Download PDF
Diabetologie und Stoffwechsel 2012; 7(6): 429-433
DOI: 10.1055/s-0032-1330327
Editorial
© Georg Thieme Verlag KG Stuttgart · New York

Frühe Insulintherapie im Netzwerk individualisierter Therapie des Typ-2-Diabetes

M. Hanefeld
Further Information

Publication History

Publication Date:
17 December 2012 (online)

Also available at
    Permissions and Reprints

Die Therapie des Typ-2-Diabetes befindet sich im Umbruch, scheinbar sichere Paradigmen müssen im Licht neuer Studienergebnisse kritisch hinterfragt werden, viele neue Therapieoptionen drängen auf den Markt, oft mit 4 oder mehr Vertretern einer Substanzklasse, jüngstes Beispiel DPPIV-Inhibitoren. Doch für die meisten etablierten Antidiabetika fehlen evidenzbasierte Daten im direkten Vergleich. Die zu Beginn des Jahrhunderts gestarteten Megatrials ADVANCE, ACCORD, VADT haben alle das Ziel, durch verbesserte Glykämiekontrolle, gemessen am HbA1c, die Inzidenz kardiovaskulärer Endpunkte zu senken, verfehlt [1] [2] [3]. Diabetes-bezogene Komplikationen, Sicherheit und Karzinomrisiko waren dabei nur sekundäre Zielgrößen. In der ACCORD stieg unter intensivierter Therapie die kardiovaskuläre Mortalität sogar um über 21 % an, weshalb diese vorzeitig beendet wurde [2]. So blieb bis zur Publikation der ORIGIN-Daten im Juni diesen Jahres [4] nur die UK-PDS als valide Outcome-Studie, die einen direkten Vergleich von 3 etablierten Therapieoptionen Metformin, Sulfonylharnstoffe und Insulin erlaubte. Nach 11 Jahren ergab sich bei neu diagnostizierten Typ-2-Diabetikern ein signifikanter Benefit für alle 3 Therapien bezüglich mikrovaskulärer Komplikationen. Die Inzidenz kardiovaskulärer Ereignisse und Gesamtsterblichkeit wurde nur durch Metformin signifikant reduziert. Die HbA1c-Werte unterschieden sich am Ende der Interventionsphase aber nicht signifikant [5] [6]. Seitdem wird Metformin unangefochten in allen Leitlinien als First Line Drug zur Therapie des Typ-2-Diabetes empfohlen [7] [8].

 

  • Literatur

  • 1 Patel A, MacMahon S, Chalmers J et al. ADVANCE Collaborative Group Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358 (24) 2560-2572
    CrossrefPubMedGoogle Scholar
  • 2 Gerstein HC, Miller ME, Genuth S ACCORD Study Group et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med 2011; 364 (09) 818-828
    CrossrefGoogle Scholar
  • 3 Duckworth W, Abraira C, Moritz T et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009; 360 (02) 129-139 . Epub 2008 Dec 17
    CrossrefPubMedGoogle Scholar
  • 4 Gerstein HC, Bosch J, Dagenais GR ORIGIN Trial Investigators et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012; 367 (04) 319-328
    CrossrefGoogle Scholar
  • 5 UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352 (9131) 837-853
    CrossrefGoogle Scholar
  • 6 UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352 (9131) 854-865 . Erratum in: Lancet 1998;352 (9139):1558.
    CrossrefGoogle Scholar
  • 7 Schernthaner G, Barnett AH, Betteridge DJ et al. Is the ADA/EASD algorithm for the management of type 2 diabetes (January 2009) based on evidence or opinion? A critical analysis. Diabetologia 2010; 53 (07) 1258-1269
    CrossrefGoogle Scholar
  • 8 Matthaei S, Bierwirth R, Fritsche A et al. Medical antihyperglycaemic treatment of type 2 diabetes mellitus: update of the evidence-based guideline of the German Diabetes Association. Exp Clin Endocrinol Diabetes 2009; 117 (09) 522-557
    Article in Thieme ConnectGoogle Scholar
  • 9 Ray KK, Seshasai SR, Wijesuriya S et al. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet 2009; 373 (9677) 1765-1772
    CrossrefPubMedGoogle Scholar
  • 10 Zoungas S, Patel A, Chalmers J et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med 2010; 363 (15) 1410-1418
    CrossrefPubMedGoogle Scholar
  • 11 McCoy RG, Van Houten HK, Ziegenfuss JY et al. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care 2012; 35 (09) 1897-1901
    CrossrefPubMedGoogle Scholar
  • 12 Ott P, Benke I, Stelzer J et al. „Diabetes in Germany“ (DIG) study. A prospective 4-year-follow-up study on the quality of treatment for type 2 diabetes in daily practice]. Dtsch Med Wochenschr 2009; 134 (07) 291-297
    Article in Thieme ConnectGoogle Scholar
  • 13 Huppertz E, Pieper L, Klotsche J et al. Diabetes Mellitus in German Primary Care: quality of glycaemic control and subpopulations not well controlled – results of the DETECT study. Exp Clin Endocrinol Diabetes 2009; 117 (01) 6-14
    Article in Thieme ConnectGoogle Scholar
  • 14 Tschöpe D, Bramlage P, Binz C et al. Incidence and predictors of hypoglycaemia in type 2 diabetes – an analysis of the prospective DiaRegis registry. BMC Endocr Disord 2012; 12 (01) 23
    CrossrefGoogle Scholar
  • 15 Inzucchi SE, Bergenstal RM, Buse JB et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012; 35 (06) 1364-1379
    CrossrefPubMedGoogle Scholar
  • 16 Groop LC, Bonadonna RC, DelPrato S et al. Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance. J Clin Invest 1989; 84 (01) 205-213
    CrossrefGoogle Scholar
  • 17 Del Prato S. Role of glucotoxicity and lipotoxicity in the pathophysiology of Type 2 diabetes mellitus and emerging treatment strategies. Diabet Med 2009; 26 (12) 1185-1192
    CrossrefGoogle Scholar
  • 18 Kjems LL, Kirby BM, Welsh EM et al. Decrease in beta-cell mass leads to impaired pulsatile insulin secretion, reduced postprandial hepatic insulin clearance, and relative hyperglucagonemia in the minipig. Diabetes 2001; 50 (09) 2001-2012
    CrossrefGoogle Scholar
  • 19 Poitout V, Robertson RP. Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev 2008; 29 (03) 351-366
    CrossrefGoogle Scholar
  • 20 Gleason CE, Gonzalez M, Harmon JS et al. Determinants of glucose toxicity and its reversibility in the pancreatic islet beta-cell line, HIT-T15. Am J Physiol Endocrinol Metab 2000; 279 (05) E997-E1002
    Google Scholar
  • 21 Ceriello A. Hypothesis: the „metabolic memory”, the new challenge of diabetes. Diabetes Res Clin Pract 2009; 94 (2) 410-415
    Google Scholar
  • 22 Li Y, Xu W, Liao Z et al. Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients is associated with improvement of beta-cell function. Diabetes Care 2004; 27 (11) 2597-2602
    CrossrefPubMedGoogle Scholar
  • 23 Xu W, Li YB, Deng WP et al. Remission of hyperglycemia following intensive insulin therapy in newly diagnosed type 2 diabetic patients: a long-term follow-up study. Chin Med J 2009; 122 (21) 2554-2559
    Google Scholar
  • 24 Chon S, Oh S, Kim SW et al. The effect of early insulin therapy on pancreatic β-cell function and long-term glycemic control in newly diagnosed type 2 diabetic patients. Korean J Intern Med 2010; 25 (03) 273-281
    CrossrefGoogle Scholar
  • 25 Bhattacharyya OK, Estey EA, Cheng AY ; Canadian Diabetes Association 2008 Update on the Canadian Diabetes Association 2008 clinical practice guidelines. Can Fam Physician 2009; 55 (01) 39-43
    Google Scholar
  • 26 Sächsische Leitlinien zur Behandlung des Typ 2 Diabetes. 2010;
    Google Scholar
  • 27 Pennartz C, Schenker N, Menge BA et al. Chronic reduction of fasting glycemia with insulin glargine improves first- and second-phase insulin secretion in patients with type 2 diabetes. Diabetes Care 2011; 34 (09) 2048-2053
    CrossrefGoogle Scholar
  • 28 Hanefeld M, Fleischmann H, Landgraf W et al. EARLY Study: Early Basal Insulin Therapy under Real-Life conditions in type 2 Diabetics. Diabetes, Stoffwechsel und Herz, Bd. 21 2012: 91-97
    Google Scholar
  • 29 Fonseca V, Gill J, Zhou R et al. An analysis of early insulin glargine added to metformin with or without sulfonylurea: impact on glycaemic control and hypoglycaemia. Diabetes Obes Metab 2011; 13 (09) 814-822
    CrossrefPubMedGoogle Scholar
  • 30 Dormandy JA, Charbonnel B, Eckland DJ 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 2005; 366 (9493) 1279-1289
    CrossrefPubMedGoogle Scholar
  • 31 Hanefeld M, Koehler C, Hoffmann C et al. Effect of targeting normal fasting glucose levels with basal insulin glargine on glycaemic variability and risk of hypoglycaemia: a randomized, controlled study in patients with early Type 2 diabetes. Diabet Med 2010; 27 (02) 175-180
    CrossrefGoogle Scholar
  • 32 Ceriello A. Basal insulin and cardiovascular and other outcomes. N Engl J Med 2012; 367 (18) 1762-1763 ; author reply 1763-1764
    Google Scholar
  • 33 Hemkens LG, Grouven U, Bender R et al. Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia 2009; 52 (09) 1732-1744
    CrossrefPubMedGoogle Scholar
  • 34 Ruiter R, Visser LE, van Herk-Sukel MP et al. Risk of cancer in patients on insulin glargine and other insulin analogues in comparison with those on human insulin: results from a large population-based follow-up study. Diabetologia 2012; 55 (01) 51-62
    CrossrefPubMedGoogle Scholar
  • 35 Mellbin LG, Malmberg K, Norhammar A et al. Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Study. Diabetologia 2011; 54 (06) 1308-1317
    CrossrefGoogle Scholar
  • 36 Anselmino M, Malmberg K, Ohrvik J et al. Evidence-based medication and revascularization: powerful tools in the management of patients with diabetes and coronary artery disease: a report from the Euro Heart Survey on diabetes and the heart. Eur J Cardiovasc Prev Rehabil 2008; 15 (02) 216-223
    CrossrefGoogle Scholar
  • 37 Kahn SE, Haffner SM, Heise MA et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355 (23) 2427-2443
    CrossrefPubMedGoogle Scholar
  • 38 Riddle M et al. Attainment and Mainternance of HbA1c < 6.5 or 7 % with titrated basal insulin or Standard case in the ORIGIN trial. Diabetes Care 2012; accepted
    Google Scholar
  • 39 Holman RR, Paul SK, Bethel MA et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359 (15) 1577-1589
    CrossrefPubMedGoogle Scholar
  • 40 Nathan DM, Cleary PA, Backlund JY et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005; 353 (25) 2643-2653
    CrossrefGoogle Scholar