We with diabetes have high rates of being hospitalized. At least 24% of adult patients with known diabetes surveyed in 1989 reported being hospitalized at least once in the previous year. This risk factor goes up with age, duration of diabetes, and the number of complications. In fact, people with diabetes are hospitalized three times more often than those without diabetes.
The effect of hyperglycemia and poor outcomes may be due to various cells and organ systems. The association of hyperglycemia and infection has long been known although unclear. It would appear that the effect of hyperglycemia on the immune system may compromise small groups of normal people, patients with diabetes of various duration and types, and animal studies. Studies consistently show that hyperglycemia causes immunosuppression. Reduction of glucose by a variety of means reverses the immune function defects.
- Hyperglycemia has numerous effects on the cardiovascular system. It impairs ischemic preconditioning as a protective mechanism for ischemic insult. Infarct size increases in with hyperglycemic state. There is proven reduced coronary collateral blood flow in moderately severe hyperglycemia.
- Hyperglycemia and thrombosis relationship have been shown with many studies.
- Inflammation and hyperglycemia. The connection between acute hyperglycemia and vascular changes likely involves inflammatory changes.
- Endothelial cell dysfunction and hyperglycemia. One proposed link between hyperglycemia and poor cardiovascular outcomes is the effect of acute hyperglycemia on vascular endothelium. In addition to serving as a barrier between blood and tissues, vascular endothelial cells play a critical role in overall homeostasis.
- Hyperglycemia and the brain. Acute hyperglycemia is associated with enhanced neuronal damage following induced brain ischemia. Many of the same factors linking hyperglycemia to cardiovascular event outcomes likely contribute to acute cerebrovascular outcomes. Specifically, in brain ischemia models exposed to hyperglycemia, hydroxyl free radicals are elevated and positively correlate with tissue damage. Likewise, antioxidants have a neuroprotective effect. Elevated glucose levels have been linked to inhibition of nitric oxide generation, increased IL-6mRNA, decreased cerebral blood flow, and evidence of vascular endothelial injury.
Is insulin therapeutic? Two large, well-done prospective studies support the relationship between insulin therapy and improved inpatient outcomes. The prevalent assumption has been that insulin attained this benefit indirectly by controlling blood glucose. However, a growing body of literature raises the question of whether insulin may have direct beneficial effects independent of its effect on blood glucose. In small studies of individuals with or without diabetes undergoing coronary bypass surgery, glucose-insulin-potassium (GIK) therapy is associated with shorter length of intubation and shorter length of stay. As therapy for patients with acute MI, GIK therapy is associated with decreased heart failure and a suggestion of increased short-term survival. Insulin treatment improves endothelial cell function and has anti-inflammatory effects. The overwhelming balance of evidence supports a beneficial effect of insulin in the acute setting. Whether these benefits are the result of a direct pharmacologic effect of insulin or represent an indirect effect by improved glucose control, enhanced glycolysis, or suppressed lipolysis is more difficult to determine.
Studies in cell cultures control for glucose but have other physiologic limitations, Nevertheless, the data are provocative and certainly leave the impression that insulin therapy in the hospital has significant potential for benefit. Considering the numerous contradictions to use of oral agents in the hospital, insulin is the clear choice for glucose manipulation in the hospitalized patient. To explain the dual role of glucose and insulin on hospital outcomes, the following relationship has been proposed by Levetan and Magee. Elevations in counterregularory hormones accelerate catabolism, hepatic gluconeogenesis, and lipolysis. These elevate blood glucose, FFA, ketones, and lactate. The rise in glucose blunts insulin secretion via the mechanism of glucose toxicity, resulting in further hyperglycemia. The vicious cycle of stress-induced hyperglycemia and hypoinsulinemia subsequently causes maladaptive responses in immune function, fuel production, and synthesis of mediators that cause further tissue and organ dysfunction. This, the combination hyperglycemia and relative hypoinsulinemia is mechanically positioned to provide a plausible explanation for poor hospital outcomes seen in observational studies.
A rapidly growing body of literature supports targeted glucose control in hospital settings with potential for improved mortality, morbidity, and health care economic outcomes. The relationship of hospital outcomes to hyperglycemia has been extensively examined. Hyperglycemia in the hospital may result from stress, decompensation of type 1 diabetes, type 2 diabetes, or other forms of diabetes and/or may be iatrogenic due to administration of pharmacologic agents, including glucocorticoids, vasopressors, etc. Distinction between decompensated diabetes and stress hyperglycemia is often not made or alternatively is not clear at the time of presentation with an acute illness. When hyperglycemia is treated along with other acute problems, outcomes are generally improved.
Observational studies suggest an association between hyperglycemia and increased mortality. Recently, investigators have reported outcomes correlated with blood glucose levels in the general medical and surgery setting. Pomposelli et al studied 97 patients with diabetes undergoing general surgery procedures. Blood glucose testing occurred every 6 hours. The authors found that a single blood glucose level > 220 mg/dl on the first postoperative day was a sensitive (85%), but relatively nonspecific (35%) predictor of nosocomial infections. Patients with a blood glucose values > 220 mg/dl had infection rates that were 2.7 times higher than the rate for patients with blood glucose values < 220mg.dl. When minor infections of the urinary tract were excluded, the relative risk for serious postoperative infection, including sepsis, pneumonia, and wound infections, was 5.7.
Umpierrez et al reviewed 1,886 admissions for the presence of hyperglycemia defined as greater than or equal to 126 mg/dl. They compared newly hyperglycemic patients (in hospital) to those with known diabetes. They found that both the new hyperglycemia and known diabetic patients were more likely to require intensive care unit care when compared with normaglycemic patients and were more likely to require transitional or nursing home care.
The observational data from these studies suggest that hyperglycemia from any etiology in the hospital on general medicine and surgery services is a significant predictor of poor outcomes, relative to outcomes for normaglycemic subjects. Patients wit hyperglycemia, with or without diabetes, had increased risk of in hospital mortality, postoperative infections, neurologic events, intensive care unit admission and increased length of stay. The Pomoselli article found that a blood glucose level of 220mg/dl separated patients at risk of infection. Research from other authors and disciplines suggest a lower threshold for optimal hospital outcomes.
Numerous articles contain data linking blood glucose levels to outcomes in acute MI and cardiac surgery for which patients receive care predominantly in the ICU setting. Three studies which show evidence for a blood glucose threshold for increases mortality in acute MI include the metaanalysis of Capes et al which reported a glucose threshold of > 109.8mg/dl for patients without diabetes and > 180mg/dl for known diabetics. The observational study of Bolk et al identified threshold blood glucoses divided by WHO classification criteria, with mortality of 19.3% for normaglycemic (< 110.8 mg/dl), which rose progressively to 44% for blood glucose > 199.8 mg/dl.
Attainment of targeted glucose control in the setting of cardiac surgery is associated with reduced mortality and risk of deep sternal wound infections. Research analysis of the cohort group in the Furnary research found a positive correlation between the average postoperative glucose level and mortality, with the lowest mortality in patients with average postoperative blood glucose < 150mg/dl. In Golden’s study, 411 diabetic patients were assessed with perioperative measurements during the first 36 hours following surgery. The overall infectious complication rate was 24.3%. After adjustment for variables, the patients with the highest mean capillary glucose readings were at increased risk for developing infections.
Observational studies in acute neurologic disorders suggest a correlation between blood glucose level, mortality, morbidity, and health outcomes in patients with stroke. Capes et al’s metaanalysis identifies an admission blood glucose > 110 mg/dl for increased mortality for acute stroke. Studies by Pulsinelli, Jorgenson and Weir et al identifies an admission blood glucose > 120mg/dl, 108mg/dl, and 144mg/dl respectively for increased severity and mortality for acute stroke. Parsons et al reported that a doubling of blood glucose from 90 to 180mg/dl was associated with 60% worsening of penumbral salvage and a 56-cm3 increase in infarct size.
The importance of caring for diabetic patients in hospital and keeping their blood glucose levels normal goes beyond morbidity and mortality studies. Of the $91.8 billion spent annually in the US for direct medical expenditures for diabetes, hospital care accounts for the single largest component of expenditures, comprising $40 billion, or 43% of the total cost. After adjustment for age, sex, and race/ethnicity, annual per capita costs for hospital care is $6,309 for persons with diabetes verses $2,971 for persons without diabetes—a coast ratio of 2.1. Similar increased hospital-related cost for diabetic patients is reported in Europe. This increased cost for hospitalization care is due to increased frequency of hospital admissions, increased length of stay, and increased cost per hospital day due to higher utilization of intensive care procedures.
For all of these reasons and more, do get the hospital’s procedure for treating patients with diabetes before you sign in. In an emergency, have a designated person in the family go over these facts with the staff and your physician. Know the methods by which you will receive your basal insulin, both on the unit and in the OR. Find out the methods used to monitor blood glucose levels and how often these will be done. Find out how hyperglycemia and hypoglycemia are treated in the hospital. If you are on oral medications, find out what will be done to treat the hypoglycemia in terms of insulin therapy and if there is a policy about this in the hospital. Ask your physician how he titrates insulin for type 2 diabetes.
If you have type 1 diabetes or if you currently take insulin with type 2 , make sure you ask to be part of the solution after you are able to. I certainly know what happens to me when I am under stress and I know how many units of insulin I need to lower my blood glucose levels. If your team does not ask before you enter the hospital, make sure you have it written down and give it to your physician. I know what the text books says about how many units of insulin I must program for the carbohydrates I eat, but I also know what I really need and which foods raise my blood glucose levels higher and faster than others. I also know which pain medications I can take and which make me ill, so I am my own expert and I make sure all of this information is at the doctor’s office and therefore it has a chance to make it to my chart. I know that intake nurses ask the right questions, but in an emergency, it is good to have all of this information available. And most of all make sure your family knows to ask about your blood glucose levels and whether they are being treated if they are too high. The results of the research as of today, proves that the more normal the better for you and your family.
BSP
