Diabetes mellitus

Diabetic complications

Topic Completed: 1 August 2012

Minor changes: 22 October 2020

Copyright: 2002-2022,, Inc.

PubMed Search: Diabetic complications[TIAB] pancreas[TI]

Deepali Jain, M.D.
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Cite this page: Jain D. Diabetic complications. website. Accessed January 17th, 2022.
Definition / general
  • 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
  • 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

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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
  • 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

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Vascular complications of diabetes
  • 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
  • #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

  • More common and more severe with diabetes mellitus
  • Necrotizing papillitis also more common
  • #4 cause of blindness in U.S.
  • Associated with retinopathy, cataracts, glaucoma
  • Peripheral, symmetric neuropathy of lower extremity most common, sensory more common than motor
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