Individualizing Insulin Therapy

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Medical Education Library

Individualizing Insulin Therapy

May 2012 · Vol. 61, No. 05 Suppl: S13-S27

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References

1. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control [published correction appears in Endocr Pract. 2009;15(7):768-770]. Endocr Pract. 2009;15(6):540-559.

2. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) [published online ahead of print April 19, 2012]. Diabetes Care. doi:10.2337/dc12-0413.

3. Lalić NM, Micić D, Antić S, et al. Effect of biphasic insulin aspart on glucose and lipid control in patients with type 2 diabetes mellitus. Expert Opin Pharmacother. 2007;8(17):2895-2901.

4. Reynolds LR, Kingsley FJ, Karounos DG, Tannock LR. Differential effects of rosiglitazone and insulin glargine on inflammatory markers, glycemic control, and lipids in type 2 diabetes. Diabetes Res Clin Pract. 2007;77(2):180-187.

5. Rosak C, Jung R, Hofmann U. Insulin glargine maintains equivalent glycemic control and better lipometabolic control than NPH insulin in type 1 diabetes patients who missed a meal. Horm Metab Res. 2008;40(8):544-548.

6. Ampudia-Blasco FJ, Girbes J, Carmena R. A case of lipoatrophy with insulin glargine: long-acting insulin analogs are not exempt from this complication. Diabetes Care. 2005;28(12):2983.-

7. Griffin ME, Feder A, Tamborlane WV. Lipoatrophy associated with lispro insulin in insulin pump therapy: an old complication, a new cause? Diabetes Care. 2001;24(1):174.-

8. Fineberg SE, Huang J, Brunelle R, Gulliya KS, Anderson JH, Jr. Effect of long-term exposure to insulin lispro on the induction of antibody response in patients with type 1 or type 2 diabetes. Diabetes Care. 2003;26(1):89-96.

9. Moyes V, Driver R, Croom A, Mirakian R, Chowdhury TA. Insulin allergy in a patient with type 2 diabetes successfully treated with continuous subcutaneous insulin infusion. Diabet Med. 2006;23(2):204-206.

10. Ghosh S, McCann V, Bartle L, Collier A, Malik I. Allergy to insulin detemir. Diabet Med. 2007;24(11):1307.-

11. Blumer I. Severe, delayed insulin detemir injection site reaction. Diabet Med. 2008;25(8):1008.-

12. Pérez E, González R, Martínez J, Iglesias J, Matheu V. Detemir insulin-induced anaphylaxis. Ann Allergy Asthma Immunol. 2009;102(2):174-175.

13. Mollar-Puchades MA, Villanueva IL. Insulin glulisine in the treatment of allergy to rapid acting insulin and its rapid acting analogs. Diabetes Res Clin Pract. 2009;83(1):e21-e22.

14. Kawasaki F, Kamei S, Tatsumi F, et al. Gallbladder edema in type 1 diabetic patient due to delayed-type insulin allergy. Intern Med. 2009;48(17):1545-1549.

15. Wang C, Ding ZY, Shu SQ, et al. Severe insulin allergy after percutaneous transluminal coronary angioplasty. Clin Ther. 2009;31(3):569-574.

16. Ozaki N, Oiso Y. Immunologic tolerance to the insulin analogue glulisine. Diabetes Care. 2010;33(3):e39.-

17. Koroscil T, Kagzi Y, Zacharias D. Failure of multiple therapies in the treatment of a type 1 diabetic patient with insulin allergy: a case report. Endocr Pract. 2011;17(1):91-94.

18. Tuerk PW, Mueller M, Egede LE. Estimating physician effects on glycemic control in the treatment of diabetes: methods, effects sizes, and implications for treatment policy. Diabetes Care. 2008;31(5):869-873.

19. Hajos TR, Polonsky WH, Twisk JW, Dain MP, Snoek FJ. Do physicians understand type 2 diabetes patients’ perceptions of seriousness; the emotional impact and needs for care improvement? A cross-national survey. Patient Educ Couns. 2011;85(2):258-263.

20. Polonsky WH, Hajos TR, Dain MP, Snoek FJ. Are patients with type 2 diabetes reluctant to start insulin therapy? An examination of the scope and underpinnings of psychological insulin resistance in a large, international population. Curr Med Res Opin. 2011;27(6):1169-1174.

21. Nam S, Chesla C, Stotts NA, Kroon L, Janson SL. Factors associated with psychological insulin resistance in individuals with type 2 diabetes. Diabetes Care. 2010;33(8):1747-1749.

22. Nakar S, Yitzhaki G, Rosenberg R, Vinker S. Transition to insulin in type 2 diabetes: family physicians’ misconception of patients’ fears contributes to existing barriers. J Diabetes Complications. 2007;21(4):220-226.

23. Snoek FJ. Breaking the barriers to optimal glycaemic control—what physicians need to know from patients’ perspectives. Int J Clin Pract Suppl. 2002;(129):80-84.

24. Korytkowski M. When oral agents fail: practical barriers to starting insulin. Int J Obes Relat Metab Disord. 2002;26(Suppl 3):S18-S24.

25. Skovlund SE, Peyrot M. The Diabetes Attitudes, Wishes and Needs (DAWN) program: a new approach to improving outcomes of diabetes care. Diabetes Spectrum. 2005;18(3):136-142.

26. Jenkins N, Hallowell N, Farmer AJ, Holman RR, Lawton J. Initiating insulin as part of the Treating To Target in Type 2 Diabetes (4-T) trial: an interview study of patients’ and health professionals’ experiences. Diabetes Care. 2010;33(10):2178-2180.

27. Levinson W, Gorawara-Bhat R, Lamb J. A study of patient clues and physician responses in primary care and surgical settings. JAMA. 2000;284(8):1021-1027.

28. Rodriguez HP, Anastario MP, Frankel RM, et al. Can teaching agenda-setting skills to physicians improve clinical interaction quality? A controlled intervention. BMC Med Educ. 2008;8:3.-

29. Solomon J. How strategies for managing patient visit time affect physician job satisfaction: a qualitative analysis. J Gen Intern Med. 2008;23(6):775-780.

30. Funnell MM, Anderson RM. Empowerment and self-management of diabetes. Clin Diabetes. 2004;22(3):123-127.

31. Funnell MM, Anderson RM. Are patients or outcomes more important? Rev Endocrinol. 2008;2(8):49-51.

32. Shaefer CF. Clinical inertia: overcoming a major barrier to diabetes management. Insulin. 2006;1(2):61-64.

33. Harris S, Yale JF, Dempsey E, Gerstein H. Can family physicians help patients initiate basal insulin therapy successfully?: randomized trial of patient-titrated insulin glargine compared with standard oral therapy: lessons for family practice from the Canadian INSIGHT trial. Can Fam Physician. 2008;54(4):550-558.

34. Centers for Disease Control and Prevention. National diabetes fact sheet national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed February 10, 2011.

35. Riddle MC, Rosenstock J, Gerich J. Insulin Glargine 4002 Study Investigators. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003;26(11):3080-3086.

36. Hermansen K, Davies M, Derezinski T, Martinez Ravn G, Clauson P, Home P. A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes [published correction appears in Diabetes Care. 2007;30(4):1035]. Diabetes Care. 2006;29(6):1269-1274.

37. Davies M, Storms F, Shutler S, Bianchi-Biscay M, Gomis R. ATLANTUS Study Group. Improvement of glycemic control in subjects with poorly controlled type 2 diabetes: comparison of two treatment algorithms using insulin glargine. Diabetes Care. 2005;28(6):1282-1288.

38. Meneghini L, Koenen C, Weng W, Selam JL. The usage of a simplified self-titration dosing guideline (303 Algorithm) for insulin detemir in patients with type 2 diabetes—results of the randomized, controlled PREDICTIVE 303 study. Diabetes Obes Metab. 2007;9(6):902-913.

39. Garber AJ, Wahlen J, Wahl T, et al. Attainment of glycaemic goals in type 2 diabetes with once-, twice-, or thrice-daily dosing with biphasic insulin aspart 70/30 (The 1-2-3 study). Diabetes Obes Metab. 2006;8(1):58-66.

40. Philis-Tsimikas A, Charpentier G, Clauson P, Ravn GM, Roberts VL, Thorsteinsson B. Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly controlled type 2 diabetes [published correction appears in Clin Ther. 2006;28(11):1967]. Clin Ther. 2006;28(10):1569-1581.

41. Blonde L, Merilainen M, Karwe V, Raskin P. TITRATE Study Group. Patient-directed titration for achieving glycaemic goals using a once-daily basal insulin analogue: an assessment of two different fasting plasma glucose targets—the TITRATE study. Diabetes Obes Metab. 2009;11(6):623-631.

42. Meneghini L, Mersebach H, Kumar S, Svendsen AL, Hermansen K. Comparison of 2 intensification regimens with rapid-acting insulin aspart in type 2 diabetes mellitus inadequately controlled by once-daily insulin detemir and oral antidiabetes drugs: the step-wise randomized study. Endocr Pract. 2011;17(5):727-736.

43. Lankisch MR, Ferlinz KC, Leahy JL, Scherbaum WA. Orals Plus Apidra and LANTUS (OPAL) study group. Introducing a simplified approach to insulin therapy in type 2 diabetes: a comparison of two single-dose regimens of insulin glulisine plus insulin glargine and oral antidiabetic drugs [published correction appears in Diabetes Obes Metab. 2010;12(5):461]. Diabetes Obes Metab 2008;10(12):1178-1185.

44. Meneghini L. Why and how to use insulin therapy earlier in the management of type 2 diabetes. South Med J. 2007;100(2):164-174.

45. Liebl A, Prager R, Binz K, Kaiser M, Bergenstal R, Gallwitz B. PREFER Study Group. Comparison of insulin analogue regimens in people with type 2 diabetes mellitus in the PREFER Study: a randomized controlled trial. Diabetes Obes Metab. 2009;11(1):45-52.

46. Braun A, Sämann A, Kubiak T, et al. Effects of metabolic control, patient education and initiation of insulin therapy on the quality of life of patients with type 2 diabetes mellitus. Patient Educ Couns. 2008;73(1):50-59.

An alternative approach to initiating basal-bolus therapy is the PREFER algorithm.⁴⁵ Here, the basal insulin dose is 10 U initially. The bolus doses are administered in a 3:1:2 ratio, so if the total of the 3 bolus doses is 12 U/d, the initial bolus doses would be 6 (breakfast), 2 (lunch), and 4 (dinner) U. The mean basal (once-daily) and bolus insulin doses observed in PREFER are shown in TABLE 12 and TABLE 13.

TABLE 12

Case study 3: Calculating initial basal-bolus insulin doses

Algorithm	Calculations	Patient MB
Meneghini⁴⁴	TDD = (total body weight [kg]) (0.5 U/kg/d) Basal insulin dose* = (50%) (TDD) Bolus insulin dose^† = (10%-20%) (TDD)	TDD = (0.5 U/kg/d)(80kg) = 40 U/d
		Basal = (50%) (40 U/d) = 20 U/d
		Bolus = (10%-20%) (40 U/d) = 4 to 8 U/meal
		CF = 1800/40 U/d = 45 mg/dL per 1 unit
PREFER⁴⁵	Basal insulin dose* = 10 U (14 U if BMI > 32 kg/m²) Bolus insulin dose^† = ratio of 3:1:2 (breakfast:lunch:dinner) Note: At week 26, the bolus insulin doses were divided into the 3 daily meals in approximately a 1:1:1 ratio
BMI, body mass index; CF, correction factor; TDD, total daily dose of insulin. *Once daily; ^†Three meals per day.

TABLE 13

Titrating the basal insulin dose using the PREFER algorithm⁴⁵

Pre-breakfast blood glucose (mg/dL)	Basal insulin dose adjustment (U)
< 56	-4
56-72	-2
73-125	No change
126-140	+2
141-160	+4
161-180	+6
181-200	+8
> 200	+10

Follow-up Visit

MB begins with basal insulin 20 U in the evening and bolus insulin at doses of 7 U before each meal. Over the next several months, MB has titrated his insulin doses; his current doses are: 32 U (basal), 11 U (bolus-breakfast), 7 U (bolus-lunch), and 10 U (bolus-dinner). He experienced 1 episode of mild hypoglycemia (SMBG, 50 mg/dL) one afternoon following a particularly active morning (TABLE 14). His current A1C is 7.4%. MB’s physician congratulates him on the progress he has made in dramatically lowering his blood glucose level—and his risk for diabetes-related complications. While MB appreciates his physician’s support and admits that he does not feel tired and generally feels better, which is likely due to resolution of glucotoxicity, he is not happy that he has gained 5.5 pounds (2.5 kg).⁴⁶ He also finds the timing and administration of bolus insulin difficult.

TABLE 14

Case study 3: Self-monitored blood glucose (mg/dL) over the previous 2 weeks

Day	Fasting	2 h Post-breakfast	2 h Post-lunch	2 h Post-dinner
Wednesday
Thursday				168
Friday	106	166	174
Saturday	88
Sunday				195
Monday	134
Tuesday				172
Wednesday	130	156
Thursday	112		168
Friday	92			164
Saturday	50	149	159	176
Sunday	94		174	210
Monday		176		184
Tuesday	117			169

Plan

Continue basal insulin once-daily in the evening.
Add metformin 500 mg BID and increase to 1000 mg BID as tolerated.
Consider weaning down the bolus insulin doses and substituting them with a GLP-1R agonist, dipeptidyl peptidase-4 inhibitor, or short-acting secretagogue. If so, continue rapid-acting insulin during transition. [Note: the following combinations are not currently approved by the US FDA: exenatide twice-daily and prandial insulin; exenatide once-weekly and insulin; liraglutide and prandial insulin; linagliptin and insulin.]

CASE STUDY 4

KW is a 62-year-old female diagnosed with T2DM 12 years ago. Treatment with lifestyle management and metformin initially provided glycemic control. Glimepiride was subsequently added and eventually the patient was started on basal insulin. The current dose of basal insulin is 60 U in the evening. Five months ago her A1C was found to be 7.9% and more recently 8.3%. She drinks alcohol occasionally and smokes. KW works as an executive secretary and has a consistent meal and activity schedule.

Clinical Impression

Following completion of the history, physical examination, and review of her laboratory data, KW’s physician concludes that her insulin regimen should be intensified (TABLE 15, TABLE 16).

TABLE 15

Case study 4: Chart notes

Physical examination	Laboratory tests	Lifestyle habits	Current therapy
Physical examination	Laboratory tests	Lifestyle habits	Glucose-lowering	Other
BP: 126/78 mm Hg Weight: 176 lb (79.2 kg) BMI: 32 kg/m² Eyes: no retinopathy Neurology: intact Skin: intact	SCr: 1.0 mg/dL Albuminuria: negative A1C: 8.3% Cholesterol Total: 172 mg/dL LDL: 96 mg/dL HDL: 46 mg/dL Triglycerides: 138 mg/dL	Exercise: sedentary Nutrition: 3 meals/d with large dinner	Metformin 1000 mg BID Basal insulin 60 U in the evening	ASA 80 mg QD Pravastatin 40 mg qHS
BMI, body mass index; BP, blood pressure; HDL, high-density lipoprotein; LDL, low-density lipoprotein; SCr, serum creatinine.

TABLE 16

Case study 4: Self-monitored blood glucose (mg/dL) over the previous 2 weeks

Day	Fasting	2 h Post-breakfast	2 h Post-lunch	2 h Post-dinner
Friday
Saturday	156			244
Sunday		253
Monday
Tuesday
Wednesday	148			227
Thursday
Friday
Saturday			179
Sunday	160
Monday
Tuesday
Wednesday
Thursday

Plan

Discontinue basal insulin.
Begin premix insulin twice daily before breakfast and dinner.
Ask KW to monitor blood glucose two times daily and, if appropriate, teach her how to self-adjust insulin doses.
Stress the importance of exercise and proper nutrition; gain agreement on short-term goals for exercise and nutrition.
Discuss the importance of smoking cessation; develop a plan.

Barriers

The physician discusses with KW that her consistent meal and activity schedule would make switching to premix insulin twice daily a good choice. KW is generally in agreement with the change, but wonders whether hypoglycemia might be more likely. She also asks if she might gain more weight in addition to the 3 pounds (1.35 kg) she has gained since starting basal insulin.