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Diabetologie und Stoffwechsel 2015; 10(02): 85-90
DOI: 10.1055/s-0034-1399251
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Inkretin-basierte Therapie: ein ergänzender Therapieansatz bei Patienten mit Typ-1-Diabetes?

Incretin-Based Therapy: a Complementary Approach in the Treatment of Patients with Type 1 Diabetes?
B. Gallwitz
1   Dept. Medicine IV, University Hospital Tübingen, Germany
,
J. Kienhöfer
2   Medical Department, Novo Nordisk Pharma GmbH, Mainz, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
27 April 2015 (online)

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Zusammenfassung

Menschen mit Typ-1-Diabetes (T1 D) leiden unter einem absoluten Insulinmangel, resultierend aus einem chronischen Autoimmunangriff auf pankreatische β-Zellen. Zudem liegt eine Dysregulation der sekretorischen Aktivität von Glucagon in pankreatischen α-Zellen vor. Trotz der zwingenden, intensivierten Insulintherapie ist die Kontrolle des Blutzuckers bei T1 D oft unzureichend und birgt ein Hypoglykämierisiko für die Patienten. Als fester Bestandteil der Therapie des Typ-2-Diabetes (T2 D) etablierten sich in den letzten Jahren Inkretin-basierte Wirkstoffe, die GLP-1 Rezeptor-Agonisten (GLP-1 RA) und Dipeptidyl-Peptidase-IV(DPP-IV)-Hemmer. Untersuchungen lassen nun auch auf einen positiven therapeutischen Nutzen bei der Behandlung von Patienten mit T1 D schließen. So deuten bisherige Studien darauf hin, dass der durch GLP-1 RA hervorgerufene glykämische Effekt bei T1 D durch eine Hemmung der sekretorischen Aktivität der α-Zellen und durch den inhibitorischen Effekt auf die Nährstoffaufnahme verursacht wird.

Abstract

People suffering from type 1 diabetes (T1 D) show absolute insulin deficiency due to a chronic autoimmune attack on pancreatic β-cells. In addition glucagon secretion in pancreatic α cells is dysregulated. Although treatment of T1 D demands intensified insulin therapy, control of blood glucose is often insufficient and patients are frequently at risk of hypoglycemia. In type 2 diabetes T2 D incretin-based substances, GLP-1 receptor agonists (GLP-1 RA) and dipeptidyl-peptidase-IV(DDP-IV)-inhibitors play an important therapeutic role. Current results from clinical trials with this class of drugs indicate a potential therapeutic benefit also for patients with T1 D. Recent findings indicate that the glycoregulatory effect of GLP-1 RA in T1 D results from inhibition of α cell secretory activity, as well as suppression of caloric uptake.

Schlüsselwörter

Typ-1-Diabetes - Inkretin - GLP-1 Rezeptor-Agonisten - Dipeptidyl-Peptidase-IV-Inhibitor

Key words

type 1 diabetes - incretin - GLP-1 receptor agonist - dipeptidyl-peptidase-IV-inhibitor
 

  • Literatur

  • 1 Devendra D, Liu E, Eisenbarth GS. Type 1 diabetes: recent developments. BMJ 2004; 328: 750-754
    CrossrefGoogle Scholar
  • 2 Brown RJ, Sinaii N, Rother KI. Too much glucagon, too little insulin: time course of pancreatic islet dysfunction in new-onset type 1 diabetes. Diabetes Care 2008; 31: 1403-1404
    CrossrefGoogle Scholar
  • 3 Meier JJ. Beta cell mass in diabetes: a realistic therapeutic target?. Diabetologia 2008; 51: 703-713
    CrossrefGoogle Scholar
  • 4 Dinneen S et al. Failure of glucagon suppression contributes to postprandial hyperglycaemia in IDDM. Diabetologia 1995; 38: 337-343
    CrossrefGoogle Scholar
  • 5 Kramer CK et al. Glucagon response to oral glucose challenge in type 1 diabetes: lack of impact of euglycemia. Diabetes Care 2014; 37: 1076-1082
    CrossrefGoogle Scholar
  • 6 Chillaron JJ et al. Type 1 diabetes, metabolic syndrome and cardiovascular risk. Metabolism 2014; 63: 181-187
    CrossrefGoogle Scholar
  • 7 Inzucchi SE 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: 1364-1379
    CrossrefPubMedGoogle Scholar
  • 8 Mojsov S, Weir GC, Habener JF. Insulinotropin: glucagon-like peptide I (7–37) co-encoded in the glucagon gene is a potent stimulator of insulin release in the perfused rat pancreas. J Clin Invest 1987; 79: 616-619
    CrossrefGoogle Scholar
  • 9 Kreymann B et al. Glucagon-like peptide-1 7–36: a physiological incretin in man. Lancet 1987; 2: 1300-1304
    Google Scholar
  • 10 Drucker DJ et al. Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci U S A 1987; 84: 3434-3438
    CrossrefGoogle Scholar
  • 11 Fehmann HC, Habener JF. Functional receptors for the insulinotropic hormone glucagon-like peptide-I (7–37) on a somatostatin secreting cell line. FEBS Lett 1991; 279: 335-340
    CrossrefGoogle Scholar
  • 12 Ahren B. Emerging dipeptidyl peptidase-4 inhibitors for the treatment of diabetes. Expert Opin Emerg Drugs 2008; 13: 593-607
    CrossrefGoogle Scholar
  • 13 Creutzfeldt WO et al. Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide I(7–36) amide in type I diabetic patients. Diabetes Care 1996; 19: 580-586
    CrossrefGoogle Scholar
  • 14 Dupre J, Behme MT, McDonald TJ. Exendin-4 normalized postcibal glycemic excursions in type 1 diabetes. J Clin Endocrinol Metab 2004; 89: 3469-3473
    CrossrefGoogle Scholar
  • 15 Ghazi T et al. Acute metabolic effects of exenatide in patients with type 1 diabetes with and without residual insulin to oral and intravenous glucose challenges. Diabetes Care 2014; 37: 210-216
    CrossrefGoogle Scholar
  • 16 Kielgast U et al. Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual beta-cell function. Diabetes Care 2011; 34: 1463-1468
    CrossrefGoogle Scholar
  • 17 Raman VS et al. The role of adjunctive exenatide therapy in pediatric type 1 diabetes. Diabetes Care 2010; 33: 1294-1296
    CrossrefGoogle Scholar
  • 18 Varanasi A et al. Liraglutide as additional treatment for type 1 diabetes. Eur J Endocrinol 2011; 165: 77-84
    CrossrefGoogle Scholar
  • 19 Rother KI et al. Effects of exenatide alone and in combination with daclizumab on beta-cell function in long-standing type 1 diabetes. Diabetes Care 2009; 32: 2251-2257
    CrossrefGoogle Scholar
  • 20 Hramiak I et al. Entero-pancreatic hormones in C-peptide positive Type 1 (TID) and lean Type 2 (T2D) diabetes mellitus. in The Ninth International Congress of Endocrinology, Nice, France: Proceedings. 1992
    Google Scholar
  • 21 Flint A et al. The once-daily human glucagon-like peptide-1 (GLP-1) analog liraglutide improves postprandial glucose levels in type 2 diabetes patients. Adv Ther 2011; 28: 213-226
    CrossrefGoogle Scholar
  • 22 Van Belle TL, Coppieters KT, Von Herrath MG. Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiological reviews 2011; 91: 79-118
    CrossrefGoogle Scholar
  • 23 Kuhadiya ND et al. Liraglutide as additional treatment to insulin in obese patients with type 1 diabetes mellitus. Endocr Pract 2013; 19: 963-967
    CrossrefGoogle Scholar
  • 24 Kuhadiya ND. ADA 2014; Poster 974.
  • 25 Deiss D, Diederich S, Kordonouri O. Erfolgreicher Einsatz von Liraglutid bei Typ-1-Diabetes und MODY. Dtsch Med Wochenschr 2011; 136: 1116-1120
    Article in Thieme ConnectGoogle Scholar
  • 26 Deacon CF. Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes Metab 2011; 13: 7-18
    CrossrefGoogle Scholar
  • 27 Foley JE et al. Effect of vildagliptin on glucagon concentration during meals in patients with type 1 diabetes. Horm Metab Res 2008; 40: 727-730
    Article in Thieme ConnectGoogle Scholar
  • 28 Kutoh E. Sitagliptin is effective and safe as add-on to insulin in patients with absolute insulin deficiency: a case series. J Med Case Rep 2011; 5: 117
    CrossrefGoogle Scholar
  • 29 Hadjiyanni I et al. Exendin-4 modulates diabetes onset in nonobese diabetic mice. Endocrinology 2008; 149: 1338-1349
    CrossrefGoogle Scholar
  • 30 Xu G et al. Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. Diabetes 1999; 48: 2270-2276
    CrossrefGoogle Scholar
  • 31 Xue S et al. Exendin-4 therapy in NOD mice with new-onset diabetes increases regulatory T cell frequency. Ann N Y Acad Sci 2008; 1150: 152-156
    CrossrefGoogle Scholar
  • 32 Merani S et al. Liraglutide, a long-acting human glucagon-like peptide 1 analog, improves glucose homeostasis in marginal mass islet transplantation in mice. Endocrinology 2008; 149: 4322-4328
    CrossrefGoogle Scholar
  • 33 Suarez-Pinzon WL et al. Combination therapy with glucagon-like peptide-1 and gastrin restores normoglycemia in diabetic NOD mice. Diabetes 2008; 57: 3281-3288
    CrossrefGoogle Scholar
  • 34 Yang Z et al. Combined treatment with lisofylline and exendin-4 reverses autoimmune diabetes. Biochem Biophys Res Commun 2006; 344: 1017-1022
    CrossrefGoogle Scholar
  • 35 Farilla L et al. Glucagon-like peptide-1 promotes islet cell growth and inhibits apoptosis in Zucker diabetic rats. Endocrinology 2002; 143: 4397-4408
    CrossrefGoogle Scholar
  • 36 Sherry NA et al. Exendin-4 improves reversal of diabetes in NOD mice treated with anti-CD3 monoclonal antibody by enhancing recovery of beta-cells. Endocrinology 2007; 148: 5136-5144
    CrossrefGoogle Scholar
  • 37 Farilla L et al. Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology 2003; 144: 5149-5158
    CrossrefGoogle Scholar
  • 38 Buteau J et al. Glucagon-like peptide-1 prevents beta cell glucolipotoxicity. Diabetologia 2004; 47: 806-815
    CrossrefGoogle Scholar
  • 39 Meier JJ et al. Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration?. Diabetologia 2005; 48: 2221-2228
    CrossrefGoogle Scholar
  • 40 de Heer J et al. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas. Diabetologia 2008; 51: 2263-2270
    CrossrefGoogle Scholar
  • 41 Kielgast U et al. Effect of glucagon-like peptide-1 on alpha- and beta-cell function in C-peptide-negative type 1 diabetic patients. J Clin Endocrinol Metab 2010; 95: 2492-2496
    CrossrefGoogle Scholar
  • 42 52 Week Trial of Liraglutide in Type 1 Diabetes (LIDO). ClinicalTrials.gov Identifier: NCT01787916.
    Google Scholar