The long-term microvascular complications of diabetes pose a major health burden. Although, much of the focus has been on the macrovascular much of the focus has been on the macrovascular complications, it is clear that the microvascular complications have a significant impact on both morbidity and mortality amongst diabetic patients. Indeed retinopathy, nephropathy, and neuropathy compete as the leading causes of premature blindness, end-stage renal disease, and non-traumatic lower-limb amputation, respectively. Furthermore, complications develop and progress in unison and indeed share many common risk factors. Effective evaluation and monitoring of these complications in clinical practice is clearly important, however, it is also relevant to clinical addressing microvascular complications, Novel intervention studies, and drug development programs diagnostic and therapeutic strategies are continually evolving in this area and will be discussed in more detail in this review.
Tapp RJ, Shaw JE, de Courten MP et al. Foot complications in Type 2 diabetes: an Australian population-based study. Diabet Med2003;20:105-13.
2.
Tapp RJ, Shaw JE, Harper CA et al. The prevalence of and factors associated with diabetic retinopathy in the Australian population. Diabetes Care2003;26:1731-7.
3.
Tapp RJ, Shaw JE, Zimmet PZ et al. Albuminuria is evident in the early stages of diabetes onset: results from the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) . Am J Kidney Dis2004;44:792-8.
4.
Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA2001;285:2486-97.
5.
Alexander CM , Landsman PB, Teutsch SM, Haffner SMNCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes2003;52:1210-14.
6.
Cuspidi C., Meani S., Fusi V. et al. Metabolic syndrome and target organ damage in untreated essential hypertensives. J Hypertens2004;22:1991-8.
7.
Leoncini G., Ratto E., Viazzi F. et al. Metabolic syndrome is associated with early signs of organ damage in nondiabetic, hypertensive patients. J Intern Med2005;257:454-60.
8.
Mule G., Nardi E., Cottone S. et al. Influence of metabolic syndrome on hypertension-related target organ damage. J Intern Med2005;257:503-13.
9.
Schillaci G. , Pirro M., Vaudo G. et al. Prognostic value of the metabolic syndrome in essential hypertension. J Am Coll Cardiol2004; 43:1817-22.
10.
Boulton AJ, Vinik AL, Arezzo JC et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care2005;28:956-62.
Malik RA, Williamson S., Abbott C. et al. Effect of angiotensin-converting-enzyme (ACE) inhibitor trandolapril on human diabetic neuropathy: randomised double-blind controlled trial. Lancet1998;352:1978-81.
13.
Ramsey SD, Newton K., Blough D. et al. Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care1999;22:382-7.
14.
Ollendorf DA , Kotsanos JG, Wishner WJ et al. Potential economic benefits of lower-extremity amputation prevention strategies in diabetes. Diabetes Care1998;21:1240-5.
15.
Miranda-Palma B., Sosenko JM, Bowker JH, Mizel MS, Boulton AJA comparison of the monofilament with other testing modalities for foot ulcer susceptibility . Diabetes Res Clin Pract2005;70:8-12.
16.
Mojaddidi M. , Quattrini C., Tavakoli M., Malik RARecent developments in the assessment of efficacy in clinical trials of diabetic neuropathy. Curr Diab Rep2005;5:417-22.
17.
Malik RA, Veves A., Walker D. et al. Sural nerve fibre pathology in diabetic patients with mild neuropathy: relationship to pain, quantitative sensory testing and peripheral nerve electrophysiology . Acta Neuropathol (Berl)2001;101:367-74.
18.
Malik RA, Tesfaye S., Newrick PG et al. Sural nerve pathology in diabetic patients with minimal but progressive neuropathy. Diabetologia2005;48:578-85.
19.
Smith AG, Russell J., Feldman EL et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care2006;29:1294-9.
20.
Novella SP, Inzucchi SE, Goldstein JMThe frequency of undiagnosed diabetes and impaired glucose tolerance in patients with idiopathic sensory neuropathy. Muscle Nerve2001;24:1229-31.
21.
Sumner CJ, Sheth S., Griffin JW et al. The spectrum of neuropathy in diabetes and impaired glucose tolerance. Neurology2003; 60:108-11.
22.
Smith AG, Howard JR, Kroll R. et al. The reliability of skin biopsy with measurement of intraepidermal nerve fiber density. J Neurol Sci2005;228:65-9.
23.
Caselli A., Rich J., Hanane T. et al. Role of C-nociceptive fibers in the nerve axon reflex-related vasodilation in diabetes. Neurology2003;60:297-300.
24.
Krishnan ST, Rayman G.The LDI flare: a novel test of C-fiber function demonstrates early neuropathy in type 2 diabetes. Diabetes Care2004;27:2930-5.
25.
McArthur JC, Stocks EA, Hauer P. et al. Epidermal nerve fiber density: normative reference range and diagnostic efficiency. Arch Neurol1998;55:1513-20.
26.
Holland NR, Stocks A., Hauer P. et al. Intraepidermal nerve fiber density in patients with painful sensory neuropathy. Neurology1997; 48:708-11.
27.
Holland NR, Crawford TO, Hauer P. et al. Small-fiber sensory neuropathies: clinical course and neuropathology of idiopathic cases. Ann Neurol1998;44:47-59.
28.
Rosenberg ME , Tervo TM, Immonen IJ et al. Corneal structure and sensitivity in type 1 diabetes mellitus. Invest Ophthalmol Vis Sci2000;41:2915-21.
29.
Oliveira-Soto L., Efron N.Morphology of corneal nerves using confocal microscopy. Cornea2001;20:374-84.
30.
Patel SV, McLaren JW, Hodge DO, Bourne WMConfocal microscopy in vivo in corneas of long-term contact lens wearers . Invest Ophthalmol Vis Sci2002;43:995-1003.
31.
Tuominen IS , Konttinen YT, Vesaluoma MH et al. Corneal innervation and morphology in primary Sjogren's syndrome. Invest Ophthalmol Vis Sci2003;44:2545-9.
32.
Lockwood A. , Hope-Ross M., Chell P.Neurotrophic keratopathy and diabetes mellitus . Eye2006;20:837-9.
33.
Hossain P., Sachdev A., Malik RAEarly detection of diabetic peripheral neuropathy with corneal confocal microscopy . Lancet2005;366:1340-3.
34.
Malik RA, Kallinikos P., Abbott CA et al. Corneal confocal microscopy: a non-invasive surrogate of nerve fibre damage and repair in diabetic patients. Diabetologia2003;46:683-8.
35.
Kallinikos P., Berhanu M., O'Donnell C., Boulton AJ, Efron N., Malik RACorneal nerve tortuosity in diabetic patients with neuropathy. Invest Ophthalmol Vis Sci2004;45:418-22.
Tesfaye S., Chaturvedi N., Eaton SE et al. Vascular risk factors and diabetic neuropathy. N Engl J Med2005;352:341-50.
38.
Martin CL, Albers J., Herman WH et al. Neuropathy among the diabete control and complications trial cohort 8 years after trial completion. Diabetes Care2006;29:340-4.
39.
Oyibo SO, Prasad YD, Jackson NJ, Jude EB, Boulton AJThe relationship between blood glucose excursions and painful diabetic peripheral neuropathy: a pilot study. Diabet Med2002 ;19:870-3.
40.
Sonnett TE, Setter SM, Campbell RKPregabalin for the treatment of painful neuropathy. Expert Rev Neurother2006;6:1629-35.
41.
Smith TRDuloxetine in diabetic neuropathy. Expert Opin Pharmacother2006;7:215-23.
42.
Parving HH, Mogensen CE, Thomas MC, Brenner BM, Cooper MEPoor prognosis in proteinuric type 2 diabetic patients with retinopathy: insights from the RENAAL study. Qjm2005;98:119-26.
43.
So WY, Kong AP, Ma RC et al. Glomerular filtration rate, cardiorenal end points, and all-cause mortality in type 2 diabetic patients. Diabetes Care2006;29:2046-52.
44.
Ravera M., Re M., Vettoretti S.Economic evaluation of angiotensin receptor blockers in type 2 diabetes, hypertension, and nephropathy. J Am Soc Nephrol2006;17:S44-S48.
45.
Sengul AM, Altuntas Y., Kurklu A., Aydin L.Beneficial effect of lisinopril plus telmisartan in patients with type 2 diabetes, microalbuminuria and hypertension. Diabetes Res Clin Pract2006;71:210-19.
46.
Epstein M.Adding spironolactone to conventional antihypertensives reduces albuminuria in patients with diabetic nephropathy. Nat Clin Pract Nephrol2006;2:310-11.
47.
Sandhu S., Wiebe N., Fried LF, Tonelli M.Statins for improving renal outcomes: a meta-analysis. J Am Soc Nephrol2006;17:2006-16.
48.
Skrivarhaug T., Fosmark DS, Stene LC et al. Low cumulative incidence of proliferative retinopathy in childhood-onset type 1 diabetes: a 24-year follow-up study . Diabetologia2006 ;49:2281-90.
49.
Roy MS, Affouf M.Six-year progression of retinopathy and associated risk factors in African American patients with type 1 diabetes mellitus: the New Jersey 725 . Arch Ophthalmol2006;124:1297-306.
50.
van Hecke MV , Dekker JM, Stehouwer CD et al. Diabetic retinopathy is associated with mortality and cardiovascular disease incidence: the EURODIAB prospective complications study. Diabetes Care2005;28:1383-9.
51.
Chew EYScreening options for diabetic retinopathy. Curr Opin Ophthalmology2006;17:519-22.
52.
Klein R., Moss SE, Sinaiko AR et al. The relation of ambulatory blood pressure and pulse rate to retinopathy in type 1 diabetes mellitus: the renin-angiotensin system study . Ophthalmology2006;113:2231-6.
53.
Early Treatment Diabetic Retinopathy Study Research Group.Grading diabetic retinopathy from stereoscopic color fundus photographs an extension of the modified Airlie House classification. ETDRS report number 10. Ophthalmology1991 ;98:786-806.
54.
Shotliff KP , Duncan G.Diabetic retinopathy: summary of grading and management criteria. Prac Diab Int2006;23:418-20.
55.
Jonas JB, Spandau UH, Kamppeter BA et al. Repeated intravitreal highdosage injections of triamcinolone acetonide for diffuse diabetic macular edema. Ophthalmology2006;113:800-04.
56.
Jonas JBIntravitreal triamcinolone acetonide for diabetic retinopathy. Dev Ophthalmol2007;39:96-110.
57.
Jorge R., Costa RA, Calucci D. et al. Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy (IBEPE study). Retina2006;26:1006-13.
58.
Palii SS, Caballero S., Jr., Shapiro G., Grant MBMedical treatment of diabetic retinopathy with somatostatin analogues . Expert Opin Investig Drugs2007;16:73-82.
59.
Aiello LP, Davis MD, Girach A. et al. Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy. Ophthalmology2006; 113:2221-30.
