> Table of Contents > Glucose Intolerance
Glucose Intolerance
Kristina McGraw, DO
Jennifer Lee, DO
Robert A. Baldor, MD, FAAFP
image BASICS
DESCRIPTION
  • Glucose intolerance is a chronic condition defined as blood glucose higher than considered normal, yet does not meet criteria levels for diabetes.
  • Individuals with impaired fasting glucose (IFG) and/or impaired glucose intolerance (IGT) have been referred to as having prediabetes:
    • IFG: 100 to 125 mg/dL
    • IGT: 140 to 199 mg/dL 2 hours after ingestion of 75 g oral glucose load
    • Hemoglobin A1c as a screening test 5.7-6.4% (1)
EPIDEMIOLOGY
  • As of 2010, it is estimated that one of every three U.S. adults ≥20 years of age have prediabetes (2).
  • An estimated 86 million people in the United States are living with prediabetes.
  • Only 11% of people with prediabetes are aware of their condition (3).
  • Prediabetes has a 37% prevalence among adults >20 years old and 51% of adults ≤65 years in the United States (4).
Incidence
  • 15-30% of people with prediabetes will develop type 2 diabetes within 5 years.
  • Prospective studies indicate that A1c range of 5.5-6.0% have a 5-year cumulative incidence from 9% to 25% for developing diabetes (2).
  • Highest incidence in American Indians/Alaska Natives, non-Hispanic blacks, and Hispanics (2)
ETIOLOGY AND PATHOPHYSIOLOGY
Insulin resistance and progressive insulin secretary defect (5)
RISK FACTORS
  • Body mass index (BMI) ≥25: overweight
  • Obesity and metabolic syndrome
  • 10-fold risk increase for future diabetes in A1c ranges 5.7-6.4%
  • History of gestational diabetes (GDM)
  • Sedentary lifestyle
  • Glucocorticoids and antipsychotic use
GENERAL PREVENTION
  • Lifestyle modification with weight reduction and increased physical activity
  • A decrease in excess body fat provides the greatest risk reduction.
  • Medical therapy: weight loss medications
    • Phentermine
    • Orlistat
    • Lorcaserin
    • Phentermine topiramate ER
  • Surgical therapy (BMI ≥35)
    • Lap band
    • Gastric sleeve
    • Gastric bypass
  • Patients with other cardiovascular risk factors (e.g., dyslipidemia, hypertension, obesity, tobacco use) should receive appropriate counseling to modify diet and exercise.
Pregnancy Considerations
  • Screening for diabetes in pregnancy is based on risk factor analysis:
    • High risk: first prenatal visit
    • Average risk: 24 to 28 weeks' gestation
  • Women with GDM should be screened for diabetes 6 to 12 weeks' postpartum (6).
COMMONLY ASSOCIATED CONDITIONS
  • Obesity (abdominal and visceral obesity)
  • Dyslipidemia with high triglycerides (TG)
  • Metabolic syndrome
  • PCOS
  • GDM
  • Low HDL
  • HTN
  • Congenital diseases (Down, Turner, Klinefelter, and Wolfram syndromes)
image DIAGNOSIS
Who to screen
  • BMI ≥25
  • Age >45 years
  • First-degree relative with diabetes
  • Low HDL <35 mg/dL
  • High TG >250 mg/dL
  • HTN: BP >140/90 mm Hg or on treatment
  • Hx of GDM
  • Physical inactivity
  • Hx of cardiovascular disease
  • Ethnic group at increased risk (non-Hispanic black, Native American, Hispanics, Asian American, Pacific Islander)
  • HgbA1c ≥5.7%, IGT, or IFG on previous testing
  • PCOS
  • Conditions associated with insulin resistance such as severe obesity or acanthosis nigricans
PHYSICAL EXAM
  • General physical exam
  • BMI assessment
DIFFERENTIAL DIAGNOSIS
  • Type A insulin resistance
  • Leprechaunism
  • Rabson-Mendenhall syndrome
  • Lipoatrophic diabetes
  • Pancreatitis
  • Cystic fibrosis
  • Hemochromatosis
  • Acromegaly
  • Cushing syndrome
  • Glucagonoma
  • Pheochromocytoma
  • Hyperthyroidism
  • Somatostatinoma
  • Aldosteronoma
  • Drug-induced hyperglycemia
    • Thiazide diuretics (high doses)
    • &bgr;-blockers
    • Corticosteroids (including inhaled corticosteroids)
    • Thyroid hormone
    • &agr;-Interferon
    • Pentamidine
    • Protease inhibitors
    • Atypical antipsychotics
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Fasting glucose
  • 2-Hour OGTT
  • HbA1c
  • Repeat screen at least at 3-year intervals with normal results or sooner depending on risk status (5).
Follow-Up Tests & Special Considerations
  • Fasting lipid profile
  • Creatinine and GFR
  • Urinalysis
  • Microalbumin-to-creatinine ratio
  • Thyroid-stimulating hormone with free T4
image TREATMENT
  • Lifestyle aimed at increasing physical activity and weight loss prevents or delays the development of diabetes in people with IGT and IFG (6)[C].
  • Exercise and lifestyle:
    • At least 150 minute/week of moderate-intensity aerobic exercise and/or at least 90 minute/week of vigorous aerobic exercise
    • Resistance exercise improves insulin sensitivity to the same extent as aerobic exercise; resistance training 3 times per week is recommended for those with type 2 diabetes
    • Smoking cessation
  • Follow-up counseling (6)[B]
  • Diabetes prevention programs are cost effective (6)[B].
    • Diabetes prevention program (participants <60 years of age, BMI ≥35 kg/m2, women with a history of gestational diabetes) showed that loss of weight through diet and exercise reduces risk of developing diabetes by 58% and demonstrated that lifestyle modification decreases risk of diabetes more than metformin.
  • Because of its effectiveness, low cost, and long-term safety, the ADA recommends consideration of metformin for prevention of diabetes in individuals with IGT [A], IFG [C], or an A1c 5.7-6.4% [C], especially for those with BMI >35kg/m2, aged <60 years, and women with history of GDM [A].
  • P.419

  • Dietary recommendations:
    • Either low-carbohydrate, low-fat calorie-restricted, or Mediterranean diets may be effective.
    • Diets high in fiber-rich foods, such as vegetables, fruits, whole grains, seeds, and nuts plus white meat sources are protective against type 2 diabetes (7).
    • Restrict beverages containing simple sugars, as they increase risk of diabetes (7).
    • Intake of polyunsaturated fatty acid (PUFA) may improve glycemic control; however, data is inconsistent regarding PUFA and other types of fatty acids (7).
    • Individuals who have prediabetes or diabetes should receive individualized medical nutrition therapy (MNT) as needed to achieve treatment goals, preferably provided by a registered dietitian familiar with the components of diabetes MNT (6).
MEDICATION
First Line
Metformin (drug of choice) 500 mg BID or 850 mg daily may reduce incidence of new-onset diabetes and BMI (level 2); contraindicated with Cr >1.5 in males and >1.4 in females increases risk of lactic acidosis (6).
Second Line
Acarbose: started as 50 mg PO once daily and titrated to 100 mg PO TID, may reduce incidence of diabetes; GI upset is common (7).
ISSUES FOR REFERRAL
  • Nutritionist
  • Diabetes educator/registered dietitian upon diagnosis
  • Exercise physiologist
  • Lifestyle coaching
ADDITIONAL THERAPIES
  • Weight loss of 5-10% improves glycemic control, increases insulin sensitivity, improves lipids, and lowers BP.
  • Alternative/botanical therapy:
    • Fenugreek, bitter melon, and cinnamon have reduced hyperglycemia and improved insulin sensitivity in studies by Deng (8) and Graf et al. (9).
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Consider self-monitoring of blood glucose.
  • At least annual monitoring for development of diabetes with HbA1c, 2-hour OGTT, or fasting glucose
  • BP should be routinely measured.
  • Annual testing for lipid abnormalities and microalbuminuria (for detection and therapy modification of incipient diabetic nephropathy)
DIET
  • Monitor carbohydrate intake.
  • Macronutrient distribution should be based on individual assessment of eating patterns, preferences, and metabolic goals.
  • Consider Mediterranean diet.
  • Maximize low glycemic index foods.
  • Low-fat (<25%) intake: Saturated fat intake should be <7% of total calories.
  • Minimize trans fat intake.
  • Low-sodium intake <2,300 mg/day
  • High-fiber (˜50 g/day; 14 g/1,000 kcal) and wholegrain intake
  • Drink ample quantities of water, minimum of 64 oz of water daily, and strictly avoid sugar-sweetened beverages.
  • Moderate alcohol intake: 1 drink/day for women; 2 drinks/day for men
PROGNOSIS
  • Individuals with IFG and/or IGT have high risk for the future development of diabetes.
  • Prediabetes increases the risk of developing type 2 diabetes, heart disease, and stroke.
  • The potential impact of interventions to reduce mortality or the incidence of cardiovascular disease has not been demonstrated to date.
  • 20-70% of individuals with prediabetes who do not lose weight, change their dietary habits, and/or engage in moderate physical activity will progress to type 2 diabetes within 3 to 6 years (7).
  • HbA1c >6.5% at age 12 to 39 years associated with increased risk of death before age 55 years compared with HbA1c <5.7%
REFERENCES
1. Nathan DM, Davidson MB, DeFronzo RA, et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care. 2007;30(3):753-759.
2. Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2014. Atlanta, GA: U.S. Department of Health and Human Services; 2014.
3. Centers for Disease Control and Prevention. Awareness of prediabetes—United States, 2005-2010. MMWR Morb Mortal Weekly Rep. 2013:62(11): 209-212.
4. Centers for Disease Control and Prevention. Prediabetes facts. http://www.cdc.gov/diabetes/basics/prediabetes.html. Accessed 2014.
5. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37(Suppl 1):S81-S90.
6. American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37(Suppl 1):S14-S80.
7. Stull AJ. Lifestyle approaches and glucose intolerance [published online ahead of print October 14, 2014]. Am J Lifestyle Med. doi: 10.1177/1559827614554186.
8. Deng R. A review of the hypoglycemia effects of five commonly used herbal food supplements. Recent Pat Food Nutr Agric. 2012;4(1):50-60.
9. Graf BL, Raskin I, Cefalu WT, et al. Plant-derived therapeutics for the treatment of metabolic syndrome. Curr Opin Investig Drugs. 2010;11(10):1107-1115.
Additional Reading
&NA;
  • Maruthur NM, Ma Y, Delahanty LM, et al. Early response to preventive strategies in the Diabetes Prevention Program. J Gen Intern Med. 2013;28(12):1629-1636.
  • Ramachandran A, Riddle MC, Kabali C, et al. Relationship between A1C and fasting plasma glucose in dysglycemia or type 2 diabetes: an analysis of baseline data from the ORIGIN trial. Diabetes Care. 2012;35(4):749-753.
Codes
&NA;
ICD10
  • E74.39 Other disorders of intestinal carbohydrate absorption
  • R73.09 Other abnormal glucose
  • R73.01 Impaired fasting glucose
Clinical Pearls
&NA;
  • Lifestyle optimization is essential for all patients with prediabetes.
  • Research shows that you can lower your risk for type 2 diabetes by 58% by losing 7% of your body weight (or 15 lb if you weigh 200 lb).
  • Exercising moderately (such as brisk walking) 30 minutes/day, 5 days a week
  • Consider concurrent cardiovascular risks and further workup as indicated clinically.
  • Patient education and lifestyle reinforcement should be emphasized in all clinical encounters.