Presentation on theme: "Guillermo E. Umpierrez, MD, FACP, FACE Professor of Medicine"— Presentation transcript:
1Manejo del Paciente Diabetico en la Unidad de Cuidados Intensivos y Sala General Guillermo E. Umpierrez, MD, FACP, FACEProfessor of MedicineDirector, Grady Hospital Clinical Research UnitEmory University School of MedicineDirector, Diabetes & Endocrinology SectionGrady Hospital CIN (Research Unit)Grady Health System
2Hiperglucemia en el Hospital: Agenda Magnitud del Problema:Cual es la frecuencia e impacto de hiperglucemia y diabetes en el hospital?Cuales criterios diagnosticos debemos de utilizar?Que niveles de glucosa son recomendables?2. Como debemos de manejar la hiperglucemia en UCI y en en sala generales?Insulina – Que tipo, regimen, y como comenzar?Incretinas – debemos de utilizarlas en el hospital?Alta hospitalaria– Cual es el papel de la HBA1c, que regimen utilizar? HbA1c?Umpierrez et al. J Clin Endocrinol Metabol. 97(1):16-38, 2012
3Distribution of patient-day-weighted mean POC-BG values for ICU Results: A total of 49,191,313 POC-BG measurements (12,176,299 ICU; 37,015,014 non-ICU) were obtained from 3,484,795 patients (653,359 ICU; 2,831,436non-ICU). The mean POC-BG was 167 mg/dL for ICU patients and 166 mg/dL for non-ICU patients. The prevalence of hyperglycemia (>180 mg/dL) was 32.2% in ICU patients and 32.0% in non-ICU patients. The prevalence of hypoglycemia (<70 mg/dL) was 6.3% in ICU patients and 5.7% in non-ICU patients.Data from ~12 million BG readings from 653,359 ICU patients - mean POC-BG: 167 mg/dLSwanson et al. Endocrine Practice, October 2011
4Hyperglycemia: Scope of the Problem DiabetesNo Diabetes50403020105040302010Patients, %26%78%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.<110>200<110>200Mean BG, mg/dLKosiborod M, et al. J Am Coll Cardiol. 2007;49(9): :283A-284A.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): :283A-284A.
5Perioperative Hyperglycemia in Patients With and Without Diabetes Undergoing CABG Surgery No-DMDMP-value# of pts150152--BMI29±633±8p<0.001Admission BG111±28171±72HbA1c6.1±0.28.0±2Pre-op BG108±23155±51Intra-op BG138±20157±31ICU BG135±16149±18Periop BG >14083%98%P=0.48Started CII88%94%P=0.06Insulin dose, Units61±84161±229Transition to basal insulin after CII48%P<0.001Pasquel et al, Endocrine Society 2014, submitted. Unpublished
6Hyperglycemia*: A Common Comorbidity in Medical-Surgical Patients in a Community Hospital 12%26%62%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.Normoglycemian = 2,020* Hyperglycemia: Fasting BG 126 mg/dlor Random BG 200 mg/dl X 2Known DiabetesNew HyperglycemiaUmpierrez G et al, J Clin Endocrinol Metabol 87:978, 2002
7Diagnosis & recognition of hyperglycemia and diabetes in the hospital setting AdmissionAssess all patients for a history of diabetesObtain laboratory BG testing on admissionNo history of diabetesBG<140 mg/dl(7.8 mmol/L)Initiate POC BG monitoring according to clinical statusNo history of diabetesBG >140 mg/dlStart POCBG monitoring x 24-48hCheck A1CA1C ≥ 6.5%History of diabetesBG monitoringUmpierrez et al. J Clin Endocrinol Metabol. 97(1):16-38, 2012
8A1C for Diagnosis of Diabetes in the Hospital HbA1c should be measured in non-diabetic subjects with hyperglycemia (BG>140 mg/dl or 7.8 mmol/L) and in subjects with diabetes if not done within 2-3 months prior to admission.In the presence of hyperglycemia, a patient with HbA1c > 6.5% can be identified as having diabetes.Implementation of A1C testing can be useful:assess glycemic control prior to admissionassist with differentiation of newly diagnosed diabetes from stress hyperglycemiadesigning an optimal regimen at the time of dischargeUmpierrez et al, J Clin Endocrinol Metabol, 2012
9Hyperglycemia in the ICU: Lecture Agenda Scope of the Problem:What is the frequency of hyperglycemia and diabetes?Why should we care about hyperglycemia in the ICU?Mechanisms for hyperglycemia in acute critical illness and ICU2. How should we manage hyperglycemia in the ICU and non-ICU settings?Insulin regimensIncretin-base regimentsOther agents?
11Hyperglycemia and Hospital Complications: What glucose level predicts complications? N= 55,530 patients records in ICU and non-ICU, Emory University Hospital.Composite of complications: pneumonia, acute renal or respiratory failure, acute MI, bacteremia, and death.Patients with admission BG >400 mg/dL, DKA, and GFR <15 were excluded.
12Thirty Day Mortality and Hospital Complications in Diabetic and Non-diabetic subjects Undergoing General Non-Cardiac Surgery***%**†#†p = 0.1* p= 0.001#p=0.017A Frisch et al. Diabetes Care, May 2010
13Adverse Events Stratified by Perioperative Hyperglycemia DiabetesNo Diabetes***The Surgical Care and Outcomes Assessment Program is a Wash- ington State quality improvement benchmarking-based initiative. We evalu- ated the relationship of perioperative hyperglycemia (>180 mg/dL) and insulin administration on mortality, reoperative interventions, and infections for pa- tients undergoing elective colorectal and bariatric surgery at 47 participating hospitals between fourth quarter of 2005 and fourth quarter of Results: Of the 11,633 patients (55.4 ± 15.3 years; 65.7% women) with a serum glucose determination on the day of surgery, postoperative day 1, or postoperative day 2, 29.1% of patients were hyperglycemic. After controlling for clinical factors, those with hyperglycemia had a significantly increased risk of infection [odds ratio (OR) 2.0; 95% confidence interval (CI), 1.63–2.44], reoperative interventions (OR, 1.8; 95% CI, 1.41–2.3), and death (OR, 2.71; 95% CI, 1.72–4.28). Increased risk of poor outcomes was observed both for patients with and without diabetes. Those with hyperglycemia on the day of surgery who received insulin had no significant increase in infections (OR, 1.01; 95% CI, 0.72–1.42), reoperative interventions (OR, 1.29; 95% CI, 0.89– 1.89), or deaths (OR, 1.21; 95% CI, 0.61–2.42). A dose-effect relationship was found between the effectiveness of insulin-related glucose control (worst 180–250 mg/dL, best <130 mg/dL) and adverse outcomes.Conclusions: Perioperative hyperglycemia was associated with adverse out- comes in general surgery patients with and without diabetes. However, patients with hyperglycemia who received insulin were at no greater risk than those with normal blood glucoses. Perioperative glucose evaluation and insulin ad- ministration in patients with hyperglycemia are important quality targets.*BG > 180 mg/dlBG < 180 mg/dl* P <0.01Proportion of Patients (%)§ p <0.05BG at any point on the day of surgery, post-op day 1 and 2N= 11,633, colorectal and bariatric surgery;29.1% with hyperglycemiaKnown et al. Ann Surg 2013
14Hyperglycemia: An Independent Marker of In-Hospital Mortality in Patients with Undiagnosed Diabetes Total In-patient Mortality16.0% *Mortality (%)3.0%1.7%Normoglycemia Known NewDiabetes Hyperglycemia* P < 0.01Umpierrez GE et al, J Clin Endocrinol Metabol 87:978, 2002
15Inpatient Hyperglycemia: ICU and non-ICU Lecture Outline What is the frequency of hyperglycemia and diabetes?What is the association between hyperglycemia and outcomes?Does treatment of hyperglycemia in ICU and non-ICU matters?What is the evidence for intensive glycemic control?How should we manage hyperglycemia in non-ICU setting
16Portland Diabetes Project: Insulin Infusion Reduces DSWI SCICII[Furnary.AnnThorac Surg.Feb.1999/p357/Fig 3]4.0SCI Group:Day of surgery: 241 mg/dLPOD #1: 206 mg/dLCII Group:Day of surgery: 199 mg/dLPOD #1: 176 mg/dL3.0DSWI (%)2.01.00.08788899091929394959697YearProspective study of 2,467 consecutive diabetics who underwent open heart surgery.DSWI, deep sternal wound infection; SCI, subcutaneous insulin; CII, continuous insulin infusion.Furnary AP, et al. Ann Thorac Surg. 1999;67:352–362.
17Hyperglycemia and surgical ICU morbidity and mortality
18Intensive Glucose Management in RCT TrialNSettingPrimary OutcomeARRRRROdds Ratio (95% CI)P-valueVan den Berghe 20061200MICUHospital mortality2.7%7.0%0.94* ( )N.S.Glucontrol 20071101ICUICU mortality-1.5%-10%1.10* ( )Ghandi 2007399ORComposite2%4.3%1.0* ( )VISEP 200853728-d mortality1.3%5.0%0.89* ( )De La Rosa 2008504SICU-4.2% *-13%*NRNICE-SUGAR 200961043-mo mortality -2.6%-10.61.14 ( )< 0.05The slide shows results of trials of glucose management in critical care patients.1-10 Some early randomized trials suggested that intensive glucose lowering can improve outcomes.1,2 However, more recent studies in the critical care population were unable to replicate earlier studies, and identified severe hypoglycemia as a significant risk of intensive glucose control.3-10 In the study by Ghandi et al,7 intensive insulin therapy during cardiac surgery did not reduce perioperative death or morbidity. In the NICE-SUGAR study,10 critically ill patients treated in the intensive glucose control group ( mg/dL) were 14% more likely to die (27.5% vs 24.9%) than were those in the conventional glucose control group ( mg/dL). Severe hypoglycemia (blood glucose ≤40 mg/dL) occurred in 6.8% of the intensive-control group versus 0.5% of the conventional-control group (P<.001).*not significantGriesdale DE, et al. CMAJ. 2009;180(8):
19No. Events/Total No. Patients Intensive Insulin Therapy and Hypoglycemic Events in Critically Ill PatientsNo. Events/Total No. PatientsStudyIITControlRisk ratio (95% CI)Van den Berghe et al39/7656/7836.65 ( )Henderson et al7/321/357.66 ( )Bland et al1/51.00 ( )111/59519/6055.94 ( )Mitchell et al5/350/3511.00 ( )Azevedo et al27/1686/1694.53 ( )De La Rosa et al21/2542/25010.33 ( )Devos et al54/55015/5513.61( )Oksanen et al7/391/519.15 ( )Brunkhorst et al42/24712/2904.11( )Iapichino et al8/453/452.67 ( )Arabi et al76/2668/2579.18 ( )Mackenzie et al50/1219/1195.46 ( )NICE-SUGAR206/301615/301413.72 ( )Overall654/613898/62095.99 ( )Hypoglycemic EventsFavors IIT Favors Control0.1110Griesdale DE, et al. CMAJ. 2009;180(8):Risk Ratio (95% CI)
20NICE-SUGAR Trial: Hypoglycemia and Mortality Figure 3 Hazard Ratio for Death According to the Occurrence of Hypoglycemia on 1 Day or More Than 1 Day and Receipt or Nonreceipt of Insulin Therapy at the Time of the First Hypoglycemic Episode. The risk of death was increased among patients who had moderate hypoglycemia on more than 1 day, as compared with just 1 day (Panel A), and among patients who were not receiving insulin when hypoglycemia first occurred, as compared with those who were receiving insulin (Panel B). The interval from the first episode of hypoglycemia to death was shorter among patients who were not being treated with insulin when hypoglycemia first occurred (P=0.004 and P<0.001 for moderate and severe hypoglycemia, respectively). The size of the squares is proportional to the number of deaths.The NICE-SUGAR Study Investigators. N Engl J Med 2012;367:
212009 AACE/ADA Recommended Target Glucose Levels in ICU Patients Starting threshold of no higher than 180 mg/dLRecommendedAcceptableNot recommended<110>180Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009;15(4).2012 Critical Society GuidelinesICU Target Glucose Goal < 150 mg/dlStart Insulin Therapy when BG ≥ 150 mg/dLMaintain BG values <180 mg/dLJacobi, et al. Crit Care Med 2012;40:3251–3276Based on the high rate of hypoglycemia and no difference in mortality in major trials, and the results of NICE –SUGAR that reported increased mortality… NEW TASK FORCE.The slide shows the recommendations for target glucose levels in critically ill patients in the intensive care setting, which were released on May 8, 2009, by the American Association of Clinical Endocrinologists and the American Diabetes Association, and published online in the June issues of Endocrine Practice and Diabetes Care. They include the following:Insulin therapy should be initiated for treatment of persistent hyperglycemia, starting at a threshold of no greater than 180 mg/dL.Once insulin therapy has been started, a glucose range of 140 to 180 mg/dL is recommended for the majority of critically ill patients.Intravenous insulin infusions are the preferred method for achieving and maintaining glycemic control in critically ill patients.Validated insulin infusion protocols with demonstrated safety and efficacy, and with low rates of occurrence of hypoglycemia, are recommended.With IV insulin therapy, frequent glucose monitoring is essential to minimize the occurrence of hypoglycemia and to achieve optimal glucose control.2012 American College of Physicians (ACP)ICU Target Glucose Goal < 200 mg/dlAnnals Intern Med 2012Moghissi 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). Accessed May 18, 2009.21
22Glycemic Targets in NON-ICU Setting Premeal BG target of <140 mg/dl (7.8 mmol/L) and random BG <180 mg/dl (10 mmol/L) for the majority of patients.Glycemic targets be modified according to clinical status.For avoidance of hypoglycemia, diabetic therapy be reassessed when BG<100 mg/dl (5.5 mmol/L).American College of Physicians recommended a target BG <200 mg/dl (11.1 mmol/L), Ann Intern Med 2012Umpierrez et al. J Clin Endocrinol Metabol. 97(1):16-38, 2012
23Hyperglycemia in the ICU: Lecture Agenda Scope of the Problem:What is the frequency of hyperglycemia and diabetes?Why should we care about hyperglycemia in the ICU?2. How should we manage hyperglycemia in the ICU and non-ICU settings?
24Strategies for Achieving Glycemic Targets in the ICU Leuven SICU Study1Yale Insulin Infusion Protocol2MICU Insulin Infusion Protocol (N=69)50100150200250300350400450122436486072HoursBlood Glucose (mg/dL)Glucommander32468101416182022Glucose (mg/dL)Van den Berghe et al. N Engl J Med. 2001;345: Goldberg PA et al. Diabetes Care. 2004;27:3. Davidson et al. Diabetes Care. 2005;28: Finfer S, et al. N Engl J Med. 2009;360(13):AdmissionDay 1Day 5Day 15Blood Glucose (mmol/L)Intensive - Mean BG 103 mg/dLConventional - Mean BG 153 mg/dLLast dayStrategies for Achieving Glycemic Targets in the ICUNICE-SUGAR4
25Intensive IV Insulin Protocols Hypoglycemia Rates inIntensive IV Insulin ProtocolsProtocolHypo definition% patientsRRLeuven SICU1<40 mg/dL5.1%7Leuven MICU219%6Glucontrol38.6%--VISEP417.4%4.11NICE SUGAR56.5%13.7GLUCO-CABG6<40 mg/dl0%Only BG < 40 mg/dl are usually reported in RCT… We must change this.Van Den Berghe G, et al. N Engl J Med. 2001:345:1359; Van Den Berghe G, et al. N Engl J Med. 2006;354: ; Brunkhorst FM et al. N Engl J Med. 2008; 358: ; Preiser JC, SCCM, 2007; Finfer S, et al. N Engl J Med. 2009;360(13): ; Umpierrez , ADA 2014
26Glycemic Values Achieved with IV Insulin ProtocolsProtocolIITCITLeuven SICU103153Leuven MICU111De la Rosa120149Glucontrol118143VISEP112151NICE SUGAR145GLUCO-CABG132154Every RCT has shown that you can achieved great BG control (even in the control group).Thus, better or different algorithms may not be the answer…IIT: Intensive insulin therapy; CIT: Control, conventional/Conservative insulin therapyResults are expressed as mean BG during hospital stay, mg/dLVan Den Berghe G, et al. N Engl J Med. 2001; Van Den Berghe G, et al. N Engl J Med. 2006;De la Rosa,et al, Crit Care 2008; Brunkhorst et al. N Engl J Med. 2008; Preiser JC, SCCM, 2007; Nice Sugar, NEJM 2009; Umpierrez 2014 (ADA, unpublished)
27Recommendations for Managing Patients With Diabetes in the Hospital Setting Antihyperglycemic TherapyInsulinRecommendedOADs Not Generally RecommendedACE/ADA Task Force on Inpatient Diabetes. Diabetes Care & 2009Diabetes Care. 2009;31(suppl 1):S1-S110..
28Insulin Therapy in patients with T2D D/C oral antidiabetic drugs on admissionInsulin naïve: starting total daily dose (TDD):0.3 U/kg to 0.5 U/kgLower doses in the elderly and renal insufficiencyPrevious insulin therapy: reduce outpatient insulin dose by 20-25%Basal bolus regimen: Half of TDD as basal and half as rapid-acting insulin before mealsUmpierrez et al, Diabetes Care 30:2181–2186, 2007; Baldwin et al, Diabetes Care 10:1970-4, 2011; Rubin et al, Diabetes Care 34:1723-8, 201128
29Sliding Scale Regular Insulin Basal Bolus Insulin Regimen Inpatient Management in non-ICU SettingSliding Scale Regular InsulinBasal Bolus Insulin RegimenIn insulin naïve patients with T2DM, does treatment with basal bolus regimen with glargine once daily and glulisine before meals is superior to sliding scale regular insulin?RABBIT-2D TRIAL:- Research Question:Umpierrez et al, Diabetes Care 30:2181–2186, 2007
30D/C oral antidiabetic drugs on admission Randomized Basal Bolus versus Sliding Scale Regular Insulin in patients with type 2 Diabetes Mellitus (RABBIT-2 Trial)D/C oral antidiabetic drugs on admissionStarting total daily dose (TDD):0.4 U/kg/d x BG between mg/dL0.5 U/kg/d x BG between mg/dLHalf of TDD as insulin glargine and half as rapid-acting insulin (glulisine)Insulin glargine - once daily, at the same time/day.Glulisine- three equally divided doses (AC)Umpierrez et al, Diabetes Care 30:2181–2186, 200730
31Rabbit 2 Trial: Changes in Glucose Levels With Basal-Bolus vs Rabbit 2 Trial: Changes in Glucose Levels With Basal-Bolus vs. Sliding Scale Insulin240Hypoglycemia rate:Basal Bolus Group:BG < 60 mg/dL: 3%BG < 40 mg/dL: noneSSRI:BG < 40 mg/dL: none220a200aabb180bBG, mg/dLbSliding-scale160140Basal-bolus120100Admit12345678910Key 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).aP<.05.Days of TherapybP<.05.Sliding scale regular insulin (SSRI) was given 4 times dailyBasal-bolus regimen: glargine was given once daily; glulisine was given before meals.0.4 U/kg/d x BG between mg/dL0.5 U/kg/d x BG between mg/dLUmpierrez GE, et al. Diabetes Care. 2007;30(9):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):
32DEAN TRIAL: Inpatient Management in non-ICU Setting Basal Bolus Insulin RegimenNPH and Regular Insulin-Spilt-Mixed RegimenIn patients with T2DM on diet, oral agents or insulin treatment, does treatment with basal bolus regimen with detemir once daily and aspart before meals is superior to NPH and Regular split-mixed insulin regimen?DEAN TRIAL:- Research Question:Umpierrez et al, J Clin Endocrinol Metab 94: 564–569, 2009
33DEAN Trial: Changes in Mean Daily Blood Glucose Concentration 240Detemir + aspartNPH + regular220200NPH/RegularBG < 40 mg/dl: 1.6%BG < 60 mg/dl: 25.4%Detemir/AspartBG < 40 mg/dl: 4.5%BG < 40 mg/dl: 32.8%DEAN Trial: HypoglycemiaP=NS180BG, mg/dL160140120In 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).100Pre-Rx123456-10BGDuration of Therapy, dData are means SEM.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):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):
34Bueno, Benitez eta al. 2012 ADA Scientific Meeting, New Orleans Randomized Controlled Study Comparing Basal Bolus with Insulin Analogs vs Human Insulins in General Medicine PatientsBasal bolus with glargine QD + glulisine AC versus NPH b.i.d. & regular AC.- 0.4 U/kg/d x BG: mg/dL- 0.5 U/kg/d x BG: mg/dLBueno, Benitez eta al ADA Scientific Meeting, New Orleans
35Basal Bolus Regimen Analogs vs. Human Insulins Algo claro es que el esquema basal-bolos funciona. El comportamiento de la medianas es similar y probablemente no hayan diferencias demostrables estadísticamente entre los 2 brazos de intervenciónBueno, Benitez eta al ADA Scientific Meeting, New Orleans
36Hypoglucemias por brazo de intervención ALLN= 134AnalogsN=66HumanN=68p-valuePatients with Hypoglycemia, n (%)49 (37)23 (35)26 (38)OR:1.16p: 0.68Severe Hypoglucemia, n (%)22 (16)517OR:2.93P:0.04Mild Hypoglucemia, n (%)954451Patients withn ≥2 episodes, n (%)26 (19)1016OR:2.08P:0.2Hasta ahora el numero y porcentaje de pacientes con hipoglucemias es igual en cada brazo, pero la distribución de los 38 episodios es diferente. Hubieron más episodios entre los que usaron humanas que en los que usaron análogos y el numero de episodios severos tambien fue mayor( más del doble.Bueno, Benitez eta al ADA Scientific Meeting, New Orleans
37Randomized study of basal bolus insulin therapy in the management of general surgery patients with T2DM (Rabbit Surgery)Research Question:In patients with T2DM on diet, oral agents or insulin treatment, does treatment with basal bolus regimen with glargine and glulisine is superior to SSRI?Primary Outcomes:Differences between groups in mean daily BGComposite of hospital complications: wound infection, pneumonia, respiratory failure, acute renal failure, and bacteremiaUmpierrez et al, Diabetes Care 34 (2):1–6, 2011
38Mean BG before meals and at bedtime during basal bolus and SSI therapy Glargine+GlulisineSliding Scale Insulin****Breakfast Lunch Dinner Bedtime*p<0.001Umpierrez et al, Diabetes Care 34 (2):1–6, 2011
39Postoperative Complications Glargine+GlulisineSliding Scale InsulinP=0.05P=0.10P=0.24P=NS* Composite of hospital complications: wound infection, pneumonia, respiratory failure, acute renal failure, and bacteremia.Umpierrez et al, Diabetes Care 34 (2):1–6, 2011
40Percent of patients with hypoglycemia during basal bolus and SSI therapy BG <70 mg/dL BG <60 mg/dL BG <40 mg/dL23510152025Insulin Glargine+ InsulinGlulisineSSIP<0.001122510152025Insulin Glargine+ InsulinGlulisineSSIP<0.0014510152025Insulin Glargine+ InsulinGlulisineSSIP=0.057There were no differences in hypoglycemia between patients treated with insulin prior to admission compared to insulin-naïve patients.Umpierrez et al, Diabetes Care 34 (2):1–6, 2011
41Insulin Treatment in in Non-ICU Setting T2DM with BG > 140 mg/dl (7.7 mmol/l)NPOUncertain oral intakeAdequateOral intakeBasal insulin- Start at U/Kg/day*- Correction doses with rapid acting insulin AC- Adjust basal as neededBasal BolusTDD: U/Kg/day½ basal, ½ bolus- adjust as neededGROUP 1. Insulin Glargine Once Daily Plus Supplemental Insulin GlulisineOral antidiabetic drugs (sulfonylureas, repaglinide, nateglinide, metformin, TZDs) will be discontinued on admission.Starting total daily insulin dose:0.5 units per kilogram of body weight per dayHalf of total daily dose will be given as insulin glargine and half as insulin glulisine.Insulin glargine will be given once daily, at the same time of the day.Insulin glulisine will be given in three equally divided doses before each meal. To prevent hypoglycemia, if a subject is not able to eat, the dose of glulisine will be held.Do you need basal bolus in ALL patients?
42Basal Plus Correction vs. Basal Bolus Basal plus supplementsStarting glargine*: units/kgCorrection with glulisine for BG >140 mg/dl per sliding scaleBasal Bolus RegimenStarting TDD*: 0.5 U/kgGlargine: U/kgGlulisine: 0.25 U/kg in three equally divided doses (AC)Correction with glulisine for BG >140 mg/dl per sliding scale* Reduce TDD to 0.15 U/kg in patients ≥70 yrs and/or serum creatinine ≥ 2.0 mg/dL* Reduce TDD to 0.3 U/kg in patients ≥70 yrs and/or serum creatinine ≥ 2.0 mg/dLUmpierrez et al, Diabetes Care 2013
43Basal-PLUS vs Basal Bolus: 300 medical & surgical non-ICU patients glargine once daily0.25 U/kg plus glulisine supplementsBasal Bolus:TDD: 0.5 U/kg/dGlargine 50%glulisine 50%Preliminary results: Basal bolus 51 patients, basal-plus: 49 patientsUmpierrez et al, Diabetes Care 2013
44Differences in glycemic control and frequency of treatment failures in patients treated with basal bolus, basal plus and sliding scale regular insulinUmpierrez et al, Diabetes Care, 2013
45Basal-PLUS vs Basal Bolus: Medicine and Surgery Patients Daily BGDaily BGBG AC & HSBG AC & HSSmiley et al, Diabetes Care 2013
46What about Incretin-Based Therapy? Management of Patients With Diabetes in Non-ICU SettingsInpatient Management in non-ICUWhat about Incretin-Based Therapy?Basal BolusorBasal PlusRegimens
47DPP-4 Therapy in Hospitalized Patients Study Type: Multicenter, prospective, open-label randomized clinical trialPatient Population: Patients with T2D admitted to general medicine and surgery services at 3 hospitals: Emory University, Grady, and University of MichiganTreatment Groups*Group 1. Sitagliptin once daily (n=30)Group 2. Sitagliptin plus glargine insulin once daily (n=30)Group 3. Basal bolus regimen with glargine once daily and lispro before meals (n=30)* All groups received supplemental doses of lispro for BG > 140 mg/dl before mealsUmpierrez et al. Care. 36(11):3430-5, 2013
48Mean Daily BG During Treatment Randomi-zationUmpierrez et al. Care. 36(11):3430-5, 2013
49Mean BG before meals and at bedtime during Treatment P=0.52P=0.57P=0.22P=0.15Data is mean ± SEUmpierrez et al. Care. 36(11):3430-5, 2013
50Mean Daily Blood Glucose (mg/dL) Randomization Blood Glucose (<180 mg/dl and >180 mg/dl) and Mean Daily Glucose concentrationp= 0.08p= 0.91Mean Daily Blood Glucose (mg/dL)Umpierrez et al. Care. 36(11):3430-5, 2013
51Recommendations for Managing Patients With Diabetes After Hospital Discharge Use admission A1C to adjust therapy at discharge10%ADD basal or REPLACE with basal/bolus9%ADD basal insulin therapy8%Adjust original therapy, ADD another agent or basal insulin7%Return to original therapyUmpierrez G et al, J Clin Endocrinol Metabol, 2012
52Discharge Insulin Algorithm Discharge TreatmentA1C < 7%A1C 7%-9%A1C >9%Re-start outpatient treatment regimen(OAD and/or insulin)Re-start outpatient oral agents and D/C on glargine once daily at 50-80% of hospital doseD/C on basal bolus at same hospital dose.Alternative: re-start oral agents and D/C on glargine once daily at 80% of hospital doseUmpierrez et al, ADA Scientific Sessions, 2012
53Hospital Discharge Algorithm Based on Admission HbA1C for the Management of Patients with T2DM 8.75%7.9%%7.35%Umpierrez et al, ADA Scientific Sessions, 2012
54Hospital Discharge Algorithm Based on Admission HbA1C for the Management of Patients with T2DM Primary outcome:- change in A1C at 4 wks and 12 wks after dischargeAll PatientsOADOAD + GlargineGlargine+ GlulisineGlargine# patients, n (%)22481 (36)61 (27)54 (24)20 (9)A1C Admission, %8.7±2.56.9±1.59.2±1.911.1±2.38.2±2.2A1C 4 Wks F/U, %7.9±1.7*7.0±1.48.0±1.4ψ8.8±1.8ψ7.7±1.7A1C 12 Wks F/U, %7.3±1.5*6.6±1.17.5±1.6*8.0±1.6*6.7±0.8*BG<70 mg/dl, n (%)62 (29)17 (22)17 (30)23 (44)5 (25)BG<40 mg/dl, n (%)7 (3)3 (4)0 (0)3 (6)The primary outcome: change in HbA1C at 4 and 12 wks after discharge.The HbA1c on admission was 8.67±2.5% and decreased to 7.86±1.7% at 4 wks and to 7.26±1.48% at 12 wks of follow-up (both, p<0.001).* p< vs. Admission A1C; ψp=0.08Umpierrez et al, ADA Scientific Sessions, 2012
55Management of diabetes in non-critical care setting So… What really have we learned?
59Guillermo E. Umpierrez, MD Thank you!Guillermo E. Umpierrez, MD
60Inpatient Management of Medical and Surgical Patients with Type 2 diabetes- ICU and non-ICU Guillermo E. Umpierrez, MD, FACP, FACEProfessor of MedicineDirector, Grady Hospital Clinical Research UnitEmory University School of MedicineDirector, Diabetes & Endocrinology SectionGrady Hospital CIN (Research Unit)Grady Health System
61External Industry Relationships * Dr. Guillermo Umpierrez, Personal/Professional Financial Relationships with IndustryExternal Industry Relationships *Company Name(s)RoleEquity, stock, or options in biomedical industry companies or publishersNoneBoard of Directors or officerRoyalties from from external entityIndustry funds toEmory for my researchSanofi-AventisMerckNovo NordiskBoehringer IngelheinInvestigator-Initiated Research Projects
62Hyperglycemia in non-critical care setting: Lecture Agenda Scope of the Problem:What is the frequency and impact of hyperglycemia and diabetes?What diagnosis criteria should we use?What target glucose should we aim?2. How should we manage hyperglycemia in ICU and non-ICU setting?Insulin regimens – Which and how to start?Incretin-base regimens – are they safe & effective?Discharge algorithm – What is the role of the admission HbA1c?Umpierrez et al. J Clin Endocrinol Metabol. 97(1):16-38, 2012
63Hyperglycemia: A Predictor of Mortality Following CABG in Diabetics 10[Furnary. Circulation.1999/ pI591/line 8-19]BG >200P<0.0001BG <2008.6n=1369n=6628Postop1.8%5.0% *Mortality*P<0.0015.86Postop Mortality (%)Adjusted for 19 clinical and operation variables3.84First Postop Glucose >2002x LOS3x Vent duration7x mortality !!!2.11.721.4<150150-175-200-225->250CABG, coronary artery bypass graft.175200225250Furnary AP et al. Circulation. 1999:100 (Suppl I): I-591.Blood Glucose (mg/dL)
64Hyperglycemia and Pneumonia Outcomes Admission glucose (mg/dl)**%**BG (mg/dl) < < <250 ≥250* p: < 0.05 vs BG < 198 mg/dl (11 mmol/L)N= 2,471 patients with CAPMcAllister et al, Diabetes Crae 28: , 2005
65Pharmacologic Therapy in Non-ICU Setting Patients treated with insulin at home require scheduled SQ insulin therapy in the hospital (1)Avoid prolonged use of sliding scale insulin as sole method for glycemic management (2)Scheduled SQ insulin consists of basal or intermediate acting insulin in combination with RAI or Regular insulin administered before meals in patients who are eating(1)Include correction insulin as a component of scheduled SQ insulin for treatment of BG above desired range (2)GE Umpierrez, R Hellman, MT Korytkowski, M Kosiborod, GA Maynard, VM Montori, JJ Seley, GV den Berghe. J Clin Endocrinol Metabol. 97(1):16-38, 2012
66Basal Bolus Insulin Regimen D/C oral antidiabetic drugs on admissionStarting total daily dose (TDD): 0.5 U/kg/dayTDD reduced to 0.3 U/kg/day in patients ≥ 70 years of age or with a serum creatinine ≥ 2.0 mg/dLHalf of TDD as insulin glargine and half as insulin glulisine*Glargine - once daily, at the same time of the dayGlulisine- three equally divided doses (AC)GROUP 1. Insulin Glargine Once Daily Plus Supplemental Insulin GlulisineOral antidiabetic drugs (sulfonylureas, repaglinide, nateglinide, metformin, TZDs) will be discontinued on admission.Starting total daily insulin dose:0.5 units per kilogram of body weight per dayHalf of total daily dose will be given as insulin glargine and half as insulin glulisine.Insulin glargine will be given once daily, at the same time of the day.Insulin glulisine will be given in three equally divided doses before each meal. To prevent hypoglycemia, if a subject is not able to eat, the dose of glulisine will be held.*If a patient was not able to eat, insulin glargine was given but, insulin glulisine was held until meals were resumed.Umpierrez et al, Diabetes Care 34 (2):1–6, 2011