Review Article
Management of Diabetes-related Hypoglycemia
Abstract
Iatrogenic hypoglycemia is the main factor limiting aggressive and optimal diabetes management. Rather than being an inevitable consequence of optimal glycemic control, however, hypoglycemia is avoidable and generally straightforward to manage when it occurs. Professional caregivers, patients, and their families are often fearful of hypoglycemia, even though most episodes are minor and easily self-treated. Understanding the factors contributing to hypoglycemia risk and how to minimize its occurrence is an essential part of diabetes care. Building on the physiologic fundamentals presented in the accompanying review, the incidence, mortality/morbidity, clinical symptoms, severity classification, and psychosocial impact of hypoglycemia are described here. Appropriate selection and titration of therapeutic agents, including insulin analogs with more predictable time-action profiles than human insulin formulations, can reduce hypoglycemia risk. Patient education about hypoglycemia prevention, including symptom recognition and necessity of rapid treatment, behavioral modification, and the importance of frequent blood glucose monitoring should accompany all therapeutic interventions.
Key Points
* The health benefits of tight glycemic control are well established and should not be compromised because of fear of hypoglycemia.
* Symptoms and plasma glucose thresholds for hypoglycemia vary from individual to individual, but common risk factors apply and can be minimized.
* Although more frequent in patients with Type 1 diabetes treated with insulin, hypoglycemia is also common in patients with Type 2 diabetes whose β-cell function has deteriorated and are using insulin, or in those treated with long-acting sulfonylurea drugs.
* Most episodes of hypoglycemia are mild or moderate and can easily be self-treated if symptoms are recognized. Family members can be trained to recognize and respond to severe episodes.
* Education, behavioral modification, and new pharmacotherapies, including rapid- and long-acting insulin analogs, premixed insulin analogs, and GLP-1 analogs, are strategies to reduce hypoglycemia risk and still maintain optimal glycemic control.
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References
1. Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes. Diabetes Care 2003;26:1902–1912.
2. 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;329:977–986.
3. Diabetes Control and Complications Trial Research Group. Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial. J Pediatr 1994;125:177–188.
4. UK Prospective Diabetes Study 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;352:837–853.
5. Zammitt NN, Frier BM. Hypoglycemia in type 2 diabetes: pathophysiology, frequency, and effects of different treatment modalities. Diabetes Care 2005;28:2948–2961.
6. Dupre J. Glycaemic effects of incretins in type 1 diabetes mellitus: a concise review, with emphasis on studies in humans. Regul Pept 2005;128:149–157.
7. Laing SP, Swerdlow AJ, Slater SD, et al. The British Diabetic Association Cohort Study, I: all-cause mortality in patients with insulin-treated diabetes mellitus. Diabet Med 1999;16:459–465.
8. Gabriely I, Shamoon H. Hypoglycemia in diabetes: common, often unrecognized. Cleve Clin J Med 2004;71:335–342.
9. Weinger K, Jacobson AM. Cognitive impairment in patients with type 1 (insulin-dependent) diabetes mellitus: incidence, mechanisms, and therapeutic implications. CNS Drugs 1998;9:233–252.
10. Cryer PE. Hypoglycaemia: the limiting factor in the glycaemic management of type I and type II diabetes. Diabetologia 2002;45:937–948.
11. American Diabetes Association. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care 2005;28:1245–1249.
12. Heller S. Reducing hypoglycaemia with insulin analogues. Int J Obes Relat Metab Disord 2002;26 (suppl 3):S31–S36.
13. Rosenstock J, Dailey G, Massi-Benedetti M, et al. Reduced hypoglycemia risk with insulin glargine: a meta-analysis comparing insulin glargine with human NPH insulin in type 2 diabetes. Diabetes Care 2005;28:950–955.
14. Chelliah A, Burge MR. Hypoglycaemia in elderly patients with diabetes mellitus: causes and strategies for prevention. Drugs Aging 2004;21:511–530.
15. Boyle PJ, Schwartz NS, Shah SD, et al. Plasma glucose concentrations at the onset of hypoglycemic symptoms in patients with poorly controlled diabetes and in nondiabetics. N Engl J Med1988;318:1487–1492.
16. Mitrakou A, Ryan C, Veneman T, et al. Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction. Am J Physiol 1991;260:E67–E74.
17. Segel SA, Paramore DS, Cryer PE. Hypoglycemia-associated autonomic failure in advanced type 2 diabetes. Diabetes 2002;51:724–733.
18. Diabetes Control and Complications Trial Research Group. Hypoglycemia in the Diabetes Control and Complications Trial. Diabetes 1997;46:271–286.
19. Leese GP, Wang J, Broomhall J, et al. Frequency of severe hypoglycemia requiring emergency treatment in type 1 and type 2 diabetes: a population-based study of health service resource use.Diabetes Care 2003;26:1176–1180.
20. Katakura M, Naka M, Kondo T, et al. Prospective analysis of mortality, morbidity, and risk factors in elderly diabetic subjects: Nagano study. Diabetes Care 2003;26:638–644.
21. Diabetes Control and Complications Trial Research Group. Epidemiology of severe hypoglycemia in the diabetes control and complications trial. Am J Med 1991;90:450–459.
22. Cranston I, Lomas J, Maran A, et al. Restoration of hypoglycaemia awareness in patients with long-duration insulin-dependent diabetes. Lancet 1994;344:283–287.
23. Cox DJ, Gonder-Frederick LA, Kovatchev BP, et al. Biopsychobehavioral model of severe hypoglycemia, II: understanding the risk of severe hypoglycemia. Diabetes Care 1999;22:2018–2025.
24. Bhansali A, Chattopadhyay A, Dash RJ. Mortality in diabetes: a retrospective analysis from a tertiary care hospital in North India. Diabetes Res Clin Pract 2003;60:119–124.
25. Veitch PC, Clifton-Bligh RJ. Long-acting sulfonylureas: long-acting hypoglycaemia. Med J Aust 2004;180:84–85.
26. Friedrich LV, Dougherty R. Fatal hypoglycemia associated with levofloxacin. Pharmacotherapy 2004;24:1807–1812.
27. Swade TF, Emanuele NV. Alcohol and diabetes. Compr Ther 1997;23:135–140.
28. Allen KV, Frier BM. Nocturnal hypoglycemia: clinical manifestations and therapeutic strategies toward prevention. Endocr Pract 2003;9:530–543.
29. Frier BM. Morbidity of hypoglycemia in type 1 diabetes. Diabetes Res Clin Pract. 2004;65 (suppl 1):S47-S52.
30. Cox DJ, Penberthy JK, Zrebiec J, et al. Diabetes and driving mishaps: frequency and correlations from a multinational survey. Diabetes Care 2003;26:2329–2334.
31. Diamond TH, Collins J, Rohl P. Motor vehicle accidents during episodes of hypoglycaemia: case reports and lessons to be learnt. Aust Fam Physician 2005;34:151–154.
32. Cheyne EH, Sherwin RS, Lunt MJ, et al. Influence of alcohol on cognitive performance during mild hypoglycaemia: implications for type 1 diabetes. Diabet Med 2004;21:230–237.
33. The Diabetes Control and Complications Trial Research Group. Influence of intensive diabetes treatment on quality-of-life outcomes in the diabetes control and complications trial. Diabetes Care1996;19:195–203.
34. Gold AE, Deary IJ, Jones RW, et al. Severe deterioration in cognitive function and personality in five patients with long-standing diabetes: a complication of diabetes or a consequence of treatment? Diabet Med 1994;11:499–505.
35. Wredling RA, Theorell PG, Roll HM, et al. Psychosocial state of patients with IDDM prone to recurrent episodes of severe hypoglycemia. Diabetes Care 1992;15:518–521.
36. Nordfeldt S, Ludvigsson J. Fear and other disturbances of severe hypoglycaemia in children and adolescents with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2005;18:83–91.
37. Strachan MW. Fear of diabetes complications. Diabetes Metab Res Rev 2005;21:262–263.
38. Gonder-Frederick LA, Cox DJ, Julian DM, et al. Hypoglycemia Awareness, Anticipation and Treatment Training. Charlottesville, University of Virginia, 1999.
39. Hermanns N, Kubiak T, Kulzer B, et al. Emotional changes during experimentally induced hypoglycaemia in type 1 diabetes. Biol Psychol 2003;63:15–44.
40. Berlin KS, Sass DA, Davies WH, et al. Brief report: parent perceptions of hypoglycemic symptoms of youth with diabetes; disease disclosure minimizes risk of negative evaluations. J Pediar Psychol2005;30:207–212.
41. Kamps JL, Roberts MC, Varela RE. Development of a new fear of hypoglycemia scale: preliminary results. J Pediar Psychol 2005;30:287–291.
42. Reach G, Zerrouki A, Leclercq D, et al. Adjusting insulin doses: from knowledge to decision. Patient Educ Couns 2005;56:98–103.
43. Gonder-Frederick L, Cox D, Kovatchev B, et al. The psychosocial impact of severe hypoglycemic episodes on spouses of patients with IDDM. Diabetes Care 1997;20:1543–1546.
44. Frier BM. Hypoglycaemia and cognitive function in diabetes. Int J Clin Pract Suppl 2001;123:30–37.
45. Wredling R, Levander S, Adamson U, et al. Permanent neuropsychological impairment after recurrent episodes of severe hypoglycaemia in man. Diabetologia 1990;33:152–157.
46. Deary IJ, Crawford JR, Hepburn DA, et al. Severe hypoglycemia and intelligence in adult patients with insulin-treated diabetes. Diabetes 1993;42:341–344.
47. Langan SJ, Deary IJ, Hepburn DA, et al. Cumulative cognitive impairment following recurrent severe hypoglycaemia in adult patients with insulin-treated diabetes mellitus. Diabetologia 1991;34:337–344.
48. Hershey T, Lillie R, Sadler M, et al. Severe hypoglycemia and long-term spatial memory in children with type 1 diabetes mellitus: a retrospective study. J Int Neuropsychol Soc 2003;9:740–750.
49. Carroll MF, Burge MR, Schade DS. Severe hypoglycemia in adults. Rev Endocr Metab Disord 2003;4:149–157.
50. Monsod TP, Tamborlane WV, Coraluzzi L, et al. Epipen as an alternative to glucagon in the treatment of hypoglycemia in children with diabetes. Diabetes Care 2001;24:701–704.
51. Banarer S, Cryer PE. Hypoglycemia in type 2 diabetes. Med Clin North Am 2004;88:1107–1116.
52. Pampanelli S, Fanelli C, Lalli C, et al. Long-term intensive insulin therapy in IDDM: effects on HbA1c, risk for severe and mild hypoglycaemia, status of counterregulation and awareness of hypoglycaemia. Diabetologia 1996;39:677–686.
53. Svoren BM, Butler D, Levine BS, et al. Reducing acute adverse outcomes in youths with type 1 diabetes: a randomized, controlled trial. Pediatrics 2003;112:914–922.
54. Khan MA, Longley J. Psychosocial aspects of diabetes: the diabetologists’ perspective. Semin Clin Neuropsychiatry 1997;2:94–98.
55. Kinsley BT, Weinger K, Bajaj M, et al. Blood glucose awareness training and epinephrine responses to hypoglycemia during intensive treatment in type 1 diabetes. Diabetes Care 1999;22:1022–1028.
56. Cox DJ, Gonder-Frederick L, Polonsky W, et al. Blood glucose awareness training (BGAT-2): long-term benefits. Diabetes Care 2001;24:637–642.
57. Dagogo-Jack S. Hypoglycemia in type 1 diabetes mellitus: pathophysiology and prevention. Treat Endocrinol 2004;3:91–103.
58. Kubiak T, Hermanns N, Schreckling HJ, et al. Assessment of hypoglycaemia awareness using continuous glucose monitoring. Diabet Med 2004;21:487–490.
59. Boland E, Monsod T, Delucia M, et al. Limitations of conventional methods of self-monitoring of blood glucose: lessons learned from 3 days of continuous glucose sensing in pediatric patients with type 1 diabetes. Diabetes Care 2001;24:1858–1862.
60. Wysocki T. The psychological context of SMBG. Diabetes Spectr 1994;7:266–270.
61. Zrebiec JA. National Study of the Certified Diabetes Educator: report on a job analysis conducted by the National Certification Board for Diabetes Educators. Diabetes Spectr 2005;18:181–185.
62. Plank J, Kohler G, Rakovac I, et al. Long-term evaluation of a structured outpatient education programme for intensified insulin therapy in patients with type 1 diabetes: a 12-year follow-up. Diabetologia 2004;47:1370–1375.
63. Cox DJ, Kovatchev B, Koev D, et al. Hypoglycemia anticipation, awareness and treatment training (HAATT) reduces occurrence of severe hypoglycemia among adults with type 1 diabetes mellitus. Int J Behav Med 2004;11:212–218.
64. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2005;28 (3 Suppl 1):S4–S9.
65. American Association of Clinical Endocrinologists. The American Association of Clinical Endocrinologists medical guidelines for the management of diabetes mellitus: the AACE system of intensive diabetes self-management: 2002 update. Endocr Pract 2002;8 (Suppl 1):40–82.
66. Trovati M, Traversa M, Cavalot F. Afternoon hypoglycaemia in type 2 diabetes: lessons from blood glucose profiles. Diabetes Nutr Metab 2002;15:439–443.
67. Levien TL, Baker DE, Campbell RK, et al. Nateglinide therapy for type 2 diabetes mellitus. Ann Pharmacother 2001;35:1426–1434.
68. Nattrass M, Lauritzen T. Review of prandial glucose regulation with repaglinide: a solution to the problem of hypoglycaemia in the treatment of type 2 diabetes? Int J Obes Relat Metab Disord 2000;24 suppl 3:S21–S31.
69. Davis S, Alonso MD. Hypoglycemia as a barrier to glycemic control. J Diabetes Complications 2004;18:60–68.
70. Oiknine R, Bernbaum M, Mooradian AD. A critical appraisal of the role of insulin analogues in the management of diabetes mellitus. Drugs 2005;65:325–340.
71. Vazquez-Carrera M, Silvestre JS. Insulin analogues in the management of diabetes. Methods Find Exp Clin Pharmacol 2004;26:445–461.
72. Hirsch IB. Insulin analogues. N Engl J Med 2005;352:174–183.
73. Home PD, Lindholm A, Hylleberg B, et al. Improved glycemic control with insulin aspart: a multicenter randomized double-blind crossover trial in type 1 diabetic patients: UK Insulin Aspert Study Group Diabetes Care 1998;21:1904–1909.
74. Anderson JH Jr, Brunelle RL, Koivisto VA, et al. Reduction of postprandial hyperglycemia and frequency of hypoglycemia in IDDM patients on insulin-analog treatment: Multicenter Insulin Lispro Study Group. Diabetes 1997;46:265–270.
75. Dailey G, Rosenstock J, Moses RG, et al. Insulin glulisine provides improved glycemic control in patients with type 2 diabetes. Diabetes Care 2004;27:2363–2368.
76. Garber AJ. Premixed insulin analogues for the treatment of diabetes mellitus. Drugs 2006;66:31–49.
77. Chapman TM, Perry CM. Spotlight on insulin detemir in type 1 and 2 diabetes mellitus. BioDrugs 2005;19:67–69.
78. Chapman TM, Perry CM. Insulin detemir: a review of its use in the management of type 1 and 2 diabetes mellitus. Drugs 2004;64:2577–2595.
79. Lepore M, Pampanelli S, Fanelli C, et al. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes 2000;49: 2142–2148.
80. Ratner RE, Hirsch IB, Neifing JL, et al. Less hypoglycemia with insulin glargine in intensive insulin therapy for type 1 diabetes: US Study Group of Insulin Glargine in Type I Diabetes. Diabetes Care 2000;23:639–643.
81. Yki-Jarvinen H, Dressler A, Ziemen M. Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes: HOE 901/3002 Study Group. Diabetes Care 2000;23:1130–1136.
82. Home P, Bartley P, Russell-Jones D, et al. Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes: a randomized clinical trial. Diabetes Care2004;27:1081–1087.
83. McCormick M, Quinn L. Treatment of type 2 diabetes mellitus: pharmacologic intervention. J Cardiovasc Nurs 2002;16:55–67.
84. Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs 2005;65:385–411.
85. Holstein A, Egberts EH. Risk of hypoglycaemia with oral antidiabetic agents in patients with Type 2 diabetes. Exp Clin Endocrinol Diabetes 2003;111:405–414.
86. Turner RC, Cull CA, Frighi V, et al. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49): UK Prospective Diabetes Study (UK PDS) Group. JAMA 1999;281:2005–2012.
87. Harris MI, Eastman RC, Cowie CC, et al. Racial and ethnic differences in glycemic control of adults with type 2 diabetes. Diabetes Care 1999;22:403–408.
88. Bell DS. Practical considerations and guidelines for dosing sulfonylureas as monotherapy or combination therapy. Clin Ther 2004;26:1714–1727.
89. Fritsche A, Schweitzer MA, Haring HU. Glimepiride combined with morning insulin glargine, bedtime neutral protamine hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med 2003;138:952–959.
90. Rolla AR, Rakel RE. Practical approaches to insulin therapy for type 2 diabetes mellitus with premixed insulin analogues. Clin Ther 2005;27:1113–1125.
91. Hermansen K, Colombo M, Storgaard H, et al. Improved postprandial glycemic control with biphasic insulin aspart relative to biphasic insulin lispro and biphasic human insulin in patients with type 2 diabetes. Diabetes Care 2002;25:883–888.
92. Raskin P, Allen E, Hollander P, et al. Initiating insulin therapy in type 2 diabetes: a comparison of biphasic and basal insulin analogs. Diabetes Care 2005;28:260–265.
93. Sheehan MT. Current therapeutic options in type 2 diabetes mellitus: a practical approach. Clin Med Res 2003;1:189–200.
94. Riddle MC, Rosenstock J, Gerich J. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003;26:3080–3086.
95. Hermansen K, Davies M, Derezinski T, et al. 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;29:1269–1274.
96. Raskin P, Allen E, Hollander P, et al. Initiating insulin therapy in type 2 diabetes: a comparison of biphasic and basal insulin analogs. Diabetes Care 2005;28:260–265.
97. Malone JK, Kerr LF, Campaigne BN, et al. 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;26:2034–2044.
98. Malone JK, Bai S, Campaigne BN, et al. Twice-daily pre-mixed insulin rather than basal insulin therapy alone results in better overall glycaemic control in patients with type 2 diabetes. Diabet Med 2005;22:374–381.
99. Kleppinger EL, Vivian EM. Pramlintide for the treatment of diabetes mellitus. Ann Pharmacother 2003;37:1082–1089.
100. Kruger DF, Gloster MA. Pramlintide for the treatment of insulin-requiring diabetes mellitus: rationale and review of clinical data. Drugs 2004;64:1419–1432.
101. Keating GM. Exenatide. Drugs 2005;65:1681–1692.
102. Barnett AH. Exenatide. Drugs Today (Barc) 2005;41:563–578.
103. Madsbad S, Schmitz O, Ranstam J, et al. Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial. Diabetes Care2004;27:1335–1342.
104. Holst JJ. Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP-IV inhibitors. Expert Opin Emerg Drugs 2004;9:155–166.
105. Deacon CF, Ahren B, Holst JJ. Inhibitors of dipeptidyl peptidase IV: a novel approach for the prevention and treatment of type 2 diabetes? Expert Opin Invest Drugs 2004;13:1091–1102.
106. Bode BW, Tamborlane WV, Davidson PC. Insulin pump therapy in the 21st century: strategies for successful use in adults, adolescents, and children with diabetes. Postgrad Med 2002;111:69–77.
107. Colquitt JL, Green C, Sidhu MK, et al. Clinical and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes. Health Technol Assess 2004;8:1–171.
108. Colquitt J, Royle P, Waugh N. Are analogue insulins better than soluble in continuous subcutaneous insulin infusion? Results of a meta-analysis. Diabet Med 2003;20:863–866.
109. Shehadeh N, Battelino T, Galatzer A, et al. Insulin pump therapy for 1-6 year old children with type 1 diabetes. Isr Med Assoc J 2004;6:284–286.
110. Litton J, Rice A, Friedman N, et al. Insulin pump therapy in toddlers and preschool children with type 1 diabetes mellitus. J Pediatr 2002;141:490–495.
111. Rami B, Nachbaur E, Waldhoer T, et al. Continuous subcutaneous insulin infusion in toddlers. Eur J Pediatr 2003;162:721–722.
112. Saha ME, Huuppone T, Mikael K, et al. Continuous subcutaneous insulin infusion in the treatment of children and adolescents with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2002;15:1005–1010.
113. Boland EA, Grey M, Oesterle A, et al. Continuous subcutaneous insulin infusion: a new way to lower risk of severe hypoglycemia, improve metabolic control, and enhance coping in adolescents with type 1 diabetes. Diabetes Care 1999;22:1779–1784.
114. Plotnick LP, Clark LM, Brancati FL, et al. Safety and effectiveness of insulin pump therapy in children and adolescents with type 1 diabetes. Diabetes Care 2003;26:1142–1146.
115. Hunger-Dathe W, Braun A, Muller UA, et al. Insulin pump therapy in patients with type 1 diabetes mellitus: results of the Nationwide Quality Circle in Germany (ASD) 1999-2000. Exp Clin Endocrinol Diabetes 2003;111:428–434.
116. Linkeschova R, Raoul M, Bott U, et al. Less severe hypoglycaemia, better metabolic control, and improved quality of life in type 1 diabetes mellitus with continuous subcutaneous insulin infusion (CSII) therapy: an observational study of 100 consecutive patients followed for a mean of 2 years. Diabet Med2002;19:746–751.
117. Herman WH, Ilag LL, Johnson SL, et al. A clinical trial of continuous subcutaneous insulin infusion versus multiple daily injections in older adults with type 2 diabetes. Diabetes Care 2005;28:1568–1573.
118. Raskin P, Bode BW, Marks JB, et al. Continuous subcutaneous insulin infusion and multiple daily injection therapy are equally effective in type 2 diabetes: a randomized, parallel-group, 24-week study.Diabetes Care 2003;26:2598–2603.
119. Weissberg-Benchell J, Antisdel-Lomaglio J, Seshadri R. Insulin pump therapy: a meta-analysis. Diabetes Care 2003;26:1079–1087.
120. Retnakaran R, Hochman J, Devries JH, et al. Continuous subcutaneous insulin infusion versus multiple daily injections: the impact of baseline A1c. Diabetes Care 2004;27:2590–2596.
121. Weinzimer SA, Doyle EA, Steffen AT, et al. Rediscovery of insulin pump treatment of childhood type 1 diabetes. Minerva Med 2004;95:85–92.
122. Radermecker RP, Scheen AJ. Continuous subcutaneous insulin infusion with short-acting insulin analogues or human regular insulin: efficacy, safety, quality of life, and cost-effectiveness. Diabetes Metab Res Rev 2004;20:178–188.
