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Chapter 5
Insulin Resistance and
the Metabolic Syndrome
The Genetics and Physiology of
Insulin Resistance
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Insulin resistance is common in persons whose
ancestors lived near the equator—Spanish/Latino,
Native American, African, Asian, and Pacific
Islanders—but the condition is found around the
world
The body cells “resist” the action of insulin; the
usual consequence is an increased production of
insulin to override the resistance at the cell level
Hyperinsulinemia (excess insulin in the blood) is
felt to play a large part in the health issues of
insulin resistance
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Insulin Resistance
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Insulin resistance is common—1 in 4 Americans
have insulin resistance; incidence is as high as 60%
in some populations
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Common cause of a variety of health conditions
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A genetic predisposition realized because of the
environment (diet issues and inadequate physical
activity)
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Metabolic syndrome rate among Chinese adolescents is
half that of U.S. adolescents, but U.S. rate is equal to rate
of Chinese American adolescents
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The Thrifty Gene
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Insulin resistance is believed to be the physiologic
mechanism that allowed populations in the past to
survive repeated bouts of famine (a survivor gene)
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Persons with insulin resistance tend to gain weight
easily in times of “plenty” and have difficulty losing
weight in times of “famine” (or periods of dieting)
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Historically high levels of physical activity (foraging for
food) with low intake of kilocalories (low food
availability) favored individuals who could maintain
their weight without a high kilocalorie intake
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U.S. adolescents’ rate of metabolic syndrome increases
proportionally to use of television, computer, and video games
(Mark and Janssen, 2008)
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Metabolic Syndrome Diagnosis
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Definition of the American Association of Clinical
Endocrinologists
Central obesity: waist >40 inches for men and >35 inches
for women; or waist-to-hip measurement >1.0 for men and
>0.8 for women; overweight also considered with body
mass index >25
Hypertension (HTN) (BP ≥130/85): insulin resistance is the
cause of HTN in 50% to 80% of cases
Dyslipidemia: triglycerides >150 with HDL cholesterol
<40 mg/dL; <50 mg/dL for women
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Hyperinsulinemia causes an enzyme, lipoprotein lipase, to be
impaired, resulting in elevated triglyceride levels
Prediabetes: FBG 110-126 mg/dL or 2-hr OGTT
>140-199 mg/dL (once diabetes has developed it is argued
that the term metabolic syndrome may not apply)
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Dyslipidemia as Shown By Lab Draw
with Triglycerides >8000 mg/dL
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Other Risk Factors Found with
the Metabolic Syndrome
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Hyperinsulinemia*:
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elevated C-peptide (indirect marker of excess insulin
production) or
 ratio of FBG: insulin <7
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Other risk factors: family hx of diabetes, HTN, CVD,
high-risk ethnicity, sedentary lifestyle, and advancing age
Polycystic ovary syndrome (PCOS): ovarian cysts with
male-pattern hair growth or loss and irregular menstrual
cycles caused by elevated androgen levels; a common
cause of infertility
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Dietary treatment same as for Insulin Resistance
Gout: high levels of uric acid in the blood; may collect as
crystals in joints (e.g., feet and/or hands)
*Hyperinsulinemia also found with some cancers
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Gout
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Painful condition related to high levels of uric acid crystals
that build up in joints (commonly feet and hands)
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Associated with the metabolic syndrome and historically
believed to have been helpful in maintaining adequate
blood pressure when salt availability was low
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May be treated with low purine diet with low intake of
meats, especially organ meats, and/or fish and legumes
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Also treated with avoidance of alcohol, slow weight loss,
and good fluid intake
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Milk and yogurt intake associated with lower levels of uric
acid crystals
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High Risk Populations
for Insulin Resistance
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Insulin resistance is common in persons
whose ancestors lived near the equator:
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Spanish (Hispanic/Latino)
Native American
African
 Asian
 Pacific Islander
However, the condition is found around the world
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The Pima Story
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Pima Indians in the Southwestern United
States have the highest rate of diabetes in
the world, but only in the last 100 years
since the Gila River was rerouted to
provide irrigation to California, resulting in
a change in lifestyle
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Pima Indians in Mexico still have a low
rate of obesity and diabetes but have
maintained their traditional diet and high
physical activity levels
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Recent Associations with
the Metabolic Syndrome
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Nonalcoholic fatty liver
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Screening advised for adolescents with
evidence of the metabolic syndrome (Fraser et al., 2007)
Hypothyroidism
Elevated CRP (C-reactive protein, a marker of
inflammation)
Elevated ferritin levels
Acanthosis nigricans (“dirty neck syndrome”
as often found in the neck area) and
cutaneous papillomas (“skin tags”)
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Acanthosis Nigricans and Cutaneous
Papillomas: “Skin Tags”
Acanthosis nigricans causes dark patches to occur on the skin, often in
the underarm area as shown, or on the neck; cutaneous papillomas or
“skin tags” are also commonly found with insulin resistance and
diabetes.
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FYI
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Nerve disease has been linked to low HDL cholesterol levels
(Pittenger et al., 2005)
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Chronic renal insufficiency linked with the metabolic
syndrome (Zoccali et al., 2007)
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Depression linked with inflammation; appears due to altered
enzyme function. The result is that the amino acid
tryptophan, normally metabolized to serotonin, is metabolized
into a different pathway (Maes et al., 2007)
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Ménière's disease linked with hyperinsulinemia (D’Avila and
Lavinsky, 2005)
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Risk of insulin resistance may be set in utero with mother’s
high kilocalorie intake or gestational diabetes (Boney et al., 2005;
Armitage et al., 2005)
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Reactive Hypoglycemia
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Controversial diagnosis
Signs and symptoms related to counterregulatory
hormones
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Glucagon leading to nausea
Adrenalin or epinephrine leading to physical tremors or
“shakes”
Cortisol leading to warm, sweaty feeling
Can cause feelings of weakness and decreased
cognitive ability with mild hypoglycemia
Reported to induce migraines
Prevent symptoms with small, frequent meals
(low-glycemic load) for control of hyperinsulinemia
and stable blood glucose
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Prevention of the
Metabolic Syndrome
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Emphasize regular physical activity
Include high-fiber foods
Increase fruits and vegetables
Avoid excess refined carbohydrates found in
beverages and processed foods
Emphasize unsaturated fats; avoid excess
saturated fat and trans fats
Maintain ideal body weight—work to prevent
excess weight gain
Include adequate sleep of about 8 hours to
help manage weight and reduce cortisol levels
(Chaput et al., 2007; Gonzalez-Ortiz and Martinez-Abundis, 2005)
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One Role of High-Fiber Foods
Related to Mineral Content
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Magnesium deficiency linked with inflammation;
increased intake controls inflammation (Rayssiguier and
Mazur, 2005); food is preferable source to control blood
pressure (Champagne, 2008)
Altered copper levels noted among persons with
diabetes (Aguilar et al., 2007)
Potassium and magnesium (with calcium and
avoidance of excess sodium) reduce blood
pressure, as found with metabolic syndrome
Vitamins and minerals with antioxidant role help
maintain health of mitochondria
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Management of the
Metabolic Syndrome
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Fat intake as high as 35% of daily kilocalories, with emphasis
on monounsaturated fats (decrease carbohydrate intake)
Inclusion of omega-3 fatty acids from cold-water fish (reduce
triglycerides, HTN, and hyperinsulinemia)
Carbohydrate intake 45% to 50% of daily kilocalories, with
emphasis on high-fiber sources (>20 g fiber) in several small
meals (low–glycemic-load meals)
Increased exercise and low kilocalorie intake to promote weight
loss
Decrease inflammation with omega-3 fats, high-magnesium
foods, and increased antioxidant vitamins (vitamin C, beta
carotene)
Moderate alcohol intake for individuals who already drink
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Medication Concerns in
Managing Insulin Resistance
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Clinicians advised to monitor clients at risk for
insulin resistance who are using certain
medications for treatment of schizophrenia
Antipsychotics associated with weight gain
should be avoided in persons with risk for
insulin resistance
Insulin-sensitizing medications may be
appropriate to reduce signs and symptoms of
PCOS
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Practical Dietary Advice
Judge these meals according to the Dietary
Guidelines and what you know about
reducing metabolic syndrome risk
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Breakfast: banana, corn flakes, whole milk,
sugar, toast with butter and jelly
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Lunch: hot dog on roll, mustard and relish,
chocolate chip cookies, cola
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Dinner: cheeseburger on roll, French fries,
coleslaw, milkshake
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