IntroductionThe frequency of hyperglycemia potential contribution tomorbidity and mortality in hospitalized patients makemeasurement of blood glucose mandatory in all patientsadmitted to the hospital whether or not known diabetes
ADA Recommendations:Diabetes Care in the Hospital All patients with diabetes admitted to the hospital should have – Their diabetes clearly identified in the medical record – An order for blood glucose monitoring, with results available to the health care team ADA. VIII. Diabetes Care in Specific Settings. Diabetes Care. 2011;34(suppl 1):S43.
Hyperglycemia Adversely Affects OutcomesDiabetes increases the risk for disorders that predisposeindividuals to hospitalization ,including cardiovasculardiseases, nephropathy, infection and lower-extremityamputations.
Hyperglycemia Adversely Affects Outcomes Hyperglycemia impacts – Mortality – Morbidity – Rate of infections – Length of hospital stay
Types Of Hyperglycemia in Hospitalized Patients
Hyperglycemia in Hospitalized Patients• Pre-existing known diabetes• Newly diagnosed diabetes• Hospital related or stress hyperglycemia
Traditionally acute hyperglycemia was definedas RBS more than 200 mg/dl* * (mcCowen et-el 2001 crit care clin 2001:17:107-24)
Stress Hyperglycemia On 2010 ADA proposed a threshold of blood sugar 140 mg/dl in patient not known to have diabetes A1c eleveted should be measured above 6.5% indicate preexisting diabetes in need for long term follow up
Strategy of In-Hospital Management of Diabetes
Strategy of In-Hospital Management of Diabetes Dose improving glycemic control improve clinical outcomes for inpatients with hyperglycemia ? What glycemic target can be recommended in different patients ?
Strategy of In-Hospital Management of Diabetes What treatment options are available for achieving optimal glycemic targets safely and effectively in specific clinical situation?
Dose improving glycemic control improve clinicaloutcomes for inpatients with hyperglycemia ?
Hyperglycemia and Hospital Mortality Normoglycemia Known diabetes New hyperglycemia 35 30 *Mortality (%) 25 20 * 15 10 * 5 0 Total Non-ICU ICU *P<.01 compared with normoglycemia and known diabetes.Umpierrez GE et al. J Clin Endocrinol Metab. 2002;87:978-982.
Hyperglycemia: An Independent Marker of ICU Mortality 31%* 30 ICU Mortality Mortality (%) 20 11% 10 10% 0 Normoglycemia Known New Diabetes HyperglycemiaUmpierrez et al. J Clin Endocrinol Metab 87:978, 2002 *P<0.01
• No doubt that hyperglycemia is associated with poor clinical outcomes• However, it does not mean that treatment of hyperglycemia will improve clinical outcomes
DIGAMI StudyDiabetes, Insulin Glucose Infusion in Acute Myocardial Infarction(1997) Acute MI With BG > 200 mg/dl Intensive Insulin Treatment IV Insulin For > 24 Hours Four Insulin Injections/Day For > 3 Months Reduced Risk of Mortality By: 28% Over 3.4 Years 51% in Those Not Previous Diagnosed Malmberg BMJ 1997;314:1512
DIGAMI Study: CVD Mortality Post-AMI .7 All Subjects (N = 620) .7 Subjects at low CV risk and .6 .6 w/ no prior insulin therapy .5 .5 (N = 272) .4 .4 .3 .3 .2 RRR=28% .2 RRR=51% .1 P=.011 .1 0 0 P=.0004 0 1 2 3 4 5 0 1 2 3 4 5 Years of Follow-up Years of Follow-up Standard treatment Intensive managementMalmberg K et al. BMJ 314: 1512-1515, 1997
Van Den Berghe et al: Intensive Insulin Therapy in Critically Ill Patients ------------------------------SICU---------------------------Prospective randomized controlled study.Enrolled 1548 SICU patients into 2 groupsIntensive therapy targeted glucose between 80-110 and the conventional range was 180-200Primary outcome was death in ICU which was 4.6 percent in the Intensive Glucose control group vs. 8.0 percent in Conventional glucose control group which was statistically significant.
Van den Berghe et al 2 Intensive Insulin Therapy in the Medical ICUProspective, randomized, controlled study of 1200 patientsSame authors and same conventional and intensive parameters as the first studyPrimary outcome was death in hospital which was 37.3% in the intensive group versus 40% in the conventional group which was statistically insignificant.
Wiener et alMeta analysis of 34 randomized trials totaling 8432 patients.Hospital mortality did not differ between tight vs. conventional glucose control.Tight glucose control was not associated with a decreased risk for new dialysis, but was a associated with a decreased risk of septicemia.Tight glucose control was associated with an increased risk of hypoglycemia.
GLUCONTROLProspective randomized control trial stopped early due to adverse events in the tight BG control group.Tight (80-110 mg/dL) vs Conventional(140-180 mg/dL) glucose control.Incidence of severe hypoglycemia (BG<40 mg/dL) was significantly more frequent in patients assigned to tighter control group. Risk of death was not increased by hypoglycemia.No difference in mortality 17% vs. 15% and the conclusion of the authors was that there are no apparent benefits of tight glucose control.
NICE-SUGAR Intensive versus Conventional Glucose Control in Critically Ill PatientsRandomized, prospective un-blinded clinical controlled trial of 6104 patients.
Patients were randomized into one of 2 groups within 24 hours of admission to the ICU if they were expected to be in the ICU for more than 3 days.The 2 groups were intensive glucose control target (80- 108 mg/dL) or the conventional control target (180mg/dL or less).
NICE-SUGAR.In the intensive control group, control of blood glucose was achieved with an insulin infusion.In the conventional group, insulin was administered if the blood glucose level exceeded 180mgdL.
NICE-SUGAR Results.829 patients(27.5%) died in the intensive control group751(24.9%) in the conventional-control group which is a difference of 2.6%.There was no statistical difference between surgical vs. medical ICU patients.
NICE-SUGAR ResultsSevere hypoglycemia(<40mg/dL) was recorded in 6.8%of patients in the intensive control group, vs. 0.5%in the conventional group.
These conflecting findinges have called to question thebenefit of tight control and highlight in the risk for severehyperglycemia so
What glycemic target can be recommended in different patients ?
ADA/AACE Target Glucose Levels in ICU PatientsICU setting: – Insulin infusion should be used to control hyperglycemia – Starting threshold of no higher than 180 mg/dl – Once IV insulin is started, the glucose level should be maintained between 140 and 180 mg/dl – Lower glucose targets (110-140 mg/dl) may be appropriate in selected patients – Targets <110 mg/dL are not recommendedNot recommended Acceptable Recommended Not recommended < 110 110-140 140-180 >180 ADA/AACE Inpatient Task Force Endocrine Practice 2009;15;1-17
AACE-ADA Consensus Statement on Inpatient Glycemic Control: ICU Glucose target 140-180mg/dlMoghissi E et al., Diabetes Care 2009;32:1344; Moghissi E etal., Endocrine Practice 2009;15:353
AACE-ADA Consensus Statement on Inpatient Glycemic Control: ICU • Lower target acceptable • ( 110-140 mg/dl )Moghissi E et al., Diabetes Care 2009;32:1344; Moghissi E etal., Endocrine Practice 2009;15:353
AACE-ADA Consensus Statement on Inpatient Glycemic Control: ICU • Tighter targets ( <110 mg/dl ) not safe; • >180 mg/dl not acceptable.Moghissi E et al., Diabetes Care 2009;32:1344; Moghissi E etal., Endocrine Practice 2009;15:353
ADA/AACE Target Glucose Levels in Non-ICU Patients Non-ICU setting:– Pre-meal glucose targets <140 mg/dL– Random BG <180 mg/dL– To avoid hypoglycemia, reassess insulin regimen if BG levels fall below 100 mg/dL– Occasional patients may be maintained with a glucose range below or above these cut-points Hypoglycemia= BG < 70 mg/dlSevere hypoglycemia= BG < 40 mg/dl ADA/AACE Inpatient Task Force Endocrine Practice 2009;15:1-17
Achieving Tight Glycemic Targets .What treatment options are available for achievingoptimal glycemic targets safely and effectively in specificclinical situation?
Achieving Tight Glycemic Targets Oral Antidiabetes Agents OR Insulin
Oral Antidiabetes Agents in the HospitalOral agents can be continued in stable patients withnormal nutritional intake, normal blood glucose levels,and stable renal and cardiac function.However, there are several potential disadvantages tousing these medications in hospital patients:
Disadvantages of most oral agents: Slow-acting / difficult to titrate
Disadvantages of insulin secretagogues(e.g. sulfonylureas and meglitinides such as glyburide,glypizide, repaglinide, etc.): • Hypoglycemia if caloric intake is reduced • Some are long-acting (hypoglycemia may be prolonged)
Disadvantages of Metformin: • Lactic acidosis can occur when used in the setting of renal dysfunction, circulatory compromise, or hypoxemia • Slow onset of action • GI complications: Nausea, diarrhea
Insulin onlyThe most powerful agent we have to control blood glucose
Conclusions Inhospital glycemic control is now recognized as a patient safety issue BG target 140 mg/dL-180 mg/dL Safe and Effective Protocols can be implemented institutionally to attain goals with acceptable hypoglycemiaAmerican Diabetes Association. Diabetes Care. 2006;29:S4-S42.
IV Insulin Therapy: Recommended Uses Best method to achieve quick glycemic control Continuous Variable Rate IV Insulin Drip Major Surgery, NPO, Unstable, MI, DKA, Hyperglycemia, Steroids, Gastroparesis, Delivery, etc Basal / Bolus Therapy when eating Bode et al. Endocr Pract. 2004;10(suppl 2):71-80
Patient with an Acute MI 53 yo male with DM 2 on SU, Metformin and Glitazone presents with an acute MI BG random is 220 mg/dl What do you recommend for glucose control? 1. Sliding scale rapid analog? 2. Basal Bolus insulin therapy? 3. IV insulin drip?
Patient with an Acute MI For acute MI with elevated glucose, you can give in type 2’s IV variable rate insulin infusion in all persons with elevated glucose
If you order an IV insulin drip ; 1- What dilution of IV insulin? 2- How often do you check the glucose?
Continuous Variable Rate IV Insulin Drip Mix Drip with 125 units Regular Insulin into 250 cc NS Starting Rate Units / hour = (BG – 60) x 0.02 where BG is current Blood Glucose and 0.02 is the multiplier Check glucose every hour and adjust drip Adjust Multiplier to keep in desired glucose target range
Continuous Variable Rate IV Insulin Drip Adjust Multiplier (initially 0.02) to obtain glucose in target range 100 to 140 mg/dL If BG > 140 mg/dL, increase by 0.01 If BG < 100 mg/dL, decrease by 0.01 If BG 100 to 140 mg/dL, no change in Multiplier If BG is < 80 mg/dL, Give D50 cc = (100 – BG) x 0.4 Give continuous rate of Glucose in IVF’s Once eating, continue drip till 2 hours post SQ insulin
The default insulin drip column < 100 off 100-109 0.5 Check BG every 1 hr and adjust rate 110-129 1.0 130-149 1.5 150-169 2.0 170-189 2.5 190-209 3.0 210-254 4.0 255-299 5.0 etc.
Converting to SC insulin If More than 0.5 u/hr IV insulin required with normal BG, start long-acting insulin (glargine) Must start SC insulin at least 2 hours before stopping IV insulin Some centers start long-acting insulin on initiation of IV insulin or the night before stopping the drip
How to Initiate Starting dose = 0.4 to 0.5 x weight in kilograms Bolus dose (aspart/lispro) = 20% of starting dose at each meal Basal dose (glargine) = 40% of starting dose given at bedtime or anytime Correction bolus = (BG - 100)/ Correction Factor, where CF = 1700/total daily dose
Starting dose = 0.45 x wgt. in kg Wt. is 100 kg; 0.45 x 100 = 45 units Bolus dose (aspart / lispro) = 20% of starting dose at each meal; 0.2 x 45 = 9 units ac (tid) Basal dose (glargine) = 40% of starting dose at HS; 0.4 x 45 = 18 units at HS Correction bolus = (BG - 100)/ CF, where CF = 1700/total daily dose; CF = 40 or 3000 / wgt kg
Calculating Initial MDI* Doses for Insulin-naïve Patients Starting dose = 0.5 × weight in kg Basal dose = 40%-50% Total prandial dose = 50%- of starting dose at bedtime 60% of starting dose, 1/3 at each meal* Do not skip correction dose even if no food eaten*Give after meals as rapid-acting analog if food intake is in doubt Adjust upwards daily by adding 50% *MDI = Multiple daily injection of correction doses to basal and bolus Thompson et al. Diabetes Spectrum. 2005;18:20-27. doses
Calculating Initial MDI* Dose: Example Assume 100-kg person with moderate insulin resistance Starting dose = 0.5 × 100 kg =50U Basal dose = Prandial doses = 0.4–0.5 x 50 U = 20-25 U at (0.5–0.6 x 50) = 25-30 U ÷ 3 or 8– bedtime 10 U at each meal* Give correction dose*Give after meals as rapid-acting analog if food intake is in doubt *MDI = Multiple daily injection Thompson et al. Diabetes Spectrum. 2005;18:20-27.
What to do depends on several questions Who is the patient? Which is the outpatient regimen? How well is it controlling glucose What is the current glucose When is the patient to eat? Why is the patient admitted
Hyperglycemia & Patients on General Medical Wards Absolute risk of adverse outcome (death or prolonged stay) increased 15% per 18-mg/dL increase in glucose levels 35 30 Mortality (%) 25 20 N=433 patients with COPD Exacerbations 15 10 5 0 < 109 109-125 126-162 >163 mg/dLBaker EH et al. Thorax. 2006;61:284-289. mg/dL mg/dL mg/dL
New AACE-ADA Consensus Statement on Inpatient Glycemic Control Moghissi E et al. Diabetes Care 2009, Endocrine Practice 2009Non–ICUSetting - Most patients: • pre-meal BG <140 mg/dL • random BG <180 mg/dL - More stringent targets may be appropriate in stable patients - Scheduled SQ insulin with basal- nutritional- correction preferred
RABBIT 2 Trial Prospective randomized trial of 130 insulin naïve T2DM non-ICU inpatients Admission blood glucose b/w 140-400 mg/dl Basal- bolus insulin with glargine and glulisine vs Regular insulin SS
Does inpatient management of hyper-glycemiarepresent a safety concerns?
Common Features Increasing Risk of Hypoglycemiain an Inpatient Setting• Advanced age• Decreased oral intake• Chronic renal failure• Liver disease• Changes in clinical status or medicationsBeta-blockers ,Corticosteroids
A person with diabetes on tube feedings What is the best insulin treatment for a DM patient on tube feedings? (BG 150 to 300 mg/dl) If unstable, first give IV insulin and determine the requirement over 24 hours and then change to SC basal (glargine Q 12 hours) with supplemental rapid acting every 4 to 6 hours. Can also use NPH Q 8 hours or regular Q 6 hours as the basal
A person with diabetes on TPN What is the best insulin treatment for a DM patient on TPN? (BG 150 to 300 mg/dl) If unstable, first give IV insulin variable drip and determine the requirement over 24 hours and then add all the insulin to the TPN bag. Continue to supplement every 4 to 6 hours with SC rapid acting insulin using BG – 100 / CF where CF is equal to 3000 divided by weight in kg. On average, CF = ~ 30 to 40
DM 1 patient in DKA (ph 7.0; BG 400mg/dl: weight 80 kg) When do you start potassium and how much? When do you start dextrose and how much? preference is 2 liters saline followed by D50.45 saline with 40 meq KCL/liter at 250 ml/hour. Monitor electrolytes Q 4 to 8 hours.
Protocol for Insulin in Hospitalized Patient Treat Any Patient With BG >140 mg/dl With Insulin – Treat Any BG >140 mg/dl with Rapid-acting Insulin (BG-100) / (3000 / wt kg) or 1700 / total daily insulin – Treat Any Recurrent BG >180 mg/dl with IV Insulin if failing SC therapy or >140 mg/dl if NPO, acute MI, perioperative, ICU, or >100 mg/dl if pregnant If More than 0.5 u/hr IV Insulin Required with Normal BG Start Long Acting Insulin
Protocol for Insulin in Hospitalized Patient Daily Total: Pre-Admission or Weight (#) x 0.2 u – 40 % as (Basal) – 60% as Rapid-acting insulin (Bolus) • Give in Proportion to Meal’s CHO Eaten BG >140 mg/dl: (BG-100) / CF CF = 1700 / Total Daily Insulin or 3000 / wgt kg Do Not Use Sliding Scale As Only Diabetes Management
All hospital patients shouldhave control blood glucose
Recommendations:Diabetes Care in the Hospital (2) Goals for blood glucose levels – Critically ill patients: 140-180 mg/dl (10 mmol/l) (A) – More stringent goals, such as 110-140 mg/dl (6.1-7.8 mmol/l) may be appropriate for selected patients, if achievable without significant hypoglycemia (C) – Non-critically ill patients: base goals on glycemic control, severe comorbidities (E) ADA. VIII. Diabetes Care in Specific Settings. Diabetes Care. 2011;34(suppl 1):S43.
Recommendations:Diabetes Care in the Hospital (3) Scheduled subcutaneous insulin with basal, nutritional, correction components (C) Use correction dose or “supplemental insulin” to correct premeal hyperglycemia in addition to scheduled prandial and basal insulin (E) Initiate glucose monitoring in any patients not known to be diabetic who receives therapy associated with high risk for hyperglycemia (B) ADA. VIII. Diabetes Care in Specific Settings. Diabetes Care. 2011;34(suppl 1):S43.
Recommendations:Diabetes Care in the Hospital (4) A hypoglycemia management protocol should be adopted and implemented by each hospital or hospital system – Establish a plan for treating hypoglycemia for each patient; document episodes of hypoglycemia in medical record and track (E) Obtain A1C for all patients if results within previous 2-3 months unavailable (E) Patients with hyperglycemia who do not have a diagnosis of diabetes should have appropriate plans for follow-up testing and care documented at discharge (E) ADA. VIII. Diabetes Care in Specific Settings. Diabetes Care. 2011;34(suppl 1):S43.
What to do depends on several questions Who How well is When is theis the it patient to patient? controlling eat? Which is glucose? What is the Why is the• Type 1? the • A1c 6.5%? current • NPO? patient• Type 2? outpatient • A1c 9.5%? glucose? • Full diet? admitted? regimen? • Orals? • BG=142? • Sepsis? • Insulin? • BG=442? • A-Fib? • Combo?
Intervention StudiesShowing Benefits Showing No Benefits• Van den Bergh-SICU • DIGAMI-2• Van den Bergh-MICU • CREATE-ECLA• DIGAMI-1 • VISEP trial • GIST-UK• Krinsley study • Intra-operative cardiac• Furnary data surgery study