Complications of diabetes mellitus

Last updated: April 1, 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.

Necrobiosis lipoidica [3]

Other complications

Insulin purging [8]

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 [15]
Overview of diabetic retinopathies
Nonproliferative retinopathy Proliferative retinopathy (PDR) Macular edema
Mechanism
Clinical features
Visual loss
  • May lead to visual loss

Distal symmetric polyneuropathy [17]

Autonomic neuropathy [18]

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

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