Rhonda Eustice, PharmD, CDE Will Power lasts about two weeks and is soluble in alcohol. Mark Twain
Diabetes Management: The Three Legged Stool Diet Medication Exercise Objectives Know the treatment goals in patients with diabetes Categorize oral diabetic agents by their sites of action List reasons for inadequate control in patients with Type 2 diabetes. Compare and contrast the onset and duration of action for the different insulin products on the market.
The A1C Debate DCCT and UKDPS Trials Tight glycemic control can significantly reduce microvascular disease HgbA1C standard goal <7% 1% decrease in HgbA1C reduced macrovascular complications by 16% DCCT Research Group. NEJM. 1993; 329:977-986 UKDPS Group. Lancet. 1998; 352:837-853 The A1C Goal Debate ACCORD Trial Results: Study stopped early due to an unexpected increase in CV deaths in the tightly controlled arm. Group with target A1C <6% experienced 20% greater mortality The increased risk of CV death observed in this group of patients was seen in subjects with an A1C >7% Did not suggest that an A1C <7% alone was the sole predictor of mortality risk ACCORD Study Group. NEJM. 2008. 358:2545-2559
The A1C Goal Debate ADVANCE Trial Results: Overall benefit for the tightly controlled group; but the benefit came from improvements in renal complications VADT Trial Results: Intensified diabetes control reduced risk of CV events provided that the intensified therapy was initiated in the first 15 years after diagnosis Individuals who had a hypoglycemic event severe enough to cause a change in consciousness had an 88% increase in CV events ADVANCE Collaborative Group. NEJM. 2008:358-2560-2572 VADT investigators. NEJM. 2009;360:129-139 Lessons in Cardioprotective Benefit Selected from Recent Trials Control A1C: Target goals are <7% (ADA) or <6.5% (AACE) Individualize therapy: Duration and initial severity of disease matters Initiate intensive therapy early on Treat comorbid conditions: BP and lipids Avoid Hypoglycemia
Are Patients Meeting ADA Clinical Practice Recommendations? NHANES 1999 2002 (N=998) NHANES = National Health and Nutrition Examination Survey Resnick HE. Diabetes Care 2006; 29: 531-537 Type 2 Diabetes Pathophysiology Defects in pancreatic β-cell secretory function pancreatic poopout Increased hepatic production of glucose leaky liver Insulin resistance in skeletal muscle, adipose tissue, and liver rusty hinge Impaired incretin effect
Oral Therapy for Type 2 Diabetes: Site of Action: Liver Metabolic Problem: Excess glucose production Medication used: Metformin (Glucophage ) Monitoring: GI intolerance LFTs, Renal Function Vitamin B12 deficiency (long term use)* BMJ 2010: 340. c2198 Oral Therapy for Type 2 Diabetes: Site of Action: Pancreas Metabolic Problem: Impaired Insulin Secretion Medication class: Sulfonylureas : (Glyburide, Glipizide, Glimepiride)* Meglitinides (Nateglinide, Repaglinide) Monitoring: Hypoglycemia* Weight gain
Oral Therapy for Type 2 Diabetes: Site of Action: Hormones Metabolic Problem: Lack of glucose-dependent insulin secretion Medication class: GLP-1 Activators: Exenatide (Byetta )*, Liraglutide (Victoza )* DPP4 Inhibitors: Sitagliptin (Januvia ), Saxagliptin (Onglyza ) Monitoring: GI intolerance* Renal Function Pancreatitis Oral Therapy for Type 2 Diabetes: Site of Action: Gut Problem: Excess dietary carbohydrate Medication class: Alpha-glucosidase inhibitors: Acarbose (Precose ), Miglitol (Glyset ) Monitoring: GI intolerance Flatulence
Oral Therapy for Type 2 Diabetes: Site of Action: Muscle Metabolic Problem: Insulin Resistance Medication class: TZDs: Rosiglitazone (Avandia ), Pioglitazone (Actos ) Rosiglitazone and CV Risk The TZD Debate Meta analysis published in NEJM June 2007 concluded that rosiglitazone is associated with a significant increase in the risk of MI RECORD Trial 5 ½ year trial to evaluate whether rosiglitazone was equivalent to metformin + sulfonylurea in terms of CV hospitalization and death No statistically significant difference between the two groups for CV death and stroke Rosiglitazone doubles the risk for heart failure Nissen, S. et al. NEJM;. 2007. 356: 2457-2471 Home, P. The Lancet; 2009. 373: 2125-2135
Recommendations for Prescribing TZDs Avoid in patients with a history of heart failure Counsel on benefits of exercise for insulin resistance Monitor for fluid retention and weight gain Monitor LFTs Triple Therapy: Sulfonylurea, Metformin, Troglitazone 16 clinics in Canada, 200 patients with HbA1C >8.5% Baseline HbA1C 9.7% HbA1C reduction -1.3% Reached target HbA1C <8% 43% Reached target HbA1C <7% 14% Yale, JF, et al. Ann Intern Med 2001; 134: 737-745
Clinical Inertia: Failure to Advance Therapy When Required Pratley, R.Diabetes Educator: 2009, 4S-11S Clinical Inertia: Failure to Advance Therapy When Required Percentage of subjects advancing when A1C >8% At insulin initiation, the average patient had: 5 years with A1C >8% 10 years with A1C >7% Brown, Diabetes Care 2004: 27: 1535-1540
Reasons for Inadequate Control in Type II Diabetes Oral agents only lower HbA1C 1 1.5% Progressive nature of the disease Treatment inertia of healthcare providers Insulin Resistance Patient Resistance Cost, Complexity, Side effects I don t want insulin Patient Barriers to Initiating Insulin Therapy Barriers Communicate to patient Failing oral therapy OAD failure is due to progressive 58% of patient believe using nature of T2DM: insulin is the best insulin means they have failed agent to control disease OAD therapy Needle phobia Fear associated with early experiences Current needles considered painless: easy to use injection systems are available; give injection of saline in office Fear of complications Casual association of insulin with Diabetic complications Complications due to uncontrolled progressive disease and insulin results in reduction of vascular damage
Physician Barriers to Insulin Therapy in Type II Diabetes Barriers Hypoglycemia Communicate to patient Severe hypoglycemia is very uncommon, teach patient what to look for & how to treat lows Weight Gain Modest and controlled by diet, exercise, continued use of metformin Patients negative Perception of insulin therapy Patient need assurance that insulin is a positive approach to achieving glycemic control The Right Insulin Plan Mimics the body s normal insulin pattern: Smaller, steady amounts between meals & rapid peaks when you eat. WWPD (What would your pancreas do?)
Insulin: Basal vs Bolus Basal (Background) Bolus (Mealtime) - Flat - Adjustable to match carbohydrate - Doesn t require or cover food - Quick onset, peak, short duration - Can vary by time of day - After meal readings show effect - Fasting/pre meals tests show effect Effect of Foods on Blood Glucose Category Carbohydrates Proteins Fats % converted to glucose in body Typical time to complete digestion 100% 50% 10% 2 hours 3-5 hours 5-6 hours Examples Pasta Rice Bread Potatoes Milk Fruit Starchy vegetables Sweets Beef Chicken Fish Pork Eggs Nuts Tofu Cottage Cheese Cheese Oils Animal Fats Butter Avocados Peanut Butter Sour Cream Ranch Dressing
Available Insulin INSULIN ONSET PEAK EFFECTIVE DURATION BOLUS: Should match food in timing and amount Rapid Acting Humalog Novolog Apidra 5-15 minutes 30-90 minutes < 5 hours R (Regular) 30-60 minutes 2-3 hours 5-8 hours BASAL: Should keep blood sugar flat between meals Intermediate N (NPH) 2-4 hours 4-10 hours 10-16 hours Long Acting Levemir 1 hour No peak 6-24 hours Lantus (glargine) 1 hour No peak 24 hours Intrapatient Variability of Basal Insulin Action Insulin Intrapatient Variability NPH 59% Glargine (Lantus ) 46% Determir (Levemir ) 27% Lepore et al. Diabetes 2000;49:2142-8.
Insulin Dosing in T1DM vs T2DM Type 1 Type 2 Needs Background coverage Needs mealtime coverage May not need mealtime coverage (check post prandial readings) Continue oral agents Once type 2, always type 2 (although now requiring insulin) Patient Case A 30 year old male with Type 1 diabetes presents for diabetes education. He reports that his blood sugars have been ranging from 50 to 300+. His morning blood sugars are always over 200. He has gained 20 pounds in the last 6 months. Labs: A1C = 8.2% Meds: Lantus 30 units bid Regular insulin per sliding scale: BG Insulin dose 150-200 2 units 201-250 4 units 251-300 6 units 301-350 8 units 351-400 10 units >400 call physician Patient reported averaging 15 units of Regular insulin daily.
Patient Case Patient Problem Cause Hypoglycemia Weight gain Too much basal insulin (Lantus 60 units/regular 10 units) Too much basal insulin, patient having to frequently treat lows Uncontrolled Blood Glucose Not optimizing basal and bolus insulins Calculating insulin needs: Patient Case Regular insulin changed to Humalog and insulin dose recalculated: Total Daily dose (TDD) (75 units) Lantus (50-60%) Humalog (40-50%) 40 units 35 units
Question Sliding Scale is used best to: 1.Meet basal insulin requirements 2.To cover carbohydrates eaten at meals 3.As a supplement to scheduled insulin to correct hyperglycemia 4.As a guide for making changes to scheduled insulin doses Question Sliding Scale is used best to: 1.Meet basal insulin requirements 2.To cover carbohydrates eaten at meals 3.As a supplement to scheduled insulin to correct hyperglycemia 4.As a guide for making changes to scheduled insulin doses
Rapid-Acting Insulin: Correction vs Mealtime Bolus Bolus (Correction): Lowers sugars that are higher than target blood glucose Sliding scale Correction Factor/Sensitivity Factor calculation Bolus (Mealtime): Covers blood sugar rise produced by carbohydrates Fixed dose Insulin-to-carb ratio Correction/Sensitivity Factor: 1650 rule: (1650/TDD = CF)
Using the Correction/Sensitivity Factor (Glucose reading) (Glucose target) CF (195 120) = 3 units of 25 Rapid acting insulin Dosing for Carb Intake: The 500 Rule & Weight Method Average U Insulin Daily (Basal + Bolus) Weight (lbs / kg) Approximate Insulin to Carb ratio 8 11 1:50 12 14 1:40 15 18 < 60 / <27 1:30 19 21 60 80 / 27 36 1:25 22 27 81 100 / 37 45 1:20 28 35 101 140 / 46 64 1:15 36 45 141 170 / 65 77 1:12 46 55 171 200 / 78 91 1:10 56 65 201 230 / 92 104 1:8 66 80 231 270 / 105 123 1:6 81 120 >270 / >123 1:5 >120 1:4
Patient Case: New insulin dose Example: CF 1:25 IC: 1:6 CF: 190 120 25 = 2.8 units Premeal sugar = 190 Carbs for meal = 70 grams IC: 70 6 =11.7 units Total: 14.5 units Options for Dosing Rapid- Acting Insulin Correction Factor + insulin-to-carb ratio (need to calculate and count carbs) Best for tight control Correction Factor + fixed dose for meal coverage (need to calculate) Sliding scale + fixed dose for meal coverage Fixed dose for meal coverage Poorest Method for tight control
Insulin Pumps Eliminate the need for multiple injections/day Use rapid acting insulin only Basal rates can be increased/decreased throughout the day Calculate bolus doses for the patient Candidates for an Insulin Pump Tolerate the physical inconvenience of wearing the device Must be able to count carbohydrates Must check BG four or more times a day Must have adequate financial resources to purchase it and to acquire the requisite education for proper use. Must be skilled in sterile technique Must keep appointments with diabetes provider to make insulin rate adjustments.
Continous Glucose Monitors Sensor under the skin measures glucose in the interstitial fluid BG calibrations are needed 2-3 times a day Used to identify trends Available to physician offices or individual patients by prescription. What can busy pharmacists do to help their diabetic patients? Counsel patients on blood glucose goals Help to make sure your patients are getting enough test strips or using the strips they can get wisely Obtain computer software for your pharmacy to download glucose monitor data to review with patients Provide information on diabetes education programs and support groups in your area.
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