None 1 4/30/15 Past Lectures n Background Data on Goals n Nuts - PDF document

4/30/15 ¡ Inpatient Hyperglycemia Rational Approach at a Time of Uncertainty How to Make Change Happen Robert J. Rushakoff, MD Professor of Medicine University of California, San Francisco robert.rushakoff@ucsf.edu Disclosures None 1 ¡

4/30/15 ¡ Past Lectures n Background Data on Goals n Nuts and Bolts on How to do day to day management n Some other interesting stuff Past Today’s Lecture n Background Data on Goals n What’s old is old; What’s new is old n Same slides – different message n Nuts and Bolts on How to do day to day management n There are better ways to teach this n Some other interesting stuff n For sure 2 ¡

4/30/15 ¡ What is inpatient diabetes care? Diabetes as a Secondary Diagnosis Inpatient Diabetes Inpatient Diabetes Goals Goals Normal glucoses for Who Cares everyone Just get patient home A high glucose means Sliding Scales are fine failure Avoid that scary Sliding Scales are banned hypoglycemia Some hypoglycemia is acceptable 3 ¡

4/30/15 ¡ Inpatient Diabetes Inpatient Diabetes Goals Goals Normal glucoses for Who Cares everyone Just get patient home A high glucose means Sliding Scales are fine failure Avoid that scary Sliding Scales are banned hypoglycemia Some hypoglycemia is acceptable Inpatient Diabetes Inpatient Diabetes Goals Goals Normal glucoses for Who Cares everyone Just get patient home A high glucose means Sliding Scales are fine failure Avoid that scary Sliding Scales are banned hypoglycemia Some hypoglycemia is acceptable 4 ¡

4/30/15 ¡ Inpatient Diabetes Inpatient Diabetes Goals Goals Normal glucoses for Who Cares everyone Just get patient home A high glucose means Sliding Scales are fine failure Avoid that scary Sliding Scales are banned hypoglycemia Some hypoglycemia is acceptable Inpatient Diabetes Goals Appropriate Glucose Control Based on physiology and outcome studies Target Glucose Levels No DKA or Hyperosmolar Coma 5 ¡

4/30/15 ¡ Target Glucose Levels No hypo- or hyperglycemia • Prevent fluid and electrolyte • Decreased post-MI mortality abnormalities secondary to osmotic diuresis • Decreased post-CABG • Improve WBC function morbidity and mortality • Improve gastric emptying • Decrease surgical complications • Earlier hospital dischange Problems With High Glucoses 6 ¡

4/30/15 ¡ Proinflammatory cytokines in response to DKA n In DKA– increased 2-3 fold: n counterregulatory hormones n proinflammatory cytokines n (tumor necrosis factor [TNF]– α , n interleukin [IL]-6, IL-8, and IL-1 β ), n markers of reactive oxygen species n markers of lipid peroxidation n C-reactive protein, and free fatty acids Metabolism 2009, 58: 443-448 Glucose and Post-CABG Morbidity and Mortality Diabetes and Coronary Artery Bypass Surgery An examination of perioperative glycemic control and outcomes • Retrospective review of 291 patients surviving 24 h post-op • 40% with retinopathy, nephropathy, or neuropathy Inpatient complications: For each 1 mmol/l (18 mg/dL) increase in post-op day 1 over 6.1 mmol/l (110 mg/dL), a 17% increased risk of complications McAlister FA et al. Diabetes Care. 2003; 26:1518-1524. 7 ¡

4/30/15 ¡ Other Associations • CABG • MI • CVA • Vascular surgery • Orthopedic Surgery High Blood Glucose Levels Associated With Increased Mortality in ICU ● Retrospective review of 259,040 critically ill patients conducted by the Veterans Affairs Inpatient Evaluation Center based in Cincinnati • Hyperglycemia was an independent predictor of mortality starting at 111 mg/dL • Effect was greatest with acute myocardial infarction, unstable angina, and stroke – Raised MI risk from 1.7 to 6 times – Raised stroke risk from 1.8 to 29 times – Raised unstable angina from 1.4 to 3 times Falciglia M et al . Crit Care Med. 2009; 37:3001-3009. 8 ¡

4/30/15 ¡ High Blood Glucose Levels Associated With Increased Mortality in ICU ● Retrospective review of 259,040 critically ill patients conducted by the Veterans Affairs Inpatient Evaluation Center based in Cincinnati • A significant but weaker effect was seen in patients with sepsis, pneumonia, and pulmonary embolism • Hyperglycemia was not found to be associated with mortality in diseases such as COPD and hepatic failure, hip fractures • In diabetes patients, the increase in mortality risk was not seen until mean glucose was >146 mg/dL Falciglia M et al. Crit Care Med . 2009; 37:3001-3009. Hyperglycemia– related mortality in critically ill patients varies with admission diagnosis Falciglia M et al. Crit Care Med . 2009; 37:3001-3009. 9 ¡

4/30/15 ¡ TPN: Adverse Outcomes Hyperglycemia Is Associated With Adverse Outcomes in Patients Receiving Total Parenteral Nutrition Cheung et al: Diabetes Care, 28:2367-2371, 2005 Risk of complications in relation to mean daily blood glucose level OR (95% CI) P Any infection 1.40 (1.08–1.82) 0.01 Septicemia 1.36 (1.00–1.86) 0.05 Acute renal failure 1.47 (1.00–2.17) 0.05 Cardiac complications 1.61 (1.09–2.37) 0.02 Death 1.77 (1.23–2.52) <0.01 Any complication 1.58 (1.20–2.07) <0.01 Glycemic Control and Outcomes of Hospitalization in Noncritically Ill Patients with Type 2 diabetes admitted with cardiac Problems or Infections n Retrospective – 378 patients n primary composite out-come included death during hospitalization, ICU transfer, initiation of enteral or parenteral nutrition, line infection, deep vein thrombosis, pulmonary embolism, rise in plasma creatinine by 1 or >2 mg/dL, new infection, an infection lasting for more than 20 days, and readmission within 30 days and between 1 and 10 months after discharge. (Endocr Pract. 2014; 20:1303-1308) 10 ¡

4/30/15 ¡ Glycemic Control and Outcomes of Hospitalization in Noncritically Ill Patients with Type 2 diabetes admitted with cardiac Problems or Infections n mean blood glucose (BG) level: n group 1 had mean BG of <180 mg/dL (n = 286; mean BG, 142 ± 23 mg/dL) n group 2 had mean BG levels >181 mg/dL (n = 92; mean BG, 218 ± 34 mg/dL; P<.0001). n Group 2 had a 46% higher occurrence of the primary outcome (P<. 0004). The rate of unfavorable events was greater in cardiac and ID patients with worse glycemic control (group 2). n Our data strongly support a positive influence of better glycemic control (average glycemia <180 mg/ dL or 10 mmol/L) on outcomes of hospitalization in patients with type 2 diabetes. (Endocr Pract. 2014; 20:1303-1308) 10 ¡ 9 ¡ 8 ¡ 7 ¡ 6 ¡ 5 ¡ 4 ¡ 3 ¡ 2 ¡ 1 ¡ 0 ¡ 0 ¡ 2 ¡ 4 ¡ 6 ¡ 8 ¡ 10 ¡ 12 ¡ 14 ¡ 16 ¡ 11 ¡

4/30/15 ¡ The association of mean glucose level and glucose variability with intensive care unit mortality in patients with severe acute pancreatitis J Crit Care. 2012 Apr;27(2):146-52. Intervention Studies 12 ¡

4/30/15 ¡ Decreased Infections Insulin infusion improves neutrophil function in diabetic cardiac surgery patients Perioperative IV insulin infusion Neutrophil phagocytic activity % baseline Control 47 Insulin 75 Rassias AJ et al. Anesth Analg. 1999; 88:1011-1016. Decreased Infections Glucose control lowers the risk of wound infection in diabetics after open-heart operations Perioperative IV insulin infusion Protocol to maintain glucoses <200 mg/dL Incidence of Deep Wound Infections (%) 1997 1999 Routine Control 2.4 2.0 “Tight” Control 1.5 0.8 Zerr KJ et al. Ann Thorac Surg. 1997;63:356-361. Furnary AP et al . Ann Thorac Surg. 1999;67:352-360. Furnary AP et al . J Thorac Cardiovasc Surg. 2003;125:1007-1021. 13 ¡

4/30/15 ¡ Decreased Mortality Glucose control decreases mortality in diabetics after open heart operations Furnary et al . J Thoracic Cardiovascular Surgery 2003, 125: 1007-1021 16 14.5 % 14 12 Mortality (%) Cardiac-related 10 mortality 8 6.0 % 6 Noncardiac- 4.1 % related Mortality 4 2.3 % 1.3 % 2 0.9 % 0 <150 150-175 175-200 200-225 225-250 >250 Declining In-Hospital Mortality in Patients Undergoing Coronary Bypass Surgery in the United States Irrespective of Presence of Type 2 Diabetes or Congestive Heart Failure Steady decline in the age-adjusted coronary artery bypass grafting (CABG)-related in-hospital mortality in recent years. (X/100,000) Clin Cardiol. 2012 Feb 23. (ahead online) 14 ¡

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4/30/15 ¡ Decreased Morbidity and Mortality Intensive Insulin Therapy in Critically Ill Patients ● Patients (all) on mechanical ventilation in ICU ● Randomly assigned to IV insulin maintaining glucoses between 80-110 mg/dL or conventional treatment (IV insulin if glucose >215 mg/dL then maintain glucose between 180-200) 12 month mortality % given insulin 24-hour dose AM glucose Intensive Main effect on patients 99 71 units 103 Intensive 4.6% in ICU >5 days Conventional 39 33 units 153 Conventional 8.6% Van den Berghe G et al. N Engl J Med. 2001;345:1359-1367. NICE-SUGAR • 6104 adults who were expected to require treatment in the ICU on 3 or more consecutive days randomized to intensive blood glucose control (target range, 81 to 108 mg/dL) or conventional blood glucose control (<180 mg/dL) • Primary endpoint death from any cause within 90 days after randomization • Baseline characteristics similar The NICE-SUGAR Study Investigators. N Engl J Med. 2009;360:1283-1297. 17 ¡