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Pancreas

Diabetes mellitus

Diabetic complications

Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 4 December 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

General
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● Main complications are microangiopathy, retinopathy, nephropathy, neuropathy – all due to hyperglycemia
● Kidneys transplanted into diabetic patients develop nephropathy within 3-5 years but kidneys from diabetic patients transplanted into normal patients have remission of nephropathy
● Strict control of diabetes delays progression of microvascular complications
● Complications are due to nonenzymatic glycosylation and disturbances in polyol pathways

Nonenzymatic glycosylation
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● Glucose + protein => Schiff base (protein - NH = CH (CHOH)4-CH2OH) => Amadori product
● (protein-NH-CH2-C=0-(CHOH)3-CH2OH => protein-protein cross linking via N-C-N bonding


Formation of irreversible products called advanced glycation end products (AGEs), such as carboxymethyllysine

● Early reactions are reversible, and related to HbA1c level
● Advanced glycosylation end products (AGE) are not reversible
● AGE traps LDL in blood vessels, enhances cholesterol deposition, accelerating atherosclerosis
● AGE inhibition antagonizes diabetic complications in experimental models

Polyol pathways
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● Important in tissues that don’t require insulin for glucose transport, i.e. nerves, lens, kidneys, blood vessels
● High intracellular glucose plus aldose reductase produces sorbitol and later fructose, causing water influx and osmotic cell injury
● In lens, causes swelling and opacity
● Inhibition of sorbitol may reduce formation of cataracts and neuropathy

 
Diagrams

Vascular complications of diabetes
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● Relative risk is 100:1
● Accelerated atherosclerosis in aorta and large/medium sized vessels
● Myocardial infarction: most common cause of death, no gender preference
● Gangrene of lower extremities

Micro description:
● Hyaline arteriolosclerosis, associated with hypertension, more common/severe in diabetes but not specific
● Amorphous hyaline thickening in arteriolar wall
● Related to severity of disease and hypertension
● Microangiopathy: diffuse basement membrane thickening with protein leakage in capillaries of skin, skeletal muscle, retina, renal glomeruli, renal medulla, renal tubules, Bowman capsule, peripheral nerves, placenta

Diabetic nephropathy
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● #2 cause of death in patients with diabetes after myocardial infarction; see Kidney nontumor chapter
● Glomeruli-capillary basement membrane thickening (grade I), mesangial expansion (grade II), nodular glomerulosclerosis (grade III), diffuse glomerulosclerosis, (grade IV)
● Also renal atherosclerosis and arteriolosclerosis
● Changes to efferent arteriole are specific for diabetes

Nodular glomerulosclerosis:
● Ball-like deposits of laminated matrix within mesangial core of lobule
● Push capillary loops to periphery, may have perinodular halos
● Called Kimmelstiel-Wilson lesion and may contain trapped mesangial cells
● Low sensitivity (10-35%) but highly specific for diabetes mellitus

Diffuse glomerulosclerosis:
● Diffuse increase in mesangial matrix, mesangial cell proliferation, basement membrane thickening
● Seen in most patients with diabetes mellitus after 10 years
● When marked, causes nephrotic syndrome
● Not specific

Pyelonephritis:
● More common and more severe with diabetes mellitus
● Necrotizing papillitis also more common

Ocular
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● #4 cause of blindness in US
● Associated with retinopathy, cataracts, glaucoma

Neuropathy
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● Peripheral, symmetric neuropathy of lower extremity most common, sensory more common than motor

End of Pancreas > Diabetes mellitus > Diabetic complications

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