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Guidelines for Managing Inpatient Hyperglycemia
- 1. Clinical Guidelines for the Management of Hyperglycemia in Hospitalized Patients in a Non-Critical Care Setting Work in Progress The Endocrine Society, European Endo Society, American Heart Association, American Diabetes Association, Society of Hospitalist Medicine, American Association of Diabetes Educators
- 3. Hyperglycemia: Scope of the Problem Kosiborod M, et al. J Am Coll Cardiol. 2007;49(9):1018-183:283A-284A. No Diabetes 26% Diabetes 50 40 30 20 10 0 <110 110-140 50 40 30 20 10 0 <110 110-140 140-170 170-200 >200 78% 140-170 170-200 >200 Mean BG, mg/dL Patients, %
- 4. Hyperglycemia*: A Common Comorbidity in Medical-Surgical Patients in a Community Hospital 62% 12% 26% Normoglycemia Known Diabetes New Hyperglycemia Umpierrez G et al, J Clin Endocrinol Metabol 87:978, 2002 n = 2,020 * Hyperglycemia: Fasting BG 126 mg/dl or Random BG 200 mg/dl X 2
- 6. IGT and Undiagnosed T2DM are Common in Acute MI and Stroke Norhammar A, et al. Lancet 2002;359:2140−4. Matz K, et al. Diabetes Care 2006;792−7. 2-hour OGTT 70 60 50 40 30 20 10 0 Norhammar (n=181) Matz (n=238) Patients (%) 66 39 Myocardial infarction Stroke IGT Undiagnosed T2DM 35 23 31 16
- 8. ADA 2010 - Categories of Increased Risk for Diabetes* ADA Clinical Practice Recommendations, January 2019 NORMAL IFG or IGT PREDIABETES DIABETES FPG < 100 mg/dl FPG > 100 - 125 mg/dl (IFG) FPG > 126 mg/dl 2-h PG < 140 mg/dl 2-h PG > 140 - 199 mg/dl (IGT) 2-h PG > 200 mg Random PG > 200 + symptoms A1C 5.7% to 6.4% ≥ 6.5%
- 10. Comparison of sensitivity and specificity achieved for the diagnosis of diabetes based on FPG, at various levels of HbA1c, from NHANES III and 1999–2004 NHANES J Clin Endocrinol Metab, July 2008, 93(7):2447–2453
- 13. Hyperglycemia and Pneumonia Outcomes BG (mg/dl) < 110 110 - <198 198 - <250 ≥ 250 * * * * * p: < 0.05 vs BG < 198 mg/dl (11 mmol/L) Admission glucose (mg/dl) % McAllister et al, Diabetes Crae 28:810-815, 2005 N= 2,471 patients with CAP
- 14. Community Acquired Pneumonia Outcomes in Patients with Diabetes % Hospitalization Mortality Pleural Effusion Concomitant Illnesses P: < 0.001 N= 660 (DM: 106 & non-DM: 554) No differences in microorganisms and bacteremia rates Falguera et al, Chest 128:3233-3239, 2005 * * * * 93 8 17 78 31 18 53 40 * Diabetes No Diabetes
- 16. Thirty Day Mortality and Inhospital Complications in diabetic and non-diabetic subjects † p = 0.1 * p= 0.001 #p=0.017 † * * * * # * % A Frisch et al. Diabetes Care, May 2010
- 17. Hyperglycemia and mortality Mean POSTSURGERY blood glucose and ODDS RATIOS for 30 day mortality in diabetic and non diabetic patients A Frisch et al. Diabetes 58 (suppl 1) A27, 2009
- 18. Hyperglycemia: An Independent Marker of In-Hospital Mortality in Patients with Undiagnosed Diabetes Total In-patient Mortality Normoglycemia Known New Diabetes Hyperglycemia 1.7% 3.0% 16.0% * Mortality (%) * P < 0.01 Umpierrez GE et al, J Clin Endocrinol Metabol 87:978, 2002
- 24. Study Type: Prospective, multicenter, randomized, open-label trial Patient Population : 130 subjects with DM2 Diet and/or oral hypoglycemic agents Umpierrez et al, Diabetes Care 30:2181–2186, 2007
- 29. Study Type: Prospective, randomized, open-label trial Patient Population : 130 subjects with DM2 Oral hypoglycemic agents or insulin therapy Study Sites : Grady Memorial Hospital, Atlanta, GA Rush University Medical Center , Chicago, IL Umpierrez et al, J Clin Endocrinol Metab 94: 564–569, 2009
- 32. DEAN Trial: Changes in Mean Daily Blood Glucose Concentration BG, mg/dL Duration of Therapy, d Data are means SEM. Detemir + aspart NPH + regular Basal-bolus regimen: detemir was given once daily; aspart was given before meals. NPH/regular regimen: NPH and regular insulin were given twice daily, two thirds in AM, one third in PM. Umpierrez GE, et al. J Clin Endocrinol Metab . 2009;94(2):564-569. P =NS 100 120 140 160 180 200 220 240 Pre-Rx BG 0 1 2 3 4 5 6-10
- 33. Blood glucose (mg/dL) Detemir + Novolog NPH + Regular DEAN-Trial
- 35. *p-values are from Wilcoxon Two-Sample Test Summary of Univariate Analyses Umpierrez et al, ADA Scientific Meeting, Poster #516, 2009 p-value * variable BG < 60 mg/dl BG < 70 mg/dl AGE 0.036 0.001 wt 0.027 0.001 A1C 0.521 0.658 Creatinine 0.011 0.002 Enrollment BG 0.166 0.319 Previous treatment 0.005 <.001 Previous insulin Rx <0.001 <.001 Treatment group <0.001 <.001
- 36. RAndomized Study of Basal Bolus Insulin Therapy in the Inpatient Management of Patients with Type 2 Diabetes Undergoing General Surgery: RABBIT Surgery Trial Guillermo E Umpierrez, Dawn Smiley, Sol Jacobs, Limin Peng, Angel Temponi, Christopher Newton, Denise Umpierrez, Patrick Mulligan, Darin Olson, Jana MacLeod, Monica Rizzo. Umpierrez et al, Preliminary data- ADA Scientific Session 2010
- 39. RABBIT SURGERY TRIAL 211 Patients with type 2 DM that underwent general surgery Glargine + Glulisine (Gla+Glu) N= 104 Group 1: 0.5 U/kg Half as glargine once daily Half as glulisine before meals Sliding scale insulin (SSRI) N= 107 OPEN - LABELED RANDOMIZATION Group 2: 4 times/day for BG >140 mg/dl
- 40. RABBIT 2 SURGERY Umpierrez et al, Preliminary data- Abstract to be submitted_ADA Scientific Session 2010
- 41. Rabbit Surgery Trial Glucose levels during Basal Bolus and SSRI Therapy * p<0.001 † p: 0.01 ŧ p: 0.02 SSI GLA+GLU
- 42. Glucose levels Before meals and Bedtime SSI Basal Bolus
- 43. Differences in BG Concentration Within Target During Hospital Stay and After 24 Hours of Treatment
- 44. Hospital Complications: Primary outcome
- 45. Umpierrez et al, Preliminary data- Abstract to be submitted_ADA Scientific Session 2010 Hypoglycemic Events
- 46. Treatment with glargine once daily plus glulisine before meals improved glycemic control and reduced hospital complications compared to SSRI in general surgery patients with T2DM. Our study indicates that basal/bolus insulin regimen is the preferred insulin regimen in the hospital management of general surgery patients with type 2 diabetes. Summary & Conclusion RABBIT 2 SURGERY
- 50. Rabbit Surgery Trial Glucose levels during Basal Bolus and SSRI Therapy * p<0.001 † p: 0.01 ŧ p: 0.02 Mainly Basal (Glargine) Insulin
- 51. 4:00 16:00 20:00 24:00 4:00 8:00 12:00 8:00 Time Glargine once daily 0.25 U/kg Basal-PLUS Insulin Regimen Insulin Action Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy . New York: Marcel Dekker; 2002:87; Nathan DM. N Engl J Med. 2002;347:1342 Aspart, Lispro or Apidra before meals per sliding scale
- 52. A1C < 7% Re-start outpatient treatment regimen (OAD and/or insulin) A1C 7%-9% Re-start outpatient oral agents and D/C on glargine once daily at 50-80% of hospital dose A1C >9% D/C on basal bolus at same hospital dose. Alternative: re-start oral agents and D/C on glargine once daily at 50-80% of hospital dose Discharge insulin Algorithm Discharge Treatment
Hinweis der Redaktion
- Using a national database derived from electronic medical records at 39 medical centers, investigators analyzed patterns of blood glucose (BG) control and documented insulin therapy among 16,534 patients hospitalized with acute myocardial infarction from January 2000 to December 2005. Of the 4940 patients (30%) with recognized diabetes mellitus (DM), nearly half (2412 patients, 49%) had mean BG >200 mg/dL during the first 24 hours after hospital admission. When the entire hospitalization was considered, 34% of DM patients had mean BG >200 mg/dL, while 61% had mean BG between 110 and 200 mg/dL, and only 5% maintained mean BG <110 mg/dL. Among patients without recognized DM, 8% had mean BG >200 mg/dL during the first 24 hours. When the entire hospitalization was considered, 4% of patients without known DM had mean BG >200 mg/dL, while 65% had mean BG between 110 and 200 mg/dL, and 31% had mean BG <110 mg/dL. Kosiborod M, Inzucchi S, Clark B, et al. National patterns of glucose control among patients hospitalized with acute myocardial infarction. J Am Coll Cardiol. 2007;49(9):1018-183:283A-284A.
- In a more recent study that involved 2020 consecutive patients admitted to a community hospital in Atlanta, we found that 64% of patients had normal glucose values, 26% had a prior history of diabetes, and that 12% of patients with hyperglycemia, as determined by 2 or more FBG > 126 or RBG > 200, did not had a know history of diabetes prior to admission.
- Data from Norhammar et al indicate that in 181 consecutive patients hospitalized with MI and no diagnosed diabetes, 66% had undiagnosed glucose abnormalities, including undiagnosed diabetes or IGT. Matz et al found, in 238 consecutive patients hospitalized with stroke, 39% had either IGT or undiagnosed diabetes in addition to 20% with known diabetes. IGT and undiagnosed DM2 are common in acute MI and stroke
- For the majority of noncritically ill patients treated with insulin, the premeal blood glucose (BG) target should generally be less than 140 mg/dL in conjunction with random BG levels less than 180 mg/dL, provided these targets can be safely achieved. To avoid hypoglycemia, consideration should be given to reassessing the insulin regimen if BG levels decline below 100 mg/dL. Modification of the regimen is necessary when BG values are <70 mg/dL, unless the event is easily explained by other factors (such as a missed meal). More stringent targets may be appropriate in stable patients in whom tight glycemic control was achieved previously. Less stringent targets may be appropriate in terminally ill patients or patients with severe comorbidities. Hypoglycemia is defined as any BG level <70 mg/dL. Severe hypoglycemia in hospitalized patients has been defined by many clinicians as BG <40 mg/dL, although this value is lower than the approximate 50 mg/dL level at which cognitive impairment begins in normal persons. Scheduled subcutaneous administration of insulin, with basal, nutritional, and correction components, is the preferred method for achieving and maintaining glucose control. Prolonged treatment with sliding-scale insulin as the sole regimen is discouraged. Noninsulin antihyperglycemic agents are not appropriate in most hospitalized patients who require treatment for hyperglycemia. Moghissi ES, Korytkowski MT, Dinardo M, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control. Endocr Pract. 2009;15(4). http://www.aace.com/pub/pdf/guidelines/InpatientGlycemicControlConsensusStatement.pdf. Accessed May 18, 2009.
- As a disclosure, I would like to state that was an investigator initiated trial sponsored by SA
- 09-00953B_CHF_CaseStudy_r16 04/07/11 19:08 RABBIT-2 Trial: Basal-Bolus Insulin Regimen Key point: In the sliding-scale group, 65 patients received regular human insulin (RHI 4 times daily for blood glucose (BG) above 140 mg/dL 1 Eating status 1 : Eating – RHI was given before each meal and at bedtime according to the “usual” column of the sliding-scale protocol. Not eating – RHI was given every 6 hours according to the “insulin sensitive” column of the sliding-scale protocol. Persistent hyperglycemia 1 : If fasting and premeal plasma glucose levels remained persistently >140 mg/dL (without hypoglycemia), the insulin dosing was progressively increased (from “insulin sensitive” to “usual” or from “usual” to “insulin resistant”) If the mean daily BG level was >240 mg/dL, or if 3 consecutive BG levels were >240 mg/dL on the maximal dose allowed by the protocol, patients were switched to the basal-bolus insulin regimen Hypoglycemia 1 : If hypoglycemia developed, the insulin dosing was decreased (from “insulin resistant” to “usual” or from “usual” to “insulin sensitive”) [1/Umpierrez. DiabetesCare.Sept. 2007/p2183/Table 1] ___________________________________________________________________________________________ Umpierrez GE, Palacio A, Smiley D, et al. Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes (RABBIT 2 trial). Diabetes Care. 2007;30:2181-2186. [Umpierrez. DiabetesCare.Sept. 2007/p2183/Table 1]
- Key Point: Patients randomized to basal-bolus therapy achieved better glycemic control compared with those receiving sliding-scale insulin delivery in a hospitalized, non – ICU setting. This multicenter, prospective, open-label, randomized study enrolled 130 nonsurgical, insulin-naïve patients with a known history of diabetes for >3 months, admitted to medical general services with a blood glucose level between 140 and 400 mg/dL. Patients were randomly assigned to receive either sliding-scale regular insulin (SSRI; n=65) 4 times daily or a basal-bolus regimen with insulins glargine and glulisine (n=65). The goal of insulin therapy was to maintain fasting and premeal blood glucose levels <140 mg/dL while avoiding hypoglycemia. Compared with the basal-bolus group, patients who received sliding-scale insulin delivery had higher mean fasting glucose (165 ± 41 vs 147 ± 36 mg/dL, respectively, P < .01), mean random glucose (189 ± 42 vs 164 ± 35 mg/dL, respectively, P < .001), and mean glucose (193 ± 54 vs 166 ± 32 mg/dL, respectively, P < .001) during the hospital stay. The overall BG difference between treatment groups was 27 mg/dL ( P < .01), with a mean daily BG difference ranging from 23 to 58 mg/dL during days 2 through 6 of therapy ( P < .01). Umpierrez GE, Smiley D, Zisman A, et al. Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes (RABBIT 2 trial). Diabetes Care. 2007;30(9):2181-2186.
- Key Point: A significant number of patients in the basal-bolus group reached the BG target of <140 mg/dL. Blood glucose levels significantly improved in patients who had failed sliding-scale insulin delivery and were switched to the basal-bolus regimen. With the BG target of <140 mg/dL, 66% (43 patients) in the basal-bolus group reached the target, while only 38% (25 patients) in the sliding-scale insulin delivery group met this goal. Fourteen percent (9 patients) of the patients treated with sliding-scale insulin delivery remained severely hyperglycemic, defined as BG >240 mg/dL, despite dose maximization. Glycemic control improved in these patients once they were switched to the basal-bolus regimen. Two patients in each group had hypoglycemia (defined as BG <60 mg/dL). No cases of severe hypoglycemia (defined as BG <40 mg/dL) were reported. Umpierrez GE, Smiley D, Zisman A, et al. Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes (RABBIT 2 trial). Diabetes Care. 2007;30(9):2181-2186.
- Since there was no a priori data to better direct the starting dose of in the inpatient setting, we arbitrarily used the working algorithm currently used at Grady Memorial/Emory hospital for those with inpatient hyperglycemia
- Since there was no a priori data to better direct the starting dose of in the inpatient setting, we arbitrarily used the working algorithm currently used at Grady Memorial/Emory hospital for those with inpatient hyperglycemia
- In the DEAN (Detemir plus Aspart vs NPH Plus Regular in Medical Patients with T2DM) trial, investigators randomized 130 nonsurgical patients with a blood glucose (BG) between 140 and 400 mg/dL to receive detemir once daily and aspart before meals (n=67) or neutral protamine Hagedorn (NPH) and regular insulin twice daily (n=63). Patients treated with detemir/aspart received half of the total daily dose (TDD) as detemir and half as aspart insulin. Detemir was given once daily at the same time of the day. Aspart was given in 3 equally divided doses with each meal. To prevent hypoglycemia, if a patient was not able to eat a given meal, the dose of aspart was held. Insulin dosage was adjusted daily according to BG values. Patients treated with NPH/regular insulin received two thirds of TDD before breakfast and one third before dinner. The insulin dose was given as two thirds NPH and one third regular insulin in the morning with breakfast, and two thirds NPH and one third regular insulin in the evening with dinner. The slide shows the changes in mean daily BG concentration. The BG target of less than 140 mg/dL before meals was achieved in 45% of the detemir/aspart group and in 48% of the NPH/regular group ( P =NS). Umpierrez GE, Hor T, Smiley D, et al. Comparison of inpatient insulin regimens with detemir plus aspart versus neutral protamine hagedorn plus regular in medical patients with type 2 diabetes. J Clin Endocrinol Metab. 2009;94(2):564-569.
- Patient self-management of diabetes in the hospital should be facilitated when appropriate. Staff understanding of new treatment modalities and the actions of new antihyperglycemic agents should be ensured through in-service training. Orally administered antihyperglycemic agents should be prescribed with caution and with observance of changing organ function, potential drug interactions, and contraindications that might arise in the hospital. Caregivers, fearing hypoglycemia, may hope to prevent hypoglycemic episodes by substituting sliding-scale management for anticipatory insulin therapy. This strategy is ineffective or even harmful if used alone. The preferred approach is to use measures for prevention of hypoglycemia that do not promote hyperglycemia. Braithwaite SS, Buie MM, Thompson CL, et al. Hospital hypoglycemia: not only treatment but also prevention. Endocr Pract. 2004;10(suppl 2):89-99.