Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Sugar and Spice status post NICE: Hypoglycemic
Document related concepts
Transcript
Sugar and Spice status post NICE: Hypoglycemic Management and Lessons Learned Half a Decade after the NICE-SUGAR trial MEGAN ALLEN, PHARMD, BCPS, BCPPS Disclosure Statement I do not have any conflicts of interest to disclose Pharmacist Objectives Discuss the pathophysiology of type 1 and 2 diabetes mellitus (DM) Compare and contrast the pharmacologic management between type 1 and 2 DM Define hypoglycemia and discuss the available treatment options Technician Objectives Discuss the pathophysiologic mechanism of types 1 and 2 diabetes mellitus (DM) Differentiate between the common pharmacologic management of types 1 and 2 DM Define hypoglycemia and understand the urgency of pharmacologic treatment Types 1 and 2 DM OVERVIEW Defining Diabetes Diabetes – disorder of the metabolic homeostasis controlled by insulin, resulting in abnormalities of carbohydrate (CHO) and lipid metabolism Type 1 DM – caused by absolute insulin deficiency, the result of a loss of beta cells of the pancreas Type 2 DM - caused by a progressive loss of insulin secretion Other Gestational DM Cystic fibrosis-related DM (CFRD) Drug or chemical induced diabetes Monogenic diabetes Diabetes Care Volume 39, Supplement 1, January 2016 Diagnostic Tests Plasma glucose criteria Fasting plasma glucose (FPG) ≥ 126 mg/dL 2 – h plasma glucose (2 – h PG) after 75 grams oral glucose tolerance test (OGTT) ≥ 200 mg/dL A1C ≥ 6.5% Classic symptoms of hyperglycemia or hyperglycemic crisis + random plasma glucose ≥ 200 mg/dL Diabetes Care Volume 39, Supplement 1, January 2016 Age Red blood cell turnover A1C Considerations Hemoglobinopathies / Anemias Diabetes Care Volume 39, Supplement 1, January 2016 Race / Ethnicity Increased Risk for Diabetes Overweight/obese adults + 1 or more additional risk factor for diabetes Testing should begin at 45 yo for ALL patients Considered in children and adolescents who are overweight/obese + 2 risk factors for diabetes Repeat tests if normal q3years FPG (100 – 125 mg/dL) or 2 – h OGTT (140 – 199 mg/dL) or A1C (5.7 – 6.4%) can be used to test for prediabetes Diabetes Care Volume 39, Supplement 1, January 2016 Type 1 and 2 DM CLASSIFICATION Type 1 DM Immune-mediated “Insulin dependent diabetes” or “juvenile-onset diabetes” 5-10% of diabetes Cellular-mediated destruction of the pancreatic beta cells Autoimmune markers: islet cell autoantibodies, autoantibodies to insulin, GAD, tyrosine phosphatases, ZnT8 Genetic predispositions Environmental markers Diabetes Care Volume 39, Supplement 1, January 2016 Idiopathic No known etiology Permanent insulinopenia and prone to ketoacidosis with no evidence of beta cell autoimmunity More common in African or Asian ancestry Type 1 DM Onset Clinical Presentation Diabetes Care Volume 39, Supplement 1, January 2016 •Presents at any age •No longer a “childhood” disease •Polyuria, polydipsia •Diabetic ketoacidosis (DKA) Type 1 DM Recommendations Blood glucose rather than A1C should be used to diagnoses acute onset Inform relatives of patients with type 1 DM of the opportunity to be tested Diabetes Care Volume 39, Supplement 1, January 2016 Type 2 DM “Non-insulin dependent diabetes” or “adult-onset diabetes” Insulin resistance and relative insulin deficiency Etiologies Excess weight increases insulin resistance Insulin secretion is defective Diabetes Care Volume 39, Supplement 1, January 2016 Type 2 DM Onset and Risk Factors Clinical Presentation • Any age • Overweight/obesity • Genetic predisposition • Racial/ethnic subgroups • Mild polyuria, polydipsia, nausea • Hypertension, hyperlipidemia, acanthosis nigricans • Rarely ketoacidosis Diabetes Care Volume 39, Supplement 1, January 2016 Type 2 DM Recommendations Testing in asymptomatic patients who are obese/overweight with 1 or more risk factors Consider testing in children and adolescents who are obese/overweight with 2 or more risk factors All patients, testing should begin at age 45 FPG, 2 – plasma glucose, A1C are all appropriate tests Diabetes Care Volume 39, Supplement 1, January 2016 Type 1 and 2 DM MONITORING AND GOALS Glycemic Monitoring Self-monitoring of blood glucose (SMBG) may guide treatment decisions for self-management for patients on insulin regimens Prior to meals/snacks, postprandially, bedtime, prior to exercise, if hypoglycemia is suspected, and driving Continuous glucose monitoring (CGM) may help lower A1C in adults with Type 1 DM Supplemental tool for SMBG for patients with hypoglycemia unawareness and/or frequent hypoglycemic episodes Diabetes Care Volume 39, Supplement 1, January 2016 A1C Testing Perform at least twice yearly in patients who are meeting goals with stable glycemic control Perform quarterly in patients who have had therapy changes or are not meeting glycemic goals May consider point of care A1C testing for more timely treatment changes Diabetes Care Volume 39, Supplement 1, January 2016 A1C Goals < 6.5% < 8% Why measure A1C? Microvascular Complications Cardiovascular Disease Glycemic Targets Diabetes Care Volume 39, Supplement 1, January 2016 •Improved glycemic control is associated with decreased microvascular complications and neuropathic complications •Appropriate as long as significant hypoglycemic is not a barrier •Lower risk of CVD events with intensive glucose control •Risks of intensive glycemic control may outweigh benefits in higher-risk patients •Needs to be discussed with the patient •Preprandial vs. postprandial glucose monitoring Glycemic Recommendations Target Goal A1C < 7% Preprandial glucose 80 – 130 mg/dL Peak postprandial glucose < 180 mg/dL Diabetes Care Volume 39, Supplement 1, January 2016 Type 1 DM PHARMACOLOGIC MANAGEMENT Recommendations Insulin therapy Multiple-dose insulin injections Continuous insulin infusion Education Matching prandial insulin dose to CHO intake, premeal blood glucose, and anticipated activity Diabetes Care Volume 39, Supplement 1, January 2016 Diabetes Control and Complications Trial (DCCT) Intensive insulin therapy or continuous insulin infusions was integral in improved glycemia and outcomes Benefit: better microvascular, macrovascular, and all-cause mortality Risk: high rate of severe hypoglycemia Since the study, insulin analogs have been developed to decrease hypoglycemia Diabetes Care Volume 39, Supplement 1, January 2016 Rapid-Acting Insulins Insulin Onset Peak Duration Lispro (Humalog®) 15 – 30 min 0.5 – 2.5 hours ≤ 5 hours Aspart (Novolog®) 15 – 20 min 1 – 3 hours 3 – 5 hours Glulisine (Apidra®) 12 – 30 min 1.6 – 2.8 hours 3 – 4 hours Oral Inhalation Afrezza® ~15 min ~ 53 min 2.5 – 3 hours Insulin lispro U-200 (Humalog® U-200) 15 min 0.5 – 1.5 hours 3 – 5 hours Insulin. In: Lexi-Comp Online™. Hudson, OH, Inc. [Accessed 21 Oct 2016]. Rapid-Acting Insulins Lispro or aspart preferred Fast onset of action May give immediately post meal Fairly predictable pharmacokinetic profiles Mixing insulins Either can be mixed with NPH Do not mix with long-acting insulins Short-Acting Insulin Insulin Onset Peak Duration Regular (Humulin R®, Novolin R®) 15 – 30 min U-100: 2.5 – 5 hours U-500: 4 – 8 hours U-100: 4 – 12 hours U-500: 13 – 24 hours Regular U-500 (Humulin R® U-500) 30 min 8 hours Up to 24 hours Insulin. In: Lexi-Comp Online™. Hudson, OH, Inc. [Accessed 21 Oct 2016]. Intermediate-acting Insulin Onset Peak Duration NPH (Humulin®, Novolin®) 1 – 2 hours 4 – 12 hours 14 – 24 hours Pro Insulin Twice daily dosing (less injections) Con Variability from dose to dose Insulin. In: Lexi-Comp Online™. Hudson, OH, Inc. [Accessed 21 Oct 2016]. Long-acting Insulin Insulin Onset Peak Duration Detemir (Levemir®) 3 – 4 hours 3 – 9 hours 5 – 7 hours Glargine (Lantus®) 3 – 4 hours No peak 10.8 to > 24 hours Degludec (Tresiba®) ~1 hour 9 hours > 24 hours Glargine U-300 (Toujeo®) 6 hours No peak 36 hours Insulin. In: Lexi-Comp Online™. Hudson, OH, Inc. [Accessed 21 Oct 2016]. Long-acting Insulin Detemir Glargine Degludec • Cannot be mixed with other insulins • Higher frequency of injection site reactions • Compared to NPH, ↓ weight gain, ↓ hypoglycemia, smoother activity profile • Cannot be mixed with other insulins • Improved glucose control compared to NPH • May ↓ frequency of hypoglycemia • Labeled as once daily dosing • Cannot be mixed with other insulins • FDA approved in adults only • Available as 100 units/mL and 200 units/mL flex touch pens Insulin. In: Lexi-Comp Online™. Hudson, OH, Inc. [Accessed 21 Oct 2016]. Combination Insulins Insulin Onset Peak Duration Aspart/Degludec (Ryzodeg® 70/30) ~14 min 2.3 hours > 24 hours Aspart protamine + insulin aspart (Novolog® Mix 70/30) 10 – 20 min 1 – 4 hours 18 – 24 hours Lispro protamine + insulin lispro (Humalog® Mix 75/25) 15 – 30 min 1 – 6.5 hours 14 – 24 hours NPH + insulin regular (Novolin® 70/30) 30 min 2 – 12 hours 18 – 24 hours Insulin. In: Lexi-Comp Online™. Hudson, OH, Inc. [Accessed 21 Oct 2016]. Insulin Clinical Pearls Self-mixing Clear before cloudy Vials of cloudy insulin must be gently rolled 10 – 20 times to mix solution Rotate injection sites to avoid lipodystrophy I:CHO Ratio Specifies how many grams of CHO are “covered” by 1 unit of insulin Example: 1:40 1 unit of insulin covers 40 g of CHO Calculation 500 / Total Daily Dose (TDD) Example: Patient is on 20 units of insulin daily, what is the I:CHO ratio? If the patient eats 50 g of CHO, how much insulin should be administered? Correction or Sensitivity Factor Specifies how many points the blood glucose will drop per unit of insulin 1800 rule used for analog insulin 1500 rule used for regular insulin Calculation Sensitivity factor (SF) = 1800 / TDD May vary depending on time of day Insulin Pens Carry insulin in a self-contained cartridge Advantages Portable, discreet, convenient Pre-filled (time-saver) Accurate dosing Disadvantages May be more expensive No all types of insulin are available Cannot be mixed Recommended to rotate injection sites Insulinpens.com Inpatient Use of Insulin Pens Institute for Safe Medication Practices (ISMP) Recognized ongoing safety concerns and recommends hospitals to reexamine policies regarding insulin pens for routine use Safety concerns Increase risk of infection when pens are used for multiple patients 2013: New York hospital may have exposed patients to HIV, hepatitis B, or hepatitis C because of the reuse of pens after changing the disposable needle Risk of needle stick injuries User technique errors ISMP Medication Safety Alert Volume 18 (3), February 2013 Pen Exceptions? U-500 insulin A specific syringe to measure doses is not available Tuberculin (TB) syringe or a U-100 syringe is recommended Doses need to be converted depending on syringe type (U-100 markings vs. volume) ISMP Recommendations US Food and Drug Administration approved Humulin R U-500 Kwikpen Set to measure in 5 unit increments Hospitals may consider use to eliminate dose conversion errors ISMP Medication Safety Alert. Quarterly Action Agenda. April 2015 Insulin Pumps Allows individualization of therapy Helps to adjust for variables Timing and type of meals Timing and type of exercise Hormonal fluctuations Allows tracking of missed bolus doses Weight gain may occur in the first few months http://www.isletsofhope.com Recommended to rotate injection sites Additional Treatment Options Pramlintide Amylin analog which delays gastric emptying, blunts pancreatic secretion of glucagon, and enhances satiety Induces weight loss and lowers insulin doses Pancreas and islet cell transplantation Pro: normalizes glucose levels Con: lifelong immunosuppression Metformin Incretin-based therapies May improve metabolic control in overweight/obese patients with poorly controlled diabetes Data in type 2 DM now being evaluated in type 1 DM Sodium-glucose cotransporter 2 inhibitors (SGLTZ) Data in type 2 DM now being evaluated in type 1 DM Diabetes Care Volume 39, Supplement 1, January 2016 Type 2 DM PHARMACOLOGIC MANAGEMENT Recommendations Metformin is preferred initial pharmacologic agent Insulin therapy in newly diagnosed type 2 DM patients who are markedly symptomatic and/or elevated blood glucose Add second agent if noninsulin monotherapy is a maximum tolerated dose and still not at goal A1C over 3 months Do not delay insulin therapy when glycemic goals are not met Diabetes Care Volume 39, Supplement 1, January 2016 Treatment Timeline Triple therapy Dual therapy Metformin Lifestyle Modifications Combination injectable therapy Diabetes Care Volume 39, Supplement 1, January 2016 Combination Therapy Each additional agent lowers A1C ~ 0.9-1.1% If A1C target not reached after 3 months, consider combination therapy with metformin AND Sulfonylurea, thiazolidinedione, DPP-4 inhibitor, SGLT2 inhibitor, GLP-1 receptor antagonist, basal insulin Meglitinides may be used instead of sulfonylureas in patients with irregular meal schedules or develop late postprandial hypoglycemia Considerations Patient preferences, goals of reducing blood glucose, minimizing side effects, cost effectiveness Diabetes Care Volume 39, Supplement 1, January 2016 Diabetes Care Volume 39, Supplement 1, January 2016 Diabetes Care Volume 39, Supplement 1, January 2016 Insulin Therapy Considered for all patients on dual combination therapy and A1C ≥ 9% Allows for goal to be met faster Beneficial in those with severe hyperglycemia (BG ≥ 300 – 350 mg/dL and/or A1C ≥ 10 – 12 % May simplify regimen as goals are met Diabetes Care Volume 39, Supplement 1, January 2016 Insulin Regimens Basal insulin is the most convenient regimen (0.1 – 0.2 units/kg) May consider intermediate insulin (NPH) in patients without history of hypoglycemia Bolus insulin Added when basal titrated to acceptable fasting blood glucose level, but A1C not at goal 1 – 3 injections of rapid acting insulin May consider GLP-1 receptor antagonist Less data in switching to a twice daily biphasic insulin analog Diabetes Care Volume 39, Supplement 1, January 2016 Diabetes Care Volume 39, Supplement 1, January 2016 Type 1 and 2 DM HOSPITALIZED PATIENTS Inpatient Recommendations Consider checking A1C on all patients with diabetes or hyperglycemia Insulin therapy should be initiated for treatment of persistent hyperglycemic (≥ 180 mg/dL) Goal sugars between 140 – 180 mg/dL May target 110 – 140 mg/dL for selected critically ill patients Basal + bolus regimen is preferred for noncritically ill patients who are NPO Sole use of sliding scale insulin is discouraged Hypoglycemia protocol should be implemented Treatment plans should be reviewed and changed to prevent hypoglycemia Should have a structured discharge plan Diabetes Care Volume 39, Supplement 1, January 2016 Glycemic Targets in Hospitalized Patients Hyperglycemia defined as BG > 140 mg/dL Admission A1C ≥ 6.5% suggests diabetes precedes admission Hypoglycemia defined as BG < 70 mg/dL Severe hypoglycemia BG < 40 mg/dL Moderate vs. Tight glycemic control???? Diabetes Care Volume 39, Supplement 1, January 2016 Normoglycemia in Intensive Care Evaluation – Survival Using Glucose Algorithm Regulation (NICE-SUGAR) Meta-analysis of over 26 studies looking at optimal blood glucose ranges for critically ill patients Intensive glucose control (BG 81 – 108 mg/dL) vs. conventional glucose control (≤ 180 mg/dL) Primary end point: death from any cause within 90 days after randomization Included 6104 patients N Engl J Med 2009;360:1283-97. 3054 intensive control 3012 conventional control NICE-SUGAR Trial Intensive Glucose Control Conventional Glucose Control 829 (27.5%) patients died 751 (24.9%) patients died 206 (6.8%) patients had severe hypoglycemia 15 (0.5%) patients had severe hypoglycemia Results • Death was not statistically significant different between treatment groups • The treatment effect was not statistically different between surgical and medical patients • Severe hypoglycemia was statistically significant (P < 0.001) • No significant different in number of days in ICU or hospital • No significant different in number of mechanical ventilation days N Engl J Med 2009;360:1283-97. NICE-SUGAR Conclusions Intensive glucose control increased mortality in critically ill adults with a number need to harm of 38 Deaths from cardiovascular causes was more common in the intensive control group Severe hypoglycemia was more common with intensive glucose control BG < 180 mg/dL resulted in lower mortality than a target of 81 – 108 mg/dL in critically ill adult patients N Engl J Med 2009;360:1283-97. NICU-SUGAR: Affecting Clinical Practice? Intensive Glucose Control Conventional Glucose Control Glycemic Control after NICESUGAR Glucose target of 140 – 180 mg/dL when insulin therapy is initiated in critically ill adults Tighter goals (110 – 140 mg/dL) if achieved without significant hypoglycemia Cardiac surgery patients Acute ischemic cardiac events Neurological patients Diabetes Care Volume 39, Supplement 1, January 2016 Type 1 and 2 DM HYPOGLYCEMIA Hypoglycemia Major limiting factor in glycemic management of types 1 and 2 DM Mild hypoglycemia may frighten individuals and is inconvenient Severe hypoglycemia is characterized by cognitive impairment Progress to unconsciousness Seizure Coma Death Injury (falls, car accident, etc.) Diabetes Care Volume 39, Supplement 1, January 2016 Hypoglycemia Signs and Symptoms Shaky Weakness or fatigue Tachycardia Irritability Sweating Headache Dizziness Blurred Vision Anxious Hypoglycemia Recommendations Ask patients about symptomatic and asymptomatic hypoglycemic events Glucose 15 – 20 g is preferred treatment for conscious patients Glucagon should be prescribed to all individuals at risk of severe hypoglycemia Hypoglycemia unawareness or one or more episodes of severe hypoglycemia necessitates evaluation of treatment regimen Patients on insulin with severe hypoglycemia or hypoglycemia unawareness should raise their glycemic targets Diabetes Care Volume 39, Supplement 1, January 2016 Hypoglycemia Treatment Ingestion of glucose or carbohydrate Pure glucose is preferred Added fat may prolong acute glycemic response Ongoing insulin activity may result in recurrent hypoglycemia unless additional food is ingested after recovery Glucagon Need to educate family members, roommates, school personnel, child care providers, etc. on the use of glucagon kits Diabetes Care Volume 39, Supplement 1, January 2016 Hypoglycemia Prevention Major part of diabetes management Recognize situations that increase risk of hypoglycemia Fasting for tests/procedures During or after intense exercise During sleep Recognize the importance of understanding hypoglycemia Increase risk of harm to self or others Diabetes Care Volume 39, Supplement 1, January 2016 Hypoglycemia in the Inpatient Setting Treatment Standardized hypoglycemia protocol is recommended Nurse initiated treatment protocol for BG < 70 mg/dL All hypoglycemic events are recommended to be reviewed Prevention Considerations: improper prescribing of hypoglycemic medications, inappropriate management of first episode, nutrition-insulin mismatch, unexpected interruption of nutrition Diabetes Care Volume 39, Supplement 1, January 2016 Hypoglycemia Inpatient Medications Treat orders as STAT Orders the pharmacy may not see Filled and sent to the floor immediately as delays in care can impact outcomes 15 – 20 g CHO Common medications (consider hypoglycemic kits) Glucose gel or glucose tabs D10, D25, and D50 bolus Glucagon Questions?
