Skip to main content

Advertisement

Log in

Metabolic syndrome therapy: Prevention of vascular injury by antidiabetic agents

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

More than 65 million Americans are currently obese. Type 2 diabetes mellitus, frequently seen in obese subjects, affects 17 million adults in the United States, with a continuous and alarmingly increasing rate. To prevent development of diabetes in those who are at high risk, it is recommended to optimize meal planning and enhance physical activity to make sustained weight reduction possible. In addition to lifestyle changes, various oral antidiabetic agents are available, with diverse mechanisms of action. Some target defective insulin secretion (sulphonylureas, benzoic acid derivatives) or glucose absorption (glycosidase inhibitors), whereas others target insulin resistance (metformin, thiazolidinediones). Patients with metabolic syndrome and diabetes have an increased risk for cardiovascular disease linked to a higher prevalence of hypertension, dyslipidemia, microalbuminuria, and altered hemostasis—parameters that may be modified by antidiabetic agents. In this article, we review the oral agents used to treat type 2 diabetes and the metabolic syndrome, and their effects on vascular tissue.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. King H, Aubert RE, Herman WH: Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care 1998, 21:1414–1431.

    Article  PubMed  CAS  Google Scholar 

  2. Aboderin I, Kaleche A, Ben-Schlomo Y, et al.: Life course perspectives on coronary heart disease, stroke, and diabetes: key issues and implications for policy and research (document WHO / NMH / NPH / 01.4). Geneva: World Health Organization; 2001.

    Google Scholar 

  3. Sowers JR, Frohlich ED: Insulin and insulin resistance: impact on blood pressure and cardiovascular disease. Med Clin North Am 2004, 88:63–82.

    Article  PubMed  CAS  Google Scholar 

  4. Harris MI: Health care and health status and outcomes for patients with type 2 diabetes. Diabetes Care 2000, 23:754–758.

    Article  PubMed  CAS  Google Scholar 

  5. Haffner SJ, Cassells H: Hyperglycemia as a cardiovascular risk factor. Am J Med 2003, 115(Suppl 8A):6S-11S. In this paper, the central role of hyperglycemia in the development of CHD and atherosclerosis in patients with diabetes is discussed. It is concluded that a multifactorial approach is needed in these patients, including aggressive treatment of CV risk factors and use of measures that may improve insulin sensitivity.

    Article  PubMed  CAS  Google Scholar 

  6. Lane JT: Microalbuminuria as a marker of cardiovascular and renal risk in type 2 diabetes mellitus: a temporal perspective. Am J Physiol Renal Physiol 2004, 286:F442-F450.

    Article  PubMed  CAS  Google Scholar 

  7. Sowers JR: Obesity as a cardiovascular risk factor. Am J Med 2003, 115(Suppl 8A):37S-41S.

    Article  PubMed  CAS  Google Scholar 

  8. UK Prospective Diabetes Study Group: Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet 1998, 352:837–853.

    Article  Google Scholar 

  9. Brayden JE: Functional roles of KATP channels in vascular smooth muscle. Clin Exp Pharmacol Physiol 2002, 29:312–316.

    Article  PubMed  CAS  Google Scholar 

  10. Gribble FM, Reimann F: Differential selectivity of insulin secretagogues mechanisms, clinical implications, and drug interactions. J Diabetes Compl 2003, 17:11–15.

    Article  Google Scholar 

  11. Keyes L, Rodman DM, Curran ED, et al.: Effect of K+ ATP channel inhibition on total and regional vascular resistance in Guinea pig pregnancy. Am J Physiol 1998, 275:H680-H688.

    PubMed  CAS  Google Scholar 

  12. Williams S, Abbott D, Morfis L, et al.: Effects of glibenclamide on blood pressure and cardiovascular responsiveness in noninsulin-dependent diabetes mellitus. J Hypertens 1998, 16:705–711.

    Article  PubMed  CAS  Google Scholar 

  13. Sundaresan P, Lykos D, Daher A, et al.: Comparative effects of glibenclamide and metformin on ambulatory blood pressure and cardiovascular reactivity in NIDDM. Diabetes Care 1997, 20:692–697.

    Article  PubMed  CAS  Google Scholar 

  14. Abbink EJ, Wollersheim H, Netten PM, et al.: Microcirculatory effects of KATP channel blockade by sulphonylurea derivatives in humans. Eur J Clin Invest 2002, 32:163–171.

    Article  PubMed  CAS  Google Scholar 

  15. Ochi H, Ikeda T: Sulphonylureas stimulate renin secretion from the perfused kidney of the rat. Nephron 1999, 81:67–71.

    Article  PubMed  CAS  Google Scholar 

  16. Peuler JD, Miller JA, Bourghi M, et al.: Disparate effect of antidiabetic drugs on arterial contraction. Metabolism 1997, 46:1199–1205.

    Article  PubMed  CAS  Google Scholar 

  17. Toyoda K, Fuji K, Ibayashi S, et al.: Role of ATP-sensitive potassium channels in brain stem circulation during hypotension. Am J Physiol 1997, 273:H1342-H1346.

    PubMed  CAS  Google Scholar 

  18. Jennings PE: Vascular benefits of gliclazide beyond glycemic control. Metabolism 2000, 49(10 Suppl 2):17–20.

    Article  PubMed  CAS  Google Scholar 

  19. De Mattia G, Laurenti O, Fava D: Diabetic endothelial dysfunction: effect of free radical scavenging in type 2 diabetic patients. J Diabetes Complications 2003, 17(2Suppl):30–35.

    Article  PubMed  Google Scholar 

  20. Dhindsa P, Davis KR, Donnelly R: Comparison of the micro- and macrovascular effects of glimepiride and gliclazide in metformin-treated patients with type 2 diabetes: a doubleblind, crossover study. Br J Clin Pharmacol 2003, 55:616–619.

    Article  PubMed  CAS  Google Scholar 

  21. Baron AD: Insulin resistance and vascular function. J Diabetes Complications 2002, 16:92–102.

    Article  PubMed  Google Scholar 

  22. Buse JB, Tan MH, Prince MJ, Erickson PP: The effects of oral anti-hyperglycaemic medications on serum lipid profiles in patients with type 2 diabetes. Diabetes Obes Metab 2004, 6:133–156.

    Article  PubMed  CAS  Google Scholar 

  23. Katakam PV, Ujhelyi MR, Hoenig M, Miller AW: Metformin improves vascular function in insulin-resistant rats. Hypertension 2000, 35:108–112.

    PubMed  CAS  Google Scholar 

  24. Kirpichnipoff D, McFarlane SI, Sowers JR: Metformin: an update: Ann Intern Med 2002, 137:25–33.

    Google Scholar 

  25. DeFronzo AM, Goodman RA, for the Multicenter Metformin Study Group: Efficacy of metformin in patients with noninsulin-dependent diabetes mellitus. N Engl J Med 1995, 333:541–549.

    Article  PubMed  CAS  Google Scholar 

  26. Fontbonne A, Charles MA, Juhan-Vaghe I, et al.: The effect of metformin on the metabolic abnormalities associated with upper body fat distribution. BIGPRO Study Group. Diabetes Care 1996, 19:920–926.

    Article  PubMed  CAS  Google Scholar 

  27. Chen XL, Panek K, Rembold CM: Metformin relaxes rat tail artery by repolarization and resultant decreases in Ca2+ influx and intracellular [Ca2+]. J Hypertens 1997, 15:269–274.

    Article  PubMed  CAS  Google Scholar 

  28. Dominguez LJ, Davidoff AJ, Srinivas PR, et al.: Effects of metformin on tyrosine kinase activity, glucose transport, and intracellular calcium in rat vascular smooth muscle. Endocrinology 1996, 137:113–121.

    Article  PubMed  CAS  Google Scholar 

  29. Ofenstein JP, Dominguez LJ, Sowers JR, Sarnaik AP: Effects of insulin and metformin on glucose metabolism in rat vascular smooth muscle. Metabolism 1999, 48:1357–1360.

    Article  PubMed  CAS  Google Scholar 

  30. Pasquali R, Gambineri A, Biscotti D, et al.: Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endocrinol Metab 2000, 85:2767–2774.

    Article  PubMed  CAS  Google Scholar 

  31. Diabetes Prevention Research Group: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002, 346:393–403. This very well-conducted study demonstrated that lifestyle intervention works well in the reduction of type 2 diabetes development. Metformin was also effective in reducing type 2 diabetes development, and it was more effective in overweight people. In view of the rapidly rising rates of obesity and diabetes worldwide, these data are extremely important and suggest that many current health problems can be avoided through diet and exercise.

    Article  Google Scholar 

  32. Manzella D, Grella R, Esposito K, et al.: Blood pressure and cardiac autonomic nervous system in obese type 2 diabetic patients: effect of metformin administration. Am J Hypertens 2004, 17:223–227.

    Article  PubMed  CAS  Google Scholar 

  33. Hundal RS, Krssak M, Dufour S, et al.: Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes 2000, 49:2063–2069.

    Article  PubMed  CAS  Google Scholar 

  34. Tessier D, Maheux P, Khalil A, Fülöp T: Effects of gliclazide versus metformin on the clinical profile and lipid peroxidation markers in type 2 diabetes. Metabolism 1999, 48:897–903.

    Article  PubMed  CAS  Google Scholar 

  35. Charles MA, Morange P, Eschwège E, et al.: Effect of metformin on weight change and on fibrinolysis and the von Willebrand factor in obese nondiabetic subjects: the BIGPRO1 Study. Biguanides and the Prevention of the Risk of Obesity. Diabetes Care 1998, 21:1967–1972.

    Article  PubMed  CAS  Google Scholar 

  36. Kahn CR, Chen L, Cohen SE: Unraveling the mechanism of action of thiazolidinediones. J Clin Invest 2000, 106:1305–1307.

    Article  PubMed  CAS  Google Scholar 

  37. Abrahamson MJ: Clinical use of thiazolidinediones: recommendations. Am J Med 2003, 115(Suppl):116S-120S.

    Article  PubMed  Google Scholar 

  38. 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 highrisk Hispanic women. Diabetes 2002, 51:2796–2803.

    Article  PubMed  CAS  Google Scholar 

  39. Patti ME, Butte AJ, Crunkhorn S, et al.: Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A 2003, 100:8466–8471.

    Article  PubMed  CAS  Google Scholar 

  40. Tang WH, Francis GS, Hoogwerf BJ, Young JB: Fluid retention after initiation of thiazolidinedione therapy in diabetic patients with established chronic heart failure. J Am Coll Cardiol 2003, 41:1394–1398.

    Article  PubMed  CAS  Google Scholar 

  41. Bakris G, Viberti G, Weston WM, et al.: Rosiglitazone reduces urinary albumin excretion in type II diabetes. J Hum Hypertens 2003, 17:7–12.

    Article  PubMed  CAS  Google Scholar 

  42. Aizawa Y, Kawabe J, Hasebe N, et al.: Pioglitazone enhances cytokine-induced apoptosis in vascular smooth muscle cells and reduces intimal hyperplasia. Circulation 2001, 104:455–460.

    PubMed  CAS  Google Scholar 

  43. Haffner SM, Greenberg AS, Weston WM, et al.: Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation 2002, 106:679–684.

    Article  PubMed  CAS  Google Scholar 

  44. Gorson DM: Significant weight gain with Rezulin therapy. Arch Intern Med 1999, 159:99.

    Article  PubMed  CAS  Google Scholar 

  45. Shinohara E, Kihara S, Ouchi N, et al.: Troglitazone suppresses intimal formation following balloon injury in insulin-resistant Zucker fatty rats. Atherosclerosis 1998, 136:275–279.

    Article  PubMed  CAS  Google Scholar 

  46. Takagi T, Yamamuro A, Tamita K, et al.: Impact of troglitazone on coronary stent implantation using small stents in patients with type 2 diabetes mellitus. Am J Cardiol 2002, 89:318–322.

    Article  PubMed  CAS  Google Scholar 

  47. Miyazaki Y, Mahankali A, Matsuda M, et al.: Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 2002, 87:2784–2791.

    Article  PubMed  CAS  Google Scholar 

  48. Mayerson AB, Hundal RS, Dufour S, et al.: The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes. Diabetes 2002, 1:797–802.

    Article  Google Scholar 

  49. Ishizuka T, Itaya S, Wada H, et al.: Differential effects of the antidiabetic thiazolidinediones troglitazone and pioglitazone on human platelet aggregation mechanism. Diabetes 1998, 47:1494–1450.

    Article  PubMed  CAS  Google Scholar 

  50. Owens DR, Luzio SD, Ismail I, Bayer T: Increased prandial insulin secretion following a single preprandial oral dose of repaglinide in patients with type 2 diabetes. Diabetes Care 2000, 23:513–523.

    Google Scholar 

  51. Hu S, Wang S, Dunning BE: Tissue selectivity of antidiabetic agent nateglinide: study on cardiovascular and beta-cell K[ATP] channels. J Pharmacol Exp Ther 1999, 291:1372–1379.

    PubMed  CAS  Google Scholar 

  52. Derosa G, Mugellini A, Ciccarelli L, et al.: Comparison between repaglinide and glimepiride in patients with type 2 diabetes mellitus: a one-year, randomized, double-blind assessment of metabolic parameters and cardiovascular risk factors. Clin Ther 2003, 25:472–484.

    Article  PubMed  CAS  Google Scholar 

  53. Scheen AJ: Is there a role for alpha-glucosidase inhibitors in the prevention of type 2 diabetes mellitus? Drugs 2003, 63:933–951.

    Article  PubMed  CAS  Google Scholar 

  54. Hanefeld M, Cagatay M, Petrowitsch T, et al.: Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. Eur Heart J 2004, 25:10–16.

    Article  PubMed  CAS  Google Scholar 

  55. Hanefeld M, Chiasson JL, Koehler C, et al.: Acarbose slows progression of intima-media thickness of the carotid arteries in subjects with impaired glucose tolerance. Stroke 2004, 35:1073–1078.

    Article  PubMed  CAS  Google Scholar 

  56. Chiasson JL, Josse RG, Gomis R, et al. for the STOP-NIDDM Trial Research Group: Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 2002, 359:2072–2077.

    Article  PubMed  CAS  Google Scholar 

  57. Grundy SM, Hansen B, Smith SC, et al.: Clinical management of metabolic syndrome. Report of the American Heart Association/ National Heart, Lung, and Blood Institute/American Diabetes Association Conference on scientific issues related to management. Circulation 2004, 109:551–556. This is the report of a joint conference from the AHA, NHLBI, and ADA, which addressed the presentation, pathogenesis, management, and unresolved issues of the metabolic syndrome.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dominguez, L.J., Sowers, J.R. Metabolic syndrome therapy: Prevention of vascular injury by antidiabetic agents. Current Science Inc 7, 110–116 (2005). https://doi.org/10.1007/s11906-005-0083-3

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-005-0083-3

Keywords

Navigation