1. Titrating Insulin to Glycemic Target Judy Bowen, MD CIM Rotation September, 2006

2. Case 1 Mrs. G, 46 y.o. was diagnosed with Type 2 DM diagnosed 5 years ago (initially treated with diet and exercise, then glipizide XL 5 mg BID and metformin 1,000 mg BID) has these Hgb A1c values q 3 months over the past year: 5.8% 6.3% 7.4% 7.8%

3. Case 1, continued Her BMI is 33, BP is 126/72, micro- albumin is 9 on lisinopril 10 mg, LDL is 89 on Lipitor 10 mg. She takes 81 mg ASA daily. Her eye exam is up-to-date and normal. Monofilament exam is normal. Your exam is normal except for her obesity. Her fasting a.m. CBGs are 140-180 What do you recommend?

4. Schematic of 24-hour glucose profile 0 100 200 6 a.m. noon6 p.m12 a.m. 6 a.m. Riddle M. AJM, 2004; 116:3S-9S

5. Initiating basal insulin therapy Add basal insulin therapy –Start with 10 units insulin in most patients –Use either NPH or glargine (both work) –NPH q HS, glargine either q HS or q AM –Glargine was associated with less nocturnal hypoglycemia (Riddle et al, Diabetes Care, 2003; 26:3080- 3086) Continue with oral agents Consider adverse effects

6. Treat-To-Target Goal: near normal fasting CBGs (~100 mg/dl) Adjust dose weekly –based on average of two previous fasting CGBs Titration: –If CBG >/= 180, increase insulin by 8 units –If CBG 140-180, increase insulin by 6 units –If CBG 120-140, increase insulin by 4 units –If CBG 100-120, increase insulin by 2 units No increase if any hypoglycemia (CBG < 72) with or without symptoms

7. Relationship of A1c to CBG 4% 5% 6% 7% 8% 9% 10% 65 100 135 170 205 240 275

8. Relationship of A1c to CBG 4% 5% 6% 7% 8% 9% 10% 65 100 135 170 205 240 275

9. Case 1, continued Mrs. G agrees to start bedtime glargine 10 units, and feels confident she can titrate using the “Treat to Target” instructions with RN follow up. Over the next 3 weeks, she achieves fasting CBGs in the 100-120 range with 20 units glargine at bedtime, and no symptoms of hypoglycemia. Her follow up Hgb A1c 3 months after starting insulin is 6.5%

10. Case 2 Mr. M, a 65 year-old patient with Type 2 DM for 10 years is on metformin 1,000 mg BID and insulin: –NPH q a.m. 30 units + Regular 10 units –NPH q p.m. (supper) 25 units + Regular 15 units His fasting CBGs are in the 120’s but his Hgb A1c is now 8.0%. He wants better control. What do you recommend?

11. Switching to Basal/Prandial Insulin To switch to glargine –Add up his current total insulin dose (80 units) –Reduce by 20% (64 units) –Give half as glargine (32 units) –Titrate using fasting CBGs and ‘treat-to-target’ To add lispro/aspart –(Onset is 5-15 min, peak is 30-90 min, duration is 3.5 – 5 hours) –Send to Diabetes Education to learn carb counting –Give remaining “half” of total dose based on meals: 10 + 10 + 12 depending on carb load

12. Pearls Insulin therapy is associated with weight gain Glargine doesn’t last 24 hours in every patient (nor is NPH predictable) We usually wait too long to start insulin in Type 2 patients Early insulin therapy may be associated with better daytime prandial secretion from native pancreas Finger sticks are more painful than insulin shots