 1, 1999 6 minutes read
The Diabetic Traveler
Abstracts & Commentary
Synopsis: It is clear that considerable information is now available regarding issues for diabetic travelers, including their compliance with medications, control of glycemia, and new technical products that enhance our ability to advise such patients. Driessen and colleagues have recently brought this group of patients to our attention in a small study from The Netherlands. We must also familiarize ourselves with newer methods for insulin administration and rapidly acting insulin preparations that, when combined with developing technology for glucose monitoring, will surely change the landscape for diabetic travelers in the future.
Sources: Driessen SL, et al. Travel-related morbidity in travelers with insulin-dependent diabetes mellitus. J Travel Med 1999;6:12-15; Dewey CM, Riley WJ. Have diabetes, will travel. Postgrad Med 1999;105:111-126.
Driessen and colleagues performed what they referred to as a small, exploratory, retrospective cohort study using telephone interviews of all insulin-dependent diabetic (IDDM) patients advised in their travel clinic over a 12-month period. The data they collected related to hypoglycemic and hyperglycemic dysregulation, infections (such as diarrhea), general health issues, physical exertion, and practical problems for their diabetic travelers. During the study period, 9385 travelers attended their travel medicine service of whom only 22 (0.2%) were known to have IDDM. They had 19 respondents (11 type-1 diabetics, 8 type-2) who could be reached—13 of whom (68%) reported metabolic dysregulation. These 13 included all but one patient with type 1 diabetes. Critical dysregulation of glycemic control requiring third-party assistance occurred in two patients. All respondents except four did not increase their frequency of blood glucose monitoring during travel; only 36% of type 1 diabetics increased their frequency of blood glucose monitoring. Three reported febrile illnesses with consequences for control of glycemia and five experienced difficulty with insulin dosage adjustments in the tropics.
More than 50% of respondents reported more dysregulation of glycemic control than in the preceding time period at home. Other problems reported by patients in this study included gastroenteritis, diarrhea, upper respiratory infection, one case of documented Q-fever, and skin infections (without foot involvement). As might be expected, travel through several time zones was associated with metabolic dysregulation for two patients, and one experienced difficulty at customs for carrying injection materials.
In their discussion, Driessen et al maintain that two travelers experienced critical dysregulation while using insulin lispro (Humalog), a rapidly acting insulin with shorter duration of action than regular insulin, and they suggest that insulin lispro not be substituted for conventional human insulin before travel. Their concerns about insulin lispro centered around a potential for post-prandial hypoglycemia. However, I do not share that view, and the use of short-acting insulins, discussed below, will likely be a critical issue in the future for improving glycemic control in such patients.
Dewey and Riley have recently published a useful article that can serve as an informative reference for healthcare providers dealing with traveling diabetic patients. They list a considerable amount of information available on the Internet from both national and international resources, including check lists for travelers with diabetes and the oft quoted Benson and Metz strategy for adjusting insulin doses in patients who are taking insulin and traveling across several time zones.
Comment by Frank J. Bia, MD, MPH
The problems encountered by patients traveling with diabetes have not been given the attention their numbers warrant, and much of what is happening to influence their lives is not yet appearing under the rubric of travel medicine literature.1 Some of what is currently appearing in the literature is either less than accurate or rapidly becoming outdated. For those advising travelers with diabetes, there are at least two major developments their patients should be familiar with, because in each instance they truly encourage compliance. If there is one clear point in the article by Driessen et al, it is that compliance with increased blood glucose monitoring and insulin administration would do much to enhance control of glycemia in traveling diabetics.
Both manufacturers of insulin in the United States, Eli Lilly and Co. and Novo Nordisk, manufacture regular insulin and mixtures of 70/30 (NPH/regular) insulin, which are available in various cartridge pen systems. Either the entire pen can be disposed of when the insulin has been used up, or a new cartridge can be inserted in the nondisposable unit. The insulin is stable, and unrefrigerated for at least a week (70/30 mixtures) and up to a month (regular insulin). With a traveler able to carry these devices as simply as he or she would a pen, the administration of insulin is much easier and compliance increases. However, one issue for control of glycemia, whether individuals are traveling, relates to the mistimed usage of regular insulin prior to meals. This is a difficult area for compliance since regular insulin must be given 30-45 minutes prior to a meal. Usually it is not. Compliance has been made much easier with the availability of insulin lispro. Any diabetic who is planning an extensive travel experience and is not yet familiar with this rapidly acting form of insulin has been short-changed some important information.
There are several advantages for travelers who gain familiarity with this rapidly-acting insulin.3-5 Because there is a strong tendency for travelers with diabetes to take their insulin immediately prior to a meal, rather than the 30-45 minutes before a meal required for regular insulin to become absorbed, the inconvenience of timed administration leads to poor control of glycemia. There is a mismatch between post-prandial carbohydrate absorption and the two- to four-hour post-injection peaking of regular insulin. In addition, there will still be circulating insulin present as the peripheral blood glucose is falling. This predisposes such patients, particularly those who exercise, to late post-prandial hypoglycemia. Driessen et al incorrectly state that "with insulin lispro a post-prandial hypoglycemia will arise more easily compared to conventional insulin, especially if the food contained few carbohydrates or physical exercise is performed immediately after the meal." The pharmacology of insulin lispro actually works against such a problem occurring.
Regular human insulin is absorbed slowly since it consists of hexamers of insulin that are crystallized around zinc molecules. To be absorbed from its subcutaneous injection site, it must first dissociate into monomers and dimers. Insulin lispro derives its name from the switching of two amino acids, proline and lysine, within the beta-chain of insulin. After subcutaneous injection, this insulin dissociates more rapidly into dimers and monomers. The peak serum concentrations of insulin lispro occur within 30-90 minutes following administration, and regardless of the site of administration, there is a better match between carbohydrate absorption and insulin availability with less chance for late-peaking regular insulin to cause post-prandial hypoglycemia.
With the general availability of small, portable glucometers for monitoring blood glucose, convenient insulin delivery devices, and rapidly acting insulin lispro, older guidelines for management of insulin administration could be altered to include more frequent monitoring and less rigid formulae for insulin administration. I prefer the method outlined by Sane and colleagues that calls for a 2-4% adjustment in insulin dosing for each time zone crossed.2 For instance, a traveler going west over 10 time zones would have his or her day lengthened and require about a 30% increase in his or her long-acting insulin. Adjustments to that regimen can be more finely tuned using insulin lispro as needed, based upon more frequent blood glucose monitoring.
This is certainly the beginning of a new story for traveling diabetics. A personal laser lancing device for obtaining a capillary blood sample weighing approximately 10 oz will be available from Chronimed (800/848-0614) in mid-1999. Since a beam of light, rather than a lancet, penetrates the skin, sharps disposal is eliminated and pain is reduced. Cell Robotics International (800/866-1533) has developed a skin patch for glucose monitoring on the forearm. Monitors that read the patch test results and can store months worth of data, by time and date, are being paired with such patch monitoring systems. Recently, Eli Lilly and Co. received approval to market a new formulation of glucagon, based upon recombinant DNA technology, in their Glucagon Emergency Kits, which eliminates dependency on animal pancreas glands for manufacture. Generalized allergic reactions and nausea/vomiting have occurred using previous animal glucagon formulations but can also occur with the new product formulation. For information or questions regarding recombinant glucagon, call 1-800-88LILLY.
This is a time of rapid change in the technology available to encourage and enhance the compliance of diabetics with glucose monitoring and insulin administration. The challenge for travel medicine specialists remains one of providing the most current useful information about such technology for our traveling population of diabetics. The end results will be fewer episodes of glycemic dysregulation and will ultimately decrease any opportunity for travel, per se, to result in further end organ damage from poorly regulated diabetes.
References
1. Mileno MD, Bia FJ. The compromised traveler. Infect Dis Clin North Am 1998;12:369-412.
2. Sane T, et al. Adjustment of insulin doses of diabetic patients during long distance flights. BMJ 1990;301:421-422.
3. Noble SL, et al. Insulin lispro: A fast-acting insulin analog. Am Fam Physician 1998;57:279-286.
4. Hollman F, Hoekstra JBL. Insulin lispro. N Engl J Med 1997;337:176-183.
5. The Medical Letter. Lispro, a rapid-onset insulin. Med Lett 1996;38:97-98.
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