Diabetes Spectrum
Volume 10 Number 1, 1997, Pages 39-41

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  In Brief
The increased risk of severe hypoglycemia is one of the main obstacles to obtaining near-normal glycemic control of type I diabetes. This article discusses steps that patients and clinicians can take to reduce these risks. It is especially important that patients’ family members and significant others be enlisted in this process.

Steps to Reduce the Risks of Severe Hypoglycemia

JoAnn Ahern, RN, MSN, CDE,
William V. Tamborlane, MD


The observation that intensive therapy leads to impaired recognition of and sympathetic responses to hypoglycemia in patients with type I diabetes1 places an extra burden on patients and clinicians who are striving for near-normal control. Since recurrent, mild hypoglycemia appears to set the stage for more severe hypoglycemic events,2 an obvious solution is to scrupulously avoid even modest biochemical hypoglycemia. Controlling early postprandial hyperglycemia while avoiding late postprandial and nocturnal hypoglycemia, however, is easier said than done.

The first step is to employ insulin replacement regimens that simulate, as closely as possible, the pattern of plasma insulin profiles that are observed in individuals without diabetes. Multiple daily injection regimens, such as regular insulin before each meal and isophane insulin at bedtime, or use of continuous subcutaneous insulin infusion (CSII) are almost invariably required. CSII also provides the capability of lowering the basal insulin infusion rate during sleep, when most severe episodes occur. To adjust for day-to-day variations in insulin needs, patients must perform frequent and accurate blood glucose measurements (including periodic middle-of-the-night sampling) with the aim of maintaining blood glucose concentrations above 3.5–4.0 mmol/l (63–72 mg/dl). Contact with a diabetes specialty team for advice and support for ongoing dosage adjustments is also needed.

Even with frequent monitoring and frequent patient contacts, the risk of severe hypoglycemia in the Diabetes Control and Complications Trial (DCCT) was increased threefold in intensively treated versus conventionally treated patients.3 The pharmacokinetics of subcutaneously administered regular insulin, including the delayed peak and prolonged duration of premeal boluses, had emerged as an important contributory factor. With CSII, for example, it was originally suggested that endogenous defense mechanisms could be relied upon to counteract such insulin-overshoot problems because they would be minimized by distributing the dose of regular insulin over the entire day.4 It was not anticipated that intensive treatment would lead to physiological adaptations that would impair protective responses to hypoglycemia.

Some of these problems may be reduced, however, by the recently introduced insulin lispro. Although insulin lispro exists in concentrated solution as hexamers, it dissociates rapidly after subcutaneous injection into monomeric insulin. Plasma insulin concentrations reach a peak in about 40 minutes, and, even after large doses, levels are back to baseline by 3–4 hours after an injection.5 Consequently, insulin lispro may promote better control of early postprandial hyperglycemia with less late postprandial hypoglycemia when incorporated in an intensive treatment regimen. Although it has not yet been approved for use in insulin pumps in the United States, preliminary results from a Canadian study indicate that it will be an effective agent for CSII therapy as well.6

Assuming that insulin lispro will not be a panacea, what other practical steps can be taken to avoid hypoglycemia or at least treat it before it becomes severe? All patients striving for normoglycemia must be forewarned that the incidence of hypoglycemia will increase with intensive therapy. The risks of hypoglycemia with intensive treatment should also be discussed with patients’ family members and significant others. They must be informed that such problems are due to limitations of the treatment and are not necessarily the fault of the patients or clinicians.

The next step is comprehensive patient and family education. Patients should be taught to adjust insulin doses based on blood glucose results, diet, and exercise. When beginning an intensive management program, they should be asked to contact their diabetes health-care provider regularly by telephone. These contacts help patients learn how to make appropriate changes in the treatment regimen and to understand why they are making them. Family members need to be taught how to recognize and manage hypoglycemic events and should be encouraged to verbalize concerns and frustrations. The patients themselves are often cavalier about severe hypoglycemia because they have no memory of the events, whereas family members have experienced the fear of trying to control an irrational individual or to treat a hypoglycemic seizure.

Patients should be taught beforehand that they may lose the autonomic signs and symptoms of hypoglycemia that they have experienced previously. Autonomic symptoms will be replaced by neuroglycopenic symptoms that must be treated immediately. Neuro-glycopenic symptoms may include drowsiness; difficulty in concentrating or completing simple mental tasks, such as dialing a phone number; blurred or double vision; or forgetting where they were going or with whom they were talking. While their autonomic symptoms did not need to be treated so quickly, these new neuroglycopenic symptoms must receive prompt attention because they occur at lower blood glucose levels. Recognition of altered symptoms of hypoglycemia is important, and blood glucose awareness training has been advocated for patients with impaired perception of warning symptoms.7

Patients should treat neuroglycopenic symptoms immediately with glucose tablets or gels. We strongly encourage all patients to carry glucose tablets on their person, not in a handbag or other bag, although they may carry additional supplies there, also. All patients should monitor blood glucose before driving if they have not eaten in the previous 2 hours. This is particularly important since severe hypoglycemia is more likely to increase the risk of accidents and injuries rather than the occurrence of potential neurological sequelae.3 If it is impossible to test blood glucose levels, patients must be advised to have a snack before driving. When taking long trips, patients should stop every 2–3 hours to check blood glucose levels and have regular snacks or meals.

Although consistency in diet may help avoid hypoglycemia, regimentation is difficult to maintain. Carbohydrate counting can be used to adjust for variations from the usual carbohydrate intake. Patients should be encouraged not to miss a meal or snack, since a severe hypoglycemic event was more likely to occur in DCCT patients on those days when they skipped a meal or snack.8 All patients should have a bedtime snack that is high in protein since this may help keep blood glucose levels from dropping too low during the night. Snack bars containing uncooked cornstarch have recently been introduced as a method of preventing nocturnal hypoglycemia.

Checking glucose levels before, during, and after exercise in order to determine how much to reduce pre-existing insulin dosage or increase food consumption will also help in avoiding hypoglycemic events. By trial and error, most patients are able to ascertain their needs for a particular exercise and thereby can decrease the amount of blood testing. Hypoglycemia can be avoided during prolonged, moderate exercise by ingesting at least 15 grams of carbohydrate every 30 minutes. This can be taken as commercial sports drinks; diluted fruit juice will also serve to replace fluid losses. Long practices or training sessions may also increase the risk of nocturnal hypoglycemia, whereas lowering the basal insulin dosage and checking 3:00 a.m. glucose values may help prevent such problems.

Patients with diabetes often tend to overtreat low glucose levels during the 15–20 minutes it takes to correct the hypoglycemic symptoms. When they later recheck their blood glucose level, the blood glucose is very high, and subsequently they give extra insulin. In order to prevent this "yo-yo" phenomenon, patients should be instructed to treat hypoglycemic reactions with commercially available glucose preparations. This assures that a calculated amount of carbohydrate is consumed in a form that can be quickly absorbed. The more rapid rise in plasma glucose allows the patient to feel better more quickly and to avoid overtreatment. We follow the 15/15 rule: 15 grams of carbohydrate followed by 15 minutes of waiting. If the blood glucose level is still too low, then the patient is instructed to take another 15 grams of carbohydrate.

Family members and friends are often better at detecting subtle changes in patients’ behavior related to hypoglycemia than are the patients themselves. We advise them to refrain from being confrontational during these episodes, since some patients become belligerent and occasionally violent. Their best strategy is to give the patient a glass of juice (or other source of carbohydrate) and not to ask whether the patient is low or feels OK. The usual response, "I’m fine, leave me alone," only makes the patient and family member more upset and angry. Family members and significant others must also be instructed on how to administer parenteral glucagon to treat severe hypoglycemic events.

Motivating patients with long-standing diabetes to adhere to the necessary care practices for intensified management can be a challenge. Complacency, apathy, and boredom can set the stage for a severe hypoglycemic event. Sometimes getting a new glucose meter or lancing device can motivate a patient to obtain more blood glucose values. Some are intrigued by computerized memory meters that allow graphs and charts to be generated from their blood glucose data. However, establishing a close relationship with a member of the diabetes treatment team to encourage and motivate may be all it takes for many patients to maintain their enthusiasm and to frequently test blood glucose levels. This, in turn, will help reduce episodes of hypoglycemia. Faxing blood testing results in order to get immediate feedback from the treatment team may also motivate patients.

Knowing that someone is always available for advice is extremely reassuring, and having 24-hour availability of a member of the team is essential to encourage patients to strive for near- normal blood glucose levels. Intensive management of diabetes is a collaborative effort, and patients must feel that their input is the most important if they are to have the confidence to make decisions about the best treatment for their diabetes.

Despite efforts to reduce the frequency of hypoglycemia, the fact remains that the most motivated, compliant, and successful patients remain at greatest risk for this potentially devastating complication of therapy. Problems with hypoglycemia, as well as the burdens of intensive insulin therapy, provide a strong impetus to make efforts for developing a true artificial pancreas or for a cure for type I diabetes through transplantation. Because neither development appears likely in the immediate future, patients and clinicians need to remember the main conclusion of the DCCT.3 That study showed that the ability of intensive therapy to markedly reduce the risk for development and progression of microvascular and neuropathic complications substantially outweighs the increased risk of adverse events, such as severe hypoglycemia.


References

1Amiel SA, Sherwin RS, Simonson DC, Tamborlane WV: Effect of intensive insulin therapy or glycemic thresholds for counterregulatory hormone release. Diabetes 37:901-907, 1988.

2Dagogo-Jack SE, Cryer PE: Hypoglycemia associated autonomic failure in insulin-dependent diabetes mellitus: recent antecedent hypoglycemia reduces autonomic responses to symptoms of, and defense against subsequent hypoglycemia. J Clin Invest 91:819-28, 1988.

3The DCCT Research Group: The effect of intensive diabetes treatment on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977-86, 1993.

4Tamborlane WV, Sherwin RS, Genel M, Felig P: Reduction to normal of plasma glucose in juvenile diabetics by subcutaneous administration of insulin with a portable infusion pump. N Engl J Med 300:573-78, 1979.

5Howey DC, Bowsher RR, Brunell RL, Woodworth JR: Lys(B28), Pro(B29)-human insulin: a rapidly absorbed analogue of human insulin. Diabetes 43:396-402, 1994.

6Zinman B, Chiasson JL, Tildesley H, Tsui E, Strack TR: Insulin lispro in CSII: results of a double-blind, crossover study. Diabetes 45 (Suppl. 2):28A, 1996.

7Cox D, Gonder-Frederick L, Polonsky W, Schlundt D, Julian D, Clarke W: A multicenter evaluation of blood glucose awareness training-II. Diabetes Care 18:523-28, 1995.

8The DCCT Research Group: Epidemiology of severe hypoglycemia in the Diabetes Control and Complications Trial. Am J Med 90:450-59, 1991.


JoAnn Ahern, RN, MSN, CDE, is a clinical coordinator of the Yale Program for Type I Diabetes, and William V. Tamborlane, MD, is chief of Pediatric Endocrinology and director of The Children’s Clinical Research Center at the Yale University School of Medicine, in New Haven, Conn.


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