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Diabetes aktuell 2011; 9(6): 267-273
DOI: 10.1055/s-0031-1295562
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© Georg Thieme Verlag Stuttgart · New York

Aspekte der modernen Diabetesbehandlung – Einfluss, Nachweis, Beurteilung und Vermeidung von Glukoseexkursionen

Aspects of Modern Diabetes Treatment – Impact, Detection, Evaluation and Avoidance of Glucose Excursions
Andreas Thomas
1   Medtronic GmbH, Meerbusch
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Publication Date:
31 October 2011 (online)

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Durch randomisierte, kontrollierte Studien wie die DCCT oder UKPDS ist belegt, dass der die durchschnittliche Glukosekonzentration repräsentierende HbA1c-Wert die Güte der Glukosestoffwechseleinstellung im Hinblick auf die Diabetesprognose einerseits gut beschreibt, andererseits aber in seiner Aussage begrenzt ist. Insbesondere reflektiert er keine Glukoseexkursionen und bietet dadurch auch keine Aussage zum Hypoglykämierisiko. Verschiedene experimentelle Untersuchungen legen aber den Schluss nahe, dass Glukoseexkursionen einen wesentlichen Einfluss auf die Entwicklung von vaskulären Schäden haben, sodass deren Vermeidung bis zum Beweis des Gegenteils als notwendig anzusehen ist. Durch die Verfügbarkeit des kontinuierlichen Glukosemonitorings (CGM) können Glukoseschwankungen seit einigen Jahren lückenlos aufgezeichnet und folglich bei der Therapieoptimierung berücksichtigt werden. Um aus den CGM-Profilen unmittelbar Schlussfolgerungen für die Diabetesprognose ziehen zu können, wurde das ”Glukosepentagon“-Modell entwickelt, für welches allerdings noch keine klinische Validierung erfolgte. Da es den HbA1c-Wert beinhaltet, erweitert es diesen im Sinne der glykämischen Variabilität. Therapeutisch gibt es eine Reihe von Optionen für die Minimierung der glykämischen Variabilität, die abschließend zusammengefasst sind.

It has been demonstrated through randomized, controlled studies such as DCCT or UKPDS that the average glucose concentration represented by the HbA1c value adequately describes on the one hand the efficacy of glucose metabolism control whereas, on the other hand, it has only limited information content. In particular it does not reflect glucose excursions and thus provides no information on the risk of hypoglycemia. Various experimental studies, however, strongly suggest that glucose excursions have a very considerable influence on the development of vascular damage; accordingly there avoidance should be considered as necessary as long as there is evidence to the contrary. With the availability of continuous glucose monitoring (CGM) in the past few years deviations in glucose concentration can be recorded over time and thus be taken into account in therapy optimization. In order to be able to obtain direct conclusions on the diabetic prognosis from the CGM profiles, the ”glucose pentagon“ has been developed it has as yet not been validated clinically. Since it includes the HbA1c value it extends this in the sense of glycemic variability. Several therapeutic options are available to minimize glycemic variability and these are summarized in the concluding text.

Key words

Diabetes - glycemic variability - continuous glucose monitoring - ”glucose pentagon“
 

  • Literatur

  • 1 Hauner H. Diabetesepidimie und Dunkelziffer. Deutscher Gesundheitsbericht Diabetes 2011. Verlag Kirchheim 2011; 8-13
    Google Scholar
  • 2 Hauner H, Köster I, von Ferber L. Ambulante Versorgung von Patienten mit Diabetes mellitus im Jahr 2001. Dtsch Med Wochenschr 2003; 128: 2638-2643
    Article in Thieme ConnectGoogle Scholar
  • 3 Liebl A, Neuß A, Spannheimer A et al. Kosten des Typ-2-Diabetes in Deutschland: Ergebnisse der CODE-2-Studie. Dtsch Med Wochenschr 2001; 126: 585-589
    Article in Thieme ConnectGoogle Scholar
  • 4 The DCCT-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
    CrossrefGoogle Scholar
  • 5 UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-853
    CrossrefGoogle Scholar
  • 6 Stratton IM, Adler AI, Neil HAW et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321: 405-412
    CrossrefPubMedGoogle Scholar
  • 7 McCarter RJ, Hempe JM, Chalew SA. Mean Blood Glucose and Biological Variation Have Greater Influence on HbA1c Levels than Glucose Instability. Diabetes Care 2006; 29: 352-355
    CrossrefGoogle Scholar
  • 8 Kerner W, Brückel J, Böhm BO. Definition, Klassifikation und Diagnostik des Diabetes mellitus. Evidenzbasierte Leitlinie DDG – Aktualisierung. 2004;
    Google Scholar
  • 9 Biondi-Zoccai GL, Abbate A, Liuzzo G, Biasucci LM. Atherothrombosis, Inflammation, and Diabetes. J Am Coll Cardiol 2003; 41: 1071-1077
    CrossrefGoogle Scholar
  • 10 Henrichs HR. HbA1c – Glycated Hemoglobin and Diabetes Mellitus. Bremen – London – Boston: UNI-MED Verlag AG; (ISBN 978-3-89599-851-3) 2009
    Google Scholar
  • 11 The Diabetes Control and Complications Trial 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
    CrossrefGoogle Scholar
  • 12 DECODE Study Group. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. Lancet 1999; 354: 617-621
    CrossrefGoogle Scholar
  • 13 DECODE Study Group. Is the current definition for diabetes relevant to mortality risk from all causes and cardiovascular and noncardiovascular diseases?. Diabetes Care 2003; 26: 688-696
    CrossrefGoogle Scholar
  • 14 Hanefeld M, Fischer S, Julius U et al. Risk factors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11-year follow up. Diabetologica 1996; 39: 1577-1583
    CrossrefPubMedGoogle Scholar
  • 15 Ohkubo Y, Kishikawa H, Araki E et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995; 28: 103-117
    CrossrefPubMedGoogle Scholar
  • 16 Shichiri M, Kishikawa H, Ohkubo Y, Wake N. Long-term results of the Kumamoto Study on optimal diabetes control in type 2 diabetic patients. Diabetes Care 2000; 23
    Google Scholar
  • 17 Piconi L, Quagliaro L, DaRos R et al. Intermittent high glucose enhances ICAM-1, VCAM-1, E-selectin and interleukin-6 expression in human umbilical endothelial cells in culture: the role of poly (ADP-ribose) polymerase. J Thromb Haemost 2004; 2: 1453-1459
    CrossrefPubMedGoogle Scholar
  • 18 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
    Google Scholar
  • 19 Monnier L, Mas E, Ginet C et al. Activation of Oxidative Stress by Acute Glucose Fluctuations Compared With Sustained Chronic Hyperglycemia in Patients With Type 2 Diabetes. JAMA 2006; 295: 1681-1687
    CrossrefPubMedGoogle Scholar
  • 20 Hanefeld M. Control of Postprandial Hyperglycemia – an essential Part of Good Diabetes Treatment and Prevention of Cardiovascular Diseases. Diabetologie und Stoffwechsel 2007; 2: 362-369
    Article in Thieme ConnectGoogle Scholar
  • 21 Hanefeld M, Koehler C, Henkel E et al. Post-challenge hyperglycaemia relates more strongly than fasting hyperglycaemia with carotid intima-media thickness: the RIAD Study. Diabetic Medicine 2000; 17: 835-840
    CrossrefGoogle Scholar
  • 22 Ceriello A, Kumar S, Piconi L, Esposito K, Giugliano D. Simultaneous Control of Hyperglycemia and Oxidative Stress Normalizes Endothelial Function in Type 1 Diabetes. Diabetes Care 2007; 30: 649-654
    CrossrefGoogle Scholar
  • 23 Monnier L, Colette C. Glycemic Variability Should we and can we prevent it?. Diabetes Care 2008; 31
    Google Scholar
  • 24 Wentholt IME, Kulik W, Michels RPJ, Hoekstra JBL, DeVries JH. Glucose fluctuations and activation of oxidative stress in patients with type 1 diabetes. Diabetologia 2008; 51: 183-190
    Google Scholar
  • 25 Krantz JS, Mack WJ, Hodis HN et al. Early onset of subclinical Atherosclerosis in young patients with type 1 diabetes. J Pediatr 2004; 145: 452-457
    CrossrefGoogle Scholar
  • 26 Juutilainen A, Letho A, Onnemaa T, Pyörälä K, Laakso M. Similarity of the Impact of Type 1 and Type 2 Diabetes on Cardiovascular Mortality in Middle-Aged Subjects. Diabetes Care 2008; 31: 714-719
    CrossrefGoogle Scholar
  • 27 Egi M, Bellomo R, Stachowski E, French CJ, Hart G. Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients. Anesthesiology 2006; 105: 244-252
    CrossrefGoogle Scholar
  • 28 Gill GV, Woodward A, Casson IF, Weston PJ. Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes - the 'dead in bed' syndrome revisited. Diabetologia 2009; 52: 42-45
    CrossrefGoogle Scholar
  • 29 Cryer PE. Hypoglycaemia: The limiting factor in the glycaemic management of Type I and Type II Diabetes. Diabetologia 2002; 45: 937-948
    CrossrefGoogle Scholar
  • 30 Cryer PE. Hypoglycemia. Pathophysiology, Diagnosis and Treatment. Oxford University Press: New York; 1997
    Google Scholar
  • 31 Schwartz NS, Clutter WE, Shah SD, Cryer PE. Glycemic thresholds for activation of glucose counterregulatory systems are higher than the threshold for symptoms. J Clin Invest 1987; 79: 777-781
    CrossrefGoogle Scholar
  • 32 Fanelli C, Pampanelli S, Epifano L et al. Relative roles of insulin and hypoglycemia on induction of neuroendocrine responses to, symptoms of, and deterioration of cognitive function in hypoglycemia in male and female humans. Diabetologia 1994; 37: 797-807
    CrossrefGoogle Scholar
  • 33 Mitrakou A, Ryan C, Veneman T et al. Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms and cerebral dysfunction. Am J Physiol 1991; 260
    Google Scholar
  • 34 Heller SR, Macdonald IA, Herbert M, Tattersall RB. Influence of sympathetic nervous system on hypoglycaemic warning symptoms. Lancet 1987; 2: 359-363
    Google Scholar
  • 35 Lingenfelser T, Buettner UW, Uhl H et al. Recovery of hypoglycaemia-associated compromised cerebral function after a short interval of euglycaemia in insulin-dependent diabetic patients. Electroencephalogr Clin Neurophysiol 1994; 92: 196-203
    Google Scholar
  • 36 Desouza C, Salazar H, Cheong B, Murgo J, Fonseca V. Association of Hypoglycemia and Cardiac Ischemia: A Study Based on Continuous Monitoring. Diabetes Care 2003; 26: 1485-1489
    CrossrefGoogle Scholar
  • 37 Veglio M, Sivieri R, Chinaglia A, Scaglione L, Perin PC. QT Interval Prolongation and Mortality in Type 1 Diabetic Patients. A 5-year cohort prospective study. Diabetes Care 2000; 23: 1381-1383
    CrossrefGoogle Scholar
  • 38 The Action to Control Cardiovascular Risk in Diabetes Study Group: Effect of Intensive Glucose Lowering in Type 2 Diabetes. N Eng J Med 2008; 358: 2545-2559
    CrossrefGoogle Scholar
  • 39 Thomas A, Schönauer M, Achermann F et al. The “glucose pentagon”: Assessing glycemic control of patients with diabetes mellitus by a model integrating different parameters from glucose profiles. Diabetes Technol Ther 2009; 11: 399-409
    CrossrefGoogle Scholar
  • 40 Skyler JS. Diabetic Complications. The Importance of Glucose Control. Endocrinol Metab Clin North Am 1996; 25: 243-254
    CrossrefGoogle Scholar
  • 41 Nathan DM, Turgeon H, Regan S. Relationship between glycated haemoglobin levels and mean glucose levels over time. Diabetologia 2007; 50: 2239-2244
    Google Scholar
  • 42 Thomas A, Heinemann L. Prognosis of Diabetes Related Complications by Continuous Glucose Monitoring Profiles: Data of the JDRF-Study Analyzed by the Glucose-Pentagon-Model (GPM). Diabetes 2011; 60 (Suppl. 01)
    Google Scholar
  • 43 Freckmann G, Hagenlocher S, Baumstark A et al. Continuous Glucose Profiles in Healthy Subjects under Everyday Life Conditions and after Different Meals. J Diabetes Sci Technol 2007; 1: 695-703
    CrossrefPubMedGoogle Scholar
  • 44 Meier JJ, Salmen S, Götze O et al. Normalisation of fasting and postprandial blood glucose with graded doses of Glucagon-Like Peptide 1 (GLP-1) in Type 2 diabetic patients. Diabetologia 2002; 45 (Suppl. 01)
    Google Scholar
  • 45 Dailey G. Beyond insulin replacement: addressing the additional needs of the diabetes patient. Diabetes Obes Metab 2008; 10 (Suppl. 02) 83-97
    CrossrefGoogle Scholar
  • 46 Gallwitz B. Liraglutide. Drugs of the Future 2008; 33: 13-20
    CrossrefGoogle Scholar
  • 47 Parhofer KG. Glucagon-like peptide 1 (GLP-1). MMW Fortschr Med 2007; 149: 41-43
    Google Scholar
  • 48 Fineman MS, Giotta MP, Thompson RG, Kolterman OG, Koda JE. Amylin response following Sustacal ingestion is diminished in type Il diabetic patients treated with insulin. Diabetologia 1996; 39 (Suppl. 01)
    Google Scholar
  • 49 Weyer C, Kim D, Burrell T et al. Mealtime Amylin Replacement with Pramlintide Markedly Reduced Postprandial Glucose Excursions When Added to Insulin Lispro in Patients with Type 1 or Type 2 Diabetes. Diabetes 2003; 52 (Suppl. 01)
    Google Scholar
  • 50 Chase HP, Saib SZ, MacKenzie T, Hansen MM, Garg SK. Post-prandial glucose excursions following four methods of bolus insulin administration in subjects with Type 1 diabetes. Diabet Med 317-321
    Google Scholar
  • 51 Lee MS, Cao M, Sajid A et al. The Dual-Wave Bolus Feature in CSII Controls Prolonged Post-Prandial Hyperglycemia Better Than Standard Bolus in Type 1 Diabetes. Diabetes 2003; 52 (Suppl. 01)
    Google Scholar
  • 52 Pickup J, Mattock M, Kerry S. Glycaemic control with continuous subcutaneous insulin infusion compared with intensive insulin injections in patients with type 1 diabetes: meta-analysis of randomized controlled trials. BMJ 2002; 324: 1-6
    CrossrefGoogle Scholar
  • 53 Bode BW, Steed RD, Davidson PC. Reduction in severe hypoglycemia with long-term continuous subcutaneous insulin infusion in type 1 diabetes. Diabetes Care 1996; 19: 324-327
    CrossrefGoogle Scholar
  • 54 Pickup J, Sutten AJ. Severe hypoglycaemia and glycaemic control in Type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion. Diabet Med 2008; 25: 765-774
    CrossrefGoogle Scholar
  • 55 The Diabetes Control and Complications Trial 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
    CrossrefGoogle Scholar
  • 56 JDRF Continuous Glucose Monitoring Study Group. Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med 2008; 359: 1464-1476
    CrossrefGoogle Scholar
  • 57 Beck RW. JDRF CGM Study Group. The effect of continuous glucose monitoring in well-controlled type 1 diabetes. Diabetes Care 2009; 32: 1378-1383
    CrossrefGoogle Scholar
  • 58 Deiss D, Bolinder J, Riveline J-P et al. Improved glycemic control in poorly controlled patients with type 1 diabetes using real-time continuous glucose monitoring. Diabetes Care 2006; 29: 2730-2732
    CrossrefPubMedGoogle Scholar
  • 59 Pickup JC, Freeman SC, Sutton AJ. The evidence base for CGM making sense of glucose sensors. Glycaemic control in type 1 diabetes during real time continuous glucose monitoring compared with self monitoring of blood glucose: meta-analysis of randomised controlled trials using individual patient data. BMJ DOI: 10.1136/bmj.d3805. 2011; 343
    Google Scholar
  • 60 Battelino T, Phillip M, Bratina N et al. Effect of continuous glucosemonitoring on hypoglycemia in type 1 diabetes. Diabetes Care 2011; 34: 795-800
    CrossrefGoogle Scholar
  • 61 Siegmund T, Kolassa R, Thomas A. Sensorunterstützte Therapie (SuP) und Sensorunterstützte Pumpentherapie (SuP). Buch Unimed Science Verlag Bremen ISBN 978-3-8374-1232 2011;
    Google Scholar
  • 62 O'Connell MA, Donath S, O'Neal DN et al. Glycaemic impact of patient-led use of sensor-guided pump therapy in type 1 diabetes: a randomised controlled trial. Diabetologia 2009; 52: 1250-1257
    CrossrefGoogle Scholar
  • 63 Raccah D, Sulmont V, Reznik Y et al. Incremental Value of Continuous Glucose Monitoring When Starting Pump Therapy in Patients With Poorly Controlled Type 1 Diabetes. Diabetes Care 2009; 32: 2245-2250
    CrossrefGoogle Scholar
  • 64 Hermanides J, Nørgaard Bruttomesso D. et al. Sensor augmented pump therapy lowers HbA1c in suboptimally controlled type 1 diabetes: a randomised controlled trial. Diabet Med 2011; 28: 1158-1167
    CrossrefGoogle Scholar
  • 65 Bergenstal RM, Tamborlane WV, Ahmann A et al. STAR 3 Study Group. Effectiveness of Sensor-Augmented Insulin-Pump Therapy in Type 1 Diabetes. N Engl J Med 2010; 363: 311-320
    Google Scholar
  • 66 Reichel A, Rietzsch H, Köhler HJ et al. Cessation of insulin infusion at night-time during CSII-therapy: comparison of regular human insulin and insulin lispro. Exp Clin Endocrinol Diabetes 1998; 106: 168-172
    Article in Thieme ConnectGoogle Scholar
  • 67 Danne T, Kordonouri O, Remus K et al. Prevention of hypoglycaemia by using low glucose suspend function in sensor-augmented pump therapy. Diabetes Technol Ther (in press) 2011; 13
    Google Scholar
  • 68 Buckingham BA, Cobry E, Clinton P et al. Preventing Hypoglycemia Using Predictive Alarm Algorithms and Insulin Pump Suspension. Diabetes Technol Ther 2009; 11: 93-97
    CrossrefPubMedGoogle Scholar