Complications of diabetes mellitus

Last updated: May 24, 2022

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Complications of diabetes mellitus can occur in patients with long-standing diabetes mellitus and are divided into macrovascular complications (e.g., coronary artery disease, stroke, peripheral artery disease) and microvascular complications (e.g., diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, diabetic foot). Diabetic nephropathy is a chronic kidney disease that results from glomerular damage induced by plasma hyperfiltration and glycosylation of the basement membrane. It is often asymptomatic in the early stages, but urine studies can show findings of microalbuminuria. In later stages, patients develop nephrotic syndrome with macroalbuminuria, foamy urine, and progressive hypertension. Diabetic retinopathy is a vascular disease of the retina that is classified as nonproliferative diabetic retinopathy, proliferative diabetic retinopathy, or diabetic maculopathy. Loss of vision is typically insidious, but acute loss of vision may occasionally result from retinal detachment, vitreous hemorrhage, or macular edema. Dilated and comprehensive eye examination help diagnose and distinguish between the subtypes. Diabetic neuropathy is characterized by damage to nerve fibers, which most commonly manifests as distal symmetrical sensory loss in the lower extremities and painful paresthesias that gradually ascend in a stocking and glove distribution. Patients often have a decreased sense of vibration on tuning fork test and a decreased sense of pressure on monofilament test. The two types of diabetic foot are neuropathic diabetic foot (due to peripheral neuropathy) and ischemic diabetic foot (due to diabetes-induced peripheral artery disease). Both manifest with recurrent infections and a painless ulcer that is typically located on the sole of the foot. Additional manifestations of neuropathic diabetic foot include warm, dry skin and palpable foot pulses, while ischemic diabetic foot also manifests with cool, pale skin and no palpable pulses. Treatment of all complications mainly comprises stringent glycemic control. In diabetic nephropathy, antihypertensive treatment is necessary to prevent further damage to the kidneys. Diabetic retinopathy is treated with laser panretinal photocoagulation or injections of intravitreal anti-vascular endothelial growth factor (VEGF). Pain management (e.g., tricyclic antidepressants, selective serotonin norepinephrine reuptake inhibitors) is used in diabetic neuropathy. Foot ulcers are treated with surgical debridement and regular wound dressing.

Acute complications

Long-term complications [1]

Macrovascular disease (atherosclerosis)

Microvascular disease

Strict glycemic control is crucial in preventing microvascular disease

Other complications

Insulin purging [7]

Diabetic nephropathy is a major cause of end stage renal disease (ESRD).

Microalbuminuria is the earliest clinical sign of diabetic nephropathy. The extent of albuminuria correlates with the risk of cardiovascular disease.

Early antihypertensive treatment delays the progression of diabetic nephropathy.

  • Epidemiology
    • After 15 years with disease, approx. 90% of patients with type 1 diabetes and approx. 25% of patients with type 2 diabetes develop diabetic retinopathy.
    • The most common cause of visual impairment and blindness in patients aged 25–74 years in the US
  • Clinical features
    • Asymptomatic until very late stages of disease
    • Visual impairment
    • Progression to blindness
  • Classification [14]
Overview of diabetic retinopathies
Nonproliferative retinopathy Proliferative retinopathy (PDR) Macular edema
Clinical features
Visual loss
  • May lead to visual loss

Distal symmetric polyneuropathy [16]

Autonomic neuropathy [17]

In about one third of patients with diabetic foot, the underlying cause is both ischemic and neuropathic.

  1. Stolar M. Glycemic Control and Complications in Type 2 Diabetes Mellitus. Am J Med. 2010; 123 (3): p.S3-S11. doi: 10.1016/j.amjmed.2009.12.004 . | Open in Read by QxMD
  2. Micheletti RG, Fishbein GA, Currier JS, Fishbein MC. Mönckeberg sclerosis revisited: a clarification of the histologic definition of Mönckeberg sclerosis.. Arch Pathol Lab Med. 2008; 132 (1): p.43-7. doi: 10.1043/1543-2165(2008)132[43:MSRACO]2.0.CO;2 . | Open in Read by QxMD
  3. Jia G, Whaley-Connell A, Sowers JR. Diabetic cardiomyopathy: a hyperglycaemia- and insulin-resistance-induced heart disease. Diabetologia. 2017; 61 (1): p.21-28. doi: 10.1007/s00125-017-4390-4 . | Open in Read by QxMD
  4. Sousa AGP, Cabral JV de S, El-Feghaly WB, Sousa LS de, Nunes AB. Hyporeninemic hypoaldosteronism and diabetes mellitus: Pathophysiology assumptions, clinical aspects and implications for management. World Journal of Diabetes. 2016; 7 (5): p.101. doi: 10.4239/wjd.v7.i5.101 . | Open in Read by QxMD
  5. Cherqaoui R, McKenzie S, Nunlee-Bland G. Diabetic Cheiroarthropathy: A Case Report and Review of the Literature. Case Rep Endocrinol. 2013; 2013 . doi: 10.1155/2013/257028 . | Open in Read by QxMD
  6. Upreti V, Vasdev V, Dhull P, Patnaik SK. Prayer sign in diabetes mellitus. Indian J Endocrinol Metab. 2013; 17 (4): p.769-770. doi: 10.4103/2230-8210.113784 . | Open in Read by QxMD
  7. Jones JM, Lawson ML, Daneman D, Olmsted MP, Rodin G. Eating disorders in adolescent females with and without type 1 diabetes: cross sectional study.. BMJ. 2000; 320 (7249): p.1563-6.
  8. Tervaert TWC, Mooyaart AL, Amann K, et al. Pathologic Classification of Diabetic Nephropathy. Journal of the American Society of Nephrology. 2010; 21 (4): p.556-563. doi: 10.1681/asn.2010010010 . | Open in Read by QxMD
  9. Alsaad KO, Herzenberg AM. Distinguishing diabetic nephropathy from other causes of glomerulosclerosis: an update. J Clin Pathol. 2007; 60 (1): p.18-26. doi: 10.1136/jcp.2005.035592 . | Open in Read by QxMD
  10. DIABETIC NEPHROPATHY. . Accessed: June 11, 2019.
  11. Moosa MR, Van der Walt I, Naicker S, Meyers AM. Important causes of chronic kidney disease in South Africa. South African Medical Journal. 2015 .
  12. Fried LF, Emanuele N, Zhang JH, Brophy M, Conner TA, Duckworth W, Leehey DJ, McCullough PA, O'Connor T, Palevsky PM, Reilly RF, Seliger SL, Warren SR, Watnick S, Peduzzi P, Guarino P. Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy. New England Journal of Medicine. 2013 .
  13. Diabetic Nephropathy Workup. Updated: March 13, 2018. Accessed: June 11, 2019.
  14. Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. The Lancet. 2010; 376 (9735): p.124-136. doi: 10.1016/s0140-6736(09)62124-3 . | Open in Read by QxMD
  15. American Diabetes Association (AMA). 11. Microvascular Complications and Foot Care: Standards of Medical Care in Diabetes−2020. Diabetes Care. 2019; 43 (Supplement 1): p.S135-S151. doi: 10.2337/dc20-s011 . | Open in Read by QxMD
  16. Callaghan BC, Price RS, Feldman EL. Distal Symmetric Polyneuropathy. JAMA. 2015; 314 (20): p.2172. doi: 10.1001/jama.2015.13611 . | Open in Read by QxMD
  17. Kamenov ZA, Traykov LD. Diabetic Autonomic Neuropathy. Springer New York ; 2012 : p. 176-193
  18. Bharucha AE, Kudva YC, Prichard DO. Diabetic Gastroparesis. Endocr Rev. 2019; 40 (5): p.1318-1352. doi: 10.1210/er.2018-00161 . | Open in Read by QxMD
  19. Choung RS, Locke RG, Schleck CD, Zinsmeister AR, Melton JL, Talley NJ. Risk of Gastroparesis in Subjects With Type 1 and 2 Diabetes in the General Population. Am J Gastroenterol. 2012; 107 (1): p.82-88. doi: 10.1038/ajg.2011.310 . | Open in Read by QxMD
  20. Bytzer P, Talley NJ, Hammer J, Young LJ, Jones MP, Horowitz M. GI symptoms in diabetes mellitus are associated with both poor glycemic control and diabetic complications. Am J Gastroenterol. 2002; 97 (3): p.604-611. doi: 10.1111/j.1572-0241.2002.05537.x . | Open in Read by QxMD
  21. Jain M, Devan S, Jaisankar D, Swaminathan G, Pardhan S, Raman R. Pupillary Abnormalities with Varying Severity of Diabetic Retinopathy. Scientific Reports. 2018; 8 (1). doi: 10.1038/s41598-018-24015-9 . | Open in Read by QxMD
  22. Sinwar PD. The diabetic foot management – Recent advance. International Journal of Surgery. 2015; 15 : p.27-30. doi: 10.1016/j.ijsu.2015.01.023 . | Open in Read by QxMD

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