Microvascular Complications of Diabetes

Microvascular Complications – involve capillaries and arterioles

Insidious Onset – become symptomatic only at a relatively severe stage, so prevention is better than any treatment

Factors –Ý blood viscosity, Ý platelet aggregation, glycosylated end products, enhanced activation of polyol pathway

(1) Diabetic Retinopathy–affects 90% of type 1 diabetic patients within 15 yrs; causes 20,000 cases of blindness/year

Diagnosis – via changes visible using an ophthalmoscope:

microaneurysm – outpouching of the retinal capillaries that appear as red dots on the retina – generally 1^st sign

retinal hemorrhages – may appear as round- or flame-shaped accumulations of blood

hard exudates – yellow, sharply demarcated lipid deposits in deep retina – impair vision when occur in macula

soft exudates – white with fuzzy borders ("cotton wool") – manifestation of nerve fiber infarction

macular edema – difficult to detect with ophthalmoscope, but can nevertheless cause significant vision loss

Two Levels of Severity:

Background Retinopathy – caused by Ý capillary permeability – no new blood vessels or visual impairment

caused by loss of pericytes, which are contractile cells that maintain vessel wall integrity
retinal surface changes and progression to prolif. retinopathy probably due to ischemia from microhemorrhage

Proliferative Retinopathy – characterized by new capillaries that extend anteriorly into vitreous humor

new capillaries rupture easily, filling eye with blood – impairs vision
connective tissue grows in, further occluding vision – can provide enough traction to detach retina

Prevention – especially control of blood sugar – aspirin/ticlopidine and blood pressure control may also help

Treatment – only recommended once visual symptoms occur

photocoagulation – destroy new vessels via argon/xenon laser burn

scatter (panretinal) laser therapy – burn holes in retina to destroy hypoxic tissue and prevent capillary growth

(2) Diabetic Nephropathy – not as common as retinopathy; affects only 30-40% of type 1 diabetic patients within 30 yrs

Diagnosis – no physical exam short of renal biopsy can conclusively identify it – indirect clues:

hyperfiltration – reactive increase in GFR early in disease (<2 years)

microalbuminuria (<300 g/day) – requires special test, 80% chance of nephropathy – but still no symptoms

macroalbuminuria (>300 g/day) – later illness – associated with ß GFR, edema, fatigue

Typical Course:

Years after onset	Lab changes	Blood pressure	Histologic changes
0-2	Ý GFR, Ý renal size	nL	Big glomeruli
2-10	microalbuminuria	Ý in some	Ý glomerular bsmnt membrane (GBM), mild Ý in mesangium
10-15	macroalbuminuria	Ý in many	Ý Ý GBM, marked Ý in mesangium
15-20	ß GFR, proteinuria	Ý in most	ß filtration surface and thickened walls of capillary loops
20+	End stage Renal Dis.	Ý in most	Obliteration of filtration surface

Prevention – especially control of blood pressure, also control of blood sugar

Treatment – control of blood pressure may slow disease; also low protein diet, ACE inhibitors (Captopril)

Captopril Þ decreases press within the capillaries of kidney Þ decreases rate of progression of nephropathy

end-stage renal disease (GFR decreased 90-95%) requires dialysis or transplant (or suffer seizures/coma)

Diabetic Neuropathy – not fatal; all type 1 diabetic patients have ß nerve conduction, 15-50% are symptomatic

Types of Presentation:

symmetric distal sensory neuropathy – most common; involves ß sensation and ß deep tendon reflexes

often numbness or pain in both feet or both legs – may be unaware of trauma (charcot joint) or infection in foot

mononeuropathy – affects a single nerve – involvement of cranial nerves III, IV, or VI can lead to double vision

unlike other forms, good glycemic control can reverse pathology; may spontaneously resolve

autonomic neuropathy – most severe; associated with reduced life expectancy – several effects:

cardiovascular – postural hypotension (drop in blood pressure as patient stands up); "fixed" tachycardia

gastrointestinal – gastroparesis (stomach paralysis) or enteroparesis (no peristalsis; diarrhea)

genitourinary – bladder dysfunction, erectile dysfunction (men), sexual dysfunction (women)

skin – Ý or ß in sweating – decreased sweating means less lubrication for feet Þ cracking Þ foot ulcers

endocrinological – impaired response to hypoglycemia, since warning signs are Epi mediated

Prevention – tight glycemic control provides 69% reduction in risk; also elimination of risk factors (smoking, EtOH)

Treatment – only available for symptoms

Macrovascular Complications – occlusion of larger vessels – leading cause of death in diabetic patients

Include MI (often without chest pain), stroke, claudication (mild leg artery blockage), gangrene (ischemic necrosis)

Mechanism – lipoproteins invade arterial walls, are oxidized, and attract macrophages (foamy because they engulf lipid)

macrophages release cytokines leading to endothelial dysfunction Þ necrosis Þ plaque Þ narrowing Þ ischemia

not a sudden event – culmination of 10-15 year process of atherosclerosis

Prevention – control of blood glucose does not help – eliminate risk factors (smoking, high blood pressure, etc.)

The Diabetic Foot – frequent target organ of several complications of diabetes mellitus

Neuropathy Þ impaired sensory feedback Þ pressure maldistribution, ulceration, trauma, Charcot foot (mult. fractures)

ulcers – usually on plantar surfaces, chronic, do not heal well – can lead to osteomyelitis (potentially life-threatening)

Macrovesicular disease Þ poor arterial flow Þ limits reparative response, increases vulnerability to gangrene

Prevention – caution, inspection, physician observation, education about injury avoidance (e.g., wear shoes all the time)