Acta Diabetologica

, Volume 50, Issue 4, pp 529–535 | Cite as

Comparison of human insulin and insulin analogues on hypoglycaemia and metabolic variability in type 1 diabetes using standardized measurements (HYPO score and Lability Index)

  • M. Pérez-Maraver
  • J. Caballero-Corchuelo
  • A. Boltana
  • R. Insa
  • J. Soler
  • E. Montanya
Original Article


To evaluate whether treatment with insulin analogues is associated with a lower risk of hypoglycaemia (HYPO score) and less glycaemic variability (Lability Index) than treatment with human insulin in patients with type 1 diabetes. In a 6-month prospective, open-labelled trial, we randomized 47 patients treated with human insulin to receive treatment with human insulin (n = 21) or insulin analogues (n = 26). HYPO score, Lability Index (LI), and hypoglycaemic episode characteristics were assessed at baseline and at the end of follow-up. A 72-h, continuous glucose monitoring was performed at the end in a subgroup of patients. Groups were compared with nonparametric tests. Significance was defined as P < 0.05. HYPO score (71.5 [36.0–162] vs. 260 [52.0–676], P < 0.05), nocturnal hypoglycaemia (0.4 vs. 1.4 events/patient/4-week, P < 0.05), and <2.5 mmol/l hypoglycaemic events were lower in insulin analogue group after 6 months. There was a trend towards a lower LI in insulin analogue group (74.3 [51.3–133] vs. 123 [76.4–171] mmol/l2/h week−1, P = 0.064). HbA1c and insulin dose were comparable between groups. In type 1 diabetes, insulin analogues were associated with a lower hypoglycaemic risk and a trend towards reduced glycaemic variability compared with human insulin. These effects occurred despite comparable metabolic control.


Insulin analogues Hypoglycaemia HYPO score Lability Index 


  1. 1.
    The Diabetes Control Complications Trial Research Group (1993) 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 329:977–986CrossRefGoogle Scholar
  2. 2.
    Kilpatrick ES, Rigby AS, Atkin SL (2008) A1c variability and the risk of microvascular complications in type 1 diabetes. Diabetes Care 31:2198–2202PubMedCrossRefGoogle Scholar
  3. 3.
    Zafon C, Creus C (2011) A comparison on insulin regimen treatment of elderly (>70 years) and younger (<70 years) type 2 diabetic patients in actual clinical practice. Acta Diabetol. doi: 10.1007/s00592-011-0289-6 (Epub ahead of print)PubMedGoogle Scholar
  4. 4.
    Gentile S, Agrusta M, Guarino G et al (2011) Metabolic consequences of incorrect insulin administration techniques in aging subjects with diabetes. Acta Diabetol 48:121–125PubMedCrossRefGoogle Scholar
  5. 5.
    Murphy N, Keane S, Ong K et al (2003) Randomized cross-over trial of insulin glargine plus lispro or NPH insulin plus regular human insulin in adolescents with type 1 diabetes on intensive insulin regimens. Diabetes Care 26:799–804PubMedCrossRefGoogle Scholar
  6. 6.
    Hirsch IB (2005) Insulin analogues. N Engl J Med 352:174–183PubMedCrossRefGoogle Scholar
  7. 7.
    Brunelle RL, Llewelyn J, Anderson J et al (1998) Meta-analysis of the effect of insulin lispro on severe hypoglycemia in patients with type 1 diabetes. Diabetes Care 21:1726–1731PubMedCrossRefGoogle Scholar
  8. 8.
    Raskin P, Guthrie R, Leiter L et al (2000) Use of insulin aspart, a fast-acting insulin analog, as the mealtime insulin in the management of patients with type 1 diabetes. Diabetes Care 23:583–588PubMedCrossRefGoogle Scholar
  9. 9.
    Chapman TM, Noble S (2002) Insulin aspart: a review of its use in the management of type 1 and 2 diabetes mellitus. Drugs 62:1945–1981PubMedCrossRefGoogle Scholar
  10. 10.
    Plank J, Siebenhofer A, Berghold A et al (2005) Systematic review and meta-analysis of short-acting insulin analogues in patients with diabetes mellitus. Arch Intern Med 165:1337–1344PubMedCrossRefGoogle Scholar
  11. 11.
    Ratner R, Hirsch IB, Neifing JL et al (2000) Less hypoglycaemia with insulin glargine in intensive insulin therapy for type 1 diabetes. Diabetes Care 23:639–643PubMedCrossRefGoogle Scholar
  12. 12.
    Hermansen K, Madsbad S, Perrild H et al (2001) Comparison of the soluble basal insulin analog insulin detemir with NPH insulin. Diabetes Care 24:296–301PubMedCrossRefGoogle Scholar
  13. 13.
    Vague P, Selam JL, Skeie S et al (2003) Insulin detemir is associated with more predictable glycemic control and reduced risk of hypoglycemia than NPH insulin in patients with type 1 diabetes on a basal-bolus regimen with premeal insulin aspart. Diabetes Care 26:590–596PubMedCrossRefGoogle Scholar
  14. 14.
    Danne T, Lupke K, Walte K, Von Schuetz W, Gall MA (2003) Insulin detemir is characterized by a consistent pharmacokinetic profile across age-groups in children, adolescent, and adults with type 1 diabetes. Diabetes Care 26:3087–3092PubMedCrossRefGoogle Scholar
  15. 15.
    Hasani-Ranjbar S, Fazlollahi MR, Mehri A, Larijani B (2011) Allergy to human insulin and specific immunotherapy with glargine; case report with review of literature. Acta Diabetol. doi: 10.1007/s00592-011-0254-4. [Epub ahead of print]PubMedGoogle Scholar
  16. 16.
    Singh SR, Ahmad F, Lal A, Yu C, Bai Z, Bennett H (2009) Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis. CMAJ 180:385–397PubMedCrossRefGoogle Scholar
  17. 17.
    Gill GV, Yudkin JS, Keen H, Beran D (2011) The insulin dilemma in resource-limited countries. A way forward? Diabetologia 54:19–24PubMedCrossRefGoogle Scholar
  18. 18.
    Vigneri R, Squatrito S, Sciacca L (2010) Insulin and its analogs: actions via insulin and IGF receptors. Acta Diabetol 47:271–278PubMedCrossRefGoogle Scholar
  19. 19.
    Sahin SB, Cetinkalp S, Ozgen AG, Saygili F, Yilmaz C (2010) The importance of anti-insulin antibody in patients with type 1 diabetes mellitus treated with continuous subcutaneous insulin infusion or multiple daily insulin injections therapy. Acta Diabetol 47:325–330PubMedCrossRefGoogle Scholar
  20. 20.
    Ryan EA, Shandro T, Green K et al (2004) Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation. Diabetes 53:955–962PubMedCrossRefGoogle Scholar
  21. 21.
    Kapellen TM, Wolf J, Rosenbauer J, Stachow R et al (2009) Changes in the use of analogue insulins in 37,206 children and adolescents with type 1 diabetes in 275 German and Austrian centers during the last twelve years. Exp Clin Endocrinol Diabetes 117:329–335PubMedCrossRefGoogle Scholar
  22. 22.
    Siebenhofer A, Planck J, Berghold A et al (2006) Short-acting insulin analogues versus regular human insulin in patients with diabetes mellitus. Cochrane Database Syst Rev 2:CD003287Google Scholar
  23. 23.
    Klein O, Lynge J, Endahl L, Damholt B, Nosek L, Heise T (2007) Albumin-bound basal insulin analogues (insulin detemir and NN344): comparable time-action profiles but less variability than insulin glargine in type 2 diabetes. Diabetes Obes Metab 9:290–299PubMedCrossRefGoogle Scholar
  24. 24.
    Ashwell SG, Amiel SA, Bilous RW et al (2006) Improved glycaemic control with insulin glargine plus insulin lispro: a multicentre, randomized, cross-over trial in people with type 1 diabetes. Diabet Med 23:285–292PubMedCrossRefGoogle Scholar
  25. 25.
    Rossetti P, Porcellati F, Bolli G, Fanelli C (2008) Prevention of hypoglycemia while achieving good glycemic control in type 1 diabetes: the role of insulin analogs. Diabetes Care 31(suppl 2):S113–S120PubMedCrossRefGoogle Scholar
  26. 26.
    Pickup JC, Kidd J, Burmiston S, Yemane N (2006) Determinants of glycaemic control in type 1 diabetes during intensified therapy with multiple daily insulin injections or continuous subcutaneous insulin infusion: importance of blood glucose variability. Diabetes Metab Res Rev 22:232–237PubMedCrossRefGoogle Scholar
  27. 27.
    Wentholt IM, Kulik W, Michels RP et al (2008) Glucose fluctuations and activation of oxidative stress in patients with type 1 diabetes. Diabetologia 51:183–190PubMedCrossRefGoogle Scholar
  28. 28.
    Ceriello A, Esposito K, Piconi L et al (2008) Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes 57:1349–1354PubMedCrossRefGoogle Scholar
  29. 29.
    Monnier L, Mas E, Ginet C et al (2006) Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 295:1681–1687PubMedCrossRefGoogle Scholar
  30. 30.
    Kovatchev BP, Cox DJ, Gonder-Frederick LA, Young-Hyman D, Schlundt D, Clarke W (1998) Assessment of risk for severe hypoglycemia among adults with IDDM: validation of the low blood glucose index. Diabetes Care 21:1870–1875PubMedCrossRefGoogle Scholar
  31. 31.
    Clarke W, Cox DJ, Gonder-Frederick LA, Julian D, Schlundt D, Polonsky W (1995) Reduced awareness of hypoglycemia in adults with IDDM: a prospective study of hypoglycemic frequency and associated symptoms. Diabetes Care 18:517–522PubMedCrossRefGoogle Scholar
  32. 32.
    Service FJ, Molnar GD, Rosewear JW et al (1970) Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes 19:644–655PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • M. Pérez-Maraver
    • 1
    • 3
    • 4
  • J. Caballero-Corchuelo
    • 1
    • 3
    • 4
  • A. Boltana
    • 1
  • R. Insa
    • 1
  • J. Soler
    • 1
    • 2
    • 3
    • 4
  • E. Montanya
    • 1
    • 2
    • 3
    • 4
  1. 1.Endocrine Unit (13-2), Hospital Universitari BellvitgeL’Hospitalet de Llobregat, BarcelonaSpain
  2. 2.Department of Clinical ScienceMedical School, University of BarcelonaBarcelonaSpain
  3. 3.Institut d′Investigació Biomèdica de Bellvitge (IDIBELL)L’Hospitalet de Llobregat, BarcelonaSpain
  4. 4.CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)BarcelonaSpain

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