Standards of medical care in diabetes: focus on updated recommendations in hospitalized patients

Although the prevalence of diabetes mellitus in hospitalized patients remains unknown, an estimated one-fourth of inpatients experience hyperglycemia.¹ Hyperglycemia is linked to poor health outcomes, and there is evidence that intensive glucose control in the hospital reduces mortality, need for dialysis, infections, and length of stay.² The American Diabetes Association (ADA) publishes clinical practice guidelines annually, which offer clinicians, patients, researchers, and payers current, evidence-based recommendations on all components of diabetes care, general treatment goals, and tools to evaluate the quality of care. The updated guidelines focus on changes in the recommendations for care of the hospitalized diabetes patient.

While the management of hyperglycemia in the hospital was traditionally considered secondary in importance to the condition that prompted admission, a growing body of literature supports close glucose control for potential improvements in  mortality, morbidity, and health economic outcomes.³ The purpose of this article is to review both the previous and updated recommendations for inpatient hyperglycemia management, as well as evidence supporting the guidelines. Additional updated recommendations will also be discussed.

2009 RECOMMENDATIONS

Recommendations from 2009 included intensive blood glucose goals for hospitalized patients. According to the recommendations, blood glucose levels in critically ill patients should be kept as close to 110 mg/dL as possible and generally less than 140 mg/dL.⁴ Van den Berghe et al conducted the study that led to the adoption of stringent blood glucose targets.⁵ In this trial, 1,200 patients were randomized to strict normalization of blood glucose (target between 80 and 110 mg/dL) with the use of insulin infusion, or to conventional therapy (insulin administered when blood glucose exceeded 215 mg/dL, with the infusion tapered when blood glucose fell below 180 mg/dL). Although intensive insulin therapy reduced blood glucose levels, inpatient mortality was not significantly reduced for those participants admitted for less than 3 days. Intensive insulin therapy significantly reduced morbidity by preventing newly acquired kidney injury, accelerating weaning from mechanical ventilation, and accelerating discharge from the ICU and hospital. There were more cases of severe hypoglycemia (blood glucose less than 40 mg/dL) in the intensive insulin treatment arm.

The results of this landmark trial should be interpreted with caution, however, as there are several limitations. The Van den Berghe trial was a single-center study and, as such, the results should be replicated at other centers before creating guidelines based on its findings. The results also demonstrate an advantage for those treated with intensive insulin regimens who stayed in the ICU for more than 3 days; however, patients who will have a prolonged hospital stay cannot be identified on admission with certainty. Moreover, there are certain barriers to widespread adoption of tight glucose control. Tight glycemic control increases the risk of severe hypoglycemia and increases the resources required to achieve normoglycemia. Further multicenter trials are necessary to confirm the preliminary findings that intensive glucose control significantly reduces inpatient morbidity and both morbidity and mortality in patients with prolonged ICU stays greater than 3 days’ duration.

2010  RECOMMENDATIONS

In 2010, the ADA released an updated position statement with recommendations for inpatienttreatment of hyperglycemia. The guidelines approach management of hyperglycemia in a more lenient manner. According to the recommendations, blood glucose levels should be maintained between 140 and 180 mg/dL in critically ill patients.⁶ These new blood glucose targets were established based on the results of the Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial.⁷ The NICE-SUGAR trial was conducted between December 2004 and November 2008 to test the hypothesis that intensive glucose control reduces mortality at 90 days. Participants were admitted to either medical or surgical intensive care units of 42 hospitals and were considered eligible if their expected length of stay was at least 3 days. Of the 6,104 participants, 3,054 were randomly assigned to intensive glucose control (target between 81 and 108 mg/dL), and 3,050 were randomly assigned to conventional glucose control (target of 180 mg/dL or less). The primary outcome measure was death from any cause within 90 days after randomization. Secondary outcome measures were survival time during the first 90 days, cause-specific death, and durations of mechanical ventilation, renal-replacement therapy, and stays in the ICU and hospital.

The results revealed no significant differences in the median number of days in the ICU or hospital or the median number of days of mechanical ventilation or renal-replacement therapy. The results also demonstrated an increased mortality in the intensive treatment arm. The intensive glucose control group had an increased absolute risk of death at 90 days of 2.6% over that of the conventional glucose control group (27.5% vs. 24.9%, respectively). As expected, there were more cases of severe hypoglycemia in the intensive treatment group.⁷

The NICE-SUGAR trial serves as a landmark in the development of hyperglycemia management protocols. It had greater statistical power, as well as a longer follow-up period, than the previous trial and therefore may reflect harm not apparent in trials with shorter follow-up and lower statistical power. Following the results published by Van den Berghe et al, intensive glucose control has been widely recommended on the assumption that treatment aimed at achieving more stringent blood glucose targets will benefit patients. However, as demonstrated by the findings of the NICE-SUGAR trial, such a stringent blood glucose target does not necessarily benefit critically ill patients and may be harmful. Furthermore, a recent meta-analysis of 26 trials, including the NICE-SUGAR trial, found a pooled relative risk (RR) of death with intensive insulin therapy of 0.93 as compared with conventional therapy. About half of the trials included reported a pooled RR of 6.0 for hypoglycemia in the intensive treatment groups.⁸ These findings further support the original results of the NICE-SUGAR trial.

There is no clear evidence for specific blood glucose levels for non-critically ill patients. Table 1 summarizes the blood glucose targets for both critically ill and non-critically ill patients according to the recommendations as well as the contributing trial.

2013 ADDITIONAL UPDATES

The ADA also addresses recommendations on the screening of type 1 diabetes in the updated position statement. Screening for type 1 diabetes has been revised to include recommendations concerning the measurement of islet autoantibodies in relatives of those with type 1 diabetes. This screening may allow for earlier identification of the onset of type 1 diabetes and may reduce the likelihood of presenting with ketoacidosis upon diagnosis. The guidelines specify that this early screening is not recommended in low-risk individuals and should be completed within the setting of a clinical study.

The Standards of Medical Care–2013 published additional recommendations for patients with type 1 or type 2 diabetes. Glucose monitoring has been revised; the new recommendations suggest that patients on multiple-dose insulin or insulin pump therapy should self-monitor their blood glucose at least prior to meals and snacks, occasionally after meals, at bedtime, prior to exercise, when they suspect low blood glucose, after treating low blood glucose, and before critical tasks such as driving. The guidelines do not discuss a number of times per day but encourage individualized testing. However, according to these recommendations, this will require testing 6 to 8 times daily for many patients.³

Recommendations also include the administration of hepatitis B vaccine to unvaccinated adults with diabetes aged 19 to 59 years. Vaccinations may be considered in those older than age 60.⁹ Blood pressure goals for patients with diabetes have been updated as well. People with diabetes and hypertension should be treated to a blood pressure goal of less than 140/80 mm Hg, as compared with previous recommendations of less than 130/80 mm Hg. Lower systolic targets (less than 130 mm Hg) may be appropriate for younger individuals, if they can be achieved without undue burden.¹⁰ Finally, dyslipidemia management has been revised to emphasize the importance of statin therapy in patients with diabetes and elevated low-density lipoprotein (LDL) levels. The initiation of statin therapy is no longer indicated by elevated LDL levels above 100 mg/dL alone, but also depends on patients’ risk factors such as history of heart attack or age over 40 years.¹¹

PHARMACIST’S ROLE

It is critical that healthcare professionals appreciate the research behind any updated recommendations. Pharmacists must be aware of newly published research supporting or opposing their hospital’s protocols. They should also recognize the importance of individualized therapy, as the Standards of Medical Care are simply guidelines to be followed in most patients and may not apply to all. Therefore, healthcare practitioners are encouraged to use their clinical knowledge and experience to provide the best possible health outcomes for their patients, in addition to following hospital protocol. As pharmacists play an active role in the multidisciplinary healthcare team, there are growing expectations that they be prepared to prevent as well as best manage hyperglycemia in the hospital. Pharmacists should monitor blood glucose levels and verify that hospital protocol is followed correctly. They may also educate nurses and other healthcare practitioners regarding the proper use of the hospital’s hyperglycemia management protocol and how to appropriately adjust the insulin based on blood glucose levels. Due to the growing awareness and acceptance of collaborative drug therapy management, pharmacists will have an expanding role in patient management in the hospital setting. For this reason, it is important that pharmacists utilize their knowledge and skills in the hospital setting and build a collaborative working relationship with the other healthcare professionals within the hospital.

REFERENCES

1. Moghissi ES, Korytkowski MT, DiNardo M, et al; American Association of Clinical Endocrinologists and American Diabetes Association. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract. 2009;15:353–369.

2. Clement S, Braithwaite SS, Magee MF, et al, on behalf of the Diabetes in Hospitals Writing Committee. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27:553–591.

3. American Diabetes Association. Standards of medical care in diabetes-2013. Position statement. Diabetes Care. 2013;36(Suppl 1):S11–S66.

4. American Diabetes Association. Standards of medical care in diabetes–2009. Position statement. Diabetes Care. 2009;32(Suppl 1):S13–S61.

5. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354:449–461.

6. American Diabetes Association. Standards of medical care in diabetes–2010. Position statement. Diabetes Care. 2010;33(Suppl 1):S11–S61.

7. Finfer S, Chittock DR, Yu-Shuo Su S, et al; NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360:1283–1297.

8. Griesdale DE, de Souza RJ, van Dam RM, et al. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ. 2009;180:821–827.

9. Centers for Disease Control and Prevention. Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2011;60:1709–1711.

10. McBrien K, Rabi DM, Campbell N, et al. Intensive and standard blood pressure targets in patients with type 2 diabetes mellitus: systematic review and meta-analysis. Arch Intern Med. 2012;172:1296–1303.

11. Collins R, Armitage J, Parish S, Sleigh P, Peto R; Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5,963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361:2005–2016.

Dr.Choy is an assistant professor in the Department of Pharmacy and Health Outcomes, Touro College of Pharmacy, and clinical pharmacist, Metropolitan Hospital, New York, N.Y; Mr Richman is PharmD candidate at Touro College of Pharmacy, New York, N.Y.

The authors report no financial disclosures as related to products discussed in this article.

Table 1. Summary of recommendations in the management of hyperglycemia

NICE-SUGAR⁶

Intensive therapy

Conventional therapy

3,010

3,012

27.5%

24.9%

6.8%

0.5%

 Updated guidelines³

Critically ill patients

Non-critically ill patients

140–180 mg/dL

Fasting glucose: <140 mg/dL

Random glucose: <180 mg/dL

Abbreviations: NICE-SUGAR, Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation trial.