Insulin Management of Hospitalized Diabetic Patients

Type 2 Diabetes Defeated

Holistic Treatments to Reverse Diabetes

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Muriel H. Nathan and Jack L. Leahy

University of Vermont College of Medicine, Burlington, Vermont

INTRODUCTION

AduJts with diabetes mellitus are admitted to the hospital more frequently than nondiabetics, often for prolonged periods. Particularly common are admissions for hyperglycemic emergencies, local or systemic infections, unstable angina or myocardial infarction, stroke, and orthopedic injuries. One would hope that hospitalization would be a time to reinforce the principles of optimal diabetes care. Instead, glycemic control in the inpatient setting, especially in insulin-treated patients, is often unsuccessful. There are many reasons for this, some relating to glycemic effects of the underlying illness or the pharmaceuticals used to treat it; dietary changes are also a factor. More troubling is that hospital staffs are often poorly trained in insulin usage—"sliding-scale" regimens are still standard medical practice despite the fact that they rarely allow stable glycemia even under ideal medical conditions (1). Further, there remains no consensus as to what constitutes optimal glycemic care for the inpatient. The past few years have seen the publication of many important studies proving the importance of rigorous outpatient glycemic control for the prevention of microvascular complications. In contrast, there is very little literature supporting benefits of aggressive gly-

cemic control for inpatients in terms of lowered morbidity, mortality, or shorter hospitalization time. Rather, many practitioners consider prevention of hypoglycemia the dominant goal for inpatients, and aim to not let the blood glucose fall below 200 mg/dl. Thus, the average practitioner is unclear about the importance, or method, for blood glucose management in the hospital.

Not surprisingly, diabetes specialists have a different philosophy. They understand the difficulty of diabetes management for inpatients, but also advocate making every effort possible to optimize glucose control. Of concern are detri-mentai effects of hyperglycemia and insulin deficiency on mental alertness, volume status, wound healing, risk of infection, and nutritional status. Also, literature is beginning to appear showing benefits of aggressive diabetes control after myocardial infarction (2,3) and coronary bypass (4), with similar benefits assumed following stroke and in infected patients (5). [Recent information has shown intensive insulin therapy lowers morbidity and mortality in patients on mechanical ventilation in a surgical intensive care unit (5a).] The recommended approach is to establish a muJtidisciplinary team of experts in inpatient diabetes management—physicians, dietitians, nurse educators, and pharmacists—to care for complex patients. Several recent reviews explain how to provide optima] nutritional and metabolic care for insulin-taking inpatients (5-10).

GENERAL PRINCIPLES Identify Patients with Diabetes

One complicating factor is that many patients are not known to have diabetes at admission. It is estimated that 50% of those with type 2 diabetes in the United States are undiagnosed. Also, as many as one-third of persons with hyperglycemia on admission have recent-onset diabetes from the acute illness or its therapy, such as steroids (11). Further confusing the issue, the diagnostic criteria for diabetes are based on blood glucose values in healthy ambulatory patients, and many physicians tend to discount newly recognized hyperglycemia in ill patients. Several years ago, a study of patients admitted with a myocardial infarction suggested that random glucose values of greater than 180 mg/dl predicted undiagnosed diabetes (12). A recent study used 200 mg/dl (10). Hyperglycemia should be looked for in every patient admitted to the hospital whether or not there is a known diagnosis of diabetes. Finding hyperglycemia should lead to appropriate inpatient therapy as well as evaluation after the acute illness of the patient's glycemic status.

Type of Diabetes

It is useful to classify patients in terms of their type of diabetes. This is of greatest importance in the outpatient setting to ensure that insulin-deficient types of diabe s

tes—type 1, pancreas damage, latent autoimmune diabetes in adults (LADA)— are identified and appropriately treated. Laboratory assessments of diabetes immune markers, such as glutamic acid decarboxylase (GAD) antibody or insulin secretion by c-peptide, may be needed, as it is now recognized that 10-15% of patients who are thought to have type 2 diabetes show presence of an autoimmune etiology (13). They are thinner on average than patients with type 2 diabetes, but phenotypic assessment alone is not able to discriminate type 2 diabetes from slow-onset type 1 diabetes in many of these patients.

Type of diabetes is less of an issue for the inpatient setting, since usage of oral hypoglycemics is generally discouraged for acutely ill patients. However, one benefit of knowing which patients have insulin deficiency is that it can be made sure that they receive 24-hour insulin coverage. Sliding-scale insulin orders are typically written to provide coverage for blood glucose values that are measured only during waking hours. Failing to give insulin during the night to insulin-deficient patients is guaranteed to cause nighttime and morning hyperglycemia, and may result in ketoacidosis. As described above, the pathogenesis of the diabetes is not always apparent from body phenotype or whether the patient was taking insulin on admission. Thus, a useful principle in the hospital is to provide 24hour coverage for all patients receiving insulin.

Nutritional Status and Required Caloric Support for the Patient

It is not possible to determine insulin coverage, in terms of either timing or dosage, without knowing your patient's schedule of nutrition. Caloric requirements for outpatients are typically 25-30 kcal/kg body weight. With illness or after surgery, caloric needs are usually higher; a useful rule of thumb is to add 25% to the above estimate if the illness is moderate and 50-100% if it is severe (9). Patients given only i.v. dextrose solutions (5%) receive far fewer calories than their estimated basal needs; an i.v. rate of 200 ml per hour provides less than 1000 kcal per day. Intravenous fluids are generally well tolerated for up to 72 hours, but after that patients who are unable to eat should receive enteral or parenteral nutrition. Because all these methods entail relatively constant 24-hour nutrient delivery, continuous insulin coverage is given using one of many protocols—i.v. infusion, 70/30 insulin every 8 hours, glargine at bedtime, Ultralente insulin every 12 hours, or Regular insulin every 4-6 hours—to attain a glucose level of 120-200 mg/dl. Our experience favors the first two methods of insulin coverage as providing the most stable around-the-clock glycemia, and in particular have found "q 8 hour 70/30 insulin" easy and effective in patients receiving i.v. glucose or continuous tube feeds who are otherwise medically stable.

Inpatients who are able to eat are ordered an ADA diet that usually provides three meals composed of 55% carbohydrates, 20% protein, and less than 30%

fat, along with a bedtime snack. Insulin coverage follows the outpatient method of combining short-acting and long-acting insulins to provide the basal and mealtime needs of the patient. Guidelines for glycemia in the hospital are generally looser (120-200 mg/dJ) than for outpatients to avoid hypoglycemia. A particularly difficult situation is when a procedure or diagnostic test causes a meal to be delayed or missed in insulin-treated patients. The patient's caregivers need to be aware of the next day's schedule so that appropriate changes in insulin coverage can be planned. Also, it is important to emphasize to the nursing staff that the patient's mealtime insulin dosage should be based on the time of the meal (30 minutes prior for Regular, and when beginning eating for lispro or aspart). If there are unexpected changes in the time of eating, the staff should hold the short-acting insulin until the appropriate time.

Inpatient Blood Glucose Monitoring

A routine part of outpatient diabetes care is self-monitoring of blood glucose to allow insulin dosage adjustments based on periodic reviews of the fingerstick data ("pattern analysis"). Inpatient units also collect bedside fingerstick data. Unfortunately, rather than being used to more precisely define insulin coverage for a patient, sliding-scale protocols generally entail one-time adjustments. It is thus common to find inpatients with blood glucose patterns over many days that show consistent periodic or persistently high blood glucose values who have had no adjustment in insulin orders. Contributing to this, many hospitals record the fingerstick data in a form that is hard to interpret, both in day-long sequence and over many days. A useful principle is to keep at the bedside a chart that shows at ¡east a week of glucose values and insulin doses in an easy-to-interpret, time-based pattern.

Most of the currently available glucose meters report "whole blood" values, which are 10-15% lower than laboratory determinations of plasma glucose. This difference must be kept in mind when setting and monitoring glycemic goaJs. Also, accuracy of the results requires that the operator use correct technique and the meter be working properly. When bedside glucose readings are unexpectedly high or low, particularly if the patient is asymptomatic, it is prudent to confirm the finding with a laboratory measurement. Also, periodically testing the proficiency of those who do bedside testing and daily checking of glucose meters is mandatory.

For inpatients with known or recently identified diabetes, glucose monitoring should be performed at meaJs and bedtime. Also, it is useful to obtain a 23 a.m. value to monitor for nocturnal hypoglycemia, particularly if the patient is sedated or has a history of hypoglycemic unawareness. For patients who are not eating, optimal timing of bedside glucose monitoring is less well defined, but

frequent measurements are important, especially if changes in medical condition are occurring that might affect glycemia.

Glycemic Goals

Many outpatient studies show the importance of near-normoglycemia to prevent complications (refer to Chapter 1), but these studies are lacking for the inpatient setting. Poorly controlled hyperglycemia in inpatients can lead to dehydration, deterioration of mental status, electrolyte imbalances, delayed wound healing, and impaired immunological responses. Glucose concentrations above 200 mg/dl have been shown in numerous studies to decrease white-blood-ceJI chemotaxis, phagocytosis, and bacterial killing, and it has been inferred that a patient's ability to fight off and cure infection is similarly affected, although this has been harder to prove. Golden et al. (4) did a chart review of 411 patients who underwent coronary bypass (CABG) to evaluate the relationship of perioperative glucose control to the subsequent risk of infectious complications. Patients were divided into quartiles based on mean postoperative blood glucose values (insulin was given as a sliding scale, and glucose measured four times a day from 7 a.m. to 9 p.m.), with quartiles 2-4 (207-352 mg/dl) compared with quartile I (121-206 mg/dl). Hyperglycemia was found to be an independent predictor for short-term risk of infection independent of age, presence or absence of proteinuria, and comorbidities.

Also of great interest is the highly publicized observation that intensive insulin treatment following an acute myocardial infarction improves long-term survival in diabetics. Best known is the Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study, which looked at patients with acute MI who had known diabetes or a blood glucose value on admission of greater than 200 mg/dl (2,3). Patients were randomized (about 300 in each group) to either a glucose-insulin infusion (see Appendix) for at least 24 hours followed by an intensive subcutaneous insulin program (four injections per day) for at least 3 months or standard practice. All patients received thrombolytic therapy followed by beta-blockade and aspirin. Admission glucose values in both groups averaged slightly more than 270 mg/dl. Glucose values in the control group averaged 210 mg/dl the day after admission and 160 mg/dl at discharge versus 173 mg/dl and 148 mg/dl, respectively, in the intensive-therapy group. One-year mortality was 30% lower in the intensive-therapy group. A recent metaanalysis supported an effect of hyperglycemia to increase in-hospital mortality following acute myocardial infarction in persons with and without known diabetes (14).

What are appropriate goals for glycemia in the hospital? HLrsch et al. (6) proposed pre-meal glucose values of 120-200 mg/dl to minimize the risk of

hypoglycemia while preventing glucosuria and osmotic diuresis. These values are reasonable in patients with changing medical, surgical, or nutrition conditions. However, in stable patients, values within the upper half of this range can often be avoided. Also, certain kinds of patients, such as those who are infected or pregnant or have had a cardiovascular event or surgery, should receive intensive diabetes management using i.v. insulin and 1- to 2-hourly bedside blood glucose values to achieve as near-normal glycemia as is safely possible.

WHY NOT SLIDING SCALES?

Hospitalized patients often have insulin orders written by "sliding scale." This regimen is popular because of the many factors that make glycemia unpredictable in inpatients, which make some practitioners uncomfortable about attempting to foresee their patients' insulin needs. Using a scale that provides insulin in response to blood glucose value seems more sensible. Unfortunately, many aspects of sliding-scale coverage cause it to work poorly in many patients: the same dosing scale is often used for patients with very different weight, illnesses, and nutrition and renal status; the dosing scale is rarely changed during the hospitalization regardless of the blood glucose values; insulin administration may be based on when the nurse measures a blood glucose value as opposed to when the patient eats; and blood glucose measurements, and thus insulin coverage, may be missed when the patient is off the floor getting a test or is otherwise not available, which causes patients with type 1 diabetes to go without insulin coverage for many hours, promoting hyperglycemia and catabolism. Another potential problem is the insulin's "running out" if the scale is written not to cover normal blood glucose values, causing glycemia to "see-saw." Thus, sliding scales often promote problems with glycemic control in the hospital.

Historical Perspective on the Use of Sliding Scales

In 1970, MacMillan wrote a paper, "The Fallacy of Insulin Adjustment by Sliding Scale" (15), that criticized this method of insulin coverage because it ignored the amount and effect of corresponding doses on previous days and did not consider the anticipated needs over the next 6-8-hour period when the insulin would have its effects. His studies, conducted in children, were based on insulin coverage for degree of glycosuria. He observed a frequent pattern of giving too much, alternating with too little, insulin—excessive doses of insulin were given for 4 + glucosuria, and the next dose of insulin would be omitted because of aglycosuria. This omission of insulin would "almost invariably" result in recurrence of strong glucosuria, leading to "repetition of the cycle" (what many now call the "roller-coaster" or "see-saw" effect). In 1991, he again wrote that "the sliding scale method of insulin adjustment is seldom effective in establishing diabetic control s

because there is no anticipation of upcoming insulin needs and dosage changes are after-the-fact reactions to existing blood sugar levels" (16). Further, he stated that control is impossible to establish with this regimen since no insulin is ordered if the patient is normoglycemic, which leads to marked hyperglycemia by the next scheduled testing. Also, nocturnal hypoglycemia may occur because the dose of insulin is determined by the level of hyperglycemia irrespective of whether it is before a meal, at bedtime, or during the night.

MacMillan's comments were made before routine bedside blood glucose testing, and it might be questioned whether today's therapy is more effective. Hanish (17) described two protocols from her hospital for sliding-scale regimens based on blood glucose testing. One gives 2 U of Regular insulin for a fingerstick of 151-200 mg/dJ and then increases 2 U for every additional 50 mg/dl, up to 450 mg/dl. The physician is called if the glucose is under 80 mg/dl or over 450 mg/dl. The second uses a starting dose of 4 U of Regular insulin but is otherwise the same. This two-page report is surprisingly well known and quoted by house officers. However, it shows that her hospital developed these scales "to decrease the possibility of transcription errors and to save physicians', nurses', and pharmacists' time." Nowhere is there any comment about how successful they were in controlling glycemia.

The effectiveness and safety of sliding scales were investigated by Queale et al. in 171 diabetic patients consecutively admitted for diabetes-unrelated reasons to cardiology or general medicine services in a large city hospital (1). Hypoglycemia was defined as ^60 mg/dl, and hyperglycemia ^300 mg/dl. Patients were followed for at least 4 days, and had to have at least four bedside fingerstick measurements daily. No uniform insulin scale was used in the study; coverage could start at 150 mg/dl (in 35%) or 200 mg/dl (in 52%), and typically increased 2 U for every 50 mg/dl. Hypoglycemia occurred in 23% of the patients (3.4/100 measurements) and hyperglycemia in 40% (9.8/100 measurements). Most telling, hyperglycemia was greatest (threefold increased risk) in the patients who received sliding-scale coverage without concomitant intermediate-acting insulin. The authors concluded that a sliding-scale regimen when used alone increased the risk of hyperglycemia, and when used in conjunction with a standing regimen provided no benefit over the standing regimen alone.

To summarize, the major (and perhaps only) advantage of a sliding-scale insulin regimen is that it is easy. More debatable are its effectiveness and safety. Sliding scales make sense when used in conjunction with a standard insulin regimen to compensate for inaccuracies in the basic insulin doses. Each day's supplement is used to adjust the next day's insulin dosage up or down if it is assumed there is an ongoing need for the change. Thus, the basic insulin program is "fine-tuned" until glycemia is as stable and close to the target range as can be achieved in the hospital. In contrast, sliding-scale therapy used on its own tends to oversimplify inpatient insulin usage. The worst form is the one-size-fits-all scale widely

practiced by house officers, as it provides a false impression that the diabetes1 is being managed when, in reality, effectively no decisions about the diabetes management are made. Often, even the patient's caregi vers do not know the blood glucose levels—the "don't ask, don't tell" approach to medical care.

INSULIN ALGORITHMS: THE PREFERRED METHOD

The preferred approach is to provide insulin coverage based on the nutritional and medical characteristics of each patient. Algorithms are programs of insulin administration that are based on the nutrition pattern of the patient, and incorporate supplemental insulin dosing to attain a target range level of glycemia. Lilley and Levine (7) stated in their review of inpatient therapy for type 2 diabetes that "The algorithm takes into account the individual patient's insulin needs, caloric load and physical activity level, as well as the timing of insulin administration relative to caloric intake. Whereas the traditional sliding-scale insulin regimen is directed at lowering existing excessive blood glucose levels, supplements are given not only to correct hyperglycemia but also to control the anticipated effects of caloric intake and other factors that play a role in glycemia."

The first comprehensive paper on insulin algorithms for inpatients was published by Hirsch et al. (6) with the comment that' 'many of our recommendations are based on common sense or are extrapolations from other situations because the data examining nonsurgical inpatient diabetes therapy are limited." Multiple guidelines were suggested—for patients with type 1 or 2 diabetes, eating, or NPO. An i.v. insulin infusion was recommended for all patients who were not eating. Those eating standard meals were given twice-daily NPH and Regular insulin (0.5-1.0 U/kg) in the usual pattern of two-thirds of the total dose before breakfast as two-thirds NPH and one-third Regular, and the remainder before supper as half NPH and half Regular. There was also an algorithm for supplemental Regular insulin (0.075 U/kg for pre-meal glucose >200 mg/dl, 0.1 U/kg for pre-meal glucose >300 mg/dl). Lilley and Levine followed the suggestions of Hirsch, but recommended lispro over Regular insulin (7). These papers are mostly discussions of the principles of what to do, as opposed to giving formulas for inpatient insulin dosing that are proven to work. This is because correctly administering subcutaneous insulin to a hospitalized diabetic patient requires daily adjusting of the insulin program and dosing to get it right, as opposed to one-size-fits-all recommendations that rarely work.

In contrast, many studies of algorithms fori.v. insulin infusions have shown an ability to attain very good glycemic control. One example is by Watts et al. in postoperative patients (18). Their insulin infusion began at 1.5 U per hour, and was adjusted every 2 hours based on specific blood glucose cutoffs: <80 mg/dl, decrease by 0.5 U per hour and give 25 ml 50% dextrose; 80-119 mg/ dl, decrease by 0.5 U per hour; 120-180 mg/dl, no change; 181-240 mg/dl,

increase by 0.5 U per hour; >240 mg/dl, increase by 0.5 U per hour and give 8 U i.v. Regular insulin. The patients given the insulin infusion reached the target glycemia level within 8 hours, and 12-24 hours after surgery had a mean glucose of 136 mg/dJ (range 120-180), whereas those on subcutaneous insulin had a mean of 208 mg/dl (range 30-306). Also striking was an absence of hypoglycemia in the i.v. insulin group.

In summary, successful inpatient diabetes management requires designing an insulin program based on the special needs of that patient, followed by blood glucose monitoring and daily adjustments of the insulin doses, all in an attempt to attain glycemia that maximizes the well-being, nutritional status, and medical outcome of the patient while minimizing his or her risk of hypoglycemia.

INPATIENT INSULIN PROGRAMS

Subcutaneous Insulin for the Patient Who Is Eating

The recommended approach in type 1 and insulin-requiring type 2 diabetes patients who are eating is shown in Table I. For those with type 2 diabetes who were taking oral agents on admission, as a general principle it is safest to discontinue oral hypoglycemics and substitute insulin in patients undergoing surgery or with major illness of any kind. The recommended program is 0.5 U/kg glargine

Table 1 Subcutaneous Insulin Program for Inpatients Who Are Eating

Calculate starting insulin doses.

Glargine 0.5 U/kg at bedtime (0.3 U/kg for conditions with concern over risk of hypoglycemia; 0.7 U/kg for those with type 2 diabetes, obesity, infections, or open wounds, or those receiving steroids or post-CABG).

Humalog 0.1 U/kg each meal (adjust downward or give after meal for inconsistent eating habits) Bedside glucose measurements at mealtimes and bedtime—supplemental lispro.

200-299 mg/dl—give extra 0.075 U/kg lispro

>300 mg dl—give extra 0.1 U/kg lispro Adjust glargine doses to attain fasting blood glucose 120-200 mg/dl. Once attained, adjust lispro to achieve pre-meal and bedtime blood glucose 120-200 mg/dl.

The suggested starting doses are for an "average" patient, and variation is common based on the unique medical circumstances of each patient.

Suggested starting program if NPH or Ultralente is used instead of glargine: 0.25 U/ kg NPH or Ultralente at breakfast and bedtime (0.15 U/kg twice daily for conditions with concern about hypoglycemia, and 0.35 U/kg for conditions with increased basal insulin needs) and 0.1 U/kg Humalog at meals.

at bedtime for basal coverage and mealtime lispro (0.1 U/kg at each meal). However, it must be emphasized that these are "average" starting doses. We frequently vary them because of many factors that affect the patient's insulin needs. For example, inconsistent eating of the delivered food is a major issue, especially in the elderly or persons who are slowly advancing their diet following abdominal surgery or an illness such as pancreatitis. Using lispro as opposed to Regular allows the nurse to give the insulin toward the end of the meal, after seeing how much has been eaten; guidelines for meal dosing based on the amount of the meal or carbohydrate consumed can be very helpful. Also, a variety of illnesses cause concern for hypoglycemia from the injected insulin because of impaired glucose production from the liver, defective nutrient influx through the bowel, or slowed insulin metabolism. Examples are renal dysfunction, poor renal perfusion from cardiac failure or volume depletion, hepatic disease, malabsorption from bowel or pancreatic disease, and hypothyroidism or adrenal insufficiency. In those cases, we tend to lower the starting dosage of glargine to 0.3 U/kg. Alternatively, basal insulin needs are higher than 0.5 U/kg in many patients, in particular those with type 2 diabetes, obesity, infections, or open wounds, or those post-CABG or receiving steroids. We prefer not to go much higher than 0.7 U/kg as a starting dose, but advance their doses quickly.

Along with these starting doses, lispro supplements are written using a scale that starts at 200 mg/dl (Table 1) to compensate for substantial hyperglycemia if the patient's insulin needs far exceed the calculated starting doses. It is important to appreciate that the supplemental doses are there as a backup. The goal is to fine-tune the standard program so that within a day or two target glycemia is achieved without the need for supplements. This is accomplished by adjusting the glargine to achieve a fasting glucose value of 120-200 mg/dl, and then the lispro doses so that pre-meal and bedtime glucose values are in the same range (2-hour post-meal values sometimes are needed to adjust the lispro). Then, each day's insulin doses are adjusted as needed based on the prior day's glucose values, insulin doses and supplements, as well as the next day's planned nutrition schedule.

NPH or Ultralente has traditionally been used to provide basal coverage, and recommended starting doses for NPH or Ultralente are listed in Table 1. However, neither is an ideal "basal" insulin because of their slow "on-off" effect, which causes peaks and valleys in insulin action that tend to bring about swings in glycemia. This is worsened by the unforeseen changes in medical condition or meal schedule that frequently occur during a hospitalization. It is thus common to underdose these insulins to avoid hypoglycemia. The "peakless" nature of glargine's action has a significant advantage in this regard. Also advantageous are its more consistent day-to-day absorption compared with Ultralente and NPH and the fact that it is given at bedtime, which avoids the problem with

NPH or Ultralente of an occasional missed injection because the patient is away from the floor for a test or procedure.

Intravenous Insulin Infusions

A continuous i.v. insulin infusion is very useful in acutely ill patients, in the postoperative period, and in those with generalized edema or dermatological disease. Also, patients who are not eating, or are getting around-the-clock nutrition by TPN or tube feeds, do very well with an insulin infusion, although methods that are less intensive in terms of nursing care are more often used. A protocol recommended by Gebhart (9) (Table 2) is based on the study of Walts et al. (18) but uses lowered glucose cutoff values that better match the whole blood method of most bedside meters. We generally start with 1.5 U per hour, analogous to Watts and colleagues' study (18). However, considerably more insulin is needed in patients who are obese, infected, or on steroids. Insulin requirements are often particularly high post-CABG in otherwise uncomplicated patients. Under these circumstances, we start a higher infusion rate of 2-3 U per hour. Although glyce-mia is easily and safely controlled with this algorithm in most patients, it requires that bedside glucose monitoring be performed frequently—every 1 -2 hours after starting the infusion until steady-state glycemia within the target range is achieved, and thereafter no less then every 4 hours in stable patients and every 2 hours in less stable patients. This is because changes in a patient's medical

Table 2 Algorithm for Continuous Intravenous Insulin Infusion

Start continuous dextrose infusion (D5/W) at 100 ml per hour

Start Regular insulin 125 U in 250 ml 0.9% saline infused by syringe pump (1 U = 2 ml)

Glucose checks every 1-2 hours

Algorithm—begin at 1.5 U per hour (up to 3 U per hour in patients who are obese, infected, on steroids, post-CABG): <80 mg/dl—Decrease rate by 1 U per hour and give 25 ml 50% dextrose i.v.

80-110 mg/dl—Decrease rate 1 U per hour 110-160 mg/dl—No change in rate 161-220 mg/dl—Increase rate 0.5 U per hour

>220 mg/dl—give 8 U Regular insulin i.v. push and increase 0.5 U per hour

Physician to be notified if <80 mg/dl or >220 mg/dl on two consecutive checks

Source: Adapted from Ref. 9.

Adjust 70/30 insulin doses to attain blood glucose 120-200 mg/dl Continue blood glucose monitoring while the patient is receiving tube feeds, and make daily adjustments in the 70/30 insulin doses as needed

If the tube feeds are unexpectedly discontinued, glycemia is closely monitored (every 1-2 hours), and i.v. glucose started if needed (blood glucose <100 mg/dl)

Tube feeds are generally not recommended in patients with gastroparesis, because jejunal feeding is usually more successful.

ft manage their diabetes medications. This issue was discussed in a recent review of perioperative management of diabetes (8). Table 4 shows a suggested protocol.

Oral diabetes medications are held the morning of the procedure, and generally restarted once the patient is tolerating food after the procedure, although with dye-based studies the patient must wait 48 hours to restart metformin. It is safest to have a glucose-containing i.v. (D5/W) running during the procedure at — 100 ml per hour. Blood glucose should be measured before and after the procedure, and supplements of Regular insulin (5-10 U) given for glucose values above 120 mg/dl. This is done by the hospital or office nursing staff in the periop-

erative period. If insulin is likely to be needed after the procedure, it is important to teach the patient or a family member injection technique ahead of time, and to ensure that they have Regular' insulin as well as injection equipment at home. Prefilled insulin pens are particularly convenient for this purpose.

For patients who take insulin, it is recommended that the procedure or test be is scheduled for early morning. Generally, the usual dosage of long-acting insulin is taken the night before, but it can be lowered 10-20% if food intake at supper is less than normal or patient is using glargine. The morning of the procedure, the patient takes half of his or her usual morning dose of long-acting

ft daily insulin dose divided by 24. This is when the HbAlc of the patient is reasonably good (arbitrarily, <8.5%). For example, a patient taking 5-8 units of lispro at meals and 12 units of NPH at breakfast and 8 units of NPH at bedtime with HbAlc of 7.5% would be started at 0.8 U per hour (half of the total dose of ~40 units divided by 24). In patients with a higher HbA|C, it is prudent to increase 25% for HbAlc <10%, and 50% for HbAlc >10%. In the patient described above but with an HbA,c of 10.2%, the starting infusion rate would be 1.2 U per hour. Blood glucose values are measured hourly (including during the surgery), and

glucose goals at the start of the hospitalization that are known by all the patient's caregivers—nurses, dieticians and physicians. Also needed is a system for recording die bedside glucose data in a way that is visible and easy to interpret. Effective communication between services and floors is essential. This is particularly true when transferring patients with diabetes to another service or floor; a fail-safe mechanism must be in place that prevents a prolonged omission of insulin because of failure by the new caregivers to expeditiously implement the insulin program.

Most institutions have access to inpatient diabetes consultants. They should

Pharm 54:1046-1047, 1997.

18. Watts NB, Gebhart SP, Clark RV, Phillips LS. Postoperative management of diabetes mellitus: steady-state glucose control with bedside algorithm for insulin adjustment. Diabetes Care 10:722-728, 1987.

19. Scheen A, Castillo M, Jandrain B, Krzentowski G, Henrivaux P, Luyckx AS, Lefebvre PJ. Metabolic alterations after a two-hour nocturnal interruption of a continuous subcutaneous insulin infusion. Diabetes Care 7:338-342, 1984.

20. Gavin LA. Perioperative management of the diabetic patient. Endocrinol Metab Clin North Am 21:457-475, 1992.

21. Fehmann HC, Goke R, Goke B. Cell and molecular biology of the incretin hormones

Copyright © Marcel Dekker, Inc. All rights reserved.

z aiaoetes;.

Diabetic ketoacidosis (DKA) is characterized by a high blood glucose level, ketonemia and ketonuria, and metabolic acidosis. The hyperosmolar syndrome entails hyperglycemia and profound dehydration without significant ketoacidosis. The most common term in general use for this syndrome is nonketotic hyperosmolar coma. However, since few patients actually present in coma (<10%), most experts prefer to call this entity nonketotic hyperosmolar syndrome (NKH).

person-years for NKH while DKA was 14/100,000 person-years (13). Because DKA and NKH represent a continuum of hyperglycemic decompensation, patients can present with a mixture of the two; a review of admissions to a large city hospital found pure NKH in 32% of patients with uncontrolled diabetes, and mixed hyperosmolarity and ketoacidosis in another 18% (14).

The reported mean age of patients with NKH is 57-69 years. Newly diagnosed diabetes is present in 33-60%. NKH can occur during hospitalization for other illnesses, and in one study 18% of cases were transferred from skilled nursing facilities (15). To increase recognition and reporting of this diabetic emer-

secretion. Consequently, during fasting exactly enough insulin is produced so that glucose production is enhanced and glucose utilization is lowered to preserve normoglycemia—i.e., not too little, causing hypoglycemia, or too much so that hyperglycemia occurs. Also, the production of ketones is controlled so that "starvation ketonuria," not ketoacidosis, is observed.

In DKA, the profound insulin deficiency of type 1 diabetes allows the system to spiral out of control. Hyperglycemia occurs, causing an osmotic diuresis and eventual dehydration, which further raises the levels of the catecholamine hormones. The results are:

ft ever, one study suggests that they may also improve counterregulatory hormone defenses. Because hypoglycemia may lake from 1 to 6 months to become clinically manifest given the slow time to maximal effect for these drugs, some patients find the hypoglycemia unexpected. Insulin-dose reductions of 25% or more may be required. Figure 7 illustrates how the insulin dose-response curve influences the reoccurrence of hypoglycemia despite dose reductions in such situations.

SUMMARY

Hypoglycemia is the biggest obstacle to excellent control of diabetes with insulin. The physiological defects that create most of the risk—hypoglycemia un-awareness and defective insulin counterregulation—appear in many patients to be largely reversible simply by avoiding hypoglycemia. Identifying those at increased risk is very important since their goals may be adjusted for safety. Full treatment of hypoglycemia is crucial for the safety of patients. Modem insulin therapy is tailored toward avoidance of hypoglycemia. It avoids insulin peaks at times of known susceptibility to hypoglycemia, such as during sleep, and anticipates needs for therapy rather than simply reacting to high and low blood sugars, increasingly, insulin-therapy strategies are recommended that mimic physiological insulin secretion using a basal-bolus approach. This is accomplished partly through use of insulin preparations that more accurately mimic the way ¡3 cells secrete insulin.

REFERENCES

American Diabetes Association Position Statement. Standards of medical care for patients with diabetes mellitus. Diabetes Care 24(suppJ l):S33-S43. 2001. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977-986, 1993.

UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet 352(9131):837-853. 1998. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352(9l3l):854-865, 1998.

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