Clinical utility of insulin and insulin analogs

Islets

Volumn 5, Issue 2, 2013, Pages 67-78

  Sanlioglu, Ahter D ^a   Altunbas, Hasan Ali ^a   Balci, Mustafa Kemal ^a   Griffith, Thomas S ^b   Sanlioglu, Salih ^a  

^a AKDENIZ UNIVERSITY   (Turkey)

^b UNIVERSITY OF MINNESOTA   (United States)

Author keywords

Diabetes; Genetic engineering; Insulin; Insulin analogues

Indexed keywords

BOVINE INSULIN; HUMAN INSULIN; INSULIN; INSULIN ASPART; INSULIN DEGLUDEC; INSULIN DERIVATIVE; INSULIN DETEMIR; INSULIN GLARGINE; INSULIN GLULISINE; INSULIN LISPRO; INSULIN ZINC SUSPENSION; ISOPHANE INSULIN; LONG ACTING INSULIN; PIG INSULIN; PROINSULIN; RECOMBINANT HUMAN INSULIN; SHORT ACTING INSULIN;

DIABETES MELLITUS; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; INSULIN RELEASE; INSULIN TREATMENT; NONHUMAN; REVIEW;

DIABETES; GENETIC ENGINEERING; INSULIN; INSULIN ANALOGUES;

ANIMALS; DIABETES MELLITUS, TYPE 1; DIABETES MELLITUS, TYPE 2; DIABETIC ANGIOPATHIES; DRUG MONITORING; EVIDENCE-BASED MEDICINE; HUMANS; HYPERGLYCEMIA; HYPOGLYCEMIC AGENTS; INSULIN; INSULIN, REGULAR, HUMAN; RECOMBINANT PROTEINS;

EID: 84879348878     PISSN: 19382014     EISSN: 19382022     Source Type: Journal    
DOI: 10.4161/isl.24590     Document Type: Review

References (90)

1. Guariguata L. By the numbers: new estimates from the IDF Diabetes Atlas Update for 2012. Diabetes Res Clin Pract 2012; 98:524-5; PMID:23217268; http://dx.doi.org/10.1016/j.diabres.2012.11.006
2. Ginter E, Simko V. Global prevalence and future of diabetes mellitus. Adv Exp Med Biol 2012; 771:35-41; PMID:23393669
3. DF Diabetes Atlas Group. Update of mortality attributable to diabetes for the IDF Diabetes Atlas: Estimates for the year 2011. Diabetes Res Clin Pract 2013; 100:277-9; PMID: 23506763; http://dx.doi.org/10.1016/j.diabres.2013.02.005
4. Marchetti P, Dotta F, Lauro D, Purrello F. An overview of pancreatic beta-cell defects in human type 2 diabetes: implications for treatment. Regul Pept 2008; 146:4-11; PMID:17889380; http://dx.doi.org/10.1016/j.regpep.2007.08. 017
5. Sanlioglu AD, Dirice E, Elpek O, Korcum A F, Balci MK, Omer A, et al. High levels of endogenous tumor necrosis factor-related apoptosis-inducing ligand expression correlate with increased cell death in human pancreas. Pancreas 2008; 36:385-93; PMID:18437085; http://dx.doi.org/10.1097/MPA. 0b013e318158a4e5 (Pubitemid 351591581)
6. Fsadni P, Fsadni C, Fava S, Montefort S. Correlation of worldwide incidence of type 1 diabetes (DiaMond) with prevalence of asthma and atopic eczema (ISAAC). Clin Respir J 2012; 6:18-25; PMID:21501393; http://dx.doi.org/ 10.1111/j.1752-699X.2011.00239.x
7. Glaser B. Type 2 diabetes: hypoinsulinism, hyperinsulinism, or both? PLoS Med 2007; 4:e148; PMID:17407388; http://dx.doi.org/10.1371/journal.pmed.0040148 (Pubitemid 46658761)
8. Sanlioglu AD, Griffith TS, Omer A, Dirice E, Sari R, Altunbas HA, et al. Molecular mechanisms of death ligand-mediated immune modulation: a gene therapy model to prolong islet survival in type 1 diabetes. J Cell Biochem 2008; 104:710-20; PMID:18247339; http://dx.doi.org/10.1002/jcb.21677 (Pubitemid 351830823)
9. Gruessner RW, Sutherland DE, Najarian JS, Dunn DL, Gruessner AC. Solitary pancreas transplantation for nonuremic patients with labile insulin-dependent diabetes mellitus. Transplantation 1997; 64:1572-7; PMID:9415558; http://dx.doi.org/10.1097/00007890-199712150-00011 (Pubitemid 28047385)
10. Kahraman S, Dirice E, Hapil FZ, Ertosun MG, Ozturk S, Griffith TS, et al. Tracing of islet graft survival by way of in vivo fluorescence imaging. Diabetes Metab Res Rev 2011; 27:575-83; PMID:21584921; http://dx.doi.org/10. 1002/dmrr.1216
11. Shapiro AM, Lakey JR, Paty BW, Senior PA, Bigam DL, Ryan EA. Strategic opportunities in clinical islet transplantation. Transplantation 2005; 79:1304-7; PMID:15912095; http://dx.doi.org/10.1097/01.TP.0000157300.53976.2A (Pubitemid 40734790)
12. Sanlioglu AD, Karacay B, Balci MK, Griffith TS, Sanlioglu S. Therapeutic potential of VIP vs. PACAP in diabetes. J Mol Endocrinol 2012; 49:R157-67; PMID:22991228; http://dx.doi.org/10.1530/JME-12-0156
13. Sanlioglu AD, Altunbas HA, Balci MK, Griffith TS, Sanlioglu S. Insulin gene therapy from design to beta cell generation. Expert Rev Mol Med 2012; 14:e18; PMID:23062285; http://dx.doi.org/10.1017/erm.2012.12
14. Owerbach D, Bell GI, Rutter WJ, Brown JA, Shows TB. The insulin gene is located on the short arm of chromosome 11 in humans. Diabetes 1981; 30:267-70; PMID:7009275; http://dx.doi.org/10.2337/diabe-tes.30.3.267 (Pubitemid 11026326)
15. Walker MD, Edlund T, Boulet AM, Rutter WJ. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes. Nature 1983; 306:557-61; PMID:6358900; http://dx.doi.org/10.1038/306557a0 (Pubitemid 14203819)
16. Weiss MA. Proinsulin and the genetics of diabetes mellitus. J Biol Chem 2009; 284:19159-63; PMID:19395706; http://dx.doi.org/10.1074/jbc.R109.009936
17. Steiner D F, Rouillé Y, Gong Q, Martin S, Carroll R, Chan SJ. The role of prohormone convertases in insulin biosynthesis: evidence for inherited defects in their action in man and experimental animals. Diabetes Metab 1996; 22:94-104; PMID:8792089
18. Liu M, Ramos-Castañeda J, Arvan P. Role of the connecting peptide in insulin biosynthesis. J Biol Chem 2003; 278:14798-805; PMID:12590147; http://dx.doi.org/10.1074/jbc.M212070200 (Pubitemid 36799805)
19. O'Rahilly S, Gray H, Humphreys PJ, Krook A, Polonsky KS, White A, et al. Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. N Engl J Med 1995; 333:1386-90; PMID:7477119; http://dx.doi.org/10.1056/NEJM199511233332104
20. Doyle ME, Egan JM. Pharmacological agents that directly modulate insulin secretion. Pharmacol Rev 2003; 55:105-31; PMID:12615955; http://dx.doi.org/10. 1124/pr.55.1.7 (Pubitemid 36268400)
21. Rhodes CJ, Halban PA. Newly synthesized proinsulin/insulin and stored insulin are released from pancreatic B cells predominantly via a regulated, rather than a constitutive, pathway. J Cell Biol 1987; 105:145-53; PMID:3301864; http://dx.doi.org/10.1083/jcb.105.1.145 (Pubitemid 17101250)
22. Campbell RK, Campbell LK, White JR. Insulin lispro: its role in the treatment of diabetes mellitus. Ann Pharmacother 1996; 30:1263-71; PMID:8913409. (Pubitemid 26367449)
23. Galloway JA. New directions in drug development: mixtures, analogues, and modeling. Diabetes Care 1993; 16(Suppl 3):16-23; PMID:8299473 (Pubitemid 23348317)
24. Nesher R, Cerasi E. Modeling phasic insulin release: immediate and time-dependent effects of glucose. Diabetes 2002; 51(Suppl 1):S53-9; PMID:11815459; http://dx.doi.org/10.2337/diabetes.51.2007.S53 (Pubitemid 34761495)
25. Grammer L. Insulin allergy. Clin Rev Allergy 1986; 4:189-200; PMID:2421863
26. Fineberg SE, Kawabata T T, Finco-Kent D, Fountaine RJ, Finch GL, Krasner AS. Immunological responses to exogenous insulin. Endocr Rev 2007; 28:625-52; PMID:17785428; http://dx.doi.org/10.1210/er.2007-0002 (Pubitemid 47606649)
27. Ginsberg BH. The role of technology in diabetes therapy. Diabetes Care 1994; 17(Suppl 1):50-5; PMID:8088225 (Pubitemid 24162004)
28. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329:977-86; PMID:8366922; http://dx.doi.org/10.1056/NEJM199309303291401 (Pubitemid 23307905)
29. Hirsch IB. Insulin analogues. N Engl J Med 2005; 352:174-83; PMID:15647580; http://dx.doi.org/10.1056/NEJMra040832 (Pubitemid 40096614)
30. Zinman B, Tildesley H, Chiasson JL, Tsui E, Strack T. Insulin lispro in CSII: results of a double-blind crossover study. Diabetes 1997; 46:440-3; PMID:9032100; http://dx.doi.org/10.2337/diabetes.46.3.440 (Pubitemid 27090273)
31. Howey DC, Bowsher RR, Brunelle RL, Woodworth JR. [Lys(B28), Pro(B29)]-human insulin. A rapidly absorbed analogue of human insulin. Diabetes 1994; 43:396-402; PMID:8314011; http://dx.doi.org/10.2337/diabetes.43.3.396 (Pubitemid 24064246)
32. Burge MR, Castillo KR, Schade DS. Meal composition is a determinant of lispro-induced hypoglycemia in IDDM. Diabetes Care 1997; 20:152-5; PMID:9118763; http://dx.doi.org/10.2337/diacare.20.2.152 (Pubitemid 27051552)
33. Rys P, Pankiewicz O, Łach K, Kwaskowski A, Skrzekowska-Baran I, Malecki MT. Efficacy and safety comparison of rapid-acting insulin aspart and regular human insulin in the treatment of type 1 and type 2 diabetes mellitus: a systematic review. Diabetes Metab 2011; 37:190-200; PMID:21333580; http://dx.doi.org/10.1016/j.diabet.2010.12.003
34. Lih A, Hibbert E, Wong T, Girgis CM, Garg N, Carter JN. The role of insulin glulisine to improve glycemic control in children with diabetes mellitus. Diabetes Metab Syndr Obes 2010; 3:403-12; PMID:21437110
35. Garnock-Jones K P, Plosker GL. Insulin glulisine: a review of its use in the management of diabetes mellitus. Drugs 2009; 69:1035-57; PMID:19496630; http://dx.doi.org/10.2165/00003495-200969080-00006
36. Richards J P, Stickelmeyer M P, Flora DB, Chance RE, Frank BH, DeFelippis MR. Self-association properties of monomeric insulin analogs under formulation conditions. Pharm Res 1998; 15:1434-41; PMID:9755897; http://dx.doi.org/10.1023/ A:1011961923870 (Pubitemid 28427933)
37. Zoete V, Meuwly M, Karplus M. Study of the insulin dimerization: binding free energy calculations and per-residue free energy decomposition. Proteins 2005; 61:79-93; PMID:16080143; http://dx.doi.org/10.1002/prot.20528 (Pubitemid 41262919)
38. Rosenstock J, Fonseca V, McGill JB, Riddle M, Hallé J P, Hramiak I, et al. Similar progression of diabetic retinopathy with insulin glargine and neutral prot-amine Hagedorn (NPH) insulin in patients with type 2 diabetes: a long-term, randomised, open-label study. Diabetologia 2009; 52:1778-88; PMID:19526210; http://dx.doi.org/10.1007/s00125-009-1415-7
39. Gerstein H, Yusuf S, Riddle MC, Ryden L, Bosch J. Origin Trial Investigators. Rationale, design, and baseline characteristics for a large international trial of cardiovascular disease prevention in people with dysglycemia: the ORIGIN Trial (Outcome Reduction with an Initial Glargine Intervention). Am Heart J 2008; 155:26-32, e1-6; PMID:18082485
40. Gerstein HC, Bosch J, Dagenais GR, Díaz R, Jung H, Maggioni A P, et al.; ORIGIN Trial Investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012; 367:319-28; PMID:22686416; http://dx.doi.org/10.1056/NEJMoa1203858
41. Bolli GB, Consoli A, Giaccari A. Early insulin treatment in type 2 diabetes: ORIGINal sin or valuable choice as ORIGINal treatment? An open debate on the ORIGIN study results. Nutr Metab Cardiovasc Dis 2012; 22:1007-12; PMID:23199612; http://dx.doi.org/10.1016/j.numecd.2012.10.004
42. 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. Diabetes Care 2006; 29:1269-74; PMID:16732007; http://dx.doi.org/10.2337/dc05-1365 (Pubitemid 44125921)
43. McFarlane SI. Insulin therapy and type 2 diabetes: management of weight gain. J Clin Hypertens (Greenwich) 2009; 11:601-7; PMID:19817944; http://dx.doi.org/10.1111/j.1751-7176.2009.00063.x
44. Zinman B, Fulcher G, Rao PV, Thomas N, Endahl LA, Johansen T, et al. Insulin degludec, an ultra-long-acting basal insulin, once a day or three times a week versus insulin glargine once a day in patients with type 2 diabetes: a 16-week, randomised, open-label, phase 2 trial. Lancet 2011; 377:924-31; PMID:21396703; http://dx.doi.org/10.1016/S0140-6736(10)62305-7
45. Birkeland KI, Home PD, Wendisch U, Ratner RE, Johansen T, Endahl LA, et al. Insulin degludec in type 1 diabetes: a randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine. Diabetes Care 2011; 34:661-5; PMID:21270174; http://dx.doi.org/10.2337/dc10-1925
46. Wang F, Surh J, Kaur M. Insulin degludec as an ultralong-acting basal insulin once a day: a systematic review. Diabetes Metab Syndr Obes 2012; 5:191-204; PMID:22826637; http://dx.doi.org/10.2147/DMSO.S21979
47. Robinson JD, Neumiller JJ, Campbell RK. Can a new ultra-long-acting insulin analogue improve patient care? Investigating the potential role of insulin degludec. Drugs 2012; 72:2319-25; PMID:23145524; http://dx.doi.org/10. 2165/11642240-000000000-00000
48. Nasrallah SN, Reynolds LR. Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin? Clin Med Insights Endocrinol Diabetes 2012; 5:31-7; PMID:22879797; http://dx.doi.org/10.4137/CMED.S9494
49. Heise T, Tack CJ, Cuddihy R, Davidson J, Gouet D, Liebl A, et al. A new-generation ultra-long-acting basal insulin with a bolus boost compared with insulin glargine in insulin-naive people with type 2 diabetes: a randomized, controlled trial. Diabetes Care 2011; 34:669-74; PMID:21285389; http://dx.doi.org/10.2337/dc10-1905
50. Meneghini L, Atkin SL, Gough SC, Raz I, Blonde L, Shestakova M, et al.; NN1250-3668 (BEGIN FLEX) Trial Investigators. The Efficacy and Safety of Insulin Degludec Given in Variable Once-Daily Dosing Intervals Compared With Insulin Glargine and Insulin Degludec Dosed at the Same Time Daily: A 26-week, randomized, open-label, parallel-group, treat-to-target trial in individuals with type 2 diabetes. Diabetes Care 2013; 36:858-64; PMID:23340894; http://dx.doi.org/10.2337/dc12-1668
51. Heller S, Buse J, Fisher M, Garg S, Marre M, Merker L, et al.; BEGIN Basal-Bolus Type 1 Trial Investigators. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet 2012; 379:1489-97; PMID:22521071; http://dx.doi.org/10.1016/S0140-6736(12)60204-9
52. Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, et al. Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2006; 29:1963-72; PMID:16873813; http://dx.doi.org/10.2337/dc06- 9912 (Pubitemid 44156663)
53. American Diabetes Association. Standards of medical care in diabetes - 2008. Diabetes Care 2008; 31(Suppl 1):S12-54; PMID:18165335; http://dx.doi.org/10.2337/dc08-S012 (Pubitemid 351520688)
54. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al.; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). 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). Diabetes Care 2012; 35:1364-79; PMID:22517736; http://dx.doi.org/10.2337/dc12- 0413
55. Davila E P, Florez H, Trepka MJ, Fleming LE, Niyonsenga T, Lee DJ, et al. Strict glycemic control and mortality risk among US adults with type 2 diabetes. J Diabetes Complications 2011; 25:289-91; PMID:21658973; http://dx.doi.org/10.1016/j.jdiacomp.2011.03.004
56. Meece J. Dispelling myths and removing barriers about insulin in type 2 diabetes. Diabetes Educ 2006; 32(Suppl):9S-18S; PMID:16439485; http://dx.doi.org/10.1177/0145721705285638 (Pubitemid 43206838)
57. Peyrot M, Rubin RR, Khunti K. Addressing barriers to initiation of insulin in patients with type 2 diabetes. Prim Care Diabetes 2010; 4(Suppl 1):S11-8; PMID:20394886; http://dx.doi.org/10.1016/S1751-9918(10)60004-6
58. Grunberger G. The need for better insulin therapy. Diabetes Obes Metab 2013; 15(Suppl 1):1-5; PMID:23448196; http://dx.doi.org/10.1111/dom.12061
59. Hartman I. Insulin analogs: impact on treatment success, satisfaction, quality of life, and adherence. Clin Med Res 2008; 6:54-67; PMID:18801953; http://dx.doi.org/10.3121/cmr.2008.793
60. Sallé A, Ryan M, Guilloteau G, Bouhanick B, Berrut G, Ritz P. 'Glucose control-related' and 'non-glucose control-related' effects of insulin on weight gain in newly insulin-treated type 2 diabetic patients. Br J Nutr 2005; 94:931-7; PMID:16351770; http://dx.doi.org/10.1079/BJN20051592 (Pubitemid 43092425)
61. Khunti K, Caputo S, Damci T, Dzida GJ, Ji Q, Kaiser M, et al.; on behalf of the SOLVE Study Group. The safety and efficacy of adding once-daily insulin detemir to oral hypoglycaemic agents in patients with type 2 diabetes in a clinical practice setting in 10 countries. Diabetes Obes Metab 2012; e-pub ahead of print; PMID:22830956; http://dx.doi.org/10.1111/j.1463-1326.2012.01665.x
62. Nichols GA, Gomez-Caminero A. Weight changes following the initiation of new anti-hyperglycaemic therapies. Diabetes Obes Metab 2007; 9:96-102; PMID:17199724; http://dx.doi.org/10.1111/j.1463-1326.2006.00580.x (Pubitemid 44921047)
63. Heise T, Pieber TR. Towards peakless, reproducible and long-acting insulins. An assessment of the basal analogues based on isoglycaemic clamp studies. Diabetes Obes Metab 2007; 9:648-59; PMID:17645556; http://dx.doi.org/ 10.1111/j.1463-1326.2007.00756.x (Pubitemid 47261846)
64. Ashwell SG, Gebbie J, Home PD. Twice-daily compared with once-daily insulin glargine in people with Type 1 diabetes using meal-time insulin aspart. Diabet Med 2006; 23:879-86; PMID:16911626; http://dx.doi.org/10.1111/j.1464- 5491.2006.01913.x (Pubitemid 44141077)
65. Mohn A, Marcovecchio M, Chiarelli F. Insulin analogues. N Engl J Med 2005; 352:1822-4, author reply 1822-4; PMID:15858198; http://dx.doi.org/10.1056/ NEJM200504283521721 (Pubitemid 40570937)
66. Plank J, Siebenhofer A, Berghold A, Jeitler K, Horvath K, Mrak P, et al. Systematic review and meta-analysis of short-acting insulin analogues in patients with diabetes mellitus. Arch Intern Med 2005; 165:1337-44; PMID:15983281; http://dx.doi.org/10.1001/archinte.165.12.1337 (Pubitemid 40973416)
67. Hemkens LG, Grouven U, Bender R, Günster C, Gutschmidt S, Selke G W, et al. Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia 2009; 52:1732-44; PMID:19565214; http://dx.doi.org/10.1007/s00125-009-1418-4
68. Varewijck AJ, Janssen JA. Insulin and its analogues and their affinities for the IGF1 receptor. Endocr Relat Cancer 2012; 19:F63-75; PMID:22420005; http://dx.doi.org/10.1530/ERC-12-0026
69. Lucidi P, Porcellati F, Rossetti P, Candeloro P, Andreoli AM, Cioli P, et al. Metabolism of insulin glargine after repeated daily subcutaneous injections in subjects with type 2 diabetes. Diabetes Care 2012; 35:2647-9; PMID:23086139; http://dx.doi.org/10.2337/dc12-0271
70. Pierre-Eugene C, Pagesy P, Nguyen TT, Neuillé M, Tschank G, Tennagels N, et al. Effect of insulin analogues on insulin/IGF1 hybrid receptors: increased activation by glargine but not by its metabolites M1 and M2. PLoS One 2012; 7:e41992; PMID:22848683; http://dx.doi.org/10.1371/journal. pone.0041992
71. Silverstein J, Klingensmith G, Copeland K, Plotnick L, Kaufman F, Laffel L, et al.; American Diabetes Association. Care of children and adolescents with type 1 diabetes: a statement of the American Diabetes Association. Diabetes Care 2005; 28:186-212; PMID:15616254; http://dx.doi.org/10.2337/diacare.28.1.186 (Pubitemid 40095803)
72. Peters A, Laffel L; American Diabetes Association Transitions Working Group. Diabetes care for emerging adults: recommendations for transition from pediatric to adult diabetes care systems: a position statement of the American Diabetes Association, with representation by the American College of Osteopathic Family Physicians, the American Academy of Pediatrics, the American Association of Clinical Endocrinologists, the American Osteopathic Association, the Centers for Disease Control and Prevention, Children with Diabetes, The Endocrine Society, the International Society for Pediatric and Adolescent Diabetes, Juvenile Diabetes Research Foundation International, the National Diabetes Education Program, and the Pediatric Endocrine Society (formerly Lawson Wilkins Pediatric Endocrine Society). Diabetes Care 2011; 34:2477-85; PMID:22025785; http://dx.doi.org/10.2337/dc11-1723
73. Crasto W, Jarvis J, Khunti K, Davies MJ. New insulins and new insulin regimens: a review of their role in improving glycaemic control in patients with diabetes. Postgrad Med J 2009; 85:257-67; PMID:19520878; http://dx.doi.org/10. 1136/pgmj.2008.067926
74. Sung HW, Sonaje K, Liao ZX, Hsu LW, Chuang EY. pH-responsive nanoparticles shelled with chitosan for oral delivery of insulin: from mechanism to therapeutic applications. Acc Chem Res 2012; 45:619-29; PMID:22236133; http://dx.doi.org/10.1021/ar200234q
75. Heinemann L, Jacques Y. Oral insulin and buccal insulin: a critical reappraisal. J Diabetes Sci Technol 2009; 3:568-84; PMID:20144297
76. Silverman BL, Barnes CJ, Campaigne BN, Muchmore DB. Inhaled insulin for controlling blood glucose in patients with diabetes. Vasc Health Risk Manag 2007; 3:947-58; PMID:18200813
77. Siekmeier R, Scheuch G. Inhaled insulin - does it become reality? J Physiol Pharmacol 2008; 59(Suppl 6):81-113; PMID:19218634
78. Owens DR. Insulin preparations with prolonged effect. Diabetes Technol Ther 2011; 13(Suppl 1):S5-14; PMID:21668337; http://dx.doi.org/10.1089/dia.2011. 0068
79. Carchidi C, Holland C, Minnock P, Boyle D. New technologies in pediatric diabetes care. MCN Am J Matern Child Nurs 2011; 36:32-9, quiz 40-1; PMID:21204305; http://dx.doi.org/10.1097/NMC.0b013e3181fb8c3a
80. Anhalt H, Bohannon NJ. Insulin patch pumps: their development and future in closed-loop systems. Diabetes Technol Ther 2010; 12(Suppl 1):S51-8; PMID:20515308; http://dx.doi.org/10.1089/dia.2010.0016
81. Bergenstal RM, Bashan E, McShane M, Johnson M, Hodish I. Can a tool that automates insulin titration be a key to diabetes management? Diabetes Technol Ther 2012; 14:675-82; PMID:22568777; http://dx.doi.org/10.1089/dia.2011.0303
82. Jacobs PG, El Youssef J, Castle JR, Engle JM, Branigan DL, Johnson P, et al. Development of a fully automated closed loop artificial pancreas control system with dual pump delivery of insulin and glucagon. Conf Proc IEEE Eng Med Biol Soc 2011; 2011:397-400; PMID:22254332
83. Wahren J, Kallas A, Sima AA. The clinical potential of C-peptide replacement in type 1 diabetes. Diabetes 2012; 61:761-72; PMID:22442295; http://dx.doi.org/10.2337/db11-1423
84. Kamiya H, Zhang W, Sima AA. The beneficial effects of C-Peptide on diabetic polyneuropathy. Rev Diabet Stud 2009; 6:187-202; PMID:20039008; http://dx.doi.org/10.1900/RDS.2009.6.187
85. Meyer JA, Froelich JM, Reid GE, Karunarathne WK, Spence DM. Metal-activated C-peptide facilitates glucose clearance and the release of a nitric oxide stimulus via the GLUT1 transporter. Diabetologia 2008; 51:175-82; PMID:17965850; http://dx.doi.org/10.1007/s00125-007-0853-3 (Pubitemid 350197990)
86. Khan A, Raza S, Khan Y, Aksoy T, Khan M, Weinberger Y, et al. Current updates in the medical management of obesity. Recent Pat Endocr Metab Immune Drug Discov 2012; 6:117-28; PMID:22435392; http://dx.doi.org/10.2174/ 187221412800604644
87. Oral EA. Leptin for type 1 diabetes: coming onto stage to be (or not?). Pediatr Diabetes 2012; 13:68-73; PMID:21917108; http://dx.doi.org/10.1111/j. 1399-5448.2011.00797.x
88. Freeman JS. Insulin analog therapy: improving the match with physiologic insulin secretion. J Am Osteopath Assoc 2009; 109:26-36; PMID:19193822
89. Garber AJ, King AB, Del Prato S, Sreenan S, Balci MK, Muñoz-Torres M, et al.; NN1250-3582 (BEGIN BB T2D) Trial Investigators. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet 2012; 379:1498-507; PMID:22521072; http://dx.doi.org/10.1016/S0140-6736(12) 60205-0
90. Tahrani AA, Bailey CJ, Barnett AH. Insulin degludec: a new ultra-longacting insulin. Lancet 2012; 379:1465-7; PMID:22521058; http://dx.doi.org/10.1016/S0140-6736(12)60527-3 Division