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Glucose Intolerance

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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 hyperglycemiaThiazide diuretics (high doses)β-blockersCorticosteroids (including inhaled corticosteroids)Thyroid hormoneα-InterferonPentamidineProtease inhibitorsAtypical 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 exerciseResistance exercise improves insulin sensitivity to the same extent as aerobic exercise; resistance training 3 times per week is recommended for those with type 2 diabetesSmoking 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.