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Glucose Intolerance

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  • 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)

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

HISTORY


  • No clear symptoms
  • Polyuria
  • Polydipsia
  • Weight loss
  • Blurred vision
  • Polyphagia

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)
    • β-blockers
    • Corticosteroids (including inhaled corticosteroids)
    • Thyroid hormone
    • α-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

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].
  • 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).

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 whole-grain 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%

COMPLICATIONS


  • Cardiovascular disease
  • PAD
  • Stroke: 2 to 4 times higher risk
  • Ketoacidosis
  • Sexual dysfunction
  • Gastroparesis
  • Nephropathy and potential for renal failure
  • Retinopathy and potential for loss of vision
  • Peripheral and autonomic neuropathy

REFERENCES


11 Nathan  DM, Davidson  MB, DeFronzo  RA, et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care.  2007;30(3):753-759.22 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; 2014.33 Centers for Disease Control and Prevention. Awareness of prediabetes-United States, 2005-2010. MMWR Morb Mortal Weekly Rep.  2013:62(11): 209-212.44 Centers for Disease Control and Prevention. Prediabetes facts. http://www.cdc.gov/diabetes/basics/prediabetes.html. Accessed 2014.55 American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care.  2014;37(Suppl 1):S81-S90.66 American Diabetes Association. Standards of medical care in diabetes-2014. Diabetes Care.  2014;37(Suppl 1):S14-S80.77 Stull  AJ. Lifestyle approaches and glucose intolerance [published online ahead of print October 14, 2014]. Am J Lifestyle Med.  2014. http://doi: 10.1177/1559827614554186.88 Deng  R. A review of the hypoglycemia effects of five commonly used herbal food supplements. Recent Pat Food Nutr Agric.  2012;4(1):50-60.99 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


  • 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


ICD10


  • E74.39 Other disorders of intestinal carbohydrate absorption
  • R73.09 Other abnormal glucose
  • R73.01 Impaired fasting glucose
  • R73.02 Impaired glucose tolerance (oral)

ICD9


  • 271.3 Intestinal disaccharidase deficiencies and disaccharide malabsorption
  • 790.29 Other abnormal glucose
  • 790.21 Impaired fasting glucose
  • 790.22 Impaired glucose tolerance test (oral)

SNOMED


  • 9414007 Impaired glucose tolerance (disorder)
  • 102660008 Abnormal glucose level
  • 390951007 Impaired fasting glycaemia

CLINICAL PEARLS


  • 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.
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