Dr. Smitherman is assistant professor of medicine, Department of Internal Medicine, Baylor College of Medicine, Ben Taub General Hospital, Houston, and a peer reviewer for DynaMed. Dr. Alper is medical director of clinical reference products for EBSCO Publishing, in Ipswich, Mass., and editor-in-chief of DynaMed (www.dynamicmedical.com), a database of comprehensive updated summaries covering nearly 2,000 clinical topics.

Description
• Metabolic findings between normal glucose homeostasis and diabetes, often referred to as “prediabetes”

ICD-9 codes
• 790.21 impaired fasting glucose
• 790.22 impaired glucose tolerance test (oral)
• 790.29 other abnormal glucose

Definitions
• Impaired glucose tolerance (IGT)
— Defined as two-hour 75-g oral glucose tolerance test levels 140-199 mg/dL (7.8-11 mmol/L)
— Normal levels on this test <140 mg/dL (7.8 mmol/L)
• Impaired fasting glucose (IFG)— Defined as fasting plasma glucose levels 100-125 mg/dL (5.6-6.9 mmol/L)
— Normal fasting glucose <100 mg/dL (5.6 mmol/L)

Prevalence
• 26% of U.S. adults (estimated 54 million) have IFG, based on National Health Examination and Nutrition Survey 1999-2002.

Causes
• Insulin resistance—usually receptor or post-receptor defect
— Most often seen with obesity and metabolic syndrome
— Metabolic syndrome complex includes abdominal obesity, low HDL, high triglycerides, hypertension, diabetes.
— Factors involved: family history, sedentary lifestyle, weight gain, age
• Relatively insufficient insulin secretion (beta-cell dysfunction)

Likely risk factors
• Patients with obesity or metabolic syndrome most often affected
• Lack of exercise, poor diet, current smoking
• Possible risk factor—exposure to “diabetic environment” in utero

Complications
• IGT/IFG associated with increased risk of type 2 diabetes
• 4%-9% annual incidence of type 2 diabetes in patientswith IGT
• IGT is independent risk factor for acute MI

Associated conditions
• Metabolic syndrome
• Coronary artery disease (CAD): 70%-80% of patients with CAD had diabetes or abnormal glucose tolerance in international study
• Gestational diabetes/polycystic ovary syndrome
• Mildly impaired cognitive function in elderly

Clinical evaluation
• Polyuria, polydipsia, polyphagia, numbness or tingling in hands or feet, fatigue, frequent infections, blurred vision, or erectile dysfunction may suggest diabetes mellitus.
• Ask about hypertension, hyperlipidemia, obesity, recurrent yeast infections, renal disease, eye disease, neuropathy, heart disease.
• Ask women about history of gestational diabetes, polycystic ovary syndrome, delivery of infant with macrosomia.
• Consider family history of diabetes, CAD, kidney disease, and eye disease.
• Ask about diet, exercise, substance use.
• Pay close attention to funduscopic exam, foot hygiene, skin lesions, and sensation/proprioception.

Rule out
• Drug-induced hyperglycemia and medication effects
— Thiazide diuretics (high doses), beta blockers, protease inhibitors, atypical antipsychotics, corticosteroids, niacin, pentamidine, raloxifene, and gatifloxacin
• Cushing’s syndrome or Cushing’s disease

Testing to consider
• Fasting plasma glucose
• Oral glucose tolerance test
• Glycohemoglobin (HbA1c portion)

Treatment and prevention
• Lifestyle interventions (diet/weight loss, activity) should be first choice for treatment.
• Use of pharmacologic agents as substitute for lifestyle modification discouraged
— Consider drug therapy when aggressive lifestyle interventions unsuccessful, though not established thatprevention of type 2 diabetes delays or prevents complications (vs. treatment once diabetes is diagnosed)
— Insufficient evidence to recommend specific drug for type 2 diabetes prevention
• Interventions shown in randomized trials to reduce progression to diabetes
— Lifestyle interventions (diet, activity, weight loss)
— Metformin (Glucophage) 850 mg p.o. twice daily (less effective than lifestyle intervention)
— Acarbose (Prandase, Precose) 50 mg p.o. once daily titrated to 100 mg p.o. three times daily (might reduce incidence of MI)
— Rosiglitazone (Avandia) 8 mg p.o. once daily (increases risk for congestive heart failure and possibly myocardial ischemic complications)
— Orlistat (Xenical) 120 mg p.o. three times daily
• Inconclusive evidence for statins, fibrates, antihypertensive agents, ACE inhibitors, angiotensin receptor blockers, and estrogen

Prognosis
• IGT/IFG associated with increased risk of progression to type 2 diabetes, mortality, and cardiovascular disease outcomes
• Risk for progression to type 2 diabetes higher with fasting glucose 110-125 mg/dL (6.1-6.9 mmol/L) than with fasting glucose 100-109 mg/dL (5.6-6.1 mmol/L)

Screening recommendations
• U.S. Preventive Services Task Force
— Insufficient evidence to recommend for or against routinely screening asymptomatic adults for type 2 diabetes, IGT, or IFG
— Screen adults with hypertension or hyperlipidemia.
• American Diabetes Association
— In absence of risk factors, consider screening at three-year intervals beginning at age 45, especially if BMI ≥25.
— In patients with previously identified IGT or IFG, start screening at younger age or screen more often.
— In patients with gestational diabetes and postpartum IFG or IGT, screen annually.
— Fasting plasma glucose preferred, more convenient and less expensive than oral glucose tolerance testing

References available at www.dynamicmedical.com.