Microvascular Complications of Type 2 Diabetes Mellitus

Author(s): Charles Faselis*, Alexandra Katsimardou, Konstantinos Imprialos, Pavlos Deligkaris, Manolis Kallistratos, Kiriakos Dimitriadis.

Journal Name: Current Vascular Pharmacology

Volume 18 , Issue 2 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Type 2 diabetes mellitus (T2DM) is a chronic, non communicable, multisystem disease that has reached epidemic proportions. Chronic exposure to hyperglycaemia affects the microvasculature, eventually leading to diabetic nephropathy, retinopathy and neuropathy with high impact on the quality of life and overall life expectancy. Sexual dysfunction is an often-overlooked microvascular complication of T2DM, with a complex pathogenesis originating from endothelial dysfunction.

Objective: The purpose of this review is to present current definitions, epidemiological data and risk factors for diabetic retinopathy, nephropathy, neuropathy and sexual dysfunction. We also describe the clinical and laboratory evaluation that is mandatory for the diagnosis of these conditions.

Methods: A comprehensive review of the literature was performed to identify data from clinical studies for the prevalence, risk factors and diagnostic methods of microvascular complications of T2DM.

Results: Diabetic nephropathy and retinopathy affect approximately 25% of patients with T2DM; diabetic neuropathy is encountered in almost 50% of the diabetic population, while the prevalence of erectile dysfunction ranges from 35-90% in diabetic men. The duration of T2DM along with glycemic, blood pressure and lipid control are common risk factors for the development of these complications. Criteria for the diagnosis of these conditions are well established, but exclusion of other causes is mandatory.

Conclusion: Early detection of microvascular complications associated with T2DM is important, as early intervention leads to better outcomes. However, this requires awareness of their definition, prevalence and diagnostic modalities.

Keywords: Diabetes mellitus, diabetic kidney disease, diabetic retinopathy, diabetic neuropathy, erectile dysfunction, microvascular complications.

[1]
Ogurtsova K, da Rocha Fernandes JD, Huang Y, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract 2017; 128: 40-50.
[2]
Zelnick LR, Weiss NS, Kestenbaum BR, et al. Diabetes and CKD in the United States population, 2009-2014. Clin J Am Soc Nephrol 2017; 12: 1984-90.
[3]
Tuttle KR, Bakris GL, Bilous RW, et al. Diabetic kidney disease: A report from an ADA consensus conference. Diabetes Care 2014; 37: 2864-83.
[4]
de Zeeuw D. Microalbuminuria as an Early marker for cardiovascular disease. J Am Soc Nephrol 2006; 17: 2100-5.
[5]
Care D, Suppl SS. Microvascular complications and foot care: Standards of medical care in diabetes 2018. Diabetes Care 2018; 41: S105-18.
[6]
Levin A, Stevens PE, Bilous RW, et al. Kidney disease: Improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013; 3: 1-150.
[7]
Anders H-J, Huber TB, Isermann B, et al. CKD in diabetes: Diabetic kidney disease versus nondiabetic kidney disease. Nat Rev Nephrol 2018; 14: 361-77.
[8]
Fiorentino M, Bolignano D, Tesar V, et al. Renal biopsy in patients with diabetes: A pooled meta-analysis of 48 studies. Nephrol Dial Transplant 2017; 32: 97-110.
[9]
Zhuo L, Ren W, Li W, et al. Evaluation of renal biopsies in type 2 diabetic patients with kidney disease: A clinicopathological study of 216 cases. Int Urol Nephrol 2013; 45: 173-9.
[10]
Sharma SG, Bomback AS, Radhakrishnan J, et al. The modern spectrum of renal biopsy findings in patients with diabetes. Clin J Am Soc Nephrol 2013; 8: 1718-24.
[11]
Suarez MLG, Thomas DB, Barisoni L, et al. Diabetic nephropathy: Is it time yet for routine kidney biopsy? World J Diabetes 2013; 4: 245.
[12]
Mogensen CE. Microalbuminuria, blood pressure and diabetic renal disease: Origin and development of ideas. Diabetologia 1999; 42: 263-85.
[13]
Gæde P, Tarnow L, Vedel P, et al. Remission to normoalbuminuria during multifactorial treatment preserves kidney function in patients with type 2 diabetes and microalbuminuria. Nephrol Dial Transplant 2004; 19: 2784-8.
[14]
Retnakaran R, Cull CA, Thorne KI, et al. Risk factors for renal dysfunction in type 2 diabetes. Diabetes 2006; 55: 1832-9.
[15]
Penno G, Solini A, Bonora E, et al. Clinical significance of nonalbuminuric renal impairment in type 2 diabetes. J Hypertens 2011; 29: 1802-9.
[16]
Pugliese G. Updating the natural history of diabetic nephropathy. Acta Diabetol 2014; 51: 905-15.
[17]
Lynch SK, Abràmoff MD. Diabetic retinopathy is a neurodegenerative disorder. Vision Res 2017; 139: 101-7.
[18]
Yau JWY, Rogers SL, Kawasaki R, et al. Global Prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012; 35: 556-64.
[19]
Sabanayagam C, Banu R, Chee ML, et al. Incidence and progression of diabetic retinopathy: A systematic review. Lancet Diabetes Endocrinol 2018; 8587: 1-10.
[20]
Prospective UK, Study D. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-53.
[21]
Turner R, Holman RR, Stratton IM, et al. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998; 217: 703-13.
[22]
Keech A, Mitchell P, Summanen P, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): A randomised controlled trial. Lancet 2007; 370: 1687-97.
[23]
ACCORD Study Group, ACCORD Eye Study Group, Chew EY, et al. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010; 363: 233-44.
[24]
Moss SE, Klein R, Kessler SD, et al. Comparison Between ophthalmoscopy and fundus photography in determining severity of diabetic retinopathy. Ophthalmology 1985; 92: 62-7.
[25]
Vujosevic S, Benetti E, Massignan F, et al. Screening for diabetic retinopathy: 1 and 3 nonmydriatic 45-degree digital fundus photographs vs. 7 standard early treatment diabetic retinopathy study fields. Am J Ophthalmol 2009; 148: 111-8.
[26]
Chin EK, Ventura B V, See K-Y, et al. Nonmydriatic fundus photography for teleophthalmology diabetic retinopathy screening in rural and urban clinics. Telemed e-Health 2014; 20: 102-8.
[27]
Wessel MM, Aaker GD, Parlitsis G, et al. Ultra-wide-field angiography improves the detection and classification of diabetic retinopathy. Retina 2012; 32: 785-91.
[28]
Goebel W, Kretzchmar-Gross T. Retinal thickness in diabetic retinopathy: A study using optical coherence tomography (OCT). Retina 2002; 22: 759-67.
[29]
Nesper PL, Soetikno BT, Zhang HF, et al. OCT angiography and visible-light OCT in diabetic retinopathy. Vision Res 2017; 139: 191-203.
[30]
Bolster NM, Giardini ME, Bastawrous A. The diabetic retinopathy screening workflow: Potential for smartphone imaging. J Diabetes Sci Technol 2016; 10: 318-24.
[31]
Russo A, Mapham W, Turano R, et al. Comparison of smartphone ophthalmoscopy with slit-lamp biomicroscopy for grading vertical cup-to-disc ratio. J Glaucoma 2016; 25: e777-81.
[32]
Bobb-Semple A, Ruvuma S, Onyango J, et al. Validity of smartphone fundus photography in diagnosing diabetic retinopathy at Mbarara Regional Referral Hospital, South Western. Uganda: J Opthalmol Eastern Central Southern Africa 2017; pp. 45-52.
[33]
Wilkinson CP, Ferris FL, Klein RE, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 2003; 110: 1677-82.
[34]
Boulton AJM, Malik RA, Arezzo JC, et al. Diabetic somatic neuropathies. Diabetes Care 2004; 27: 1458-86.
[35]
Ang L, Jaiswal M, Martin C, et al. Glucose control and diabetic neuropathy: lessons from recent large clinical trials. Curr Diab Rep 2014; 14: 1-15.
[36]
Pop-Busui R, Boulton AJM, Feldman EL, et al. Diabetic neuropathy: A position statement by the American diabetes association. Diabetes Care 2017; 40: 136-54.
[37]
Thomas P. Classification, differential diagnosis and staging of diabetic peripheral neuropathy. Diabetes 1997; 46: S54-7.
[38]
Dyck PJ, Albers JW, Andersen H, et al. Toronto expert panel on diabetic neuropathy. Diabetic polyneuropathies: Update on research definition, diagnostic criteria and estimation of severity. Diabetes Metab Res Rev 2011; 27: 620-8.
[39]
Albers JW, Pop-Busui R. Diabetic neuropathy: Mechanisms, emerging treatments and subtypes. Curr Neurol Neurosci Rep 2014; 14: 473.
[40]
Tesfaye S, Boulton AJM, Dyck PJ, et al. Diabetic neuropathies: Update on definitions, diagnostic criteria, estimation of severity and treatments. Diabetes Care 2010; 33: 2285-93.
[41]
Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: A randomized prospective 6-year study. Diabetes Res Clin Pract 1995; 28: 103-17.
[42]
Ismail-Beigi F, Craven T, Banerji MA, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: An analysis of the ACCORD randomised trial. Lancet 2010; 376: 419-30.
[43]
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: 129-39.
[44]
Charles M, Ejskjaer N. Prevalence of neuropathy and peripheral arterial disease and the impact of treatment in people with screen-detected type 2 diabetes: The ADDITION-Denmark study. Diabetes Care 2011; 34: 2244-9.
[45]
Singleton JR, Marcus RL, Jackson JE, et al. Exercise increases cutaneous nerve density in diabetic patients without neuropathy. Ann Clin Transl Neurol 2014; 1: 844-9.
[46]
Petropoulos IN, Ponirakis G, Khan A, et al. Diagnosing diabetic neuropathy: Something old, something new. Diabetes Metab J 2018; 42: 255-69.
[47]
Freeman R. Not all neuropathy in diabetes is of diabetic etiology: Differential diagnosis of diabetic neuropathy. Curr Diab Rep 2009; 9: 423-31.
[48]
Gorson KC, Ropper AH. Additional causes for distal sensory polyneuropathy in diabetic patients. J Neurol Neurosurg Psychiatry 2006; 77: 354-8.
[49]
Callaghan BC, Kerber KA, Lisabeth LL, et al. Role of neurologists and diagnostic tests on the management of distal symmetric polyneuropathy. JAMA Neurol 2014; 71: 1143-9.
[50]
Pop-Busui R, Evans GW, Gerstein HC, et al. Effects of cardiac autonomic dysfunction on mortality risk in the Action To Control Cardiovascular Risk In Diabetes (ACCORD) trial. Diabetes Care 2010; 33: 1578-84.
[51]
Serhiyenko VA, Serhiyenko AA. Cardiac autonomic neuropathy: Risk factors, diagnosis and treatment. World J Diabetes 2018; 9: 1-24.
[52]
NIH Consensus Development Panel on Impotence. Impotence - NIH Consensus Conference. JAMA 2013; 270: 83-90.
[53]
Malavige LS, Levy JC. Erectile dysfunction in diabetes mellitus. J Sex Med 2009; 6: 1232-47.
[54]
Imprialos KP, Stavropoulos K, Doumas M, et al. Sexual dysfunction, cardiovascular risk and effects of pharmacotherapy. Curr Vasc Pharmacol 2018; 16: 130-42.
[55]
Lewis RW. Epidemiology of erectile dysfunction. Urol Clin North Am 2001; 28: 209-16.
[56]
Corona G, Giorda CB, Cucinotta D, et al. Sexual dysfunction at the onset of type 2 diabetes: The interplay of depression, hormonal and cardiovascular factors. J Sex Med 2014; 11: 2065-73.
[57]
Vlachopoulos CV, Terentes-Printzios DG, Ioakeimidis NK, et al. Prediction of cardiovascular events and all-cause mortality with erectile dysfunction: A systematic review and meta-analysis of cohort studies. Circ Cardiovasc Qual Outcomes 2013; 6: 99-109.
[58]
Ma RCW, So WY, Yang X, et al. Erectile dysfunction predicts coronary heart disease in type 2 diabetes. J Am Coll Cardiol 2008; 51: 2045-50.
[59]
Chuang Y, Chung M, Wang P, et al. Albuminuria is an Independent risk factor of erectile dysfunction in men with type 2 diabetes. J Sex Med 2012; 9: 1055-64.
[60]
Chew SK, Taouk Y, Xie J, et al. Relationship between diabetic retinopathy, diabetic macular oedema and erectile dysfunction in type 2 diabetics. Clin Exp Ophthalmol 2013; 41: 683-9.
[61]
Cander S, Coban S, Altuner S, et al. Prevalence and correlates of erectile dysfunction in type 2 diabetes mellitus: A cross-sectional single-center study among Turkish patients. Metab Syndr Relat Disord 2014; 12: 324-9.
[62]
Rosen RC, Riley A, Wagner G, et al. The international index of erectile function (IIEF): A multidimensional scale for assessment of erectile dysfunction. Urology 1997; 49: 822-30.
[63]
Glina S, Sharlip ID, Hellstrom WJG. Modifying risk factors to prevent and treat erectile dysfunction. J Sex Med 2013; 10: 115-9.
[64]
Kalter-Leibovici O, Wainstein J, Ziv A, et al. Clinical, socioeconomic, and lifestyle parameters associated with erectile dysfunction among diabetic men. Diabetes Care 2005; 28: 1739-44.
[65]
Manolis A, Doumas M. Sexual dysfunction: The ‘prima ballerina’ of hypertension-related quality-of-life complications. J Hypertens 2008; 26: 2074-84.
[66]
Mulligan T, Frick MF, Zuraw QC, et al. Prevalence of hypogonadism in males aged at least 45 years: The HIM study. Int J Clin Pract 2006; 60: 762-9.
[67]
Hatzimouratidis K, Amar E, Eardley I, et al. Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol 2010; 57: 804-14.
[68]
Bachmann G, Avci D. Evaluation and management of female sexual dysfunction. endocrinologist 2004; 14: 337-45.
[69]
Pontiroli AE, Cortelazzi D, Morabito A. Female sexual dysfunction and diabetes: A systematic review and meta-analysis. J Sex Med 2013; 10: 1044-51.
[70]
Maseroli E, Scavello I, Vignozzi L. Cardiometabolic risk and female sexuality-part I. risk factors and potential pathophysiological underpinnings for female vasculogenic sexual dysfunction syndromes. Sex Med Rev 2018; 6(4): 508-24.
[71]
Wiegel M, Meston C, Rosen R. The female sexual function index (FSFI): Cross-validation and development of clinical cutoff scores. J Sex Marital Ther 2005; 31: 1-20.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 18
ISSUE: 2
Year: 2020
Page: [117 - 124]
Pages: 8
DOI: 10.2174/1570161117666190502103733
Price: $65

Article Metrics

PDF: 43
HTML: 1

Special-new-year-discount