1. UKPDS 16. UK Prospective diabetes study 16.
Overview of 6 years’ therapy of type II diabetes:
a progressive disease. UK Prospective Diabetes
Study Group. Diabetes 1995;44:1249–58.
2. National Institute for Clinical Excellence. NICE
Clinical Guideline No. 15. Type 1 diabetes:
diagnosis and management of type 1 diabetes in
children, young people and adults. 2004. URL:
http://www.nice.org.uk/page.aspx?o=213575.
Accessed July 2007.
3. Gerich JE. Novel insulins: expanding options in
diabetes management. Am J Med 2002;113:308–16.
4. Cefalu WT. Concept, strategies, and feasibility of
noninvasive insulin delivery. Diabetes Care 2004;
27:239–46.
5. Diabetes UK. Fact Sheet No. 2. Diabetes: the
figures. 2005. URL: http://www.diabetes.org.uk/
infocentre/fact/fact2.htm. Accessed January 2006.
6. National Institute for Clinical Excellence. Full
guidance on the use of continuous subcutaneous
insulin infusion for diabetes. 2003.
URL: http://www.nice.org.uk/page.aspx?o=TA057
guidance. Accessed July 2007.
7. Reichard P, Nilsson BY, Rosenqvist U. The effect of
long-term intensified insulin treatment on the
development of microvascular complications of
diabetes mellitus. N Engl J Med 1993;329:304–9.
8. Diabetes Control and Complications Trial (DCCT)
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.
9. Ohkubo Y, Kishikawa H, Araki E, Miyata T,
Isami S, Motoyoshi S, et al. Intensive insulin
therapy prevents the progression of diabetic
microvascular complications in Japanese patients
with non-insulin-dependent diabetes mellitus: a
randomized prospective 6-year study. Diabetes Res
Clin Pract 1995;28:103–17.
10. UK Prospective Diabetes Study (UKPDS) Group.
Intensive blood-glucose control with
sulphonylureas or insulin compared with
conventional treatment and risk of complications
in patients with type 2 diabetes (UKPDS 33).
Lancet 1998;352:837–53.
11. Stratton IM, Adler AI, Neil HA, Matthews DR,
Manley SE, Cull CA, et al. Association of glycaemia
with macrovascular and microvascular
complications of type 2 diabetes (UKPDS 35):
prospective observational study. BMJ 2000;
321:405–12.
12. Khaw KT, Wareham N, Luben R, Bingham S,
Oakes S, Welch A, et al. Glycated haemoglobin,
diabetes, and mortality in men in Norfolk cohort
of European Prospective Investigation of Cancer
and Nutrition (EPIC–Norfolk). BMJ 2001;
322:15–18.
13. American Diabetes Association. Standards of
medical care in diabetes. Diabetes Care 2004;
27 (Suppl 1):S15–35.
14. Monnier L, Lapinski H, Colette C. Contributions
of fasting and postprandial plasma glucose
increments to the overall diurnal hyperglycemia of
type 2 diabetic patients: variations with increasing
levels of HbA1c. Diabetes Care 2003;26:881–5.
15. Atkinson MA, Maclaren NK. The pathogenesis of
insulin-dependent diabetes mellitus. N Engl J Med
1994;331:1428–36.
16. Foulis AK, Liddle CN, Farquharson MA,
Richmond JA, Weir RS. The histopathology of the
pancreas in type 1 (insulin-dependent) diabetes
mellitus: a 25-year review of deaths in patients
under 20 years of age in the United Kingdom.
Diabetologia 1986;29:267–74.
17. Gepts W. Pathologic anatomy of the pancreas in
juvenile diabetes mellitus. Diabetes 1965;
14:619–33.
18. Eriksson J, Franssila-Kallunki A, Ekstrand A,
Saloranta C, Widen E, Schalin C, et al. Early
metabolic defects in persons at increased risk for
non-insulin-dependent diabetes mellitus. N Engl J
Med 1989;321:337–43.
19. Weir GC, Bonner-Weir S. Insulin secretion in
non-insulin-dependent diabetes mellitus. In
LeRoith D, Taylor SI, Olefsky JM, editors. Diabetes
mellitus. Philadelphia, PA: Lippincott, Williams and
Wilkins; 2000. pp. 503–8.
20. Leahy JL. Natural history of beta-cell dysfunction
in NIDDM. Diabetes Care 1990;13:992–1010.
21. Levy J, Atkinson AB, Bell PM, McCance DR,
Hadden DR. Beta-cell deterioration determines
the onset and rate of progression of secondary
dietary failure in type 2 diabetes mellitus: the
10-year follow-up of the Belfast Diet Study. Diabet
Med 1998;15:290–6.
22. Bagust A, Beale S. Deteriorating beta-cell function
in type 2 diabetes: a long-term model. QJM 2003;
96:281–8.
23. Wright A, Burden AC, Paisey RB, Cull CA,
Holman RR. Sulfonylurea inadequacy: efficacy of
addition of insulin over 6 years in patients with
type 2 diabetes in the UK Prospective Diabetes
Study (UKPDS 57). Diabetes Care 2002;25:330–6.
24. DeFronzo RA. Pharmacologic therapy for type 2
diabetes mellitus. Ann Intern Med 1999;
131:281–303.
25. Koro CE, Bowlin SJ, Bourgeois N, Fedder DO.
Glycemic control from 1988 to 2000 among US
adults diagnosed with type 2 diabetes: a
preliminary report. Diabetes Care 2004;27:17–20.
26. UK Prospective Diabetes Study (UKPDS) Group.
Effect of intensive blood-glucose control with
metformin on complications in overweight
patients with type 2 diabetes (UKPDS 34). Lancet
1998;352:854–65.
27. Peyrot M, Rubin RR, Lauritzen T, Skovlund SE,
Snoek FJ, Matthews DR, et al. Resistance to insulin
therapy among patients and providers: results of
the cross-national Diabetes Attitudes, Wishes, and
Needs (DAWN) study. Diabetes Care 2005;
28:2673–9.
28. Malone JK, Kerr LF, Campaigne BN, Sachson RA,
Holcombe JH, Lispro Mixture-Glargine Study
Group. Combined therapy with insulin lispro Mix
75/25 plus metformin or insulin glargine plus
metformin: a 16-week, randomized, open-label,
crossover study in patients with type 2 diabetes
beginning insulin therapy. Clin Ther 2004;
26:2034–44.
29. Janka HU, Plewe G, Riddle MC, Kliebe-Frisch C,
Schweitzer MA, Yki-Jarvinen H. Comparison of
basal insulin added to oral agents versus twicedaily
premixed insulin as initial insulin therapy for
type 2 diabetes. Diabetes Care 2005;28:254–9.
30. Raskin P, Allen E, Hollander P, Lewin A,
Gabbay RA, Hu P, et al. Initiating insulin therapy
in type 2 diabetes: a comparison of biphasic and
basal insulin analogs. Diabetes Care 2005;28:260–5.
31. Diabetes Trials Unit. Treating To Target in Type 2
diabetes (4-T) study. 2005. URL: www.dtu.ox.ac.uk/
index.php?maindoc=/4-T/overview.php. Accessed
July 2007.
32. National Institute for Clinical Excellence.
Algorithm for the management of blood glucose
in adults with type 2 diabetes, from Inherited
Clinical Guideline G: Management of type 2
diabetes: management of blood glucose.
London: NICE; 2002. URL: www.nice.org.uk/
page.aspx?o=36737. Accessed July 2007.
33. Peters J, Stevenson M, Beverley C, Lim JN,
Smith S. The clinical effectiveness and costeffectiveness
of inhaler devices used in the routine
management of chronic asthma in older children:
a systematic review and economic evaluation.
Health Technol Assess 2002;6(5).
34. Rave KM, Nosek L, de la Pena A, Seger M,
Ernest CS, Heinemann L, et al. Dose response of
inhaled dry-powder insulin and dose equivalence
to subcutaneous insulin lispro. Diabetes Care
2005;28:2400–5.
35. Chowdhury TA, Escudier V. Poor glycaemic control
caused by insulin induced lipohypertrophy. BMJ
2003;327:383–4.
36. Gonen B, Rubenstein A, Rochman H, Tanega SP,
Horwitz DL. Haemoglobin A1: an indicator of the
metabolic control of diabetic patients. Lancet 1977;
ii:734–7.
37. Jadad AR, Moore RA, Carroll D, Jenkinson C,
Reynolds DJ, Gavaghan DJ, et al. Assessing the
quality of reports of randomized clinical trials: is
blinding necessary? Control Clin Trials 1996;
17:1–12.
38. Spitzer WO, Lawrence V, Dales R, Hill G,
Archer MC, Clark P, et al. Links between passive
smoking and disease: a best-evidence synthesis. A
report of the Working Group on Passive Smoking.
Clin Invest Med 1990;13:17–42.
39. Khan KS, ter Riet G, Glanville J, Sowden A,
Kleijnen J. Undertaking systematic reviews of research
on effectiveness: CRD’s guidance for those carrying out
and commissioning reviews. CRD Report 4. 2nd ed.
York: Centre for Reviews and Dissemination; 2001.
40. Cappelleri JC, Cefalu WT, Rosenstock J,
Kourides IA, Gerber RA. Treatment satisfaction in
type 2 diabetes: a comparison between an inhaled
insulin regimen and a subcutaneous insulin
regimen. Clin Ther 2002;24:552–64.
41. Cefalu WT, Skyler JS, Kourides IA, Landschulz WH,
Balagtas CC, Cheng SL, et al. Inhaled human
insulin treatment in patients with type 2 diabetes
mellitus. Ann Intern Med 2001;134:203–7.
42. Cefalu WT. Inhaled insulin: a proof-of-concept
study. Ann Intern Med 2001;134:795.
43. Heise T, Tusek C, Stephan JA, Krasner A,
Landschulz WH, Sha S, et al. Postprandial glucose
control unaffected by insulin antibodies associated
with inhaled insulin [poster]. Diabetologia 2004;
47:864.
44. Hollander PA, Blonde L, Rowe R, Mehta AE,
Milburn JL, Hershon KS, et al. Efficacy and safety
of inhaled insulin (Exubera) compared with
subcutaneous insulin therapy in patients with type
2 diabetes: results of a 6-month, randomized,
comparative trial. Diabetes Care 2004;27:2356–62.
45. Testa MA, Turner RR, Hayes JF, Simonson DC.
Patient satisfaction with insulin therapy in type 2
diabetes: a randomized trial of injectable vs.
inhaled insulin [abstract]. Diabetes 2002;51:544.
46. Quattrin T, Belanger A, Bohannon NJ,
Schwartz SL. Efficacy and safety of inhaled insulin
(Exubera) compared with subcutaneous insulin
therapy in patients with type 1 diabetes: results of a 6-month, randomized, comparative trial. Diabetes
Care 2004;27:2622–7.
47. Su M, Testa MA, Turner RR, Simonson DC.
The relationship between regimen burden and
psychological well being in persons with type 1
diabetes: inhaled vs injectable insulin [abstract].
Diabetes 2002;51:1843.
48. Testa MA, Turner RR, Hayes JF, Simonson DC.
Patient satisfaction and quality of life in type 1
diabetes: a randomized trial of injectable vs.
inhaled insulin [abstract]. Diabetes 2001;50:A45.
49. Gerber RA, Cappelleri JC, Kourides IA,
Gelfand RA. Treatment satisfaction with inhaled
insulin in patients with type 1 diabetes: a
randomized controlled trial. Diabetes Care 2001;
24:1556–9.
50. Skyler JS, Cefalu WT, Kourides IA, Landschulz WH,
Balagtas CC, Cheng SL, et al. Efficacy of inhaled
human insulin in type 1 diabetes mellitus: a
randomised proof-of-concept study. Lancet 2001;
357:331–5.
51. Skyler JS, Weinstock RS, Raskin P, Yale JF,
Barrett E, Gerich JE, et al. Use of inhaled insulin
in a basal/bolus insulin regimen in type 1 diabetic
subjects: a 6-month, randomized, comparative
trial. Diabetes Care 2005;28:1630–5.
52. Testa MA, Turner RR, Hayes JF, Simonson DC.
Intensive therapy and patient satisfaction in type 1
diabetes: a randomized trial of injected vs. inhaled
insulin [abstract]. Diabetologia 2001;44:8.
53. Dumas R, England RD, Riese RJ, Teeter JG.
Exubera is well tolerated and achieves tight
glycemic control in patients with type 1 diabetes.
Diabetes 2005;54:A87.
54. Hermansen K, Ronnemaa T, Petersen AH,
Bellaire S, Adamson U. Intensive therapy with
inhaled insulin via the AERx insulin diabetes
management system: a 12-week proof-of-concept
trial in patients with type 2 diabetes. Diabetes Care
2004;27:162–7.
55. Wollmer P, Clauson P. Evaluation of lung function
in patients with type 2 diabetes using the AERx®
insulin diabetes management system (iDMS)
[abstract]. Diabetes 2003;52:A108.
56. Garg S, Rosenstock J, Muchmore D, De La Pena A,
Sun B, Silverman B. Safety and efficacy of
preprandial human insulin inhalation powder
(HIIP) delivered by the Lilly/Alkermes inhaled
insulin system versus injectable insulin in patients
with type 1 diabetes (T1D). Diabetes 2005;54:A89.
57. Cappelleri JC, Gerber RA, Kourides IA,
Gelfand RA. Development and factor analysis of a
questionnaire to measure patient satisfaction with
injected and inhaled insulin for type 1 diabetes.
Diabetes Care 2000;23:1799–803.
58. Zambanini A, Newson RB, Maisey M, Feher MD.
Injection related anxiety in insulin-treated
diabetes. Diabetes Res Clin Pract 1999;46:239–46.
59. Gerber RA, Cappelleri JC, Nadkarni S, Petrie CD,
Rosenstock J. Balancing compliance, patient
satisfaction and improved glycaemic control in
patients with type 1 and type 2 diabetes: longterm
studies with inhaled insulin (Exubera®
[abstract]. Diabetologia 2002;45:751.
60. Rosenstock J, Cappelleri JC, Bolinder B,
Gerber RA. Patient satisfaction and glycemic
control after 1 year with inhaled insulin (Exubera)
in patients with type 1 or type 2 diabetes. Diabetes
Care 2004;27:1318–23.
61. Rosenstock J. Mealtime rapid-acting inhaled
insulin (Exubera®) improves glycemic control in
patients with type 2 diabetes failing combination
oral agents: a 3-month, randomized, comparative
trial [abstract]. Diabetes 2002;51:535.
62. DeFronzo R. Efficacy and safety of inhaled insulin
(Exubera®) compared with rosiglitazone in type 2
diabetes patients not optimally controlled on diet
and exercise: results of a 3-month, randomized,
comparative trial [abstract]. Diabetes 2003;52:A38.
63. Testa MA, Hayes JF, Turner RR, Simonson DC.
Quality of life improvements in type 2 diabetes
when Exubera is added after failure on metformin
monotherapy: an international randomized phase
3 trial [abstract]. Diabetes 2004;53:A437.
64. Testa MA, Turner RR, Hayes JF, Scranton RE,
Simonson DC. Satisfaction and quality of life with
sulfonylurea plus either metformin or exubera: an
international randomized phase 3 trial [abstract].
Diabetes 2004;53:A115.
65. Weiss SR, Cheng SL, Kourides IA, Gelfand RA,
Landschulz WH, Inhaled Insulin Phase II Study
Group. Inhaled insulin provides improved
glycemic control in patients with type 2 diabetes
mellitus inadequately controlled with oral agents:
a randomized controlled trial. Arch Intern Med
2003;163:2277–82.
66. Barnett A. Efficacy and one-year pulmonary safety
of inhaled insulin (Exubera) as adjunctive therapy
with metformin or glibenclamide in type 2
diabetes patients poorly controlled on oral agent
monotherapy [abstract]. Diabetes 2004;53:A107.
67. Freemantle N, Blonde L, Duhot D, Hompesch M,
Eggertsen R, Hobbs FD, et al. Availability of
inhaled insulin promotes greater perceived
acceptance of insulin therapy in patients with type
2 diabetes. Diabetes Care 2005;28:427–8.
68. Skyler JS. Long-term, sustained efficacy, and safety
of inhaled insulin after 4 years of continuous
therapy [abstract]. Diabetologia 2004;47:863.
69. Cefalu WT, Serdarevic-Pehar M. Long-term use of
Exubera in type 2 diabetes: observations on
glycemic control, pulmonary function and antibody formation [abstract]. Diabetes 2005;
54:A88.
70. Valente AX, Langer R, Stone HA, Edwards DA.
Recent advances in the development of an inhaled
insulin product. Biodrugs 2003;17:9–17.
71. Himmelmann A, Jendle J, Mellen A, Petersen AH,
Dahl UL, Wollmer P. The impact of smoking on
inhaled insulin. Diabetes Care 2003;26:677–82.
72. Henry RR, Mudaliar S, Chu N, Kim D,
Armstrong D, Davis TT, et al. Young and elderly
type 2 diabetic patients inhaling insulin with the
AERx insulin diabetes management system: a
pharmacokinetic and pharmacodynamic
comparison. J Clin Pharmacol 2003;43:1228–34.
73. McElduff A, Mather LE, Kam PC, Clauson P.
Influence of acute upper respiratory tract infection
on the absorption of inhaled insulin using the
AERx insulin diabetes management system. Br J
Clin Pharmacol 2005;59:546–51.
74. Patton JS, Bukar JG, Eldon MA. Clinical
pharmacokinetics and pharmacodynamics of
inhaled insulin. Clin Pharmacokinet 2004;
43:781–801.
75. Kim D, Mudaliar S, Chinnapongse S, Chu N,
Boies SM, Davis T, et al. Dose–response
relationships of inhaled insulin delivered via the
Aerodose insulin inhaler and subcutaneously
injected insulin in patients with type 2 diabetes.
Diabetes Care 2003;26:2842–7.
76. Kapitza C, Hompesch M, Scharling B, Heise T.
Intrasubject variability of inhaled insulin in type 1
diabetes: a comparison with subcutaneous insulin.
Diabetes Technol Ther 2004;6:466–72.
77. Heinemann L. Variability of insulin absorption
and insulin action. Diabetes Technol Ther 2002;
4:673–82.
78. Mellen A, Himmelmann A, Jendle J, Wollmer P.
Pharmacokinetics and intra-subject variability of
inhaled insulin in healthy smokers and nonsmokers.
Diabetes 2001;50:A126.
79. Pfutzner A, Mann AE, Steiner SS.
Technosphere/insulin – a new approach for
effective delivery of human insulin via the
pulmonary route. Diabetes Technol Ther 2002;
4:589–94.
80. Perera AD, Kapitza C, Nosek L, Fishman RS,
Shapiro DA, Heise T, et al. Absorption and
metabolic effect of inhaled insulin: intrapatient
variability after inhalation via the Aerodose insulin
inhaler in patients with type 2 diabetes. Diabetes
Care 2002;25:2276–81.
81. White JR, Campbell RK. Inhaled insulin: an
overview. Clinical Diabetes 2001;19:13–16.
82. Weerakkody G, Gonzales C, Muchmore D,
Chien J. Estimating dose equivalence for new
routes of drug administration. J Biopharm Stat
2004;14:1021-36.
83. Fineberg SE, Kawabata T, Finco-Kent D, Liu C,
Krasner A. Antibody response to inhaled insulin in
patients with type 1 or type 2 diabetes. J Clin
Endocrinol Metab 2005;90:3287–94.
84. EURODIAB Substudy 2 Study Group. Decreased
prevalence of atopic diseases in children with
diabetes. J Pediatr 2000;137:470–4.
85. Heinemann L, Traut T, Heise T. Time–action
profile of inhaled insulin. Diabet Med 1997;
14:63–72.
86. Mueller E, Maxion-Bergemann S, Gultyaev D,
Walzer S, Freemantle N, Mathieu C, et al.
Development and validation of the Economic
Assessment of Glycemic Control and Long-Term
Effects of diabetes (EAGLE) model. Diabetes Technol
Ther 2006;8:219–36.
87. Polonsky W, Fisher L, Dowe S, Edelman S. Why do
patients resist insulin therapy? [abstract]. Diabetes
2003;52:A417.
88. Polonsky WH, Fisher L, Guzman S, Villa-
Caballero L, Edelman SV. Psychological insulin
resistance in patients with type 2 diabetes: the
scope of the problem. Diabetes Care 2005;
28:2543–5.
89. National Institute for Clinical Excellence. Full
guidance on the use of patient-education models
for diabetes. 2003. URL: http://www.nice.org.uk/
page.aspx?o=TA060guidance. Accessed July 2007.
90. Aviles-Santa L, Sinding J, Raskin P. Effects of
metformin in patients with poorly controlled,
insulin-treated type 2 diabetes mellitus. A
randomized, double-blind, placebo-controlled
trial. Ann Intern Med 1999;131:182–8.
91. Skinner TC, Carey ME, Dallosso HM, Davies MJ,
Heller S, Khunti K, et al. Illness beliefs and
prevalence of depression at diagnosis in
individuals with type 2 diabetes: baseline results
from the DESMOND randomised controlled trials.
Diabet Med 2007;24(Suppl 1):A56.
92. UK Prospective Diabetes Study (UKPDS) 6.
Complications in newly diagnosed type 2 diabetic
patients and their association with different
clinical and biochemical risk factors. Diabetes Res
1990;13:1–11.
93. Gerber RA, Hauber AB, Bolinder B, Johnson FR.
Diabetes patients’ stated preference for insulin
therapies: trading health for convenience
[abstract]. Diabetologia 2004;47:755. Additional
information kindly provided by Pfizer in form of
poster.
94. Hauber AB, Johnson FR, Sauriol L, Lescrauwaet B.
Risking health to avoid injections: stated
preferences of Canadians with diabetes [poster].
Diabetologia 2004;47:761.
95. Dolan P, Roberts J. Modelling valuations for
EQ-5D health states: an alternative model using
differences in valuations. Med Care 2002;40:442–6.
96. Dolan P. Modeling valuations for EuroQol health
states. Med Care 1997;35:1095–108.
97. Coffey JT, Brandle M, Zhou H, Marriott D,
Burke R, Tabaei BP, et al. Valuing health-related
quality of life in diabetes. Diabetes Care 2002;
25:2238–43.
98. Bagust A, Beale S. Modelling EuroQol healthrelated
utility values for diabetic complications
from CODE-2 data. Health Econ 2005;14:217–30.
99. Redekop WK, Koopmanschap MA, Stolk RP,
Rutten GE, Wolffenbuttel BH, Niessen LW.
Health-related quality of life and treatment
satisfaction in Dutch patients with type 2 diabetes.
Diabetes Care 2002;25:458–63.
100. Clarke P, Gray A, Holman R. Estimating utility
values for health states of type 2 diabetic patients
using the EQ-5D (UKPDS 62). Med Decis Making
2002;22:340–9.
101. Turner R, Cull C, Holman R. United Kingdom
Prospective Diabetes Study 17: a 9-year update of
a randomized, controlled trial on the effect of
improved metabolic control on complications in
non-insulin-dependent diabetes mellitus. Ann
Intern Med 1996;124:136–45.
102. Acharya S, Philip S, Viswanath AK, Waugh NR,
Pearson DWM. Body mass index and glycaemic
control in late-adolescents and young adults with
type 1 diabetes mellitus. Diabetes UK, Annual
Professional Conference. 29–31 March 2006,
Birmingham, UK.
103. DeVries JH. Mealtime inhaled insulin lowers
fasting glucose: a look at possible explanations.
Diabetologia 2005;48:1–2.
104. National Research Register (Department of
Health). Exubera Real World Classic. 2005. URL:
http://www.nrr.nhs.uk/ViewDocument.asp?ID=
N0217155973. Accessed July 2007.
105. Insulin inhalation – Pfizer/Nektar Therapeutics:
HMR 4006, inhaled PEG-insulin–Nektar,
PEGylated insulin–Nektar. Drugs R D 2004;
5:166–70.
106. Medical News Today. Phase 3 safety study for
inhaled insulin – Lilly and Alkermes. 2005. URL:
http://www.medicalnewstoday.com/medicalnews.php?
newsid=28004. Accessed July 2007.
107. Leach C, Kuo MC, Perkins K, Bueche B, Guo LH,
Bentley M, et al. Dry powder formulation of
inhaled PEG-insulin yields prolonged systemic
activity in dogs [abstract]. Diabetes 2003;
52:A105–6.
108. Arbit E. The physiological rationale for oral
insulin administration. Diabetes Technol Ther
2004;6:510–17.
109. Gordon Still J. Development of oral insulin:
progress and current status. Diabetes Metab Res Rev
2002;18:S29–37.
110. Modi P, Mihic M, Lewin A. The evolving role of
oral insulin in the treatment of diabetes using a
novel RapidMist™ system. Diabetes Metab Res Rev
2002;18:S38–42.
111. Cernea S, Kidron M, Wohlgelernter J, Modi P,
Raz I. Dose–response relationship of oral insulin
spray in healthy subjects. Diabetes Care 2005;
28:1353–7.
112. Gomez-Perez FJ, Rull JA. Insulin therapy: current
alternatives. Arch Med Res 2005;36:258–72.
113. Nathan DM, Buse JB, Davidson MB, Heine RJ,
Holman RR, Sherwin R, et al. Management of
hyperglycaemia 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. Diabetologia 2006;
49:1711–21.
114. Goudswaard AN, Furlong NJ, Rutten GE, Stolk RP,
Valk GD. Insulin monotherapy versus
combinations of insulin with oral hypoglycaemic
agents in patients with type 2 diabetes mellitus.
Cochrane Database Syst Rev 2004;CD003418.
115. Douek IF, Allen SE, Ewings P, Gale EA, Bingley PJ.
Continuing metformin when starting insulin in
patients with type 2 diabetes: a double-blind
randomized placebo-controlled trial. Diabet Med
2005;22:634–40.
116. Strowig SM, Raskin P. Combination therapy using
metformin or thiazolidinediones and insulin in the
treatment of diabetes mellitus. Diabetes Obes Metab
2005;7:633–41.
117. Bailey CJ. Treating insulin resistance in type 2
diabetes with metformin and thiazolidinediones.
Diabetes Obes Metab 2005;7:675–91.
118. Gerstein HC, Yale JF, Harris SB, Issa M,
Stewart JA, Dempsey E. A randomized trial of
adding insulin glargine vs. avoidance of insulin in
people with type 2 diabetes on either no oral
glucose-lowering agents or submaximal doses of
metformin and/or sulphonylureas. The Canadian
INSIGHT (Implementing New Strategies with
Insulin Glargine for Hyperglycaemia Treatment)
Study. Diabet Med 2006;23:736–42.
119. Hayward RA, Manning WG, Kaplan SH,
Wagner EH, Greenfield S. Starting insulin therapy
in patients with type 2 diabetes: effectiveness,
complications, and resource utilization. JAMA
1997;278:1663–9.
120. Yki-Jarvinen H, Ryysy L, Nikkila K, Tulokas T,
Vanamo R, Heikkila M. Comparison of bedtime
insulin regimens in patients with type 2 diabetes
mellitus. A randomized, controlled trial. Ann
Intern Med 1999;130:389–96.
121. Aas AM, Bergstad I, Thorsby PM, Johannesen O,
Solberg M, Birkeland KI. An intensified lifestyle
intervention programme may be superior to
insulin treatment in poorly controlled type 2
diabetic patients on oral hypoglycaemic agents:
results of a feasibility study. Diabet Med 2005;
22:316–22.
122. Aas AM, Seljeflot I, Torjesen PA, Diep LM,
Thorsby PM, Birkeland KI. Blood glucose
lowering by means of lifestyle intervention has
different effects on adipokines as compared with
insulin treatment in subjects with type 2 diabetes.
Diabetologia 2006;49:872–80.
123. Schuyler MR, Niewoehner DE, Inkley SR,
Kohn R. Abnormal lung elasticity in juvenile
diabetes mellitus. Am Rev Respir Dis 1976;113:
37–41.
124. Schernthaner G, Haber P, Kummer F, Ludwig H.
Lung elasticity in juvenile-onset diabetes mellitus.
Am Rev Respir Dis 1977;116:544–6.
125. Sandler M, Bunn AE, Stewart RI. Pulmonary
function in young insulin-dependent diabetic
subjects. Chest 1986;90:670–5.
126. Kodolova IM, Lysenko LV. Morphological changes
in the lung blood vessels in diabetes mellitus. Arkh
Patol 1979;41:31–6.
127. Vracko R, Thorning D, Huang TW. Basal lamina
of alveolar epithelium and capillaries: quantitative
changes with aging and in diabetes mellitus. Am
Rev Respir Dis 1979;120:973–83.
128. Weynand B, Jonckheere A, Frans A, Rahier J.
Diabetes mellitus induces a thickening of the
pulmonary basal lamina. Respiration 1999;
66:14–19.
129. Farina J, Furio V, Fernandez-Acenero MJ, Muzas
MA. Nodular fibrosis of the lung in diabetes
mellitus. Virchows Archiv 1995;427:61–3.
130. Kodolova IM, Lysenko LV, Saltykov BB.
Changes in the lungs in diabetes mellitus. Arkh
Patol 1982;44:35–40.
131. Vracko R, Pecoraro RE, Carter WB. Overview
article: basal lamina of epidermis, muscle fibers,
muscle capillaries, and renal tubules: changes with
aging and in diabetes mellitus. Ultrastruct Pathol
1980;1:559–74.
132. Watanabe K, Senju S, Toyoshima H, Yoshida M.
Thickness of the basement membrane of bronchial
epithelial cells in lung diseases as determined by
transbronchial biopsy. Respir Med 1997;91:
406–10.
133. Kida K, Utsuyama M, Takizawa T, Thurlbeck WM.
Changes in lung morphologic features and
elasticity caused by streptozotocin-induced
diabetes mellitus in growing rats. Am Rev Respir
Dis 1983;128:125–31.
134. Popov D, Simionescu M. Alterations of lung
structure in experimental diabetes, and diabetes
associated with hyperlipidaemia in hamsters.
Eur Respir J 1997;10:1850–8.
135. Mompeo B, Popov D, Sima A, Constantinescu E,
Simionescu M. Diabetes-induced structural
changes of venous and arterial endothelium and
smooth muscle cells. J Submicrosc Cytol Pathol
1998;30:475–84.
136. Plopper CG, Morishige WK. Alterations in the
ultrastructure of nonciliated bronchiolar epithelial
(Clara) cells by streptozotocin-induced diabetes in
rats. Am Rev Respir Dis 1979;120:1137–43.
137. Popov D, Hasu M, Costache G, Stern D,
Simionescu M. Capillary and aortic endothelia
interact in situ with nonenzymatically glycated
albumin and develop specific alterations in early
experimental diabetes. Acta Diabetol 1997;
34:285–93.
138. Asanuma Y, Fujiya S, Ide H, Agishi Y.
Characteristics of pulmonary function in patients
with diabetes mellitus. Diabetes Res Clin Pract
1985;1:95–101.
139. Bell D, Collier A, Matthews DM, Cooksey EJ,
McHardy GJ, Clarke BF. Are reduced lung
volumes in IDDM due to defect in connective
tissue? Diabetes 1988;37:829–31.
140. Innocenti F, Fabbri A, Anichini R, Tuci S,
Pettina G, Vannucci F, et al. Indications of reduced
pulmonary function in type 1 (insulin-dependent)
diabetes mellitus. Diabetes Res Clin Pract 1994;
25:161–8.
141. Primhak RA, Whincup G, Tsanakas JN,
Milner RD. Reduced vital capacity in insulindependent
diabetes. Diabetes 1987;36:324–6.
142. Schnack C, Festa A, Schwarzmaier-D’Assie A,
Haber P, Schernthaner G. Pulmonary dysfunction
in type 1 diabetes in relation to metabolic longterm
control and to incipient diabetic
nephropathy. Nephron 1996;74:395–400.
143. Strojek K, Ziora D, Sroczynski JW, Oklek K.
Pulmonary complications of type 1 (insulindependent)
diabetic patients. Diabetologia
1992;35:1173–6.
144. Maccioni FJ, Colebatch HJ. Lung volume and
distensibility in insulin-dependent diabetes
mellitus. Am Rev Respir Dis 1991;143:1253–6.
145. Ozmen B, Celik P, Yorgancioglu A, Ozmen B,
Ozmen D, Cok G. Pulmonary function parameters
in patients with diabetes mellitus. Diabetes Res Clin
Pract 2002;57:209–11.
146. Benbassat CA, Stern E, Kramer M, Lebzelter J,
Blum I, Fink G. Pulmonary function in patients
with diabetes mellitus. Am J Med Sci 2001;
322:127–32.
147. Mori H, Okubo M, Okamura M, Yamane K,
Kado S, Egusa G, et al. Abnormalities of
pulmonary function in patients with non-insulindependent
diabetes mellitus. Intern Med 1992;
31:189–93.
148. Cooper BG, Taylor R, Alberti KG, Gibson GJ.
Lung function in patients with diabetes mellitus.
Respir Med 1990;84:235–9.
149. Heimer D, Brami J, Lieberman D, Bark H.
Respiratory muscle performance in patients with
type 1 diabetes. Diabet Med 1990;7:434–7.
150. Matsubara T, Hara F. The pulmonary function and
histopathological studies of the lung in diabetes
mellitus. Nippon Ika Daigaku Zasshi 1991;
58:528–36.
151. Niranjan V, McBrayer DG, Ramirez LC, Raskin P,
Hsia CC. Glycemic control and cardiopulmonary
function in patients with insulin-dependent
diabetes mellitus. Am J Med 1997;103:504–13.
152. Sandler M, Bunn AE, Stewart RI. Cross-section
study of pulmonary function in patients with
insulin-dependent diabetes mellitus. Am Rev Respir
Dis 1987;135:223–9.
153. Guvener N, Tutuncu NB, Akcay S, Eyuboglu F,
Gokcel A. Alveolar gas exchange in patients with
type 2 diabetes mellitus. Endocr J 2003;50:663–7.
154. Marvisi M, Bartolini L, del Borrello P, Brianti M,
Marani G, Guariglia A, et al. Pulmonary function
in non-insulin-dependent diabetes mellitus.
Respiration 2001;68:268–72.
155. Ramirez LC, Dal Nogare A, Hsia C, Arauz C,
Butt I, Strowig SM, et al. Relationship between
diabetes control and pulmonary function in
insulin-dependent diabetes mellitus. Am J Med
1991;91:371–6.
156. Minette P, Buysschaert M, Rahier J, Veriter C,
Frans A. Pulmonary gas exchange in life-long
nonsmoking patients with diabetes mellitus.
Respiration 1999;66:20–4.
157. Fuso L, Cotroneo P, Basso S, De Rosa M, Manto A,
Ghirlanda G, et al. Postural variations of
pulmonary diffusing capacity in insulin-dependent
diabetes mellitus. Chest 1996;110:1009–13.
158. Lange P, Groth S, Kastrup J, Mortensen J,
Appleyard M, Nyboe J, et al. Diabetes mellitus,
plasma glucose and lung function in a crosssectional
population study. Eur Respir J 1989;
2:14–9.
159. Lange P, Groth S, Mortensen J, Appleyard M,
Nyboe J, Schnohr P, et al. Diabetes mellitus and
ventilatory capacity: a five year follow-up study.
Eur Respir J 1990;3:288–92.
160. Walter RE, Beiser A, Givelber RJ, O’Connor GT,
Gottlieb DJ. Association between glycemic state
and lung function: the Framingham Heart Study.
Am J Respir Crit Care Med 2003;167:911–16.
161. Enright PL, Kronmal RA, Higgins M, Schenker M,
Haponik EF. Spirometry reference values for
women and men 65 to 85 years of age.
Cardiovascular health study. Am Rev Respir Dis
1993;147:125–33.
162. Engstrom G, Janzon L. Risk of developing
diabetes is inversely related to lung function:
a population-based cohort study. Diabet Med
2002;19:167–70.
163. Barrett-Connor E, Frette C. NIDDM, impaired
glucose tolerance, and pulmonary function in
older adults. The Rancho Bernardo Study. Diabetes
Care 1996;19:1441–4.
164. Davis T, Edelman SV. Insulin therapy in type 2
diabetes. Med Clin North Am 2004;88:865–95.
165. Davis TM, Knuiman M, Kendall P, Vu H,
Davis WA. Reduced pulmonary function and its
associations in type 2 diabetes: the Fremantle
Diabetes Study. Diabetes Res Clin Pract 2000;
50:153–9.
166. Klein BE, Moss SE, Klein R, Cruickshanks KJ.
Is peak expiratory flow rate a predictor of
complications in diabetes? The Wisconsin
Epidemiologic Study of Diabetic Retinopathy.
J Diabetes Complications 2001;15:301–6.
167. Klein BE, Moss SE, Klein R, Cruickshanks KJ,
Wisconsin Epidemiologic Study of Diabetic
Retinopathy. Peak expiratory flow rate:
relationship to risk variables and mortality: the
Wisconsin Epidemiologic Study of diabetic
retinopathy. Diabetes Care 2001;24:1967–71.
168. Bergenstal R. Efficacy and safety of inhaled insulin
(Exubera®) compared with rosiglitazone in type 2
diabetes patients not optimally controlled on diet
and exercise: results of a 3-month, randomised,
comparative trial [abstract]. Diabetologia 2003;
46:801.
169. Bergenstal R. Achieving target HbAIC in studies
with inhaled insulin in type 2 diabetes [poster].
Diabetologia 2004;47:866.
170. Cefalu WT. Mealtime rapid-acting inhaled insulin
(Exubera) improves glycaemic control in patients
with type 2 diabetes failing combination oral
agents: a 3-month, randomised, comparative trial
[abstract]. Diabetologia 2002;45:807.
171. DeFronzo RA, Bergenstal RM, Cefalu WT,
Pullman J, Lerman S, Bode BW, et al. Efficacy of
inhaled insulin in patients with type 2 diabetes not
controlled with diet and exercise: a 12-week,
randomized, comparative trial. Diabetes Care
2005;28:1922–8.
172. Simonson DC, Turner RR, Hayes JF, Scranton RE,
Testa MA. Improving quality of life in type 2
diabetes when Exubera® is added after failure on
metformin: a multicenter, international trial
[abstract]. Diabetologia 2004;47:865.
173. Testa MA, Turner RR, Hayes JF, Scranton RE,
Simonson DC. An international trial of
sulfonylurea plus either metformin or Exubera®:
impact on quality of life and treatment satisfaction
[abstract]. Diabetologia 2004;47:9.
174. Department of Health. NHS reference costs 2004,
Appendix 4. London: Department of Health; 2005.
175. Clarke P, Gray A, Legood R, Briggs A, Holman R.
The impact of diabetes-related complications on
healthcare costs: results from the United Kingdom
Prospective Diabetes Study (UKPDS Study No. 65).
Diabet Med 2003;20:442–50.
176. Joint Formulary Committee. British National
Formulary, 49th edn. London: British Medical
Association and Royal Pharmaceutical Society of
Great Britain; 2005.
177. Gordois A, Scuffham P, Shearer A, Oglesby A. The
health care costs of diabetic nephropathy in the
United States and the United Kingdom. J Diabetes
Complications 2004;18:18–26.
178. Gordois A, Scuffham P, Shearer A, Oglesby A,
Tobian JA. The health care costs of diabetic
peripheral neuropathy in the US. Diabetes Care
2003;26:1790–5.
179. Joint Formulary Committee. British National
Formulary, 51st edn. London: British Medical
Association and Royal Pharmaceutical Society of
Great Britain; 2006.