Hypoglycaemia in Type 2 diabetes

Abstract

The primary cause of hypoglycaemia in Type 2 diabetes is diabetes medication—in particular, those which raise insulin levels independently of blood glucose, such as sulphonylureas (SUs) and exogenous insulin. The risk of hypoglycaemia is increased in older patients, those with longer diabetes duration, lesser insulin reserve and perhaps in the drive for strict glycaemic control. Differing definitions, data collection methods, drug type/regimen and patient populations make comparing rates of hypoglycaemia difficult. It is clear that patients taking insulin have the highest rates of self‐reported severe hypoglycaemia (25% in patients who have been taking insulin for > 5 years). SUs are associated with significantly lower rates of severe hypoglycaemia. However, large numbers of patients take SUs in the UK, and it is estimated that each year > 5000 patients will experience a severe event caused by their SU therapy which will require emergency intervention. Hypoglycaemia has substantial clinical impact, in terms of mortality, morbidity and quality of life. The cost implications of severe episodes—both direct hospital costs and indirect costs—are considerable: it is estimated that each hospital admission for severe hypoglycaemia costs around £1000. Hypoglycaemia and fear of hypoglycaemia limit the ability of current diabetes medications to achieve and maintain optimal levels of glycaemic control. Newer therapies, which focus on the incretin axis, may carry a lower risk of hypoglycaemia. Their use, and more prudent use of older therapies with low risk of hypoglycaemia, may help patients achieve improved glucose control for longer, and reduce the risk of diabetic complications.

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References 75

1. 1.

   Defining and reporting hypoglycaemia in diabetes. Diabetes Care. 2005;28:1245-1249.

   Not in our library10.2337/diacare.28.5.1245

2. 2.

   Hypoglycemia. Can J Diabetes. 2003;27:S43-S45.

   Not in our library

3. 3.

   Note for guidance on clinical investigation of medicinal products in the treatment of diabetes mellitus. 2006.

   Not in our library

4. 4.

   Holstein A, Plaschke A, Egberts EH. Clinical characterization of severe hypoglycaemia—a prospective population based study. Exp Clin Endocrinol Diabetes. 2003;111:364-369.

   Not in our library10.1055/s-2003-42728

5. 5.

   Service FJ, Dale AJ, Elveback LR, Jiang NS. Insulinoma: clinical and diagnostic features of 60 consecutive cases. Mayo Clin Proc. 1976;51:417-429.

   Not in our library

6. 6.

   Marks V. The measurement of blood glucose and the definition of hypoglycaemia. Horm Metab Res. 1976;(Suppl. 6):1-6.

   Not in our library

7. 7.

   Cryer PE, Davis SN, Shamoon H. Hypoglycaemia in diabetes. Diabetes Care. 2003;26:1902-1912.

   Not in our library10.2337/diacare.26.6.1902

8. 8.

   Maran A, Lomas J, Macdonald IA, Amiel SA. Lack of preservation of higher brain function during hypoglycaemia in patients with intensively treated insulin dependent diabetes mellitus. Diabetologia. 1995;38:1412-1418.

   Not in our library10.1007/bf00400601

9. 9.

   Fanelli CG, Paramore DS, Hershey T, Terkamp C, Ovalle F, Craft S, et al. Impact of nocturnal hypoglycemia on hypoglycemic cognitive dysfunction in type 1 diabetes. Diabetes. 1998;47:1920-1927.

   Not in our library10.2337/diabetes.47.12.1920

10. 10.

    Cranston IA, Lomas J, Maran A, Macdonald IA, Amiel SA. Restoration of hypoglycaemia awareness in patients with long duration insulin dependent diabetes. Lancet. 1994;344:283-287.

    Not in our library10.1016/s0140-6736(94)91336-6

11. 11.

    Banarer S, Cryer PE. Hypoglycemia in type 2 diabetes. Med Clin North Am. 2004;88:1107-1116.

    Not in our library10.1016/j.mcna.2004.04.003

12. 12.

    Segal SA, Paramore DS, Cryer PE. Hypoglycemia-associated autonomic failure in advanced type 2 diabetes. Diabetes. 2002;51:724-733.

    Not in our library10.2337/diabetes.51.3.724

13. 13.

    Peacey SR, Rostami-Hodjegan A, George E, Tucker GT, Heller SR. The use of tolbutamide-induced hypoglycemia to examine the intraislet role of insulin in mediating glucagon release in normal humans. J Clin Endocrinol Metab. 1997;82:1458-1461.

    Not in our library10.1210/jcem.82.5.3910

14. 14.

    Del Prato S, Pulizzi N. The place of sulfonylureas in the therapy for type 2 diabetes mellitus. Metabolism. 2006;55(Suppl. 1):S20-S27.

    Not in our library10.1016/j.metabol.2006.02.003

15. 15.

    Miller CD, Phillips LS, Ziemer DC, Gallina DL, Cook CB, El-Kebbi IM. Hypoglycemia in patients with type 2 diabetes mellitus. Arch Intern Med. 2001;161:1653-1659.

    Not in our library10.1001/archinte.161.13.1653

16. 16.

    Ben-Ami H, Nagachandran P, Mendelson A, Edoute Y. Drug-induced hypoglycemic coma in 102 diabetic patients. Arch Intern Med. 1999;159:281-284.

    Not in our library10.1001/archinte.159.3.281

17. 17.

    Nattrass M, Lauritzen T. Review of prandial glucose regulation with repaglinide: a solution to the problem of hypoglycemia in the treatment of type 2 diabetes? Int J Obesity. 2000;24(Suppl. 3):S21-S31.

    Not in our library10.1038/sj.ijo.0801422

18. 18.

    Sotiropoulos A, Skliros EA, Tountas C, Apostolou U, Peppas TA, Pappas SI. Risk factors for severe hypoglycemia in type 2 diabetic patients admitted to hospital in Piraeus, Greece. East Mediterr Health J. 2005;11:485-489.

    Not in our library

19. 19.

    Shorr RI, Ray WA, Daugherty JR, Griffin MR. Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas. Arch Intern Med. 1997;157:1681-1686.

    Not in our library

20. 20.

    van Staa T, Abenhaim L, Monette J. Rates of hypoglycemia in users of sulphonylureas. J Clin Epidemiol. 1997;50:735-741.

    Not in our library10.1016/s0895-4356(97)00024-3

21. 21.

    Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet. 1998;352:837-853.

    Not in our library

22. 22.

    Leese GP, Wang J, Broomhall J, Kelly P, Marsden A, Morrison W, et al. Frequency of severe hypoglycemia requiring emergency treatment in type 1 and type 2 diabetes. Diabetes Care. 2003;26:1176-1180.

    Not in our library10.2337/diacare.26.4.1176

23. 23.

    Henderson JN, Allen KV, Deary IJ, Frier BM. Hypoglycaemia in insulin-treated Type 2 diabetes: frequency, symptoms and impaired awareness. Diabet Med. 2003;20:1016-1021.

    Not in our library10.1046/j.1464-5491.2003.01072.x

24. 24.

    Jaap AJ, Jones GC, McCrimmon RJ, Deary IJ, Frier BM. Perceived symptoms of hypoglycaemia in elderly Type 2 diabetic patients treated with insulin. Diabet Med. 1998;15:398-401.

    Not in our library10.1002/(sici)1096-9136(199805)15:5<398::aid-dia595>3.0.co;2-b

25. 25.

    Matyka K, Evans M, Lomas J, Cranston I, Macdonald I, Amiel SA. Altered hierarchy of protective responses against severe hypoglycemia in normal aging in healthy men. Diabetes Care. 1997;20:135-141.

    Not in our library10.2337/diacare.20.2.135

26. 26.

    Trovati M, Burzacca S, Mularoni E, Massucco P, Cavalot F, Mattiello L, et al. Occurrence of low blood glucose concentrations during the afternoon in type 2 (non-insulin-dependent) diabetic patients on oral hypoglycaemic agents: importance of blood glucose monitoring. Diabetologia. 1991;34:662-667.

    Not in our library10.1007/bf00400996

27. 27.

    Guillausseau PJ. Monitoring of metabolic control in patients with non-insulin-dependent diabetes mellitus on oral hypoglycaemic agents: value of evening blood glucose determination. Diabet Med. 1997;14:798-802.

    Not in our library10.1002/(sici)1096-9136(199709)14:9<798::aid-dia420>3.0.co;2-c

28. 28.

    Heller S, Chapman J, McCloud J, Ward J. Unreliability of reports of hypoglycaemia by diabetic patients. BMJ. 1995;310:440.

    Not in our library10.1136/bmj.310.6977.440

29. 29.

    Leiter LA, Yale J-F, Chiasson J-L, Harris SB, Kleinstiver P, Sauriol L. Assessment of the impact of fear of hypoglycemic episodes on glycemic and hypoglycemic management. Can J Diabetes. 2005;29:186-192.

    Not in our library

30. 30.

    Wright AD, Cull CA, Macleod KM, Holman RR. Hypoglycemia in Type 2 diabetic patients randomized to and maintained on monotherapy with diet, sulfonylurea, metformin, or insulin for 6 years from diagnosis: UKPDS73. J Diabetes Complications. 2006;20:395-401.

    Not in our library10.1016/j.jdiacomp.2005.08.010

31. 31.

    Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355:2427-2443.

    Not in our library10.1056/nejmoa066224

32. 32.

    Dormandy J, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive study (PROspective pioglitazone Clinical Trial In macrovascular Events): a randomised controlled trial. Lancet. 2006;366:1279-1289.

    Not in our library10.1016/s0140-6736(05)67528-9

33. 33.

    Josse RG, Chiasson JL, Ryan EA, Lau DC, Ross SA, Yale JF, et al. Acarbose in the treatment of elderly patients with type 2 diabetes. Diabetes Res Clin Pract. 2003;59:37-42.

    Not in our library10.1016/s0168-8227(02)00176-6

34. 34.

    UK prospective study of therapies of maturity onset diabetes: I. Effect of diet, sulphonylurea, insulin or biguanide therapy on fasting glucose and bodyweight over one year. Diabetologia. 1983;24:404-411.

    Not in our library

35. 35.

    Examining hypoglycaemic risk in diabetes: effect of treatment and type of diabetes. Diabetologia. 2007;50:1140-1147.

    Not in our library10.1007/s00125-007-0599-y

36. 36.

    Stahl M, Berger W. Higher incidence of severe hypoglycemia leading to hospital admission in type 2 diabetic patients treated with long acting versus short acting sulphonylureas. Diabet Med. 1999;16:586-590.

    Not in our library10.1046/j.1464-5491.1999.00110.x

37. 37.

    Tessier D, Dawson K, Tetrault JP, Bravo G, Meneilly GS. Glibenclamide vs. gliclazide in type 2 diabetes of the elderly. Diabet Med. 1994;11:974-980.

    Not in our library10.1111/j.1464-5491.1994.tb00256.x

38. 38.

    Holstein A, Plaschke A, Egberts EH. Lower incidence of severe hypoglycaemia in patients with type 2 diabetes treated with glimepiride versus glibenclamide. Diabetes Metab Res Rev. 2001;17:467-473.

    Not in our library10.1002/dmrr.235

39. 39.

    Holstein A, Plaschke A, Hammer C, Eqberts EH. Characteristics and time course of severe glimepiride versus glibenclamide induced hypoglycaemia. Eur J Clin Pharmacol. 2003;59:91-97.

    Not in our library10.1007/s00228-003-0592-4

40. 40.

    Moses R. A review of clinical experience with the prandial glucose regulator, repaglinide, in the treatment of type 2 diabetes. Expert Opin Pharmacother. 2000;1:1455-1467.

    Not in our library10.1517/14656566.1.7.1455

41. 41.

    Moses R, Slobodniuk R, Boyages D, Colaquiri S, Kidson W, Carter J, et al. Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with Type 2 diabetes. Diabetes Care. 1999;22:119-124.

    Not in our library10.2337/diacare.22.1.119

42. 42.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

43. 43.

    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;130:389-396.

    Not in our library10.7326/0003-4819-130-5-199903020-00002

44. 44.

    Yki-Jarvinen H, Kauppinen-Makelin R, Tiikkainen M, Vahatalo M, Virtamo H, Nikkila K, et al. Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study. Diabetologia. 2006;49:442-451.

    Not in our library10.1007/s00125-005-0132-0

45. 45.

    Yki-Jarvinen H, Kauppila M, Kujansuu E, Lahti J, Marjanen T, Niskanen L, et al. Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus. N Engl J Med. 1992;327:1426-1433.

    Not in our library10.1056/nejm199211123272005

46. 46.

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

    Not in our library10.2337/diacare.28.6.1282

47. 47.

    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;28:2673-2679.

    Not in our library10.2337/diacare.28.11.2673

48. 48.

    Nauck MA, Kleine N, Orskov C, Holst JJ, Willms B, Creutzfeldt W. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7–36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia. 1993;36:741-744.

    Not in our library10.1007/bf00401145

49. 49.

    Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006;29:2632-2637.

    Not in our library10.2337/dc06-0703

50. 50.

    Charbonnel B, Karasik A, Liu J, Wu M, Meininger G. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care. 2006;29:2638-2643.

    Not in our library10.2337/dc06-0706

51. 51.

    Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diab Obesity Metab. 2007;9:194-205.

    Not in our library10.1111/j.1463-1326.2006.00704.x

52. 52.

    Garber AJ, Schweizer A, Baron MA, Rochotte E, Dejager S. Vildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetes failing thiazolidinedione monotherapy: a randomized, placebo-controlled study. Diabetes Obes Metab. 2007;9:166-174.

    Not in our library10.1111/j.1463-1326.2006.00684.x

53. 53.

    Rosenstock J, Baron MA, Camisasca RP, Cressier F, Couturier A, Dejager S. Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes. Diabetes Obes Metab. 2007;9:175-185.

    Not in our library10.1111/j.1463-1326.2006.00698.x

54. 54.

    DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005;28:1092-1100.

    Not in our library10.2337/diacare.28.5.1092

55. 55.

    Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004;27:2628-2635.

    Not in our library10.2337/diacare.27.11.2628

56. 56.

    Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005;28:1083-1091.

    Not in our library10.2337/diacare.28.5.1083

57. 57.

    Greco D, Angileri G. Drug induced severe hypoglycemia in type 2 diabetic patients aged 80 years or older. Diab Nutr Metab. 2004;17:23-26.

    Not in our library

58. 58.

    Campbell IW. Metformin and the sulphonylureas: the comparative risk. Horm Metab Res Suppl. 1985;15:105-111.

    Not in our library

59. 59.

    Hitchen L. Doctors are failing to tell diabetic people about UK driving rules. BMJ. 2006;332:812.

    Not in our library10.1136/bmj.332.7545.812-d

60. 60.

    Lundkvist J, Berne C, Bolinder B, Jonsson L. The economic and quality of life impact of hypoglycemia. EurJ Health Econ. 2005;50:197-202.

    Not in our library10.1007/s10198-005-0276-3

61. 61.

    Davis RE, Morrissey M, Peters JR, Wittrup-Jensen K, Kennedy-Martin T, Currie CJ. Impact of hypoglycaemia on quality of life and productivity in type 1 and type 2 diabetes. Curr Med Res Opin. 2005;21:1477-1483.

    Not in our library10.1185/030079905x61929

62. 62.

    Quality of life in type 2 diabetic patients is affected by complications not by intensive policies to improve blood glucose or blood pressure control. Diabetes Care. 1999;22:1125-1136.

    Not in our library10.2337/diacare.22.7.1125

63. 63.

    Curtis L, Netten A. Unit Costs of Health and Social Care. 2006.

    Not in our library

64. 64.

    Holstein A, Plaschke A, Egberts EH. Incidence and costs of severe hypoglycemia. Diabetes Care. 2002;25:2109.

    Not in our library10.2337/diacare.25.11.2109

65. 65.

    Allicar M, Megas F, Houzard S, Baroux A, Le Thai F, Augendre-Ferrante B. Frequency and costs of hospital stays for hypoglycemia in France in 1995. Presse Med. 2000;29:657-661.

    Not in our library

66. 66.

    Cryer PE, Childs BP. Negotiating the barrier of hypoglycemia in diabetes. Diabetes Spectrum. 2002;15:20-27.

    Not in our library

67. 67.

    Cox DJ, Irvine A, Gonder-Frederick L, Nowacek G, Butterfield J. Fear of hypoglycemia: quantification, validation and utilization. Diabetes Care. 1987;10:617-621.

    Not in our library10.2337/diacare.10.5.617

68. 68.

    Sauriol L, Yale JF, Chiasson JL, Harris S, Leiter L, Kleinstiver S. Fear of hypoglycemia in people with type 1 and type 2 diabetes: the AID hypo on QoL study. 2006.

    Not in our library

69. 69.

    Davis S, Alonso MD. Hypoglycaemia as a barrier to glycemic control. J Diabetes Complic. 2004;18:60-68.

    Not in our library10.1016/s1056-8727(03)00058-8

70. 70.

    Garber A, Marre M, Blonde L, Allavoine T, Howlett H, Lehert P, et al. Influence of initial hyperglycemia, weight and age on the blood glucose lowering efficacy and incidence of hypoglycaemic symptoms with a single-tablet metformin-glibenclamide therapy (Glucovance) in type 2 diabetes. Diabetes Obes Metab. 2003;5:171-179.

    Not in our library10.1046/j.1463-1326.2003.00259.x

71. 71.

    Pitale S, Kernan-Schroeder D, Emanuele N, Sawin C, Sacks J, Abraira C. Health related quality of life in the VA Feasibility Study on glycemic control and complications in Type 2 diabetes mellitus. J Diabetes Complications. 2005;19:207-211.

    Not in our library10.1016/j.jdiacomp.2004.12.002

72. 72.

    Ritholz MD, Jacobson AM. Living with hypoglycemia. J Gen Intern Med. 1998;13:799-804.

    Not in our library10.1046/j.1525-1497.1998.00243.x

73. 73.

    Browne D, Avery L, Turner BC, Kerr D, Cavan DA. What do patients with diabetes know about their tablets? Diabet Med. 2000;17:528-531.

    Not in our library10.1046/j.1464-5491.2000.00327.x

74. 74.

    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;321:405-412.

    Not in our library10.1136/bmj.321.7258.405

75. 75.

    Khaw K-T, 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.

    Not in our library10.1136/bmj.322.7277.15

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