II. Epidemiology

  1. Prevalence in U.S.
    1. Total estimated at 86 million
    2. Affects 33% of adults and 4% of teens (90% of adults are unaware of diagnosis)

III. Pathophysiology

  1. Diminished Insulin response results in hyperinsulinemia
    1. Fewer Insulin receptors on cells
    2. Less Glucose transporter (Glut 4) in cells
  2. Hyperinsulinemia predisposes to cardiovascular disease
  3. Precursor to Type II Diabetes Mellitus

IV. Risk Factors

  1. Strong Family History of Diabetes Mellitus
  2. Prior Gestational Diabetes Mellitus or Fetal Macrosomia
  3. Obesity
    1. Body Mass Index 30 kg/m2 or higher
    2. Waist to hip ratio increased
      1. Men: 1.0 or higher
      2. Women: 0.8 or higher
    3. Waist Circumference
      1. Men: >40 inches or 102 cm
      2. Women: >35 inches or 88 cm

V. Diagnosis: Three or more conditions below

  1. Insulin Resistance (see labs below)
  2. Hypertension (Blood Pressure 130/85 or higher)
    1. Seen in up to 40% of Metabolic Syndrome patients
  3. Hyperlipidemia (see labs below)
  4. Coronary Artery Disease
  5. Polycystic Ovary Syndrome
  6. Acanthosis Nigricans
  7. HAIR-AN Syndrome
  8. Abdominal Obesity
    1. Men with Waist Circumference >40 inches or 102 cm
    2. Women with Waist Circumference >35 inches or 88 cm

VI. Labs

  1. Screening Indications (repeat every 3 years)
    1. See Risk Factors above
    2. Body Mass Index >25 kg/m2 (>23 kg/m2 in asian patients)
    3. Family History of Diabetes Mellitus
    4. Prior history of Gestational Diabetes
    5. Age over 45 years
    6. HDL Cholesterol <35 mg/dl
    7. Serum Triglycerides >250 mg/dl
    8. Polycystic Ovary Syndrome
    9. Hypertension
  2. Impaired Glucose Metabolism
    1. Hemoglobin A1C 5.7 to 6.4%
    2. Fasting Glucose: 100 to 125 mg/dl
      1. Known as Impaired Fasting Glucose
      2. New guidelines suggest bottom cut-off of 100 mg/dl
      3. Metabolic Syndrome defined as 110 mg/dl or higher
    3. Two hour Glucose Tolerance Test (75 g): 140-199 mg/dl
      1. Known as Impaired Glucose Tolerance
  3. Lipid Profile
    1. Serum Triglycerides >150 mg/dl
    2. Serum very Low Density Lipoprotein (VLDL) increased
    3. Serum HDL Cholesterol decreased
      1. Men <40 mg/dl
      2. Women <50 mg/dl
  4. Best lab markers for Insulin Resistance
    1. Plasma Insulin level (or Glucose to Insulin Ratio)
    2. Plasma Triglyceride levels
    3. Triglyceride to HDL ratio
    4. McLaughlin (2003) Ann Intern Med 139:802-9 [PubMed]

VII. Management: Prevention of progression to Diabetes

  1. Key goals: 7% weight loss and 150 min/week Exercise
    1. Consider referral to intensive lifestyle intervention program
      1. Example: National Diabetes Prevention Program
        1. https://www.cdc.gov/diabetes/prevention/index.html
      2. May delay type 2 diabetes by 4 years and decrease overall diabetes Incidence 34% in 10 years
        1. Knowler (2009) Lancet 374(9702):1677-86 [PubMed]
    2. Weight Reduction (if Overweight)
      1. Lose 7% of body weight
    3. Moderate aerobic Exercise for 30 minutes every day
      1. Example: Brisk walking for total of 150 min/week
  2. Decreased Caloric Intake
    1. Keep fat intake <30% with saturated fat <10%
    2. Salad, vegetables, fruits
    3. Whole grains and legumes
    4. Fish high in Omega-3 Fatty Acids and lean meats
    5. Reduce intake of simple sugars
  3. Foods associated with improved Insulin sensitivity
    1. Dietary Fiber
      1. Increase to15 gram per 1000 calories
    2. Coffee
      1. Salazar-Martinez (2004) Ann Intern Med 140:1-8 [PubMed]
      2. Tuomilehto (2004) JAMA 291:1213-9 [PubMed]
    3. Cinnamon (1/2 teaspoon per day)
      1. Studies used 1-3 g/day of cassia cinnamon (chinese cinnamon, C. aromaticum, C. cassia)
      2. Appears to have Insulin-like activity, may increase Insulin sensitivity and may improve lipid profile
      3. May decrease Fasting Glucose by up to 25 mg/dl
      4. (2017) Presc Lett 24(12): 71
      5. Costello (2016) J Acad Nutr Diet 116(11):1794-1802 [PubMed]
      6. Khan (2003) Diabetes Care 26(12):3215-8 +PMID:14633804 [PubMed]
    4. Moderate Alcohol consumption
      1. Howard (2004) Ann Intern Med 140:211-9 [PubMed]
  4. Consider pharmacologic agents for Glucose control
    1. Indications
      1. Hemoglobin A1C >5.7% despite 3-6 months of lifestyle changes
    2. First-line (preferred)
      1. Glucophage (Metformin)
        1. Initial: 500 mg orally daily
        2. Next: 850 mg orally twice daily (indicated if Hemoglobin A1C>5.7% after 3 months)
    3. Second-line (indicated if Glucophage contraindicated or not tolerated)
      1. Pioglitazone (Actos)
      2. Acarbose (Precose)

VIII. Management: Cardiac Risk Management

  1. Same as Diabetes Mellitus and Coronary Artery Disease
  2. Aspirin 81 mg PO qd
  3. Hyperlipidemia
    1. LDL Cholesterol <100 mg/dl
    2. HDL Cholesterol >40 mg/dl (50 mg/dl in women)
    3. Triglycerides <150 mg/dl
    4. Statins are preferred agents
      1. Sowers (2003) Am J Cardiol 91:14B-22B [PubMed]
  4. Hypertension
    1. Goal Blood Pressure < 125/75 mmhg
    2. Consider ACE Inhibitor or Angiotensin Blocker

IX. Course

  1. Metabolic Syndrome or Prediabetes is high risk for progression to Type II Diabetes Mellitus
    1. Up to 15-30% of Prediabetes patients will develop Diabetes Mellitus within 5 years
  2. Diabetes Prevention Program (DPP)
    1. Basic diet and Exercise: 11% develop diabetes per year
      1. Diet, Exercise, and weight loss maintained for 3 years prevents Diabetes Mellitus (NNT 7)
    2. Metformin
      1. Metformin 850 twice daily with diet and Exercise: 7.8% develop DM per year
      2. Metformin maintained for 3 years prevents Diabetes Mellitus (NNT 14)
    3. Intensive diet, Exercise: 4.8% develop diabetes per year
      1. Classes and coaches
      2. Weight Reduction of 7%
  3. Reference
    1. (1999) Diabetes Care 22:623-34 [PubMed]

X. Resources

Images: Related links to external sites (from Bing)

Related Studies

Ontology: Insulin Resistance (C0021655)

Definition (MSH) Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.
Definition (NCI) Decreased sensitivity to circulating insulin which may result in acanthosis nigicrans, elevated insulin level or hyperglycemia.
Concepts Pathologic Function (T046)
MSH D007333
SnomedCT 48606007
English Resistance, Insulin, Insulin Resistance [Disease/Finding], insulin resistance (diagnosis), Drug resistance to insulin, Insulin resistance, Drug resistance to insulin (disorder), Insulin Resistance, insulin resistance
Italian Insulino-resistenza, Resistenza all'insulina
Japanese インスリン抵抗性, インスリンテイコウセイ
Swedish Insulinresistens
Finnish Insuliiniresistenssi
Czech Inzulinová rezistence, inzulinová rezistence, insulin - rezistence, inzulínová rezistence
Spanish resistencia a la insulina, resistencia a la insulina (trastorno), resistencia a la insulina de causa farmacológica, resistencia a la insulina de causa farmacológica (trastorno), Resistencia a la insulina, Resistencia a la Insulina
Polish Oporność na insulinę, Insulinooporność
Hungarian Insulin resistentia
Norwegian Insulinresistens
Portuguese Insulinorresistência, Resistência à Insulina
Dutch insulineresistentie, Insulineresistentie, Resistentie, insuline-
French Insulinorésistance, Insulino-résistance, Résistance à l'insuline
German Insulinresistenz

Ontology: Microvascular Angina (C0206064)

Definition (MSHCZE) ANGINA PECTORIS nebo angina jako bolest na hrudi s normálním koronárním arteriogramem a pozitivním NÁMAHOVÝM TESTEM. Příčina tohoto syndromu je neznámá. I když má rozpoznání syndromu klinickou důležitost, jeho prognóza je výborná. Syndrom se liší od METABOLICKého SYNDROMu X, který je charakteristický rezistencí na insulin (INSULIN – REZISTENCE) a hyperinsulinémií, která zvyšuje riziko kardiovaskulárních nemocí. R
Definition (MSH) ANGINA PECTORIS or angina-like chest pain with a normal coronary arteriogram and positive EXERCISE TEST. The cause of the syndrome is unknown. While its recognition is of clinical importance, its prognosis is excellent. (Braunwald, Heart Disease, 4th ed, p1346; Jablonski Dictionary of Syndromes & Eponymic Diseases, 2d ed). It is different from METABOLIC SYNDROME X, a syndrome characterized by INSULIN RESISTANCE and HYPERINSULINEMIA, that has increased risk for cardiovascular disease.
Concepts Disease or Syndrome (T047)
MSH D017566
SnomedCT 194869009, 233845001
English Angina Pectoris with Normal Coronary Arteriogram, Angina, Microvascular, Chest pain norm cor angio, Microvascular Angina [Disease/Finding], cardiac syndrome x, syndrome x, microvascular angina, Microvascular angina, Syndrome X (Cardiac), Cardiac syndrome X (disorder), Cardiac Syndrome X, Cardiac syndrome X, Chest pain with normal coronary angiography, Cardiac syndrome X (finding), Microvascular Angina, Syndrome X, Cardiac, Angina Syndrome Xs, Angina Syndrome X, Angina X Syndromes, Angina X Syndrome, Syndrome X, Angina, Syndrome Xs, Angina, Syndrome, Angina X, X Syndrome, Angina, Syndrome X, syndrome X
Swedish Mikrovaskulär angina
Czech srdce - syndrom X, mikrovaskulární angina pectoris, angina pectoris s normálním koronarografickým nálezem, Kardiální syndrom X, Mikrovaskulární angína
Finnish Mikrovaskulaarinen angina
French Angor microvasculaire, Angine de poitrine à coronarographie normale, Angor à coronaires saines, Angine microvasculaire, Syndrome cardiaque X, Angor avec coronaires normales, Angine de poitrine à coronaires saines, Angor à coronarographie normale, Syndrome X cardiaque
Spanish Síndrome X Anginoso, Síndrome cardiaco X, Angina microvascular, síndrome cardíaco X (hallazgo), síndrome cardíaco X, Angina Microvascular, Angina Pectoris con Arteriograma Coronario Normal, Síndrome Cardíaco X, Síndrome X Cardíaco
Italian Angina pectoris con arteriogramma coronarico normale, Sindrome da angina, Angina microvascolare, Sindrome cardiaca X, Sindrome X cardiaca, Sindrome X
Portuguese Síndrome X Anginosa, Angina microvascular, Síndrome X cardíaca, Angina Microvascular, Angina Pectoris com Coronariografia Normal, Síndrome Cardíaca X, Síndrome X Cardíaca
Polish Zespół X kardiologiczny, Sercowy zespół X, Dusznica mikronaczyniowa, Dławica mikronaczyniowa
Japanese X症候群-心臓性, 心X症候群, シンXショウコウグン, ビショウケッカンセイキョウシンショウ, シンドロームX-心臓性, 微小血管性狭心症, 心臓性X症候群, 心臓性シンドロームX, 正常冠動脈造影図型狭心症, 狭心症-微小血管性, 狭心症-正常冠動脈造影図型
Dutch cardiaal syndroom X, microvasculaire angina, Angina pectoris met normaal coronair arteriogram, Angina, microvasculaire, Syndroom X, Cardiaal syndroom X, Microvasculaire angina, Syndroom X, angineus, Syndroom X, cardiaal
German mikrovaskulaere Angina pectoris, Herzsyndrom X, Angina pectoris mit normalem Koronararteriogramm, Syndrom X, X-Syndrom, Angina, mikrovaskuläre
Hungarian Microvascularis angina, Cardialis x syndroma
Norwegian Syndrom X, Angina pectoris med normalt koronart angiogram, Mikrovaskulær angina

Ontology: Impaired glucose tolerance (C0271650)

Definition (NCI) A condition referring to fasting plasma glucose levels being less than 140 mg per deciliter while the plasma glucose levels after a glucose tolerance test being more than 200 mg per deciliter at 30, 60, or 90 minutes. It is observed in patients with diabetes mellitus. Other causes include immune disorders, genetic syndromes, and cirrhosis.
Definition (NCI_CTCAE) A disorder characterized by an inability to properly metabolize glucose.
Definition (MSH) A pathological state in which BLOOD GLUCOSE level is less than approximately 140 mg/100 ml of PLASMA at fasting, and above approximately 200 mg/100 ml plasma at 30-, 60-, or 90-minute during a GLUCOSE TOLERANCE TEST. This condition is seen frequently in DIABETES MELLITUS, but also occurs with other diseases and MALNUTRITION.
Concepts Disease or Syndrome (T047)
MSH D018149
ICD10 R73.09
SnomedCT 190752008, 154720005, 267426009, 9414007
English Glucose Intolerance, Glucose Intolerances, Intolerances, Glucose, Intolerance, Glucose, Glucose intolerance, IGT - Impair glucose tolerance, glucose intolerance (diagnosis), glucose intolerance, impaired glucose tolerance, impaired glucose tolerance (diagnosis), prediabetes, Glucose tolerance impaired, Impaired glucose tolerance, Glucose Intolerance [Disease/Finding], chemicals diabetes, chemical diabetes, glucose impaired tolerance, Intolerance;glucose, malabsorption of glucose, diabetes chemical, latent diabetes, glucose malabsorption, Glucose: [intolerance] or [malabsorption] (disorder), Glucose: [intolerance] or [malabsorption], Chemical diabetes, Latent diabetes, Prediabetic nonclinical diabetes, IGT - Impaired glucose tolerance, Malabsorption of glucose, Impaired glucose tolerance (disorder), Malabsorption of glucose (disorder), chemicals; diabetes, diabetes; chemical, diabetes; latent, glucose; intolerance, glucose; malabsorption, intolerance; glucose, latent; diabetes, malabsorption; glucose, Impaired glucose tolerance, NOS, Impaired;glucose tolerance
Italian Tolleranza al glucosio alterata, Diabete chimico, Diabete latente, Intolleranza al glucosio
Dutch chemische diabetes, latente diabetes, glucose-intolerantie, chemisch; diabetes, diabetes; chemisch, diabetes; latent, glucose; intolerantie, glucose; malabsorptie, intolerantie; glucose, latent; diabetes, malabsorptie; glucose, glucosetolerantie aangetast, Glucose-intolerantie, Intolerantie, glucose-
French Diabète latent, Diabète chimique, Intolérance au glucose
German chemischer Diabetes, latenter Diabetes, eingeschraenkte Glukosetoleranz, Glukoseintoleranz
Portuguese Intolerância à glucose, Diabetes química, Diabetes latente, Tolerância à glucose alterada, Intolerância à Glucose
Spanish Diabetes química, Intolerancia a la glucosa, Diabetes latente, diabetes latente, diabetes química, mala absorción de glucosa (trastorno), mala absorción de glucosa, seudodiabetes, trastorno de la tolerancia a la glucosa (trastorno), trastorno de la tolerancia a la glucosa, Alteración de la tolerancia a la glucosa, Intolerancia a la Glucosa
Japanese 化学的糖尿病, 耐糖能障害, 潜在性糖尿病, ブドウ糖不耐性, タイトウノウショウガイ, センザイセイトウニョウビョウ, ブドウトウフタイセイ, カガクテキトウニョウビョウ
Swedish Glukosintolerans
Finnish Glukoosi-intoleranssi
Czech Intolerance glukózy, Latentní diabetes, Porušená glukózová tolerance, Chemický diabetes, glukosa - tolerance porušená, glukózová intolerance, porucha glukózové tolerance, porušená glukózová tolerance, poruchy glukózové tolerance
Polish Nietolerancja glukozy
Hungarian Glucose intolerantia, Latens diabetes, Kémiai diabetes, Csökkent glucose tolerancia
Norwegian Glukoseintoleranse

Ontology: Prediabetes syndrome (C0362046)

Definition (MEDLINEPLUS)

Prediabetes means you have blood glucose, or blood sugar, levels that are higher than normal but not high enough to be called diabetes. Glucose comes from the foods you eat. Too much glucose in your blood can damage your body over time. If you have prediabetes, you are more likely to develop type 2 diabetes, heart disease, and stroke.

Most people with prediabetes don't have any symptoms. Your doctor can test your blood to find out if your blood glucose levels are higher than normal. If you are 45 years old or older, your doctor may recommend that you be tested for prediabetes, especially if you are overweight.

Losing weight - at least 5 to 10 percent of your starting weight - can prevent or delay diabetes or even reverse prediabetes. That's 10 to 20 pounds for someone who weighs 200 pounds. You can lose weight by cutting down on the amount of calories and fat you eat and being physically active at least 30 minutes a day. Being physically active makes your body's insulin work better. Your doctor may also prescribe medicine to help control the amount of glucose in your blood.

NIH: National Institute of Diabetes and Digestive and Kidney Diseases

Definition (MSH) The time period before the development of symptomatic diabetes. For example, certain risk factors can be observed in subjects who subsequently develop INSULIN RESISTANCE as in type 2 diabetes (DIABETES MELLITUS, TYPE 2).
Definition (CSP) state of latent impairment of carbohydrate metabolism in which the criteria for diabetes mellitus are not all satisfied; sometimes controllable by diet alone; called also impaired glucose tolerance and impaired fasting glucose.
Concepts Disease or Syndrome (T047)
MSH D011236
ICD10 R73.09
SnomedCT 15777000, 9414007
English Prediabetic State, Prediabetic States, State, Prediabetic, States, Prediabetic, prediabetic state, [D]Prediabetes, Pre-diabetes, Pre-diabetic, Prediabetic State [Disease/Finding], prediabetes, Pre diabetes, pre diabetics, pre diabetic, pre-diabetes, pre-diabetic, Prediabetes (disorder), Prediabetic state, Prediabetes syndrome, Prediabetes, Pre-diabetes NOS, pre diabetes
Dutch prediabetisch, prediabetes, Prediabetes, Prediabetische toestand, Toestand, prediabetische
French Prediabétique, Prediabète, État prédiabétique, Prédiabète
German Prae-Diabetes, prae-diabetisch, Prädiabetischer Zustand
Italian Pre-diabetico, Pre-diabete, Prediabete, Stato prediabetico
Portuguese Pré-diabietes, Pré-diabético, Pré-diabetes, Diabetes Pré-Clínico, Estado Pré-Diabético, Pré-Diabetes
Spanish Prediabético, prediabetes (concepto no activo), prediabetes, Diabetes Preclínica, Prediabetes, Estado Prediabético
Japanese 前糖尿病性, トウニョウビョウゼンショウ, ゼントウニョウビョウセイ, 前糖尿病, 前糖尿病状態, 糖尿病前症
Swedish Prediabetisk fas
Czech prediabetes, Latentní diabetes, Prediabetes
Finnish Latentti diabetes
Polish Stan przedcukrzycowy
Hungarian Prediabeteses, Prediabetes
Norwegian Prediabetisk tilstand, Prediabetisk fase, Prediabetes

Ontology: Impaired fasting glycaemia (C1272092)

Concepts Finding (T033)
ICD9 790.21
ICD10 R73.01
SnomedCT 390937007, 390731003, 389984002, 390951007
Italian Glicemia a digiuno alterata
English [D]Impaired fasting glycaemia (context-dependent category), impaired fasting glucose (diagnosis), impaired fasting glucose, [D]Impaired fasting glycaemia, [D]Impaired fasting glycaemia (situation), [D]Impaired fasting glucose, Impaired fasting glycaemia (disorder), Impaired fasting glycaemia, Impaired fasting glycaemia -RETIRED-, Impaired fasting glucose
Japanese 空腹時血中ブドウ糖不良, クウフクジケッチュウブドウトウフリョウ
Spanish [D]glucemia en ayunas alterada (categoría dependiente del contexto), [D]glucemia en ayunas alterada (situación), [D]glucemia en ayunas alterada, glucemia en ayunas alterada (trastorno), glucemia en ayunas alterada, Alteración de glucosa en ayunas
Czech Porušená glykemie na lačno
Hungarian Kóros éhomi glucose
French Glucose à jeun altéré
Portuguese Alteração da glucose em jejum
Dutch verminderde nuchtere glucose
German Nuechternglukose krankhaft