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Introduction

Over the past decade, there has been a revolution in the care of diabetic patients. Long term prospective research studies, demonstrating that improving glucose control decreases microvascular disease(1-4), have led to a new standard of care for ambulatory care.

Contemporary inpatient diabetes protocols have been successfully employed to manage diabetic patients who are not eating (NPO). New protocols have also been implemented to manage hypoglycemia (5-8). Not withstanding the availability of these inpatient protocols, and the general revolution in outpatient diabetes management, in most cases inpatient management remains a neglected area. The customary protocols utilized in most institutions reflect the diabetes management tools of the 1970's or earlier, rather than these new approaches.

Patients with diabetes are often highly educated about their diabetes and the reasons for good metabolic control. Poor inpatient management of their diabetes and resultant poor glucose control creates a frustrating experience and sends a confusing message to the patient about the importance of glucose control.

In this review, evidence that improving inpatient diabetes management changes hospitalization outcomes will be shown. Strategies for improving diabetes inpatient management and implementing these changes are also discussed.

What is Inpatient Diabetes Care ?

The emphasis on inpatient diabetes care has traditionally centered on treatment of diabetic ketoacidosis (DKA) and hyperosmolar nonketotic coma, and the newly diagnosed diabetic patient. This focus has been misplaced. Poor glucose control, as measured by glycosylated hemoglobin level, has been associated with an increased risk for hospitalization (9, 10). Patients with diabetes have a 2.2 to 4-fold increase in hospitalization rate compared to the nondiabetic population(9-11).

Inpatient hospital costs represent approximately 63% ($65.2 billion in 1992) of the annual healthcare cost for diabetes (12). The majority of this expense is for hospitalized patients with a secondary, not primary, diagnosis of diabetes. Thus, management of patients hospitalized for heart disease, infections, surgery, etc most often characterizes inpatient diabetes care. It is estimated that inpatient expenditures for diabetics with general medical problems (infections, etc) are twice that for treatment of chronic complications of diabetes (13). In addition, these diabetic patients are hospitalized about 1-3 days longer than their nondiabetic counterparts. The estimated average cost for a hospitalized nondiabetic patient is $12,200 compared to $23,500 for a diabetic patient (14). Compounding the problem, though an inpatient today is more acutely ill than in the past, the length of stay is shorter(15) In addition, hospitalized patients who are found to have previously unrecognized hyperglycemia and/or diabetes at the time of their hospitalization have been an overlooked population. It is estimated that 26% of hospitalized patients with diabetes were not aware of this diagnosis prior to their hospitalization(16).

Goal for Inpatient Glucose Control

The goal for glucose control is to avoid the undesirable short-term effects of hypo- and hyperglycemia. From a practical standpoint, this means that glucoses should be between 100 to 200 mg/dl. Glucoses under 200mg/dl should decrease the short-term diabetes complications that may occur during a hospitalization, while lower glucoses (with a HgA1c goal of about 7%) are desired for the long-term prevention of microvascular and macrovascular disease. Hypoglycemia should be avoided to prevent counterregulatory hormone induced cardiovascular complications.

Factors Influencing Glucose Control In Hospitalized Patients with a High Glucose Level

The major factors that need to be overcome in order to achieve glucose control in the hospitalized diabetic patient are:

1. Increased counterregulaotry hormones
• This situation usually occurs in the perioperative period with increased insulin resistance due to increased catecholamines, cortisol, growth hormone and glucagon
2. Unpredictable eating
• From illness
• NPO for tests
• Changing meal times
3. Changing IV glucose rates
4. Lack of exercise
5. Unusual timing of insulin injections
• Injection may be ordered on a timed basis, not having any relationship to meal
• Insulin often given after meal is eaten
6. Use of medications such as glucocorticoids and catecholamines

Epidemiological and small retrospective studies show diabetes increases morbidity and mortality for myocardial infarction(6, 17-21), coronary bypass surgery (22-26(, and stroke(27-31). More specifically, when glucoses are elevated (generally greater than 200 mg/dl) there may be:

1. Fluid and electrolyte abnormalities secondary to osmotic diuresis
2. Decreased WBC function (32-44)
3. Delayed gastric emptying (45, 46)
4. Increased surgical complications including:
• Relative risk for "serious" postoperative nosocomial infections increased by a factor of 5.7 when glucose >220 mg/dl (47)
• Relative odds of wound infection increased to 1.17 with glucoses were 207-227 and 1.78-1.86 when glucoses were >253. (48)
5. Delayed hospital discharge:
• Length of stay was compared for patients in "control" (glucose 60-250 mg/dl) and those with "fluctuating" glucoses (glucose <60 or >250 mg/dl)( 49).

• 	Length of Stay (days)
  	Glucoses in Control	Fluctuating Glucoses
  Acute Myocardial Infarction	4.1	6.7
  CABG	6.3	8.2
  Community Acquired Pneumonia	4.5	6.3

6. Double the mortality risk in patients admitted with a stroke(28, 50, 51).

Intervention Studies: Evidence That Improving Glucose Control Improves Outcomes

The above studies indicated that high glucose levels are associated with a poor outcome. Illustrative data showing that improving glucose control improves outcomes is listed below.

1. Improved WBC function
• Perioperative insulin infusion improves neutrophil phagocytic activity to 75% of baseline activity compared to only 47% in a control group( 52).
2. Decreased infections
• Perioperative intravenous insulin infusion designed to keep glucoses <200 mg/dl reduces the risk of wound infection in diabetics after open heart operations. Incidence of Deep Wound Infections decreased from 2.4 to 1.5% (53)
  2.0 to 0.8% (54)
3. Decreased postoperative mortality
• Diabetes team followed patients and controlled glucoses using perioperative IV insulin infusion and algorithm based SQ premeal insulin. Mortality of diabetic patients undergoing CABG in 1993-1996 was reduced to level of nondiabetics. Nationally, diabetic patients had 50% higher mortality(55).
• Use of IV insulin for CABG patients
4. Decreased post myocardial infarction morbidity and mortality
• DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) study group treated perimyocardial infarction diabetic patients with IV insulin infusion and then algorithm based SQ premeal insulin (for one year).56-58Mortality at 1 year was 26% in the control patients compared to 19% in the study patients.
  Mortality at 3.4 years was 44% in the control patients compared to 33% in the study patients
5. Decreased morbidity and mortality in critically ill patients
• A comparison of patients with plasma glucoses between 80-110 mg/dl (intensive treatment), and those given insulin only if glucoses were >215 mg/dl and then maintained 180-200 mg/dl (control)59 indicate that:
  Intensive insulin treatment decreased overall mortality from the control rate of 8% to 4.6% (p<0.04). In addition, the intensive treatment decreased sepsis by 46%, need for dialysis by 41%, and these patients were less likely to require prolonged ventilatory support and intensive care.
6. Decreased length of stay
• Use of an inpatient diabetes consultation service decreased length of stay by 56%(60).

Glucose Control Goal

Avoid use of Insulin "Sliding Scale"
While "Sliding Scale" insulin protocols remain the mainstay for inpatient glucose control, this method does not work. "Sliding Scale" methodology dates to diabetes monitoring by urine glucose levels. The tape that was used for the test would change colors depending on how much glucose was in the urine. Insulin was then given based on the change in color. This was called "rainbow coverage." Unfortunately, whether urine or plasma glucose is used, there is no physiologic basis for this form of insulin therapy. Patients therefore tend to have "roller coaster glucose control." Under this protocol, the patient would not receive insulin when their glucose level is normal. A few hours later their glucose level increases because no insulin had been given. Insulin is then administered for the elevated glucose level and a few hours later the glucose level returns to normal. This cycle is repeated again and again. (See figure 1)

Figure 1.

Under treatment with a "Sliding Scale," patients with Type 1 DM will go into DKA. If a patient with Type 1 diabetes does not receive insulin for their "normal glucose," they will be insulinopenic by their next glucose check, and likely be ketotic. As many patients who are thought to have Type 2 diabetes may actually have Type 1 diabetes, it is difficult to predict who is at risk for DKA.

Finally, in the typical "Sliding Scale," no insulin is given for a glucose <150 mg/dl. For a glucose of 151-200 mg/dl5, 7, 8 2 or 3 units of insulin may be given, for 201-250 3 or 4 units, on so on. Imagine a typical insulin resistant Type 2 diabetic patient who has been well controlled on a total of 80 units per day (in split doses). Is it any wonder that this patient will have marked hyperglycemia upon admission to the hospital and treatment with the "Sliding Scale" described above!

The only study (61) of the use of insulin "Sliding Scales," concluded that there was no benefit in their use. In the accompanying editorial, Sawin wrote:

Protocol For Treatment Of The NPO Diabetic Patient

The preferred method of managing a diabetic patient who is not eating is an intravenous insulin drip. The key features are a fixed dextrose drip and an algorithm allowing the patient to receive the amount of insulin required to maintain their glucose level from 120-180 mg/dl.

The form that we currently use for this (see NPO Diabetic Order Sheet PDF. You need Acrobat Reader to see this document) was initially adapted from the regimens published by Nelson Watts et al from Emory University (5) and Pezzarossa et al from Parma (6). This regimen has also been modified and used at other institutions(7, 8, 63).

The algorithm:

1. Targets a glucose range that would minimize hypo or hyperglycemia
2. Uses a fixed dextrose infusion to reduce chance of hypoglycemia
3. Uses a simple algorithm for individualizing the rate of insulin infusion.

Figure 2.

The algorithm used by Watts et al is shown in figure 2. The striking finding is the wide variation in insulin requirements to maintain glucose levels in the 120-180 range. Infusion rates varied from 0.5 to 5 Units per hour in the initial study (figure 3). The glucose results are shown in figure 4. In figure 5, the final glucose levels and the incidence of hypoglycemia are shown. Overall, the patients in the algorithm treated group had glucoses in the expected range and less hypo and hyperglycemia.

Figure 3.

Figure 4.

Figure 5.

Generally, as the acute illness resolves the insulin requirement slowly decreases (as expected). Problems with this regimen can be from one of the following:

1. Inappropriate interruption of dextrose (for transfusion, etc.,)
2. Rapid improvement in patient, or sudden decrease in administered steroids, without making a one-time decrease in insulin administration rate. The algorithm may be too slow to catch up to this with hypoglycemia occurring.
3. IV tubing not primed. Insulin will bind to glass or plastic bottles and tubing. If insulin is mixed in the IV bag and the tubing is not primed, then >50 cc of fluid will need to be infused before the patient is receiving the concentration of insulin that is expected. Thus the first 50 cc of mixed insulin solution should be run through all the tubing and discarded (64).

Protocol For Insulin Use In Patient Who Is Eating

There are no studies on the proper way to administer insulin to a hospitalized patient who is eating. As described above, the standard "insulin sliding scale" does not achieve the stated goals.

We have developed an order form (see sq insulin PDF. You need Acrobat Reader to see this document) to help with the physiologic use of insulin in the inpatient setting. By its very nature, the form leads away from the "Sliding Scale." The form allows for different premeal doses of short acting insulin, with adjustments made for the actual glucose value. Physiologic insulin replacement is impossible without a formal order sheet. This type of order form also helps limit a common error of giving large doses of regular insulin at bedtime due to ingrained use of "Sliding Scales." In that case, regular insulin is often given when only the NPH or other long acting insulin should be given.

Insulin Dosing (also see page 2 of the sq insulin PDF. You need Acrobat Reader to see this document).

1. Patients who are on insulin at home and well controlled, they should receive their usual insulin regimen.
2. Insulin requirements vary widely from patient to patient. Type 1 diabetic patients who are insulin sensitive may require 0.5 U/kg per day, but requirements vary from patient to patient, and also vary with underlying infection, stress, etc. Type 2 diabetic patients, who by definition are insulin resistant, may have insulin requirements several fold higher than those of Type 1 patients.
3. In general, for a typical hospital meal, a Type 1 diabetic patient will require approximately 5 units of short acting insulin to maintain their glucose level. As previously mentioned, this is just a crude estimate, and doses for any individual may be much higher or lower.
4. NOTE: given the above description of insulin dosing, if 5 units of insulin in an insulin sensitive patient is required to maintain glucose levels, then the idea of giving 2 units when blood sugar is >200 (as with typical "Sliding Scale") makes absolutely no sense.

There are three sections on the subcutaneous insulin form: (see sq insulin PDF. You need Acrobat Reader to see this document)

Oral Hypoglycemic Agents

Sulfonylureas increase the risk of hypoglycemia in well-controlled patients due to unpredictable eating and tests requiring the patient to be NPO. These drugs may be continued, but only with caution.

In general, metformin should be discontinued for most hospitalized patients. Currently, hospitalized patients are more acutely ill than years ago and will often have contraindications to use of this drug (infection, congestive heart failure, need for intravenous contrast study- any process increasing risk for lactic acidosis).

The thiazolidinediones (rosiglitazone and pioglitazone) may be continued for most patients. Caution should be exercised in patients at risk for congestive heart failure as both of these drugs may cause significant fluid retention leading to edema and congestive heart failure. Recall the metabolic effects of these drugs may take weeks to appear and will continue for weeks or months after their discontinuation.

Diabetes Diet

Not withstanding specific diet orders, most patients receive the same "diabetes" meal. On average, a hospitalized diabetic consumes about 1100 calories per day with about 50-70% carbohydrate and 20-25% fat. Ordering an 1800 calorie "ADA" diet is not useful as it does not reflect either the actual diet the patient eats as an outpatient, nor even the diet they actually eat as an inpatient. It remains most prudent to order a "no concentrated sweets" diet. This will avoid inappropriate juices and alike on the meal tray.

Glucocorticoids and Diabetes

In diabetic patients, glucocorticord use adversely impacts glucose control. In addition, "steroid diabetes" can occur in up to 25% of patients previously thought to be nondiabetic (65). The glucose elevation is predominantly postprandial hyperglycemia with a notable lack of fasting hyperglycemia. This pattern reflects the steroid induced inhibition of glucose uptake into fat and muscle, with much less effect on gluconeogenesis. Additionally, a general resistance to insulin occurs66.
In general, the glucose pattern consists of normal or minimally elevated fasting glucoses and extremely elevated glucoses in the afternoon and evening. The patterns are variable and often unpredictable.

Short Term Treatment

The major mistake made in these patients is the use of an insulin "Sliding Scale." The patient will have a relatively low fasting glucose resulting in no insulin being given. The glucose by dinner will be high, often >300-400. A large dose of insulin is given for this glucose level. This dose then results in nocturnal and fasting hypoglycemia, as the glucose will drop anyway with the postprandial effect disappearing overnight. The optimal treatment is to use large doses of insulin at breakfast and lunch, with often no insulin in the evening. This protocol can be accomplished by either using short acting insulin at breakfast and lunch, or NPH and short acting insulin before breakfast. It should be noted that very high insulin doses may be required, with >40 units given for the "normal" fasting glucose.

Long Term Treatment

Long term, use of a thiazolidendione and/or metformin may be of great benefit as these drugs work to reverse the specific metabolic abnormalities secondary to the glucocorticoids. This result has been shown in animal, but not human studies.
Occasionally, sulfonylureas may be used. In this case a short acting agent such at tolbutamide may be given before breakfast and dinner. Longer acting agents have the potential to cause overnight hypoglycemia. A similar option would be to use rapaglinide before meals, as it is also less likely to cause overnight hypoglycemia.

TPN and Diabetes

Typically insulin is added to the TPN solution bag. A better technique, allowing more rapid glucose control, and more rapid estimate of total insulin needs, is to have a separate IV insulin drip (as described for NPO - perioperative patients). When the glucose is controlled, the insulin may then be added to the TPN solution. Similar methods to this have been successfully tested in the past. 67 Not only did this form of insulin management improve glucose control, there was a savings of >7 liters of TPN solution per patient.

Hyperalimentation and Diabetes

As with TPN, the quickest way to obtain glucose control is to utilize the IV insulin drip. Once the glucoses are controlled, if the feeding is to be long term, the 24-hour insulin dose can be split in half and given as q12h NPH insulin injections. While this is not ideal treatment, it is a pragmatic compromise. In the future, newer long acting insulins may allow for improvements in the regimen.

NPO For Short Procedure

For early morning short procedures, the easiest approach is to just hold the medications and food until after the procedure. The patient can then eat and be given the usual AM medications and/or insulin.

If the procedure is scheduled for later in the morning, then glucose control becomes more difficult. Most patients who are only on oral hypoglycemia agents can have the medications held and restarted later that day. The patients taking insulin would do best on an intravenous insulin infusion. However, this measure is generally not utilized for this short of a time. Most patients will do well receiving about 1/3 to 1/2 of their usual AM insulin. Patients using an insulin pump can continue on their basal insulin infusion rate.

The best plan for a patient scheduled for a procedure in the afternoon is to reschedule the procedure for the early morning. If this is not possible, the patient on oral agents should wait and take the medication after the procedure. For patients on insulin, it is best to have them on an insulin infusion. Patients using an insulin pump can continue on their basal insulin infusion rate. It is possible to give the patient intermediate or long acting insulin, approximately 1/3 to 1/2 of the total daytime dose, but this does not allow for fine adjustments.

Patients who are now using insulin glargine as their basal insulin may be handled like a patient on an insulin pump. They should continue the glargine as basal insulin and only take their short acting insulin when they are ready to resume eating.

Conclusion

Not enough attention has been placed on the management of diabetic patients hospitalized with diabetes as a secondary diagnosis. Old ineffective protocols remain in widespread use. Using the forms and protocols described in this chapter should help improve inpatient diabetes management and bring it in line with outpatient care.