Diabetes aktuell 2019; 17(07): 272-279
DOI: 10.1055/a-1031-2237
Schwerpunkt
© Georg Thieme Verlag Stuttgart · New York

Hypoglykämien bei Diabetes mellitus: häufig und gefährlich

Prävention und Therapie
Andreas Holstein
1   Medizinische Klinik I, Klinikum Lippe-Detmold
,
David J.F. Holstein
2   Integriertes Forschungs- und Behandlungszentrum AdipositasErkrankungen, Universität Leipzig
› Author Affiliations
Further Information

Publication History

Publication Date:
26 November 2019 (online)

ZUSAMMENFASSUNG

Schwere Hypoglykämien führen häufig zu Verletzungen und sind mit einer mehr als 2-fach erhöhten kardiovaskulären Mortalität und Morbidität assoziiert. Hauptrisikofaktoren für Hypoglykämien bei Typ-1-Diabetes sind Störungen der Hypoglykämie-Wahrnehmung bzw. rekurrente Hypoglykämien, während bei Typ-2-Diabetes komplexe geriatrische Multimorbidität und kognitive Einschränkungen dominieren. Individuelle (Re-)Schulungen der Patienten bilden die Grundlage der Prävention. Therapieziele sollten unter Wertung des Patientenwunsches, der Komorbiditäten, des Hypoglykämierisikos, der Lebenserwartung u.a. individuell festgelegt werden. Bei Typ-2-Diabetes und Hypoglykämie-Vulnerabilität sind Antidiabetika ohne intrinsisches Hypoglykämierisiko (DPP-4-Hemmer, GLP-1-Analoga, SGLT-2-Hemmer) in der Zweitlinien-Therapie nach Metformin zu bevorzugen. Moderne CGM-Technologien tragen dazu bei, insbesondere gefährliche nächtliche Hypoglykämien zu reduzieren und die Hypoglykämie-Wahrnehmung zu verbessern. Auch CSII und wahrscheinlich der Einsatz moderner Basalinsulinanaloga senken das Hypoglykämierisiko bei Typ-1- bzw. Typ-2-Diabetes. Die simultane Transplantation von Pankreas und Niere, die isolierte Pankreastransplantation und Inseltransplantation führen nicht nur zur (temporären) Insulinunabhängigkeit, sondern vermeiden auch Hypoglykämien. Die primäre Therapie bei bewusstseinsgestörten Patienten mit schwerer Hypoglykämie besteht in der streng intravenösen Gabe von 50 ml 40 %iger Glukose als Bolus. Alternativ kann die Gabe von 1 mg Glukagon intramuskulär erfolgen. Ältere komorbide oder verletzte Diabetespatienten, Sulfonylharnstoff-Hypoglykämien und Hypoglykämien unter Alkoholkonsum oder Analgetika-/Sedativa-Medikation bedürfen obligat der stationären Überwachung.

 
  • Literatur

  • 1 Marchesini G, Veronese G, Forlani G. et al The management of severe hypoglycemia by the emergency system: the HYPOTHESIS study. Nutr Metab Cardiovasc Dis 2014; 24: 1181-1188 doi:10.1016/j.numecd.2014.05.012
  • 2 Goto A, Arah OA, Goto M. et al Severe hypoglycaemia and cardiovascular disease: systematic review and meta-analysis with bias analysis. BMJ 2013; 347: f4533 doi:10.1136/bmj.f4533
  • 3 Zinman B, Marso SP, Christiansen E. et al Hypoglycemia, Cardiovascular Outcomes, and Death: The LEADER Experience. Diabetes Care 2018; 41: 1783-1791 doi:10.2337/dc17-2677
  • 4 Standl E, Stevens SR, Armstrong PW. et al Increased risk of severe hypoglycemic events before and after cardiovascular outcomes in TECOS suggests an at-risk type 2 diabetes frail patient phenotype. Diabetes Care 2018; 41: 596-603 doi:10.2337/dc17-1778
  • 5 American Diabetes Association. Glycemic Targets. Diabetes Care 2017; 40 (Suppl. 01) S48-S56 doi:10.2337/dc17-S009
  • 6 International Hypoglycemia Study Group Glucose Concentrations of Less Than 3.0 mmol/L (54 mg/dL) Should Be Reported in Clinical Trials: A Joint Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2017; 40: 155-157 doi:10.2337/dc16-2215
  • 7 Seaquist ER, Anderson J, Childs B. et al Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care 2013; 36: 1384-1395 doi:10.2337/dc12-2480
  • 8 UK Hypoglycaemia Study Group Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia 2007; 50: 1140-1147 doi:10.1007/s00125-007-0599-y
  • 9 Wright AD, Cull CA, Mcleod KM. et al Hypoglycemia in Type 2 diabetic patients randomized to and maintained on monotherapy with diet, sulfonylurea, metformin, or insulin for 6 years from diagnosis: UKPDS73. J Diabetes Complicat 2006; 20: 395-401 doi:10.1016/j.jdiacomp.2005.08.010
  • 10 DCCT Research Group Epidemiology of severe hypoglycemia in the Diabetes Control and Complications Trial. Am J Med 1991; 90: 450-459
  • 11 Holstein A, Patzer OM, Machalke K. et al Substantial increase in incidence of severe hypoglycemia between 1997-2000 and 2007-2010: a German longitudinal population-based study. Diabetes Care 2012; 35: 972-975 doi:10.2337/dc11-1470
  • 12 Müller N, Lehmann T, Gerste B. et al Increase in the incidence of severe hypoglycaemia in people with Type 2 diabetes in spite of new drugs: analysis based on health insurance data from Germany. Diabet Med 2017; 34: 1212-1218 doi:10.1111/dme.13397
  • 13 Zhong VW, Juhaeri J, Cole SR. et al Incidence and Trends in Hypoglycemia Hospitalization in Adults With Type 1 and Type 2 Diabetes in England, 1998-2013: A Retrospective Cohort Study. Diabetes Care 2017; 40: 1651-1660 doi:10.2337/dc16-2680
  • 14 Wang H, Donnan PT, Leese CJ. et al Temporal changes in frequency of severe hypoglycemia treated by emergency medical services in types 1 and 2 diabetes: a population-based data-linkage cohort study. Clin Diabetes Endocrinol 2017; 3: 7 doi: 10.1186/s40842-017-0045-0
  • 15 Lipska KJ, Yao X, Herrin J. et al Trends in Drug Utilization, Glycemic Control, and Rates of Severe Hypoglycemia, 2006-2013. Diabetes Care 2017; 40: 468-475 doi:10.2337/dc16-0985
  • 16 Lee AK, Lee CJ, Huang ES. et al Risk factors for severe hypoglycemia in black and white adults with diabetes. The Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care 2017; 40: 1661-1667 doi:10.2337/dc17-0819
  • 17 Pramming S, Thorsteinsson B, Bendtson I. et al Symptomatic hypoglycaemia in 411 type 1 diabetic patients. Diab Med 1991; 8: 217-222 doi:10.1111/j.1464-5491.1991.tb01575.x
  • 18 Pedersen-Bjergaard U, Pramming S, Heller SR. et al Severe hypoglycaemia in 1076 adult patients with type 1 diabetes: influence of risk markers and selection. Diabetes Metab Res Rev 2004; 20: 479-486 doi:10.1002/dmrr.482
  • 19 Wohland T, Holstein JD, Patzer OM. et al New risk and protective factors for severe hypoglycaemia in people with type 1 diabetes. Nutr Metab Cardiovasc Dis 2017; 27: 407-414 doi:10.1016/j.numecd.2016.12.006
  • 20 Holstein A, Wohland T, Patzer OM. et al Accumulation of severe hypoglycemia at weekends and in warm seasons in patients with type 1 diabetes but not with type 2 diabetes. J Diabetes Complications 2016; 30: 1308-1314 doi:10.1016/j.jdiacomp.2016.05.026
  • 21 Lipska KJ, Warton EM, Huang ES. et al HbA1c and risk of severe hypoglycemia in type 2 diabetes: the Diabetes and Aging Study. Diabetes Care 2013; 36: 3535-3542 doi:10.2337/dc13-0610
  • 22 Davies MJ, D’Alessio DA, Fradkin J. et al Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018; 41: 2669-2701 doi:10.2337/dci18-0033
  • 23 Deutsche Diabetes Gesellschaft S2k-Leitlinie Diagnostik, Therapie und Verlaufskontrolle des Diabetes mellitus im Alter. 2. Aufl 2018 AWMF-Registernummer: 057-017. Im Internet: www.deutsche-diabetes-gesellschaft.de/fileadmin/Redakteur/Leitlinien/Evidenzbasierte_Leitlinien/2018/057_017_LL_Alter_Gesamtdokument_20180713.pdf Stand: 29.10.2019
  • 24 Sämann A, Mühlhauser I, Bender R, et al.. et al Glycaemic control and severe hypoglycaemia following training in flexible, intensive insulin therapy to enable dietary freedom in people with type 1 diabetes: a prospective implementation study. Diabetologia 2005; 48: 1965-1970 doi:10.1007/s00125-005-1905-1
  • 25 Iqbal A, Heller SR. The role of structured education in the management of hypoglycaemia. Diabetologia 2018; 61: 751-760 doi:10.1007/s00125-017-4334-z
  • 26 Little SA, Speight J, Leelarathna L. et al Sustained Reduction in Severe Hypoglycemia in Adults With Type 1 Diabetes Complicated by Impaired Awareness of Hypoglycemia: Two-Year Follow-up in the HypoCOMPaSS Randomized Clinical Trial. Diabetes Care 2018; 41: 1600-1607 doi:10.2337/dc17-2682
  • 27 Leiter LA, Boras D, Woo VC. et al Dosing irregularities and self-treated hypoglycemia in Type 2 diabetes: results from the Canadian cohort of an international survey of patients and healthcare professionals. Can J Diabetes 2014; 38: 38-44 doi:10.1016/j.jcjd.2013.08.270
  • 28 Kern W, Holstein A, Moenninghoff C. et al Self-reported Hypoglycaemic Events in 2 430 Patients with Insulin-treated Diabetes in the German Sub-population of the HAT Study. Exp Clin Endocrinol Diabetes 2017; 125: 592-597 doi:10.1055/s-0043-112350
  • 29 Bergenstal RM, Tamborlane WV, Ahmann A. et al Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes. N Engl J Med 2010; 363: 311-320 doi:10.1056/NEJMoa1002853
  • 30 Bergenstal RM, Klonoff DC, Garg SK. et al Threshold-based insulin-pump interruption for reduction of hypoglycemia. N Engl J Med 2013; 369: 224-232 doi:10.1056/NEJMoa1303576
  • 31 Martin CT, Criego AB, Carlson AL. et al Advanced Technology in the Management of Diabetes: Which ComesFirst—Continuous Glucose Monitor or Insulin Pump?. Curr Diab Rep 2019; 19: 50 doi:10.1007/s11892-019-1177-7
  • 32 Ly TT, Nicholas JA, Retterath A. et al Effect of sensor-augmented insulin pump therapy and automated insulin suspension vs standard insulin pump therapy on hypoglycemia in patients with type 1 diabetes: a randomized controlled trial. JAMA 2013; 310: 1240-1247
  • 33 Van Beers CA, DeVries JH, Kleijer SJ. et al Continuous Glucose Monitoring for patients with type 1 diabetes and impaired awareness of hypoglycaemia (IN CONTROL): a randomized, open-label, crossover trial. Lancet Diabetes, Endocrinol 2016; 4: 893-902 doi:10.1001/jama.2013.277818
  • 34 Heinemann L, Freckmann G, Ehrmann D. et al Real-time continuous glucose monitoring in adults with type 1 diabetes and impaired hypoglycaemia awareness or severe hypoglycaemia treated with multiple daily insulin injections (HypoDE): a multicenter, randomized controlled trial. Lancet 2018; 391: 1367-1377 doi:10.1016/S0140-6736(18)30297-6
  • 35 Bolinder J, Antuna R, Geehoed-Duijvestin P. et al Novel glucose-sensing technology and hypoglycaemia in type 1 diabetes : a multicentre, non-masked, randomized controlled trial. Lancet 2016; 388: 2254-2263 doi:10.1016/S0140-6736(16)31535-5
  • 36 Haak T, Hanaire H, Ajjan R. et al Flash glucose-sensing technology as a replacement for blood glucose monitoring for the management of insulin-treated type 2 diabetes: a multicenter, open-label, randomized, controlled trial. Diabetes Ther 2017; 8: 55-73 doi: 10.1007/s13300-016-0223-6
  • 37 Tyndall V, Stimson RH, Zammitt NN. et al Marked improvement in HbA1c following commencement of flash glucose monitoring in people with type 1 diabetes. Diabetologia 2019; 62: 1349-1356 doi:10.1007/s00125-019-4894-1
  • 38 Graveling AJ, Frier BM. The risks of nocturnal hypoglycaemia in insulin-treated diabetes. Diabetes Res Clin Pract 2017; 133: 30-39 doi:10.1016/j.diabres.2017.08.012
  • 39 Frier BM, Ratzki-Leewing A, Harris SB. Reporting of hypoglycaemia in clinical trials of basal insulins: a need for Consensus. Diabetes Metab Obes 2019; 21: 1529-1542 doi:10.1111/dom.13732
  • 40 Monami M, Marchionni N, Mannucci E. Long-acting insulin analogues vs. NPH human insulin in type 1 diabetes. A meta-analysis. Diabetes Obes Metab 2009; 11: 372-378 doi:10.1111/j.1463-1326.2008.00976.x
  • 41 Singh SR, Ahmad F, Lal A. et al Efficacy and safety of insulin analogues for the management of diabetes mellitus: A meta-analysis. CMAJ 2009; 180: 385-397 doi:10.1503/cmaj.081041
  • 42 Heller S, Buse J, Fisher M. et al Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet 2012; 379: 1489-1497 doi:10.1016/S0140-6736(12)60204-9
  • 43 Bode BW, Buse JB, Fisher M. et al Insulin degludec improves glycaemic control with lower nocturnal hypoglycaemia risk than insulin glargine in basal-bolus treatment with mealtime insulin aspart in Type 1 diabetes (BEGIN® Basal-Bolus Type 1): 2-year results of a randomized clinical trial. Diabet Med 2013; 30: 1293-1297 doi:10.1111/dme
  • 44 Ratner RE, Gough SCL, Mathieu C. et al Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2 and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials. Diabetes Obes Metab 2013; 15: 175-184 doi:10.1111/dom.12032
  • 45 Lane W, Bailey TS, Gerety G. et al Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomized Clinical Trial. JAMA 2017; 318: 33-44 doi:10.1001/jama.2017.7115
  • 46 Agesen RM, Alibegovic AC, Andersen HU. et al The effect of insulin degludec on risk of symptomatic nocturnal hypoglycaemia in subjects with type 1 diabetes and high risk of nocturnal severe hypoglycaemia (the HypoDeg trial): study rationale and design. BMC Endocr Disord 2019; 19: 78 doi:10.1186/s12902-019-0408-x
  • 47 Marso SP, McGuire GK, Zinman B. et al Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes. NEJM 2017; 377: 723-732 doi:10.1056/NEJMoa1615692
  • 48 Wysham C, Bhargava A, Chaykin L. et al Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 2 Diabetes: The SWITCH 2 Randomized Clinical Trial. JAMA 2017; 318: 45-56 doi:10.1001/jama.2017.7117
  • 49 Rosenstock J, Cheng A, Ritzel R. et al More Similarities Than Differences Testing Insulin Glargine 300 Units/mL Versus Insulin Degludec 100 Units/mL in Insulin-Naive Type 2 Diabetes: The Randomized Head-to-Head BRIGHT Trial. Diabetes Care 2018; 41: 2147-2154 doi:10.2337/dc18-0559
  • 50 Lombardo C, Perrone VG, Amorese G. et al Update on pancreatic transplantation on the management of diabetes. Minerva Med 2017; 108: 405-418 doi:10.23736/S0026-4806.17.05224-7
  • 51 Holstein A, Wunsch A. Pancreas transplantation alone in a nonuremic woman with type 1 diabetes mellitus and total unawareness of hypoglycaemia. Diabetologie 2011; 6: 329-330 doi:10.1055/s-0031-1283751
  • 52 Lablanche S, Vantyghem MC, Kessler L. et al Islet transplantation versus insulin therapy in patients with type 1 diabetes with severe hypoglycaemia or poorly controlled glycaemia after kidney transplantation (TRIMECO): a multicentre, randomised controlled trial. Lancet Diabetes Endocrinol 2018; 6: 527-537 doi:10.1016/S2213-8587(18)30078-0
  • 53 Villani M, deCourten B, Zoungas S. et al Emergency treatment of hypoglycaemia: a guideline and evidence review. Diabet Med 2017; 34: 1205-1211 doi:10.1111/dme.13379
  • 54 Deutsche Diabetes Gesellschaft S3-Leitlinie Therapie des Typ-1-Diabetes. 2. Aufl 2018 AWMF-Registernummer: 057-013. Im Internet: www.awmf.org/uploads/tx_szleitlinien/057-013m_S3-Therapie-Typ-1-Diabetes_2018-04.pdf Stand: 29.10.2019
  • 55 Rickels MR, Ruedy KJ, Foster NC. et al Intranasal glucagon for treatment of insulin-induced hypoglycemia in adults with type 1 diabetes: a randomized crossover noninferiority study. Diabetes Care 2016; 39: 264-270 doi:10.2337/dc15-1498
  • 56 Holstein A, Hammer C, Hahn M. et al Severe sulphonylurea-induced hypoglycaemia - a problem of uncritical prescription and deficiencies of diabetes care in geriatric patients. Expert Opin Drug Saf 2010; 9: 675-681 doi:10.1517/14740338.2010.492777
  • 57 Holstein A, Beil W, Kovacs P. CYP2C metabolism of oral antidiabetic drugs--impact on pharmacokinetics, drug interactions and pharmacogenetic aspects. Expert Opin Drug Metab Toxicol 2012; 8: 1549-1563 doi:10.1517/17425255.2012.722619
  • 58 Vaccaro O, Masulli M, Nicolucci A. et al Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial. Lancet Diabetes Endocrinol 2017; 5: 887-897 doi:10.1016/S2213-8587(17)30317-0
  • 59 Rosenstock J, Kahn SE, Johansen OE. et al Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes. The CAROLINA Randomized Clinical Trial. JAMA 2019; 322: 1155-1166 doi:10.1001/jama.2019.13772