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Research Article| Volume 118, ISSUE 5, SUPPLEMENT , 21-26, May 2005

Intensifying insulin therapy in patients with type 2 diabetes mellitus

  • Irl B. Hirsch
    Correspondence
    Requests for reprints should be addressed to Irl B. Hirsch, MD, Diabetes Care Center, Division of Endocrinology, University of Washington Medical Center, 1959 NE Pacific Street, Box 356176, Seattle, Washington 98195.
    Affiliations
    Diabetes Care Center, Division of Endocrinology, University of Washington School of Medicine, Seattle, Washington, USA, Seattle, Washington, USA.
    Search for articles by this author
      The current paradigm for pharmacologic management of type 2 diabetes mellitus (DM) is to progress with oral agents until severe insulin deficiency develops, at which time insulin can be initiated. Reexamination of data from the Diabetes Control and Complications Trial (DCCT) suggests that glycemic variability may be an important factor involved in the pathogenesis of microvascular complications. It is now appreciated that oxidative stress from overproduction of reactive oxygen species may be the result of this glycemic variability, suggesting that an overemphasis of basal insulin may not be the ideal strategy for insulin replacement, even though basal insulin is often the only insulin used initially. Although finding the best insulin program for treatment of type 2 DM is an important area of research, almost all patients with severe insulin deficiency will require both basal and prandial replacement. Use of adequate lag times (time between injecting the prandial insulin and eating), U-500 insulin (500 U/mL human regular insulin), and home blood glucose monitoring to determine “glycemic trend” are important tools that are readily available to all patients.

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      References

        • UK Prospective Diabetes Study Group
        Effect of intensive blood glucose with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34).
        Lancet. 1998; 352: 837-853
        • Inzucchi S.E.
        Oral antihyperglycemic therapy for type 2 diabetes.
        JAMA. 2002; 287: 360-372
        • Garber A.J.
        • Donovan Jr, D.S.
        • Dandona P.
        • Bruce S.
        • Park J.S.
        • et al.
        Efficacy of glyburide/metformin tablets compared with initial monotherapy in type 2 diabetes.
        J Clin Endocrinol Metab. 2003; 88: 3598-3604
        • DeFronzo R.A.
        • Goodman A.M.
        • Multicenter Metformin Study Group
        Efficacy of metformin in patients with non–insulin-dependent diabetes mellitus.
        N Engl J Med. 1995; 333: 541-549
        • Gavin L.A.
        • Barth J.
        • Arnold D.
        • Shaw R.
        Troglitazone add-on therapy to a combination of sulfonylureas plus metformin achieved and sustained effective diabetes control.
        Endocr Pract. 2000; 6: 305-310
        • American Diabetes Association
        Standards of medical care in diabetes.
        Diabetes Care. 2004; 27: S15-S35
        • American College of Endocrinology
        American College of Endocrinology Consensus Statement on Guidelines for Glycemic Control.
        Endocr Pract. 2002; 8: 5-11
        • Saydah S.H.
        • Fradkin J.
        • Cowie C.C.
        Poor control of risk factors for diabetes among adults with previously diagnosed diabetes.
        JAMA. 2004; 291: 335-342
        • The Diabetes Control and Complications 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
        • The Diabetes Control and Complications Trial (DCCT) Research Group
        The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial.
        Diabetes. 1995; 44: 968-983
        • The Diabetes Control and Complications Research Group
        Implementation protocols in the Diabetes Control and Complications Trial.
        Diabetes Care. 1995; 18: 361-376
        • Brownlee M.
        Biochemistry and molecular cell biology of diabetic complications.
        Nature. 2001; 414: 813-820
        • Risso A.
        • Mercuri F.
        • Quagliaro L.
        • et al.
        Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture.
        Am J Physiol Endocrinol Metab. 2001; 281: E924-E930
        • Quagliaro L.
        • Piconi L.
        • Assalone R.
        • et al.
        Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells.
        Diabetes. 2003; 52: 2795-2804
        • Fong D.S.
        • Aiello L.
        • Gardner T.W.
        • et al.
        Position statement.
        Diabetes Care. 2004; 27: S84-S87
        • American Diabetes Association
        Position statement.
        Diabetes Care. 2004; 27: S79-S83
        • Dewitt D.E.
        • Hirsch I.B.
        Outpatient therapy for type 1 and type 2 diabetes.
        JAMA. 2003; 289: 2254-2264
        • Skyler J.S.
        Insulin treatment.
        in: Lebovitz H.E. Therapy for Diabetes Mellitus and Related Disorders. 4th ed. American Diabetes Association, Alexandria, VA2004: 207-223
        • Riddle M.C.
        • Rosenstock J.
        • Gerich J.
        The Treat-to-Target Trial.
        Diabetes Care. 2003; 26: 3080-3086
        • Bastyr III, E.J.
        • Stuart C.A.
        • Brodows R.G.
        • et al.
        • IOEZ Study Group
        Therapy focused on lowering postprandial glucose, not fasting glucose, may be superior for lowering HbA1c..
        Diabetes Care. 2000; 23: 1236-1241
        • Mudaliar S.
        • Lindberg F.A.
        • Joyce M.
        • et al.
        Insulin aspart (B28 Asp-insulin).
        Diabetes Care. 1999; 22: 1501-1506
        • Burge M.R.
        • Castillo K.R.
        • Schade D.S.
        Meal composition is a determinant of lispro-induced hypoglycemia in IDDM.
        Diabetes Care. 1997; 20: 152-155
        • Hay L.C.
        • Wilmshurst E.G.
        • Fulcher G.
        Unrecognized hypo- and hyperglycemia in well-controlled patients with type 2 diabetes mellitus.
        Diabetes Technol Ther. 2003; 5: 19-26
        • Raskin P.
        • Bode B.W.
        • Marks J.B.
        • et al.
        Continuous subcutaneous insulin infusion and multiple daily injection therapy are equally effective in type 2 diabetes.
        Diabetes Care. 2003; 26: 2598-2603
        • Hirsch I.B.
        Insulin analogues.
        N Engl J Med. 2005; 352: 174-183
        • D’Eliseo P.
        • Blaauw J.
        • Milicevic Z.
        • Wyatt J.
        • Ignaut D.A.
        • Malone J.K.
        Patient acceptability of a new 3.0 ml pre-filled insulin pen.
        Curr Med Res Opin. 2000; 16: 125-133
        • Knee T.S.
        • Seidensticker D.F.
        • Walton J.L.
        • et al.
        A novel use of U-500 insulin for continuous subcutaneous insulin infusion in patients with insulin resistance.
        Endocr Pract. 2003; 9: 181-186
        • Garg R.
        • Lawrence I.G.
        • Akinsola M.O.
        • et al.
        Improved glycemic control in severely insulin resistant, insulin-treated diabetic patients with U500 human actrapid over two year follow-up [abstract].
        Diabetologia. 2004; 47: A58