Microvascular and Macrovascular Complications of Diabet...

Microvascular and Macrovascular Complications of Diabetes

Microvascular and Macrovascular Complications of Diabetes
Clinical Diabetes 26:77-82, 2008
DOI: 10.2337/diaclin.26.2.77

Michael J. Fowler, MD

Introduction
Diabetes is a group of chronic diseases characterized by hyperglycemia. Modern medical care uses a vast array of lifestyle and pharmaceutical interventions aimed at preventing and controlling hyperglycemia. In addition to ensuring the adequate delivery of glucose to the tissues of the body, treatment of diabetes attempts to decrease the likelihood that the tissues of the body are harmed by hyperglycemia.

The importance of protecting the body from hyperglycemia cannot be overstated; the direct and indirect effects on the human vascular tree are the major source of morbidity and mortality in both type 1 and type 2 diabetes. Generally, the injurious effects of hyperglycemia are separated into macrovascular complications (coronary artery disease, peripheral arterial disease, and stroke) and microvascular complications (diabetic nephropathy, neuropathy, and retinopathy). It is important for physicians to understand the relationship between diabetes and vascular disease because the prevalence of diabetes continues to increase in the United States, and the clinical armamentarium for primary and secondary prevention of these complications is also expanding.

Microvascular Complications of Diabetes
Diabetic retinopathy
Diabetic retinopathy may be the most common microvascular complication of diabetes. It is responsible for ~ 10,000 new cases of blindness every year in the United States alone.1 The risk of developing diabetic retinopathy or other microvascular complications of diabetes depends on both the duration and the severity of hyperglycemia. Development of diabetic retinopathy in patients with type 2 diabetes was found to be related to both severity of hyperglycemia and presence of hypertension in the U.K. Prospective Diabetes Study (UKPDS), and most patients with type 1 diabetes develop evidence of retinopathy within 20 years of diagnosis.2,3 Retinopathy may begin to develop as early as 7 years before the diagnosis of diabetes in patients with type 2 diabetes.1 There are several proposed pathological mechanisms by which diabetes may lead to development of retinopathy.

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REFERENCES

1 Fong DS, Aiello LP, Ferris FL 3rd, Klein R: Diabetic retinopathy. Diabetes Care 27:2540 -2553, 2004[Free Full Text]

2 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 (UKPDS 33). Lancet352 : 837-853,1998[Medline]

3 Keenan HA, Costacou T, Sun JK, Doria A, Cavellerano J, Coney J, Orchard TJ, Aiello LP, King GL: Clinical factors associated with resistance to microvascular complications in diabetic patients of extreme disease duration: the 50-year medalist study. Diabetes Care30 : 1995-1997,2007[Free Full Text]

4 Gabbay KH: Hyperglycemia, polyol metabolism, and complications of diabetes mellitus. Annu Rev Med 26:521 -536, 1975[Medline]

5 Gabbay KH: Aldose reductase inhibition in the treatment of diabetic neuropathy: where are we in 2004? Curr Diab Rep 4:405 -408, 2004[Medline]

6 Kunisaki M, Bursell SE, Clermont AC, Ishii H, Ballas LM, Jirousek MR, Umeda F, Nawata H, King GL: Vitamin E prevents diabetes-induced abnormal retinal blood flow via the diacylglycerol-protein kinase C pathway. Am J Physiol 269:E239 -E246, 1995[Medline]

7 Aiello LP, Pierce EA, Foley ED, Takagi H, Chen H, Riddle L, Ferrara N, King GL, Smith LE: Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci U S A92 : 10457-10461,1995[Abstract/Free Full Text]

8 Watkins PJ: Retinopathy. BMJ 326:924 -926, 2003[Free Full Text]

9 Gross JL, de Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, Zelmanovitz T: Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care 28: 164-176,2005[Abstract/Free Full Text]

10 Chaturvedi N, Bandinelli S, Mangili R, Penno G, Rottiers RE, Fuller JH: Microalbuminuria in type 1 diabetes: rates, risk factors and glycemic threshold. Kidney Int 60: 219-227,2001[Medline]

11 Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR: Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int 63:225 -232, 2003[Medline]

12 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 329:977 -986, 1993[Abstract/Free Full Text]

13 Heart Outcomes Prevention Evaluation Study Investigators: Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet355 : 253-259,2000[Medline]

14 Rossing K, Jacobsen P, Pietraszek L, Parving HH: Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial. Diabetes Care 26:2268 -2274, 2003[Abstract/Free Full Text]

15 American Diabetes Association: Standards of medical care in diabetes—2007 [Position Statement]. Diabetes Care 30:S4 -S41, 2007[Free Full Text]

16 Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, Malik RA, Maser RE, Sosenko JM, Ziegler D: Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care 28:956 -962, 2005[Free Full Text]

17 Abbott CA, Carrington AL, Ashe H, Bath S, Every LC, Griffiths J, Hann AW, Hussein A, Jackson N, Johnson KE, Ryder CH, Torkington R, Van Ross ER, Whalley AM, Widdows P, Williamson S, Boulton AJ: The North-West Diabetes Foot Care Study: incidence of, and risk factors for, new diabetic foot ulceration in a community-based patient cohort. Diabet Med19 : 377-384,2002[Medline]

18 Maser RE, Mitchell BD, Vinik AI, Freeman R: The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis. Diabetes Care 26:1895 -1901, 2003[Abstract/Free Full Text]

19 Boyle PJ: Diabetes mellitus and macrovascular disease: mechanisms and mediators. Am J Med 120: S12-S17,2007[Medline]

20 Beckman JA, Creager MA, Libby P: Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA287 : 2570-2581,2002[Abstract/Free Full Text]

21 Laing SP, Swerdlow AJ, Slater SD, Burden AC, Morris A, Waugh NR, Gatling W, Bingley PJ, Patterson CC: Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia46 : 760-765,2003[Medline]

22 Paterson AD, Rutledge BN, Cleary PA, Lachin JM, Crow RS: The effect of intensive diabetes treatment on resting heart rate in type 1 diabetes: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Diabetes Care 30:2107 -2112, 2007[Abstract/Free Full Text]

23 Hogan P, Dall T, Nikolov P: Economic costs of diabetes in the US in 2002. Diabetes Care 26: 917-932,2003[Abstract/Free Full Text]

24 Kannel WB, McGee DL: Diabetes and cardiovascular disease: the Framingham study. JAMA 241:2035 -2038, 1979[Abstract]

25 Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M: Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med339 : 229-234,1998[Abstract/Free Full Text]

26 Buse JB, Ginsberg HN, Bakris GL, Clark NG, Costa F, Eckel R, Fonseca V, Gerstein HC, Grundy S, Nesto RW, Pignone MP, Plutzky J, Porte D, Redberg R, Stitzel KF, Stone NJ: Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care30 : 162-172,2007[Abstract/Free Full Text]

27 Almdal T, Scharling H, Jensen JS, Vestergaard H: The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: a population-based study of 13,000 men and women with 20 years of follow-up. Arch Intern Med 164:1422 -1426, 2004[Abstract/Free Full Text]

28 Avogaro A, Giorda C, Maggini M, Mannucci E, Raschetti R, Lombardo F, Spila-Alegiani S, Turco S, Velussi M, Ferrannini E: Incidence of coronary heart disease in type 2 diabetic men and women: impact of microvascular complications, treatment, and geographic location. Diabetes Care30 : 1241-1247,2007[Abstract/Free Full Text]

29 Lehto S, Ronnemaa T, Pyorala K, Laakso M: Predictors of stroke in middle-aged patients with non-insulin-dependent diabetes. Stroke27 : 63-68,1996[Abstract/Free Full Text]

30 Laing SP, Swerdlow AJ, Carpenter LM, Slater SD, Burden AC, Botha JL, Morris AD, Waugh NR, Gatling W, Gale EA, Patterson CC, Qiao Z, Keen H: Mortality from cerebrovascular disease in a cohort of 23 000 patients with insulin-treated diabetes. Stroke 34:418 -421, 2003[Abstract/Free Full Text]

31 Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, Raskin P, Zinman B: Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 353:2643 -2653, 2005[Abstract/Free Full Text]

32 U.K. Prospective Diabetes Study Group: Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ 317:713 -720, 1998[Abstract/Free Full Text]

33 U.K. Prospective Diabetes Study Group: Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ317 : 703-713,1998[Abstract/Free Full Text]

34 Lindholm LH, Ibsen H, Dahlof B, Devereux RB, Beevers G, de Faire U, Fyhrquist F, Julius S, Kjeldsen SE, Kristiansson K, Lederballe-Pedersen O, Nieminen MS, Omvik P, Oparil S, Wedel H, Aurup P, Edelman J, Snapinn S: Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 359:1004 -1010, 2002[Medline]

35 Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller JH: Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 364:685 -696, 2004[Medline]

36 Collins R, Armitage J, Parish S, Sleigh P, Peto R: MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet361 : 2005-2016,2003[Medline]

37 Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, Huttunen JK, Kaitaniemi P, Koskinen P, Manninen V, Maenpaa H, Malkonen M, Manttari M, Norola S, Pasternack A, Pikkarainen J, Romo M, Sjoblom T, Nikkila E.: Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia: safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med317 : 1237-1245,1987[Abstract]

38 Koskinen P, Manttari M, Manninen V, Huttunen JK, Heinonen OP, Frick MH: Coronary heart disease incidence in NIDDM patients in the Helsinki Heart Study. Diabetes Care 15:820 -825, 1992[Abstract]

39 Manninen V, Elo MO, Frick MH, Haapa K, Heinonen OP, Heinsalmi P, Helo P, Huttunen JK, Kaitaniemi P, Koskinen P, Maenpaa H, Malkonen M, Manttari M, Norola S, Pasternack A, Pikkarainen J, Romo M, Sjoblom T, Nikila E: Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. JAMA 260:641 -651, 1988[Abstract]


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