Treatment of diabetes in metabolic syndrome
Authors:
T. Pelikánová 1,2
Authors‘ workplace:
Centrum diabetologie IKEM Praha, přednostka prof. MUDr. Terezie Pelikánová, DrSc.
1; Subkatedra diabetologie IPVZ Praha, vedoucí prof. MUDr. Terezie Pelikánová, DrSc.
2
Published in:
Vnitř Lék 2009; 55(7-8): 637-645
Category:
134th Internal Medicine Day - 23rd Vanysek's Day Brno 2009 - Vanysek's Lecture
Overview
Hyperglycaemia is a typical feature of metabolic syndrome (MeTS) and one of its independent diagnostic criteria. The term includes impaired glucose homeostasis (impaired fasting glucose and impaired glucose tolerance) and type 2 diabetes mellitus. Although glycaemic control has been shown to lower the risk of microvascular events, the effect of intensive glycaemic control on macrovascular outcomes is less clear. Epidemiological studies show hyperglycaemia, particularly the postprandial one, to be a clear risk factor for cardiovascular (CV) mortality and morbidity. However, the intervention studies are less conclusive. The large interventional studies published in 2008 and 2009 (UKPDS, VADT, ACCORD, ADVANCE, RECORD) advocate the controlling of nonglycemic risk factors (through blood pressure control, lipid lowering with statin therapy, aspirin therapy, and lifestyle modifications) as the primary strategies for reducing the burden of CV disease in people with diabetes, and demonstrated the need for individualized approach to the patients’ care in terms of blood glucose control. The patients with shorter duration of type 2 diabetes and without established atherosclerosis might reap CV benefit from intensive glycemic control. Conversely, it is possible that potential risks of intensive glycaemic control (hypoglycaemia) may outweigh its benefits in other patients, such as those with a very long duration of diabetes, known history of severe hypoglycemia, advanced atherosclerosis, and advanced age/frailty. According to the latest recommendations of the Czech Diabetes Society that are in line with the European and US standards the best way to protect type 2 diabetic patients against coronary and cerebrovascular disease is to target all cardiovascular risk factors (blood pressure treatment, including lipid-lowering with statins, aspirin prophylaxis, smoking cessation, and healthy lifestyle behaviors hypertension, dyslipidemia, obesity and other symptoms of metabolic syndrome. The target HbA1c levels in patients with the low CV risk shoul be below 4.5%. Less strict goals (HbA1c below 6%) may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, or extensive comorbid conditions or those with long‑standing diabetes. The individual targets should be achieved safely (without hypoglycaemias). Slow advancing in diabetes compensation is preferred. Lifestyle changes are the cornerstone of therapy. Metformin is the drug of choice; its administration, together with lifestyle changes, should be initiated immediately after the diagnoses of diabetes. If monotherapy does not provide satisfactory glucose control, other oral antidiabetic agents or insulin are added to the combination. Since it is not known which hypoglycaemic agents are beneficial from the perspective of long‑term patient prognosis, the selection is liberal. Contraindication of the various farmaceuticals must be respected. It is possible to use a range of different combinations, metformin is administered with a glitazone (zero risk of hypoglycaemias is the advantage) with sulphonylurea derivatives (low price is the advantage) with glinides, with incretins, acarbose, antiobesity agents or insulin. The next step is a triple combination of hypoglycaemic agents with different mechanisms of action. Therapy also includes education focusing on changes to dietary and lifestyle habits, including smoking cessation, and education related to the prevention of complications, with particular regard to prevention of diabetic foot and atherosclerosis.
Key words:
metabolic syndrome – hyperglycaemia – oral antidiabetic agents – insulin – therapy
Sources
1. Kahn R, Buse J, Ferrannini E et al. The metabolic syndrome: time for a critical appraisal. Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 2005; 48: 1684–1699.
2. Grundy SM, Cleeman JI, Daniels SR et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005; 112: 2735–2752.
3. The IDF Consensus Worldwide Definition of the Metabolic Syndrome 2005. Available from: http://www.idf.org/webdata/docs/Metabolic_syndrome_definition.pdf.
4. Association AD. Standards of medical care in diabetes – 2009. Diabetes Care 2006; 29 (Suppl 1): S4–S42.
5. Rydén L, Standl E, Bartnik M et al. Guidelines on diabetes, pre‑diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J 2007; 28: 88–136.
6. Standardy péče o diabetes mellitus 2. typu. Standardy České diabetologické společnosti. 2009 (www.diab.cz). Diabetologie, metabolismus, endokrinologie, výživa 2009; v tisku.
7. Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009; 58: 773–795.
8. Gastaldelli A, Ferrannini E, Miyazaki Y et al. Beta‑cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study. Diabetologia 2004; 47: 31–39.
9. Festa A, Williams K, D’Agostino R jr et al. The natural course of beta‑cell function in nondiabetic and diabetic individuals: the Insulin Resistance Atherosclerosis Study. Diabetes 2006; 55: 1114–1120.
10. Deng S, Vatamaniuk M, Huang X et al. Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects. Diabetes 2004; 53: 624–632.
11. U.K. prospective diabetes study 16. Overview of 6 years’ therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group. Diabetes 1995; 44: 1249–1258.
12. Kahn SE, Haffner SM, Heise MA et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355: 2427–2443.
13. Kulkarni RN. The islet beta‑cell. Int J Biochem Cell Biol 2004; 36: 365–371.
14. Buchanan TA, Xiang AH, Peters RK et al. Preservation of pancreatic beta‑cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high‑risk hispanic women. Diabetes 2002; 51: 2796–2803.
15. Unger RH. Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology 2003; 144: 5159–5165.
16. Shimabukuro M, Zhou YT, Levi M et al. Fatty acid‑induced beta cell apoptosis: a link between obesity and diabetes. Proc Natl Acad Sci USA 1998; 95: 2498–2502.
17. Rakatzi I, Mueller H, Ritzeler O et al. Adiponectin counteracts cytokine and fatty acid‑induced apoptosis in the pancreatic beta‑cell line INS-1. Diabetologia 2004; 47: 249–258.
18. Newsholme P, Haber EP, Hirabara SM et al. Diabetes associated cell stress and dysfunction: role of mitochondrial and non‑mitochondrial ROS production and activity. J Physiol 2007; 583: 9–24.
19. Scheuner D, Kaufman RJ. The unfolded protein response: a pathway that links insulin demand with beta‑cell failure and diabetes. Endocr Rev 2008; 29: 317–333.
20. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352: 837–853.
21. Patel A, MacMahon S, Chalmers J et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358: 2560–2572.
22. Nesto RW. Correlation between cardiovascular disease and diabetes mellitus: current concepts. Am J Med 2004; 116 (Suppl 5A): 11S–22S.
23. 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: 1279–1289.
24. Malmberg K, Ryden L, Wedel H et al. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J 2005; 26: 650–661.
25. 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: 1577–1589.
26. 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: 129–139.
27. Gerstein HC, Miller ME, Byington RP et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358: 2545–2559.
28. Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA 2002; 287: 2563–2569.
29. 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: 2643–2653.
30. Gerstein HC, Yusuf S, Bosch J et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006; 368: 1096–1105.
31. Chiasson JL, Josse RG, Gomis R et al. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA 2003; 290: 486–494.
32. Home PD, Pocock SJ, Beck-Nielsen H et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 2009; 373: 2125-2135.
33. Pelikánová T. Léčba inzulinem v éře inzulinových analog. In: Pelikánová T (ed.) Trendy soudobé diabetologie XI. Praha: Galén 2007: 181–245.
34. Raz I, Wilson PW, Strojek K et al. Effects of prandial versus fasting glycemia on cardiovascular outcomes in type 2 diabetes: the HEART2D trial. Diabetes Care 2009; 32: 381–386.
35. Association AD. Standards of medical care in diabetes – 2009. Diabetes Care 2009; 32 (Suppl 1): S13–S61.
36. Nathan DM, Buse JB, Davidson MB et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009; 32: 193–203.
37. Skyler JS, Bergenstal R, Bonow RO et al. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA diabetes trials: a position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association. Diabetes Care 2009; 32: 187–192.
38. Gaede P, Lund-Andersen H, Parving HH et al. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 2008; 358: 580–591.
Labels
Diabetology Endocrinology Internal medicineArticle was published in
Internal Medicine
2009 Issue 7-8
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