Case Study: The Recipe for Diabetes Success in the Hospital

Presentation

N.D., a 48-year-old, obese, African-American man, was admitted to intensive care unit with crushing, substernal chest pain. This was associated with dizziness, nausea, vomiting, and diaphoresis. The electrocardiogram on admission revealed T wave inversions in the anterior and lateral leads. He ruled in for a myocardial infarction (MI) by serial cardiac enzymes. His glucose level on admission was 203 mg/dl with a bicarbonate of 24 mg/dl. A hemoglobin A_1c (HbA_1c) performed in the hospital revealed a value of 8.1%.

The patient’s father had a history of heart disease and had suffered a heart attack at the age of 52 years. His grandmother had a history of type 2 diabetes controlled with insulin. N.D. stated that for a few months before admission, he had been feeling fatigued and had been experiencing increased urination, especially at night.

N.D. is a computer programmer and had led a sedentary lifestyle, without a regular exercise regimen. He had steadily gained weight over the years, to his present weight of 220 lb. He does not smoke and occasionally drinks beer on the weekend. He consistently drinks more heavily during an annual Super Bowl party in January of each year.

Commentary

Ingredients for diabetes success

• Regardless of whether this patient has “stress hyperglycemia” or unrecognized diabetes, treat aggressively with intravenous rather than subcutaneous insulin coverage.

• Understand that definitive diabetes is not necessary to demonstrate improved outcomes by controlling glucose as close to normal as possible.

• Realize that morbidity and mortality from stroke, MI, and bypass surgery are affected most by glucose levels in the hospital.

Does controlling hyperglycemia in the hospital really matter?

The data on the importance of controlling glucose in the hospital span diverse disciplines of medicine. Studies in the areas of stroke, MI, bypass surgery, and wound and nosocomial infections all point to the tremendous potential to reduce morbidity and mortality among hospitalized patients with hyperglycemia. It is essential that hyperglycemia is identified from the time of hospital admission and that therapy is implemented to achieve and maintain glucose levels as close to normal as possible regardless of a patient’s primary reason for admission or previous diabetes status.

In the United States, there are more than 4.2 million hospitalizations annually among people with diabetes.1 Additionally, there are as many as 1.5 million hospitalized individuals who have significant hyperglycemia but no history of diabetes.2 Identification of and therapeutic interventions to treat hyperglycemia must be initiated in tandem with the presenting medical problem rather than days after admission, when many of the acute issues have already been addressed. Existing data strongly suggest that an early and aggressive approach to the management of hyperglycemia may reduce mortality, morbidity, excessive hospital stays, and added costs.

Diabetes is the secondary, not primary, problem.

Hyperglycemia is often overlooked when a hospitalized patient is acutely ill and facing a life-threatening illness. A common scenario is that of a patient admitted with an acute MI or cerbrovascular accident who is coincidentally found to have an elevated admission glucose value. Often, such patients have no history of glucose intolerance.

For patients who do have pre-existing diabetes, physicians routinely discontinue their patients’ previous outpatient diabetes regimen and initiate sliding-scale insulin coverage in the hospital.3 Many physicians consider this practice the standard of care. Concerns about precipitating hypoglycemia may limit more aggressive strategies for managing hyperglycemia, particularly when many of these patients are not tolerating regular meals or their intake is being limited for a variety of reasons, including pending surgical procedures or diagnostic tests.

Despite the ease and high frequency of use, sliding-scale insulin coverage often results in a deterioration of, rather than an improvement in, glycemic control.3 While concerns about hypoglycemia are warranted, hyperglycemia, regardless of whether a previous diabetes diagnosis has been made, may pose even greater risks by reducing hospital survival rates among patients admitted with stroke or MI.4–6

Is hyperglycemia caused by stress or diabetes? It doesn’t matter—treat it.

There are no unique diagnostic criteria to account for stress in acutely ill patients, nor are there recommendations for making a definitive diagnosis of diabetes in the hospital. Despite the well-defined pathophysiology of intercurrent illness and surgery on carbohydrate metabolism that may lead to hyperglycemia, many studies have also demonstrated that stress may result in diminished glucose values.7–19 This reduction in glucose seen in times of stress is frequently attributed to insufficient administration of exogenous glucose.

Among hospitalized patients with acute MI, an admission glucose value of ≥180 mg/dl predicted undiagnosed diabetes rather than stress hyperglycemia in a study in which newly recognized hyperglycemic individuals had subsequent glucose tolerance testing performed 2 months after hospital discharge.4,5

The Diabetes Insulin-Glucose in Acute Myocardial Infarction (DIGAMI) trial demonstrated significant reductions in mortality when an intensive insulin regimen was administered to hyperglycemic patients hospitalized with acute MI.4,5 Subjects in the DIGAMI study included all patients with glucose values >198 mg/dl without regard to previous diabetes status. Nearly 15% of the study population did not have a history of glucose intolerance.

Is the hospital really the time to consider diabetes? Yes.

Mortality rates among patients with diabetes are known to be significantly higher than those of nondiabetic individuals.20 The Whitehall Study reported a mortality rate of 12/1,000 person-years for nondiabetic individuals, a rate of 40 for people with undiagnosed diabetes, and a rate of 27 for people with diagnosed diabetes.21 The Paris Prospective Study demonstrated comparable differences between the mortality rates among patients with undiagnosed diabetes (23%) versus those with a definitive diagnosis of diabetes (20%) and patients without diabetes (9%).22 In both studies, 60–70% of the deaths were attributed to cardiovascular disease.23

Where is the best place to find unrecognized diabetes? In the hospital.

It is estimated that 5.3 million Americans have undiagnosed diabetes. As many as one-third of the patients who have significant hyperglycemia during their hospital admission do not have a history of diabetes.2 Given the 7- to 10-year delay between the actual onset of diabetes and the time of diagnosis, there is a high likelihood that patients exhibiting hyperglycemia without a history of glucose intolerance may indeed have unrecognized diabetes.20 The beneficial impact of interventions that improve hyperglycemia and lead to better outcomes is based on the presence of diabetes regardless of whether a physician has made the diabetes diagnosis.

Health care providers should assume that a hyperglycemic patient has diabetes and initiate treatment to control glucose levels as close to normal as possible. Further evaluation of the patient’s diabetes status can occur after hospitalization. Failure to treat and address hyperglycemia in the hospital is a missed opportunity to not only reduce hospital morbidity and mortality, but also initiate interventions that may delay the long-term complications of diabetes.

What if the hyperglycemia is caused by medication? Treat it like diabetes.

Often medications such as steroids and thiazide diuretics, which have been associated with worsening glycemic control, are required in the care of patients with diabetes. Dozens of medications have been described as inducing diabetes, yet there has been poor documentation of the glycemic status of patients using the offending drugs before these drugs were initiated.

Decades ago, corticosteroids were studied as a means of unmasking impaired glucose tolerance.24 When evaluating the impact of corticosteroids on normal control subjects, only 3% had positive glucose tolerance tests when pretreated with corticosteroids.

Other studies among corticosteroid-treated individuals have found that fewer than 20% of steroid-treated individuals develop diabetes. This indicates that hyperglycemia in the setting of the hospital should be assumed to be diabetes,25,26 even when medications that potentially produce hyperglycemia are required to treat another medical problem. In such cases, treatment of hyperglycemia should be initiated.

Is there a diagnostic role for HbA_1c? Maybe.

Many clinicians have advocated the use of HbA_1c measurement in the diagnosis of diabetes.27–30 But although an elevated HbA_1c measured when hyperglycemia is first noted can help determine that the hyperglycemia existed before hospitalization, a normal HbA_1c concentration does not preclude the diagnosis of diabetes. In one study, normal HbA_1c concentrations measured during hospital admission did not exclude the diagnosis of diabetes when glucose tolerance testing was performed after discharge.31

As more laboratories adopt the standardized methodologies for performing HbA_1c as established by the National Glycohemoglobin Standardization Program (NGSP), it will be easier to establish guidelines for the diagnosis of diabetes based on elevated HbA_1c concentrations. Laboratories certified by the NGSP all have equivalent HbA_1c assays and can be compared nationally regardless of location or laboratory performing the test. When the NGSP’s norms and ranges for HbA_1c are adopted universally, the HbA_1c assay may become a more useful tool for establishing the pre-existence of hyperglycemia before a hospital admission. Normal HbA_1c concentrations in the hospital setting still will not preclude the diagnosis of diabetes, however, and such patients will still need follow-up to evaluate diabetes status.

Diabetes isn’t the reason for admission, so why treat it? Hyperglycemia DOES impact the primary medical problem.

Ninety percent of hospitalizations among patients with a known diagnosis of diabetes are for reasons other than diabetes. Approximately 75% of hospital admissions for people with diabetes are attributable to cardiovascular disease.32 When hyperglycemia is not addressed until after the presenting medical problems have been treated, the length of hospital stay can be significantly longer than that of nondiabetic patients with similar primary diagnoses. Addressing diabetes along with other acute problems results in not only improved outcomes, but also potentially shorter hospital stays.33

Shouldn’t the MI be managed first? Treat the hyperglycemia aggressively and sequentially with the MI.

Diabetes has been demonstrated to be an independent risk marker for morbidity and mortality among patients who have suffered an MI.4,5,34–37 Soler and Frank observed that patients with the highest glucose values following an acute MI also had the highest mortality rates.34

The DIGAMI study underscores the importance of early and aggressive interventions designed to bring glucose levels into the normal range regardless of a patient’s prior diabetes status.4,5 This large, randomized, prospective trial enrolled 620 patients with admission glucose values of >198 mg/dl. Hyperglycemic individuals were randomized to receive either conventional diabetes care or intravenous insulin followed by four insulin injections daily.

One year after admission, there was a 30% reduction in mortality among the intervention patients. The greatest benefits from intensive insulin therapy were seen in the subgroup that included patients without a history of diabetes, who had a 58% risk reduction in hospital mortality and a 52% risk reduction in mortality when followed for 1 year when compared to conventionally treated patients.

When outcomes were tracked for a mean of 3.4 years, intervention patients had a 25% lower death rate. The DIGAMI study demonstrated that for every nine patients receiving intensive glucose control, one life was saved.

Summary and clinical keys

Inpatient studies have been designed to evaluate the impact of potentially correcting the pathophysiological changes that accompany hyperglycemia. Studies among patients with MI suggest that treatment of hyperglycemia can potentially affect morbidity and mortality, and similar benefits may apply to controlling hyperglycemia regardless of whether patients have a prior diagnosis of diabetes.

• When patients present with an acute illness and hyperglycemia, it is often difficult to differentiate stress hyperglycemia from previously undiagnosed diabetes.

• The lack of a definitive diagnosis of diabetes should not preclude aggressive glycemic management, especially in patients with suspected MI.

• Hyperglycemia accompanied by an elevated HbA_1c concentration suggests previously undiagnosed diabetes.

• The DIGAMI study demonstrated that for every nine patients receiving intensive glucose control regardless of their baseline diabetes status, one life was saved.