Complications of Diabetes Mellitus

Mark E. Molitch, M.D.
Feinberg School of Medicine, Northwestern University

Saul Genuth, M.D.
Case Western Reserve University School of Medicine

Retinopathy
Nephropathy
Neuropathy

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Retinopathy

Definition/Key Clinical Features
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

• Nonproliferative (background) retinopathy
  • Most common form
  • Microaneurysms
  • Dot hemorrhages
  • Hard lipid exudates
  • Macular edema
• Preproliferative retinopathy
  • Blot hemorrhages
  • Soft exudates
  • Intraretinal microvascular abnormalities
  • Venous beading
  • Macular edema
• Proliferative retinopathy
  • Preretinal hemorrhages
  • Vitreous hemorrhage
  • Retinal detachment
  • Macular edema

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Best Tests

• Dilated and comprehensive eye exam by ophthalmologist
  • Annually in most diabetic patients
  • More often during pregnancy
  • Every 2 yr in patients achieving glycemic goals and without cardiovascular disease

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Best Therapy

• Maintain glucose levels near normal (Hemoglobin A_1c [HbA_1c] < 7%)
• Proliferative retinopathy: panretinal scatter photocoagulation
• Macular edema: laser treatment
• Vitreous hemorrhage that does not clear or with scarring and debris: vitrectomy

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Best References

Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. JAMA 287:2563, 2002 [PMID 12020338]

Ferris FL 3rd, et al: N Engl J Med 341:667, 1999 [PMID 10460819]

Fong DS, et al: Diabetes Care 26:226, 2003 [PMID 12502685]

Willams GA: Adv Stud Ophthalmol 3:13, 2006

Williams R, et al: Eye 18:963, 2004 [PMID 15232600]

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Nephropathy

Definition/Key Clinical Features
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

• Thickening of capillary basement membrane
• Causes microalbuminuria (30–299 mg/day)
• Macroalbuminuria (= 300 mg/day)
• Falling glomerular filtration rate (GFR)
• Hypertension
• Affects 35%–45% of patients with type 1 diabetes
• Affects 10%–20% of patients with type 2 diabetes
• Incidence peaks at 15–17 yrs of diabetes, then declines

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Best Tests

• Urinary albumin measurement, annually
• Serum creatinine measurement, annually, with calculated GFR

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Best Therapy

• Maintain near-normal glycemic levels (Hb A_1c < 7%)
• Maintain good blood pressure control (<130/80 mm Hg)
  • Restrict dietary sodium
  • Antihypertensive agents: three or more drugs usually needed
    • ACE inhibitor or ARB for first drug
    • Diuretic for second drug
    • ACE inhibitor or ARB for third drug, if not chosen for first
    • Calcium channel blocker: alternative choice
    • Beta blockers can mask hypoglycemia during insulin therapy
• Protein restriction if GFR continues to fall
• Renal transplantation: better outcomes than dialysis

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Best References

Epidemiology of Diabetes Interventions and Complications (EDIC)/Diabetes Control and Complications Trial (DCCT) Study Group: JAMA 290:2159, 2003 [PMID 14570951]

Bakris GL, et al: Am J Kidney Dis 36:646, 2000 [PMID 10977801]

Mogensen CE, et al: Diabet Med 21:4, 2004 [PMID 14706048]

Gross JL, et al: Diabetes Care 28:164, 2005 [PMID 15616252]

Karalliedde J, et al: J Hum Hypertens 20:239, 2006 [PMID 16452996]

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Neuropathy

Definition/Key Clinical Features
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

• Peripheral Neuropathy
  • Symmetrical
  • Affects up to 60% of patients
  • Numbness, tingling in toes and feet
  • Hypoesthesia or anesthesia
  • Foot ulcers
  • Pain
• Carpal tunnel and other entrapment syndromes
• Autonomic Neuropathy
  • Male impotence
  • Female anorgasmia
  • Difficulty voiding and urinary retention
  • Impaired gastric emptying, early satiety, emesis
  • Diarrhea or constipation
  • Orthostatic hypotension
  • Decreased sweating and vasomotor tone in legs
  • Resting sinus tachycardia
• Amyotrophy
  • Occurs mostly in elderly men
  • 1- to 2-year course
  • Severe pain, weakness in thigh muscles
  • Muscle infarcts
  • Severe depression, cachexia, weight loss

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Best Tests

• Examination for distal polyneuropathy at diagnosis and annually
  • Test for vibration sensation using 128 mHz tuning fork
  • Test Achilles tendon reflexes
  • Test sensation with 10 g monofilament
• Clinical assessment for autonomic neuropathy: 5 yr after diagnosis in type 1 diabetes, at diagnosis in type 2
• Inspection of insensate feet at every visit
• Comprehensive foot exam annually

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Best Therapy

• Maintain near-normal glycemic levels (HbA_1c < 7%)
• Duloxetine, pregabalin, and tricyclic antidepressants: first-tier therapy
• Carbamazepine, gabapentin, lamotrigine, tramadol, venlafaxine: second-tier therapy
• Prevent foot ulcers; treat aggressively with broad-spectrum antibiotics
• Autonomic neuropathy
  • Gastroparesis: frequent small feedings and parenteral or liquid oral metoclopramide
  • Feeding jejunostomy
  • Tetracycline, clonidine, somatostatin for diarrhea
  • Oral bethanechol, bladder compression, catheterization for bladder dysfunction
  • Compression stockings, ample sodium intake, fludrocortisone for orthostatic hypotension
  • For impotence: phosphodiesterase V inhibitors (dangerous in coronary disease), alprostadil, vacuum pumps, penile implants

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  Best References

  Martin CL, et al: Diabetes Care 29:340, 2006 [PMID 16443884]

  Eaton S, et al: Diabetes Rev 7:312, 1999

  Vinik AI: Am J Med 107(suppl 2B):17S, 1999 [PMID 10484041]

  Argoff CE, et al: Mayo Clin Proc 81(suppl 4):S3, 2006 [PMID 16608048]

  Cavanagh PR, et al: Lancet 366:1725, 2005 [PMID 16291067]

Mark E. Molitch, M.D., has received research support from Sanofi-Aventis, Inc., Eli Lilly & Co., Novo-Nordisk, Inc., and Pfizer, Inc. and has served as a consultant to Sanofi-Aventis, Inc., Novo-Nordisk, Inc., and Abbott Laboratories. Saul Genuth, M.D., has no commercial relationships with manufacturers of products or providers of services discussed in this module.