1. Michael Doldan, D.O. Family Medicine Sisters of Charity Hospital

2. Introduction The American Diabetes Association (ADA) estimates that 23.6 million Americans have this disease. This represents 7.8% of the total population. Patients with diabetes are hospitalized three times more frequently than patients without the disease. The exact prevalence of diabetes in hospitalized patients is unknown, but 12.4% of adult patients discharged from U.S. hospitals in 2000 carried a discharge diagnosis of diabetes; only 8% of these patients were admitted with diabetes as their primary diagnosis.

4. Introduction Managing hyperglycemia in the hospital setting may prove to be more difficult because of stress on the body and its subsequent hormonal effects, concomitant illness stemming from exacerbation of co-morbidities, changes in dietary intake, and cessations/alterations of medication regimens. Additionally, maintenance of tight glycemic control in diabetic hospitalized patients is a relatively new focus resulting from recent studies that have defined therapeutic goals and demonstrated improved patient outcomes.

5. Introduction Studies show that hyperglycemia adversely affects immune function, the cardiovascular system, the brain, and a host of other pathways implicated in the morbidity and mortality attributed to acute hyperglycemia. Some studies have demonstrated that elevation of serum glucose results in impairment of white blood cell function, specifically that of phagocytes. Older research demonstrated that reducing serum glucose levels translates to better WBC function and phagocytosis. Although the data are limited, studies evaluating the effect of hyperglycemia on immune function consistently show that improving glycemic control improves immune function.

6. Introduction The macrovascular effects of long-standing diabetes on the cardiovascular system are well documented. However, acute hyperglycemia negatively affects mechanisms, such as ischemic preconditioning, that protect the heart against ischemic damage. Even moderately elevated serum glucose levels may decrease coronary blood flow and cause myocyte death through either apoptosis or cellular injury resulting from exaggerated ischemic reperfusion. In acute hyperglycemia, blood pressure and heart rate may increase and the risk of arrhythmias such as QTc prolongation is greater. In addition, inflammation and endothelial-cell dysfunction caused by hyperglycemia in the setting of acute illness contribute to cardiovascular complications.

7. Introduction Hyperglycemia may increase a patient's risk of thrombosis. Elevations in blood glucose levels, even for a short time, have been shown to increase platelet activation and aggregation. Increased Von Willebrand factor activity and thromboxane A 2 production occur during episodes of hyperglycemia and may contribute to the increased risk of clot formation seen in hospitalized patients with hyperglycemia. Diabetic patients carry a much greater risk of cardiovascular disease caused by ischemia, but this risk appears to be unrelated to hypertension, hyperlipidemia, or smoking. These findings may explain the mechanism by which patients with hyperglycemia experience increased rates of thrombosis.

8. Introduction Brain tissue also may be affected by hyperglycemia. When a stroke occurs, the ischemic penumbra is considered to be viable but appears to be the region that is sensitive to the effects of hyperglycemia. Animal studies have found that outcomes are worse in acute brain ischemia when hyperglycemia is present. Published studies evaluating outcomes with respect to hyperglycemia and stroke in humans for the most part have been retrospective or observational, but they also have shown worse outcomes. A recent, more controlled trial did not demonstrate that tight glycemic control improved outcomes in acute stroke, but the investigators suggested that further study is warranted.

11. Introduction This study assessed the management of inpatient hyperglycemia in non-critical diabetic patients at SOCH by analyzing the data that came about as a result of the following six questions: 1) What percentage of the total patient population studied were placed on an insulin regimen of any kind and what type of insulin were they started on? 2) What glucose values corresponded with the administration of the above regimen at the time of admission? 3) Once placed on an insulin regimen, what percentage of patients had their insulin regimens adjusted at any point during their hospitalization? 4) What glucose values corresponded with the modification of the above regimen that prompted the change? 5) What percentage of Type I diabetics who were on basal-bolus- supplemental (BBS) coverage at home received it while in the hospital? 6) What percentage of Type I diabetics were started on BBS coverage on the day of admission?

12. Hypothesis Greater than 50% of the Type I and Type II diabetic patients that were studied were placed on an insulin regimen of some kind during their hospital course. Of those patients placed on an insulin regimen, irrespective of their designation of type I or type II DM and their consequent pre-hospital medications, the majority of patients are being placed on sliding scale insulin (SSI) as a solo insulin regimen. The blood glucose (BG) and finger stick blood glucose (FSBG) levels that correspond with the administration of an insulin regimen at the time of admission will show consistent hyperglycemia.

13. Hypothesis Even when an insulin regimen is started, the percentage of patients that get it adjusted in response to persistently elevated glucose levels will be minimal to non-existant. In the patients who do have their insulin regimens modified during the course of their hospital stay, the corresponding glucose levels at the time that change is made will be elevated.

14. Hypothesis The percentage of Type I Diabetics, that were on a BBS insulin regimen at home, that were started on a BBS regimen during the course of their hospital stay, will be small. The percentage of Type I Diabetics, that were on a BBS insulin regimen at home, that were started on a BBS regimen on the day of admission, will be small.

15. Methods Inpatient randomized retrospective chart review of 50 patients, carrying a previous diagnosis of Type I or Type II diabetes, was performed at Sisters of Charity Hospital in Buffalo, New York. There were 25 Type I Diabetics and 25 Type II Diabetics in the study. The primary diagnosis that prompted their hospital admission was not required to be Type I or Type II DM, or complications occuring as a result of uncontrolled DM. Inclusion criteria consisted of randomly chosen diabetic patients admitted to Sisters of Charity Hospital between the dates of January 2009 to April 2010. Exclusions included neonates and children.

16. Methods The designation of Type I or Type II DM assigned to patients in the study was determined by both a thorough review of the admission history and physical, as well as the scrutinization of the patient’s home medications. The glucose values recorded consisted of both fasting and non-fasting levels. The glucose values recorded were either the BG or the FSBG values, as both were not available in some cases.

17. The Study Was Based Upon the Following Questions: 1. How many total patients were placed on insulin of any kind? 2. What glucose value prompted the changed in this insulin regiment? 3. How many total patients had their chosen insulin regiments altered? 4. What glucose value prompted the change in this insulin regiments? 5.How many type 1 diabetics were placed on basal- bolus- supplemental coverage? 6. How many type 1 diabetics were started on basal- bolus supplemental coverage on the day of admission?

18. Percent of Patients That Received Insulin and the Specific Type That They Received

19. BG and/or FSBG Levels That Corresponded With the Initiation of Insulin Administration

20. Percent of Patients Without Insulin Adjustments Compared to Percent With Insulin Adjustments The Average BG and FSBG Values of Those Who Did Receive Insulin Adjustments at the Time of Change

21. The Percentage of Type 1 Diabetics Who Were On a BBS Insulin Regimen at Home Who Received BBS Coverage During their Hospital Stay The Percentage of Type 1 Diabetics Who Were On a BBS Insulin Regimen at Home Who Received BBS Coverage On the Day of Admission

22. Conclusions The data demonstrated that 64% of the patients studied did receive some form of insulin coverage during their hospital course. The prescribed regimen, however, was SSI 38% of the time. Because of the unpredictable absorption kinetics of regular insulin and the reactive nature of the efforts at glucose control, the sliding scale is non- physiological and ineffective in controlling glucose and prone to inducing delayed hypoglycemia.

23. Conclusions The average of the BG and FSBG levels that corresponded with the initiation of insulin administration was 182 mg/dL. This would appear to indicate that the threshold for initiating insulin regimen’s of any type is too high. This observed outcome may be the direct result of a paucity or absence of studies directly correlating specific levels of hyperglycemia with specific adverse outcomes. The lack of evidence based guidelines places providers in a precarious position as they do not want to put the patient in a hypoglycemic state and as such a relative level of hyperglycemia seems to be tolerated.

24. Conclusions Only 20% of the patients in this study had their insulin regimen’s changed during the course of their admission once they were instituted. This observation appears to demonstrate a lack of adaptation to their state-specific physiologic insulin requirements as well as a lack of recognition that their co morbid illness alters their metabolic state and potentially predisposes them to hyperglycemia, thus proportionally increasing their insulin requirements and necessitating institution of an insulin regimen that more closely mimics that found in the physiologic state in a non-diabetic individual.

25. Conclusions The majority of type 1 diabetics that were on a BBS regimen at home were not put on the same regimen or a comparable regimen during the course of their hospital stay. Given that patient’s who are admitted to the hospital have a tendency to be hyperglycemic, for all the reasons previously discussed, it would seem reasonable to start them back on their home BBS regimen at a bare minimum (presuming that their home insulin regimen’s were providing adequate glucose control). This would provide less fluctuation of the patients glucose levels and more time to adjust the regimen accordingly during their hospital course.

26. Conclusions The majority of type I diabetics that were placed on a BBS regimen were not done so on the day of admission, which may demonstrates a lack of urgency on the part of the provider in recognizing the significance of even slightly elevated blood sugars in the inpatient setting and its potential adverse effects on the patient.

27. Limitations of The Study: Small sample size. Due to the small sample size even a few measurements of marked hyperglycemia may scue the average glucose readings thus decreasing the power of the study. This study was only done at one hospital. The glucose values used were both fasting and non- fasting The glucose values were not differentiated between Type I and Type II diabetics There was no range of hyperglycemia studied

28. Further Studies An inpatient retrospective chart review of hyperglycemia in the hospital setting in the context of a large multicenter trial. An inpatient retrospective chart review of hyperglycemia in the hospital setting in the context of post-prandial glucose levels only Trials comparing basal and SSI as stand alone therapy in hyperglycemic control in the inpatient setting. Compare morbidity and mortality of Type 1 diabetes versus Type 2 diabetes in the inpatient setting.

29. Questions?

30. References Hospital admission guidelines for diabetes. Diabetes Care 2004; 27 Suppl 1:S103. Hypoglycemia and clinical outcomes in patients with diabetes hospitalized in the general ward, Turchin A; Matheny ME; Shubina M; Scanlon JV; Greenwood B; Pendergrass ML, Diabetes Care. 2009 Jul;32(7):1153-7.

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32. Reference Inzucchi, SE. Clinical practice. Management of hyperglycemia in the hospital setting. N Engl J Med 2006; 355:1903. Umpierrez GE; Isaacs SD; Bazargan N; You X; Thaler LM; Kitabchi AE. An independent marker of in- hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab. 2009 Feb;94(2):564-9. Epub 2008 Nov 18.

33. References Wesorick, D, O'Malley, C, Rushakoff, R, et al. Management of diabetes and hyperglycemia in the hospital: a practical guide to subcutaneous insulin use in the non-critically ill, adult patient. J Hosp Med 2008; 3:17. Guillermo E. Umpierrez, MD, Dawn Smiley, MD, Ariel Zisman, MD, Luz M. Prieto, MD, Andres Palacio, MD, Miguel Ceron, MD, Alvaro Puig, MD, Roberto Mejia, PHD. Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients With Type 2 Diabetes (RABBIT 2 Trial), Diabetes Care 2007; DOI: 10.2337/dc07- 0295. Clinical trial reg. no. NCT00394407, clinicaltrials.gov.