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Normoglykämie als Therapieziel der Diabetesbehandlung — Konzept und Realisierung

Normoglycemia as therapeutic goal in the treatment of diabetes — Concept and realisation

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Summary

In diabetic patients (near-)normoglycemic control of blood glucose can only rarely be achieved by conventional insulin treatment. Novel strategies for this goal include transplantation of pancreatic tissue (whole organ, segment or isolated islets), the artificial pancreas with continuous blood glucose monitoring, insulin pump treatment and the intensified conventional treatment both of the latter including self-measurement of blood glucose and self-adaptation of the insulin dosis. The results of pancreas transplantation in recent years have shown a marked improvement, the one-year survival rate of a functioning organ is in the range of 50–70%. Due to the lifelong immunosuppression pancreas transplantation should be considered in diabetic patients who need a kidney transplantation and for this reason already require immunosuppression. In spite of encouraging results in animals islet transplantation in humans has been disappointing to date. The artificial pancreas at present cannot be used for long-term treatment mainly due to the problems of the glucose sensor. The application of insulin pump treatment without continuous monitoring of blood glucose (open loop) and intensified conventional treatment both can lead to improved glycemic control in spite of a more flexible life style. Only this way of treatment made it possible to perform randomized prospective studies in diabetic patients on the effect of (near-)normoglycemic control on secondary complications. The first results show a tendency towards a positive effect on mild to moderate diabetic retinopathy over 2 years. Thus, every juvenile diabetic patient should be informed about these possibilities of treatment. To definitely answer this question a large randomized prospective controlled trial including 1400 patients (Diabetes Control and Complications Trial, DCCT trial) is currently performed over 5 years both with respect to the influence of near-normoglycemia on existing secondary complications as also on their prevention.

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Literatur

  1. Albisser AM, Leibel BS, Ewart TG, Davidovac Z, Botz CK, Zingg W (1974) An artificial endocrine pancreas. Diabetes 23:389–396

    Google Scholar 

  2. Assal JP, Mühlhauser I, Pernet A, Gfeller R, Jörgens V, Berger M (1985) Patient education as the basis for diabetes care in clinical practice and research. Diabetologia 28:602–613

    Google Scholar 

  3. Banting FG, Best CH (1922) The internal secretion of the pancreas. J Lab Clin Med 7:251–266

    Google Scholar 

  4. Berger M (1989) Long-term efficacy and safety of intensified insulin treatment strategies. In: Creutzfeldt W, Lefèbvre P (eds) Diabetes mellitus: Pathophysiology and treatment. Springer, Berlin Heidelberg New York, pp 225–233

    Google Scholar 

  5. Berthoud HR, Trimble ER, Siegel EG, Bereiter DA, Jeanrenaud B (1980) Cephalic phase insulin secretion in normal and islet transplanted rats. Am J Physiol 239:E336-E340

    Google Scholar 

  6. Brownlee M, Cerami A, Vlassara H (1988) Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. New Engl J Med 318:1315–1321

    Google Scholar 

  7. Borch-Johnson K, Andersen PK, Deckert T (1985) The effect of proteinuria on relative mortality in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 28:580–596

    Google Scholar 

  8. Brinchmann-Hansen O, Dahl-Jörgensen K, Hanssen KF, Sandvik L (1988) The response of diabetic retinopathy to 41 months of multiple insulin injections, insulin pumps, and conventional insulin therapy. Arch Ophthalmol 106:1242–1246

    Google Scholar 

  9. Brückel J, Kerner W, Zier H, Steinbach G, Pfeiffer EF (1989) In vivo measurement of subcutaneous glucose concentrations with an enzymatic glucose sensor and a wick method. Klin Wochenschr 67:491–495

    Google Scholar 

  10. Chantelau EA, Gösseringer G, Sonnenberg GE, Berger M (1985) Moderate intake of sucrose does not impair metabolic control in pump-treated diabetic out-patients. Diabetologia 28:204–207

    Google Scholar 

  11. Corry RJ (1989) Vascularized pancreas transplantation. Diabetes 38, Suppl 1:321–322

    Google Scholar 

  12. Dahl-Jörgensen K, Brinchmann-Hansen O, Hanssen KF, Sandvik L, Aagenaes O, Aker Diabetes Group (1985) Rapid tightening of blood glucose control leads to transient deterioration in retinopathy in insulin-dependent diabetes mellitus: The Oslo Study. Br Med J 290:811–815

    Google Scholar 

  13. Dahl-Jörgensen K, Brinchmann-Hansen O, Hanssen KF, Ganes T, Kierulf P, Smeland E, Sandvik L, Aagenaes O (1986) Effect of near-normoglycemia for two years on progression of early diabetic retinopathy, nephropathy, and neuropathy: The Oslo Study. Br Med J 293:1195–1199

    Google Scholar 

  14. Dahl-Jörgensen K, Hanssen KF, Kierulf P, Bjäro T, Sandvik L, Aagenaes O (1988) Reduction of urinary albumin excretion after 4 years of continuous subcutaneous insulin infusion in insulin-dependent diabetes mellitus. The Oslo Study. Acta Endocrinologica (Copenh) 117:19–25

    Google Scholar 

  15. The DCCT Research Group (1986) The Diabetes Control and Complications Trial (DCCT): design and methodological considerations for the feasability phase. Diabetes 35:530–545

    Google Scholar 

  16. The DCCT Research Group (1988) Are continuing studies of metabolic control and microvascular complications in insulin-dependent diabetes mellitus justified? N Engl J Med 313:246–249

    Google Scholar 

  17. The DCCT Research Group (1988) Weight gain associated with intensive therapy in the Diabetes Control and Complications Trial. Diabetes Care 11:567–573

    Google Scholar 

  18. Dieterle P, Gries FA, Hepp KD, Otto H, Schöffling K (1985) Therapie des Diabetes mellitus: Einstellungskriterien und Erfolgskontrollen. Dtsch Med Wochenschr 110:477–478

    Google Scholar 

  19. Engerman RL, Kern TS (1987) Progression of incipient diabetic retinopathy during good glycemic control. Diabetes 36:808–812

    Google Scholar 

  20. Freinkel N, Dooley SL, Metzger BE (1985) Current concepts. Care of the pregnant woman with insulin-dependent diabetes mellitus. N Engl J Med 313:96–101

    Google Scholar 

  21. Hanssen KF, Dahl-Jörgensen K, Lauritzen T, Feldt-Rasmussen B, Brinchmann-Hansen O, Deckert T (1986) Diabetic control and microvascular complications: the near-normoglycemic experience. Diabetologia 29:677–684

    Google Scholar 

  22. Holman RR, Dornau TL, Mayon-White V, Howard-Williams J, Orde-Peckar C, Jenkins L, Steemson J, Rolfe R, Smith B, Barbour D, McPherson K, Poon P, Rizza C, Mann JI, Knight AH, Bron AJ, Turner RC (1983) Prevention of deterioration of renal and sensory-nerve function by more intensive management of insulin-dependent diabetic patients. A two-year randomized prospective study. Lancet 1:204–208

    Google Scholar 

  23. Hopt UT (1989) Die kombinierte Pankreas-/Nierentransplantation. Akt Endokrin Stoffw 10:70–79

    Google Scholar 

  24. Janka HU, Warram JH, Rand LI, Krolewski AS (1989) Riskfactors for progression of background retinopathy in longstanding IDDM. Diabetes 38:460–464

    Google Scholar 

  25. Jarret RJ (1988) Is insulin atherogenic? Diabetologia 31:71–75

    Google Scholar 

  26. Job D, Eschwege E, Guyot-Argenton C, Aubry JP, Tchobroutsky G (1976) Effect of multiple daily insulin injections on the course of diabetic retinopathy. Diabetes 25:463–469

    Google Scholar 

  27. Klein R, Klein BEK, Moss SE, Cavid MD, DeMets DL (1984) The Wisconsin epidemiologic study of diabetic retinopathy. II. Prevalence and risk of diabetic retinopathy when age of diagnosis is less than 30 years. Arch Ophthalmol 102:520–526

    Google Scholar 

  28. Kroc Collaborative Study Group (1985) Blood glucose control and the evolution of diabetic retinopathy and albuminuria. N Engl J Med 311:365–372

    Google Scholar 

  29. Kroc Collaborative Study Group (1988) Diabetic retinopathy after two years of intensified insulin treatment. Follow-up of the Kroc Collaborative Study. JAMA 260:37–41

    Google Scholar 

  30. Lacy PE, Finke EH, Janney CG, Davie JM (1982) Prolongation of islet xenograft survival by in vitro culture of rat megaislets in 95% O2. Transplantation 33:588–592

    Google Scholar 

  31. Landgraf R, Nusser J, Müller W, Landgraf-Leurs MMC, Thurau S, Ulbig M, Kampik A, Lachenmayr B, Hillebrand G, Schleibner S, Illner WD, Abendroth D, Land W (1989) Fate of late complications in type I diabetic patients after successful pancreas-kidney transplantation. Diabetes 38, Suppl 1:33–37

    Google Scholar 

  32. Lauritsen T, Frost-Larsen K, Larsen HW, Deckert T, The Steno Study Group (1983) Effect of 1 year of near-normal blood glucose levels on retinopathy in insulin-dependent diabetes. Lancet 1:200–204

    Google Scholar 

  33. Lauritsen T, Frost-Larsen K, Larsen HW, Deckert T, The Steno Study Group (1985) Two-year experience with continuous subcutaneous insulin infusion in relation to retinopathy and neuropathy. Diabetes 35, Suppl 3:74–79

    Google Scholar 

  34. Mehring JV v., Minkowski O (1889) Diabetes mellitus nach Pankreasexstirpation. Zentralbl Klin Med 10:393; nachlesbar auch Diabetes 38:1–6

    Google Scholar 

  35. Mühlhauser I, Bruckner I, Berger M, Cheta D, Jörgens V, Ionescu-Tirgoviste C, Scholz V, Mincu I (1987) Evaluation of an intensified insulin treatment and teaching programme as routine management of type 1 (insulin-dependent) diabetes. The Bukarest-Düsseldorf Study. Diabetologia 30:681–690

    Google Scholar 

  36. Mühlhauser I (1987) Near-normoglycemia and microvascular complications. Diabetologia 30:47–48

    Google Scholar 

  37. Nathan DM, Singer DE, Hurxthal K, Goodson JD (1984) The clinical information value of the glycosylated hemoglobin assay. N Engl J Med 310:341–346

    Google Scholar 

  38. Pfeiffer EF, Thum C, Clemens AH (1974) The artificial beta cell — a continuous control of blood sugar by external regulation of insulin infusion (glucose controlled insulin infusion system). Horm Metab Res 6:339–342

    Google Scholar 

  39. Pickup JC, Keen H, White ML, Parsons JA, Alberti KG (1979) Longterm continuous subcutaneous insulin infusion in diabetics at home. Lancet II:870–873

    Google Scholar 

  40. Pickup JC, Shaw GW, Claremont DL (1989) In vivo molecular sensing in diabetes mellitus: an implantable glucose sensor with direct electron transfer. Diabetologia 32:213–217

    Google Scholar 

  41. Pirart J (1977) Diabéte et complications dégéneratives. Presentation d'une étude prospective portant sur 4400 cas observés entre 1947 et 1973. Diabete et Metabolisme 3:97–107, 173–182 und 245–256. Auch in: Diabetes Care 1 (1978):168–188 und 252–263

    Google Scholar 

  42. Point Study Group (1988) One-year trial of a remote-controlled implantable insulin infusion system in type I diabetic patients. Lancet II:866–869

    Google Scholar 

  43. Ramsay RC, Goetz FC, Sutherland DER, Mauer SM, Robinson LL, Cantrill HC, Knobloch WH, Najarian JS (1988) Progression of diabetic retinopathy after pancreas transplantation for insulin dependent diabetes mellitus. N Engl J Med 318:208–214

    Google Scholar 

  44. Raskin P, Rosenstock J (1986) Blood glucose control and diabetic complications. Ann Int Med 105:254–263

    Google Scholar 

  45. Ritter MM, Richter WO, Schwandt P (1988) Therapie der diabetischen Gangrän durch kontinuierliche subkutane Insulintherapie. Münch Med Wochenschr 130:62–64

    Google Scholar 

  46. Sauer H (1985) Intensivierte Insulintherapie. Dtsch Med Wochenschr 110:925–928

    Google Scholar 

  47. Sharp DW (1989) Islet transplantation. Diabetes 38, Suppl 1:323–328

    Google Scholar 

  48. Shichiri M, Asakawa N, Yamasaki Y, Kawamori R, Albe H (1986) Telemetry glucose monitoring device with needletype glucose sensor: A useful tool for blood glucose monitoring in diabetic individuals. Diabetic Care 9:298–301

    Google Scholar 

  49. Siegel EG, Trapp VE, Wollheim CB, Renold A, Schmidt FH (1980) Beneficial effect of low-carbohydrate high-protein diets in long-term diabetic rats. Metabolism 29:421–427

    Google Scholar 

  50. Siegel EG, Trimble ER, Renold AE, Berthoud HR (1980) Importance of preabsorptive insulin release on oral glucose tolerance: Studies in islet transplanted rats. GUT 21:1002–1009

    Google Scholar 

  51. Siegel EG, Creutzfeldt W (1985) Stimulation of insulin release in isolated rat islets by GIP in physiological concentrations and its relation to islet cyclic AMP content. Diabetologia 28:857–861

    Google Scholar 

  52. Siegel EG (1987) Die Regulation der frühen Phase der Insulinsekretion und ihre Bedeutung für die Glukosehomöostase. Habilitationsschrift, Göttingen

    Google Scholar 

  53. Siegel EG, Creutzfeldt W (1988) Hormone responsiveness of collagenase-isolated rat islets is markedly increased by short-term maintenance in tissue culture. Horm Metab Res 20:184–185

    Google Scholar 

  54. Standl E (1987) Diabetische Mikroangiopathien. Internist 28:262–272

    Google Scholar 

  55. Standl E (1989) Hyperinsulinämie — eine Ursache der Makroangiopathie? Akt Endokr Stoffw 10:41–46

    Google Scholar 

  56. Stout RW (1987) Insulin and atheroma — an update. Lancet 1:1077–1079

    Google Scholar 

  57. Sutherland DER, Kendall DM, Moudry KC (1988) Pancreas transplantation in nonuremic, type I diabetic patients. Surgery 104:453–464

    Google Scholar 

  58. Sutherland DER, Moudry KC, Fryd DS (1989) Results of pancreas transplant registry. Diabetes 38, Suppl 1:46–54

    Google Scholar 

  59. Ziegler D, Gries FA (1988) Diabetische Neuropathie. Dtsch Med Wochenschr 113:1040–1042

    Google Scholar 

  60. Zinman B (1989) The physiologic replacement of insulin. An elusive goal. New Engl J Med 321:361–370

    Google Scholar 

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Gewidmet meinem Vater, Dr. Günther Siegel, 7448 Wolfschlugen

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Siegel, E.G. Normoglykämie als Therapieziel der Diabetesbehandlung — Konzept und Realisierung. Klin Wochenschr 68, 306–312 (1990). https://doi.org/10.1007/BF01649021

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