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Hyperglycemia and cardiovascular disease

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Abstract

Diabetes is associated with many microvascular and macrovascular complications. Hyperglycemia plays a pivotal role in the development of microvascular complications, but the actual effect of hyperglycemia on the development and progression of macrovascular complications remains unclear and even somewhat controversial, particularly in type 2 diabetes. Macrovascular complications are increased in individuals with type 2 diabetes long before there is significant hyperglycemia, and in many, but not all, studies a clear association of glucose elevations and macrovascular complications cannot be shown. The complicated nature of metabolic abnormalities in type 2 diabetes and the relative role of these associated conditions in the development of macrovascular disease make definitive conclusions somewhat difficult. In spite of these considerations, there are certain aspects of hyperglycemia associated with macrovascular disease, particularly elevations of postprandial glucoses, and a number of basic mechanisms to explain these associations that could lead to the development of cardiovascular disease. Some of these basic abnormalities include activation of the sorbital pathway, oxidative stress, advanced glycation endproducts (AGE), and AGE precursors. These changes can result in many abnormalities, such as endothelial dysfunction, alteration of protein function, increased cytokine production, and glycosylation of structural proteins. These considerations suggest that hyperglycemia may play an important, but as yet not clearly defined, role in clinical macrovascular disease. Pursuant to this, several major multisite studies are currently underway to clarify the role of hyperglycemia in cardiovascular disease in type 2 diabetes.

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References and Recommended Reading

  1. Schernthaner G: Cardiovascular mortality and morbidity in type-2 diabetes mellitus. Diabetes Res Clin Pract 1996, 31(suppl):S3-S13.

    Article  PubMed  Google Scholar 

  2. Lee WL, Cheung AM, Cape D, Zinman B: Impact of diabetes on coronary artery disease in women and men. Diabetes Care 2000, 23:962–967.

    Article  PubMed  CAS  Google Scholar 

  3. Orchard T: The impact of gender and general risk factors on the occurrence of atherosclerotic vascular disease in non-insulin-dependent diabetes mellitus. The Finnish Medical Society DUODECIM. Ann Med 1996, 28:323–333.

    PubMed  CAS  Google Scholar 

  4. Howard BV, for the Strong Heart Study Investigators: Risk factors for cardiovascular disease in individuals with diabetes. The Strong Heart Study. Acta Diabetol 1996, 33:180–184.

    PubMed  CAS  Google Scholar 

  5. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso: Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998, 339:229–235.

    Article  PubMed  CAS  Google Scholar 

  6. Saydah SH, Loria CM, Eberhardt MS, Brancati FL: Subclinical states of glucose intolerance and risk of death in the U.S. Diabetes Care 2001, 24:447–453.

    Article  PubMed  CAS  Google Scholar 

  7. Sawicki PT, Heise T, Berger M: Antihypertensive treatment and mortality in diabetic patients. Diabetologia 1997, 40:S134-S137.

    Article  PubMed  Google Scholar 

  8. Adler AI, Stratton IR, Neil AW, et al., on behalf of the UK Prospective Diabetes Study Group: Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ 2000, 321:412–419.

    Article  PubMed  CAS  Google Scholar 

  9. Goldberg IJ: Clinical Review 124. Diabetic dyslipidemia: causes and consequences. J Clin Endocrinol Metab 2001, 86:965–971.

    Article  PubMed  CAS  Google Scholar 

  10. Missov RM, Stolk RP, Van der Bom, et al.: Plasma fibrinogen in NIDDM. The Rotterdam Study. Diabetes Care. 1996, 19:157–159.

    Article  PubMed  CAS  Google Scholar 

  11. Gerstein HC: Is glucose a continuous risk factor for cardiovascular mortality? Diabetes Care 1999, 22:659–660.

    Article  PubMed  CAS  Google Scholar 

  12. Tschoepe D, Roesen P: Heart disease in diabetes mellitus: a challenge for early diagnosis and intervention. Exp Clin Endocrinol Diabetes 1998, 106:16–24.

    Article  PubMed  CAS  Google Scholar 

  13. Valmadrid CT, Klein R, Moss S, Klein BE: The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus. Arch Intern Med 2000, 160:1093–1100.

    Article  PubMed  CAS  Google Scholar 

  14. Fontbonne A: Insulin-resistance syndrome and cardiovascular complications of non-insulin dependent diabetes mellitus. Diabetes Metab (Paris) 1996, 22:305–313.

    CAS  Google Scholar 

  15. Isomaa B, Almgren P, Tuomi T, et al.: Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001, 24:683–689.

    Article  PubMed  CAS  Google Scholar 

  16. Wilson PW, Kannel WB, Silbershatz H, D’Agostino RB: Clustering of metabolic factors and coronary heart disease. Arch Intern Med 1999, 159:1104–1109.

    Article  PubMed  CAS  Google Scholar 

  17. Forrest KY, Becker DJ, Kuller LH, et al.: Are predictors of coronary heart disease and lower-extremity arterial disease in type 1 diabetes the same? A prospective study. Atherosclerosis 2000, 148:159–169.

    Article  PubMed  CAS  Google Scholar 

  18. Kuusisto, Mykkanen L, Pyorala K, Laakso M: NIDDM and its metabolic control predict coronary heart disease in elderly subjects. Diabetes 1994, 43:960–967.

    Article  PubMed  CAS  Google Scholar 

  19. Moss S, Klein R, Klein B, Meuer S: The association of glycemia and cause-specific mortality in a diabetic population. Arch Intern Med 1994, 154:2473–2479.

    Article  PubMed  CAS  Google Scholar 

  20. Meigs J, Singer D, Sullivan S, et al.: Metabolic control and prevalent cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM). The NIDDM Patient Outcomes Research Team. Am J Med 1997, 102:38–47.

    Article  PubMed  CAS  Google Scholar 

  21. Lloyd CE, Becker DJ, Ellis D, Orchard TJ: Incidence of complications in insulin-dependent diabetes mellitus: a survival analysis. Am J Epidemiol 1996, 143:431–441.

    PubMed  CAS  Google Scholar 

  22. Barrett-Connor E: Does hyperglycemia really cause coronary heart disease? Diabetes Care 1997, 20:1620–1623.

    PubMed  CAS  Google Scholar 

  23. Laakso M: Perspective in diabetes: hyperglycemia and cardiovascular disease in type 2 diabetes. Diabetes 1999, 48:937–942.

    Article  PubMed  CAS  Google Scholar 

  24. Anderson KG: Long-term glycemic control relates to mortality in type II diabetes. Diabetes Care 1995, 18:1534–1543.

    Article  Google Scholar 

  25. Hanefeld M, Fishcer S, Julius U, et al.: Risk factors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11 year follow-up. Diabetologia 1996, 39:1577–1583.

    Article  PubMed  CAS  Google Scholar 

  26. Fuller JH, Shipley MJ, rose G, et al.: Mortality from coronary heart disease and stroke in relation to degree of glycaemia: the Whitehall study. BMJ 1983, 287:867–870.

    Article  PubMed  CAS  Google Scholar 

  27. Pan WH, Cedres LB, Liu K, et al.: Relationship of clinical diabetes and asymptomatic hyperglycemia to risk of coronary heart disease mortality in men and women. Am J Epidemiol 1986, 123:504–516.

    PubMed  CAS  Google Scholar 

  28. Butler WJ, Ostrander LD Jr, Carman WJ, Lamphiear DE: Mortality from coronary heart disease in the Tecumseh study. Long-term effect of diabetes mellitus, glucose tolerance and other risk factors. Am J Epidemiol 1985, 121:541–547.

    PubMed  CAS  Google Scholar 

  29. Donahue RP, Abbot RD, Reed DM, Yano K: Postchallenge glucose concentration and coronary heart disease in men of Japanese ancestry. Honolulu Heart Program. Diabetes 1987, 36:689–692.

    Article  PubMed  CAS  Google Scholar 

  30. Qiao Q, Tuomilheto J: Glucose intolerance and cardiovascular mortality. The DECODE Study Group. Arch Intern Med 2001, 161:397–405.

    Article  Google Scholar 

  31. DECODE Study Group: Glucose intolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. 1999, 317:371–375.

    Google Scholar 

  32. Bastyr E, Stuart C, Brodows R, et al., for the IOEZ Study Group: Therapy focused on lowering postprandial glucose, not fasting glucose, may be superior for lowering HbA1c. Diabetes Care 2000, 23:1236–1241.

    Article  PubMed  CAS  Google Scholar 

  33. American Diabetes Association: Postprandial blood glucose. Diabetes Care 2001, 24:775–778.

    Article  Google Scholar 

  34. Haffner S: The importance of hyperglycemia in the non-fasting state to the development of cardiovascular disease. Endocrine Rev 1998, 19:583–592.

    Article  CAS  Google Scholar 

  35. Bonora E, Willeit J, Kiechl S, et al.: U-shaped and J-shaped relationships between serum insulin and coronary heart disease in the general population. The Bruneck Study. Diabetes Care 1998, 21:221–230.

    Article  PubMed  CAS  Google Scholar 

  36. Adler A, Neil A, Manley S, et al.: Hyperglycemia and hyperinsulinemia at diagnosis of diabetes and their association with subsequent cardiovascular disease in the United Kingdom. United Kingdom Prospective Diabetes Study (UKPDS 47). Am Heart J 1999, 138:S353-S359.

    Article  PubMed  CAS  Google Scholar 

  37. Ruige JB, Assendelft WJ, Dekker JM, et al.: Insulin and risk of cardiovascular disease: a meta-analysis. Circulation 1998, 97:996–1001.

    PubMed  CAS  Google Scholar 

  38. Duckworth WC, Saudek CD, Giobbie-Hurder A, et al.: The Veterans Affairs implantable insulin pump study. Effects on cardiovascular risk factors. Diabetes Care 1998, 21:1596–1602.

    Article  PubMed  CAS  Google Scholar 

  39. Duckworth WC, Bennett RG, Hamel FG: Insulin degradation: progress and potential. Endocrine Rev 1998, 19:608–624.

    Article  CAS  Google Scholar 

  40. Bonnefont-Rousselot D, Bastard JP, Jaudon MC, Delattre J: Consequences of the diabetic status on the oxidant/antioxidant balance. Diabetes Metab (Paris) 2000, 26:163–176.

    CAS  Google Scholar 

  41. Chappey O, Dosquet C, Wautier MP, Wautier JL: Advanced glycation end products, oxidant stress and vascular lesions. Eur J Clin Invest 1997, 27:97–0108.

    Article  PubMed  CAS  Google Scholar 

  42. Koehler HM, Koehler C, Schaper F, et al.: Postprandial plasma glucose is an independent risk factor for increased carotid intima-media thickness in non-diabetic individuals. Atherosclerosis 1999, 144:229–235.

    Article  PubMed  Google Scholar 

  43. Beisswenger PJ, Howell SK, O’Dell RM, et al.: Alpha-dicarbonyls increase in the postprandial period and reflect the degree of hyperglycemia. Diabetes Care 2001, 24:726–732.

    Article  PubMed  CAS  Google Scholar 

  44. Brownlee M: Negative consequences of glycation. Metabolism 2000, 49(2 suppl 1):9–13.

    Article  PubMed  CAS  Google Scholar 

  45. Singh R, Barden A, Mori T, Beilin L: Advanced glycation end-products: a review. Diabetologia 2001, 44:129–146.

    Article  PubMed  CAS  Google Scholar 

  46. Beisswenger PJ, Szwergold BS, Yeo KT: Glycated proteins in diabetes. Clin Lab Med 2001, 21:53–78.

    PubMed  CAS  Google Scholar 

  47. Duckworth WC, McCarren M, Abraira C: Glucose control and cardiovascular complications: the VA Diabetes Trial. Diabetes Care 2001, 24:942–945.

    Article  PubMed  CAS  Google Scholar 

  48. Abraira C, Colwell JA, Nuttall FQ, et al.: Veterans Affairs Cooperative Study on glycemic control and complications in type II diabetes (VA CSDM). Diabetes Care 1995, 18:1113–1123.

    Article  PubMed  CAS  Google Scholar 

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Duckworth, W.C. Hyperglycemia and cardiovascular disease. Curr Atheroscler Rep 3, 383–391 (2001). https://doi.org/10.1007/s11883-001-0076-x

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