Exp Clin Endocrinol Diabetes 2007; 115(4): 240-243
DOI: 10.1055/s-2007-970577
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG · Stuttgart · New York

Early Retinopathy Progression in Four Randomized Trials Comparing Insulin Glargine and Nph Insulin

M. D. Davis 1 , R. W. Beck 2 , P. D. Home 3 , J. Sandow 4 , F. L. Ferris 5
  • 1Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA
  • 2Jaeb Center for Health Research, Tampa, FL, USA
  • 3School of Medical Sciences - Diabetes, University of Newcastle upon Tyne, Newcastle upon Tyne, UK
  • 4sanofi-aventis, Frankfurt am Main, Germany
  • 5Division of Biometry and Epidemiology, National Eye Institute, Bethesda, MD, USA
Further Information

Publication History

received 11. 9. 2006 first decision 11. 9. 2006

accepted 6. 11. 2006

Publication Date:
03 May 2007 (online)

Abstract

Early worsening of diabetic retinopathy, characterized by cotton wool spots, intraretinal microvascular abnormalities and/or macular edema, can occur following improvement of glycemic control. In four randomized 28- to 52-week clinical trials comparing insulin glargine and NPH insulin in regard to glycemic control and frequency of hypoglycemia, ophthalmologic examinations and fundus photographs were included to assess frequency of early worsening of retinopathy or other early adverse ocular effects. Retinopathy progression rates at 28 weeks were 7-12% by clinical examination and 3-8% by photographic grading; corresponding rates of clinically significant macular edema (CSME) were 1-8% and 1-4%, respectively. Optic disc swelling was not observed clinically or in photographs. Two of the 24 possible comparisons (four trials, three outcomes, two assessment methods), both of which were photographic assessments in type 2 diabetes, were in/near the nominally significant range and favored NPH insulin: 28-week rates of ≥3-step retinopathy progression (insulin glargine: 16/213, 7.5%; NPH insulin: 6/220, 2.7%; p=0.028) and 52-week CSME rates (26/233, 11.2% and 14/214, 6.5%, respectively; p=0.098). Because the between-treatment differences were small and inconsistent across trials and assessment methods, and because overall rates were consistent with the natural course of diabetic retinopathy, we conclude that it is unlikely that insulin glargine carries a higher risk of early worsening or other early adverse effect than NPH insulin. These trials tended to exclude a large early adverse effect, such as optic disc swelling, but cannot assess longer-term effects; a 5-year randomized trial of insulin glargine versus NPH insulin has been initiated.Data from this manuscript have been presented as posters and published in abstract form at the European Association for the Study of Diabetes 2001 (Diabetologia 44(Suppl 1):I-IV(A287), 2001) and the Latin American Diabetes Association 2001 (11-15 November 2001, Punta del Este, Uruguay; Poster 180) congresses.

References

  • 1 Bähr M, Kolter T, Seipke G, Eckel J. Growth promoting and metabolic activity of the human insulin analogue [GlyA21, ArgB31, ArgB32] insulin (HOE 901) in muscle cells.  Eur J Pharmacol. 1997;  320 259-265
  • 2 Chantelau E. Evidence that upregulation of serum IGF-1 concentration can trigger acceleration of diabetic retinopathy.  Br J Ophthalmol. 1998;  82 ((7)) 725-730
  • 3 Ciaraldi TP, Carter L, Seipke G, Mudaliar S, Henry RR. Effects of the long-acting insulin analog insulin glargine on cultured human skeletal muscle cells: comparisons to insulin and IGF-I.  J Clin Endocrinol Metab. 2001;  86 ((12)) 5838-5847
  • 4 Dahl-Jorgensen K, Brinchmann-Hansen O, Hanssen KF, Sandvik L, Aagenaes O. Rapid tightening of blood glucose control leads to transient deterioration of retinopathy in insulin dependent diabetes mellitus: the Oslo study.  Br Med J (Clin Res Ed). 1985;  290 ((6471)) 811-815
  • 5 DCCT . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group.  N Engl J Med. 1993;  329 ((14)) 977-986
  • 6 DCCT . The effect of intensive diabetes treatment on the progression of diabetic retinopathy in insulin-dependent diabetes mellitus. Diabetes Control and Complications Trial Research Group.  Arch Ophthalmol. 1995;  113 36-51
  • 7 DCCT . Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial.  Arch Ophthalmol. 1998;  116 ((7)) 874-886
  • 8 ETDRS . Grading diabetic retinopathy from stereoscopic color fundus photographs-an extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group.  Ophthalmology. 1991a;  98 ((5 Suppl)) 786-806
  • 9 ETDRS . Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Early Treatment Diabetic Retinopathy Study Research Group.  Ophthalmology. 1991b;  98 ((5 Suppl)) 823-833
  • 10 Home PD, Rosskamp R, Forjanic-Klapproth J, Dressler A. A randomized multicentre trial of insulin glargine compared with NPH insulin in people with type 1 diabetes.  Diabetes Metab Res Rev. 2005;  21 ((6)) 545-553
  • 11 Klein R, Klein B, Moss S, Davis M, DeMets D. Wisconsin Epidemiologic Study of Diabetic Retinopathy IX. Four-year incidence and progression of diabetic retinopathy when age at diagnosis is less than 30 years.  Ophthalmology. 1989a;  107 237-243
  • 12 Klein R, Klein B, Moss S, Davis M, DeMets D. Wisconsin Epidemiologic Study of Diabetic Retinopathy X. Four-year incidence and progression of diabetic retinopathy when age at diagnosis is 30 years or more.  Arch Ophthalmol. 1989b;  107 244-249
  • 13 Klein R, Moss S, Klein B, Davis M, DeMets D. Wisconsin Epidemiologic Study of Diabetic Retinopathy XI. The incidence of macular edema.  Ophthalmology. 1989c;  96 1501-1510
  • 14 Massi Benedetti M, Humburg E, Dressler A, Ziemen M. A one-year, randomised, multicentre trial comparing insulin glargine with NPH insulin in combination with oral agents in patients with Type 2 diabetes.  Horm Metab Res. 2003;  35 ((3)) 189-196
  • 15 Ratner RE, Hirsch IB, Neifing JL, Garg SK, Mecca TE, Wilson CA. Less hypoglycemia with insulin glargine in intensive insulin therapy for Type 1 diabetes.  Diabetes Care. 2000;  23 ((5)) 639-643
  • 16 Rosenstock J, Schwartz SL, Clark Jr CM, Park GD, Donley DW, Edwards MB. Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin.  Diabetes Care. 2001;  24 ((4)) 631-636
  • 17 SRTRG . A randomized trial of sorbinol, an aldose reductase inhibitor, in diabetic retinopathy* Sorbinil Retinopathy Trial Research Group.  Arch Ophthalmol. 1990;  108 1234-1244
  • 18 Staiger K, Staiger H, Schweitzer MA, Metzinger E, Balletshofer B, Haring HU, Kellerer M. Insulin and its analogue glargine do not affect viability and proliferation of human coronary artery endothelial and smooth muscle cells.  Diabetologia. 2005;  48 ((9)) 1898-1905
  • 19 Thrailkill KM, Quattrin T, Baker L, Kuntze JE, Compton PG, Martha Jr PM. Cotherapy with recombinant human insulin-like growth factor I and insulin improves glycemic control in type 1 diabetes. RhIGF-I in IDDM Study Group.  Diabetes Care. 1999;  22 ((4)) 585-592
  • 20 Yki-Järvinen 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 ((8)) 1130-1136

Correspondence

M. D. Davis

Fundus Photograph Reading Center

Department of Ophthalmology and Visual Sciences

University of Wisconsin-Madison

406 Science Drive

Suite 400

Madison

WI 53711-1068

USA

Phone: +1/608/263/60 71

Fax: +1/608/262/18 99

Email: davis@rc.ophth.wisc.edu

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