Chapter 5Chapter 5

Insulin Resistance and Insulin Resistance and the Metabolic Syndromethe Metabolic Syndrome

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The Genetics and Physiology of The Genetics and Physiology of Insulin ResistanceInsulin Resistance

Insulin resistance is common in persons whose Insulin resistance is common in persons whose ancestors lived near the equatorancestors lived near the equator——Spanish/Latino, Spanish/Latino, Native American, African, Asian, and Pacific Native American, African, Asian, and Pacific IslandersIslanders——but the condition is found around the but the condition is found around the worldworld

The body cells “resist” the action of insulin; the The body cells “resist” the action of insulin; the usual consequence is an increased production of usual consequence is an increased production of insulin to override the resistance at the cell levelinsulin to override the resistance at the cell level

Hyperinsulinemia (excess insulin in the blood) is Hyperinsulinemia (excess insulin in the blood) is felt to play a large part in the health issues of felt to play a large part in the health issues of insulin resistanceinsulin resistance

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Insulin ResistanceInsulin Resistance

Insulin resistance is commonInsulin resistance is common——1 in 4 Americans 1 in 4 Americans have insulin resistance; incidence is as high as 60% have insulin resistance; incidence is as high as 60% in some populationsin some populations

Common cause of a variety of health conditionsCommon cause of a variety of health conditions

A genetic predisposition realized because of the A genetic predisposition realized because of the environment (diet issues and inadequate physical environment (diet issues and inadequate physical activity)activity) Metabolic syndrome rate among Chinese adolescents is Metabolic syndrome rate among Chinese adolescents is

half that of U.S. adolescents, but U.S. rate is equal to rate half that of U.S. adolescents, but U.S. rate is equal to rate of Chinese American adolescentsof Chinese American adolescents

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The Thrifty GeneThe Thrifty Gene

Insulin resistance is believed to be the physiologic Insulin resistance is believed to be the physiologic mechanism that allowed populations in the past to mechanism that allowed populations in the past to survive repeated bouts of famine (a survivor gene)survive repeated bouts of famine (a survivor gene)

Persons with insulin resistance tend to gain weight Persons with insulin resistance tend to gain weight easily in times of “plenty” and have difficulty losing easily in times of “plenty” and have difficulty losing weight in times of “famine” (or periods of dieting)weight in times of “famine” (or periods of dieting)

Historically high levels of physical activity (foraging for Historically high levels of physical activity (foraging for food) with low intake of kilocalories (low food food) with low intake of kilocalories (low food availability) favored individuals who could maintain availability) favored individuals who could maintain their weight without a high kilocalorie intaketheir weight without a high kilocalorie intake U.S. adolescents’ rate of metabolic syndrome increases U.S. adolescents’ rate of metabolic syndrome increases

proportionally to use of television, computer, and video gamesproportionally to use of television, computer, and video games(Mark and Janssen, 2008)(Mark and Janssen, 2008)

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Metabolic Syndrome DiagnosisMetabolic Syndrome Diagnosis

Definition of the American Association of Clinical Definition of the American Association of Clinical EndocrinologistsEndocrinologists

Central obesity: waist Central obesity: waist >>40 inches for men and 40 inches for men and >>35 inches 35 inches for women; or waist-to-hip measurement for women; or waist-to-hip measurement >>1.0 for men and 1.0 for men and >>0.8 for women; overweight also considered with body 0.8 for women; overweight also considered with body mass index >25mass index >25

Hypertension (HTN) (BP Hypertension (HTN) (BP ≥130/85)≥130/85): insulin resistance is the : insulin resistance is the cause of HTN in 50% to 80% of casescause of HTN in 50% to 80% of cases

Dyslipidemia: triglycerides Dyslipidemia: triglycerides >>150 with HDL cholesterol 150 with HDL cholesterol <40 mg/dL; <50 mg/dL for women<40 mg/dL; <50 mg/dL for women Hyperinsulinemia causes an enzyme, lipoprotein lipase, to be Hyperinsulinemia causes an enzyme, lipoprotein lipase, to be

impaired, resulting in elevated triglyceride levelsimpaired, resulting in elevated triglyceride levels Prediabetes: FBG 110-126 mg/dL or 2-hr OGTT Prediabetes: FBG 110-126 mg/dL or 2-hr OGTT

>140-199 mg/dL (once diabetes has developed it is argued >140-199 mg/dL (once diabetes has developed it is argued that the term that the term metabolic syndromemetabolic syndrome may not apply) may not apply)

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Dyslipidemia as Shown By Lab Draw Dyslipidemia as Shown By Lab Draw with Triglycerides >8000 mg/dLwith Triglycerides >8000 mg/dL

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Other Risk Factors Found with Other Risk Factors Found with the Metabolic Syndromethe Metabolic Syndrome

Hyperinsulinemia*:Hyperinsulinemia*: elevated C-peptide (indirect marker of excess insulin elevated C-peptide (indirect marker of excess insulin

production) or production) or ratio of FBG: insulin <7ratio of FBG: insulin <7

Other risk factors: family hx of diabetes, HTN, CVD, Other risk factors: family hx of diabetes, HTN, CVD, high-risk ethnicity, sedentary lifestyle, and advancing agehigh-risk ethnicity, sedentary lifestyle, and advancing age

Polycystic ovary syndrome (PCOS): ovarian cysts with Polycystic ovary syndrome (PCOS): ovarian cysts with male-pattern hair growth or loss and irregular menstrual male-pattern hair growth or loss and irregular menstrual cycles caused by elevated androgen levels; a common cycles caused by elevated androgen levels; a common cause of infertilitycause of infertility Dietary treatment same as for Insulin ResistanceDietary treatment same as for Insulin Resistance

Gout: high levels of uric acid in the blood; may collect as Gout: high levels of uric acid in the blood; may collect as crystals in joints (e.g., feet and/or hands)crystals in joints (e.g., feet and/or hands)

*Hyperinsulinemia also found with some cancers*Hyperinsulinemia also found with some cancers

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GoutGout

Painful condition related to high levels of uric acid crystals Painful condition related to high levels of uric acid crystals that build up in joints (commonly feet and hands)that build up in joints (commonly feet and hands)

Associated with the metabolic syndrome and historically Associated with the metabolic syndrome and historically believed to have been helpful in maintaining adequate believed to have been helpful in maintaining adequate blood pressure when salt availability was lowblood pressure when salt availability was low

May be treated with low purine diet with low intake of May be treated with low purine diet with low intake of meats, especially organ meats, and/or fish and legumesmeats, especially organ meats, and/or fish and legumes

Also treated with avoidance of alcohol, slow weight loss, Also treated with avoidance of alcohol, slow weight loss, and good fluid intakeand good fluid intake

Milk and yogurt intake associated with lower levels of uric Milk and yogurt intake associated with lower levels of uric acid crystalsacid crystals

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High Risk Populations High Risk Populations for Insulin Resistancefor Insulin Resistance

Insulin resistance is common in persons Insulin resistance is common in persons whose ancestors lived near the equator: whose ancestors lived near the equator: Spanish (Hispanic/Latino)Spanish (Hispanic/Latino) Native American Native American African African AsianAsian Pacific Islander Pacific Islander However, the condition is found around the worldHowever, the condition is found around the world

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The Pima StoryThe Pima Story

Pima Indians in the Southwestern United Pima Indians in the Southwestern United States have the highest rate of diabetes in States have the highest rate of diabetes in the world, but only in the last 100 years the world, but only in the last 100 years since the Gila River was rerouted to since the Gila River was rerouted to provide irrigation to California, resulting in provide irrigation to California, resulting in a change in lifestylea change in lifestyle

Pima Indians in Mexico still have a low Pima Indians in Mexico still have a low rate of obesity and diabetes but have rate of obesity and diabetes but have maintained their traditional diet and high maintained their traditional diet and high physical activity levelsphysical activity levels

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Recent Associations with Recent Associations with the Metabolic Syndromethe Metabolic Syndrome

Nonalcoholic fatty liverNonalcoholic fatty liver Screening advised for adolescents with Screening advised for adolescents with

evidence of the metabolic syndrome evidence of the metabolic syndrome (Fraser et al., 2007)(Fraser et al., 2007)

HypothyroidismHypothyroidism Elevated CRP (C-reactive protein, a marker of Elevated CRP (C-reactive protein, a marker of

inflammation)inflammation) Elevated ferritin levelsElevated ferritin levels Acanthosis nigricans (“dirty neck syndrome” Acanthosis nigricans (“dirty neck syndrome”

as often found in the neck area) and as often found in the neck area) and cutaneous papillomas (“skin tags”)cutaneous papillomas (“skin tags”)

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Acanthosis Nigricans and Cutaneous Acanthosis Nigricans and Cutaneous Papillomas: “Skin Tags”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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Nerve disease has been linked to low HDL cholesterol levels Nerve disease has been linked to low HDL cholesterol levels (Pittenger et al., 2005)(Pittenger et al., 2005)

Chronic renal insufficiency linked with the metabolic Chronic renal insufficiency linked with the metabolic syndrome syndrome (Zoccali et al., 2007)(Zoccali et al., 2007)

Depression linked with inflammation; appears due to altered Depression linked with inflammation; appears due to altered enzyme function. The result is that the amino acid enzyme function. The result is that the amino acid tryptophan, normally metabolized to serotonin, is tryptophan, normally metabolized to serotonin, is metabolized into a different pathwaymetabolized into a different pathway (Maes et al., 2007) (Maes et al., 2007)

Ménière's disease linked with hyperinsulinemia Ménière's disease linked with hyperinsulinemia (D’Avila and (D’Avila and Lavinsky, 2005)Lavinsky, 2005)

Risk of insulin resistance may be set in utero with mother’s Risk of insulin resistance may be set in utero with mother’s high kilocalorie intake or gestational diabetes high kilocalorie intake or gestational diabetes (Boney et al., 2005; (Boney et al., 2005; Armitage et al., 2005)Armitage et al., 2005)

FYIFYI

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Reactive HypoglycemiaReactive Hypoglycemia

Controversial diagnosisControversial diagnosis Signs and symptoms related to counterregulatory Signs and symptoms related to counterregulatory

hormoneshormones Glucagon leading to nauseaGlucagon leading to nausea Adrenalin or epinephrine leading to physical tremors or Adrenalin or epinephrine leading to physical tremors or

“shakes”“shakes” Cortisol leading to warm, sweaty feelingCortisol leading to warm, sweaty feeling Can cause feelings of weakness and decreased Can cause feelings of weakness and decreased

cognitive ability with mild hypoglycemiacognitive ability with mild hypoglycemia Reported to induce migrainesReported to induce migraines

Prevent symptoms with small, frequent meals Prevent symptoms with small, frequent meals (low-glycemic load) for control of hyperinsulinemia (low-glycemic load) for control of hyperinsulinemia and stable blood glucoseand stable blood glucose

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Prevention of the Prevention of the Metabolic SyndromeMetabolic Syndrome

Emphasize regular physical activityEmphasize regular physical activity Include high-fiber foodsInclude high-fiber foods Increase fruits and vegetablesIncrease fruits and vegetables Avoid excess refined carbohydrates found in Avoid excess refined carbohydrates found in

beverages and processed foodsbeverages and processed foods Emphasize unsaturated fats; avoid excess Emphasize unsaturated fats; avoid excess

saturated fat and trans fatssaturated fat and trans fats Maintain ideal body weightMaintain ideal body weight——work to prevent work to prevent

excess weight gainexcess weight gain Include adequate sleep of about 8 hours to Include adequate sleep of about 8 hours to

help manage weight and reduce cortisol levelshelp manage weight and reduce cortisol levels(Chaput et al., 2007; Gonzalez-Ortiz and Martinez-Abundis, 2005)(Chaput et al., 2007; Gonzalez-Ortiz and Martinez-Abundis, 2005)

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Magnesium deficiency linked with inflammation; Magnesium deficiency linked with inflammation; increased intake controls inflammation increased intake controls inflammation (Rayssiguier and (Rayssiguier and

Mazur, 2005); Mazur, 2005); food is preferable source to control blood food is preferable source to control blood pressure pressure (Champagne, 2008)(Champagne, 2008)

Altered copper levels noted among persons with Altered copper levels noted among persons with diabetes diabetes (Aguilar et al., 2007)(Aguilar et al., 2007)

Potassium and magnesium (with calcium and Potassium and magnesium (with calcium and avoidance of excess sodium) reduce blood avoidance of excess sodium) reduce blood pressure, as found with metabolic syndrome pressure, as found with metabolic syndrome

Vitamins and minerals with antioxidant role help Vitamins and minerals with antioxidant role help maintain health of mitochondriamaintain health of mitochondria

One Role of High-Fiber Foods One Role of High-Fiber Foods Related to Mineral ContentRelated to Mineral Content

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Management of the Management of the Metabolic SyndromeMetabolic Syndrome

Fat intake as high as 35% of daily kilocalories, with emphasis Fat intake as high as 35% of daily kilocalories, with emphasis on monounsaturated fats (decrease carbohydrate intake)on monounsaturated fats (decrease carbohydrate intake)

Inclusion of omega-3 fatty acids from cold-water fish (reduce Inclusion of omega-3 fatty acids from cold-water fish (reduce triglycerides, HTN, and hyperinsulinemia)triglycerides, HTN, and hyperinsulinemia)

Carbohydrate intake 45% to 50% of daily kilocalories, with Carbohydrate intake 45% to 50% of daily kilocalories, with emphasis on high-fiber sources (>20 g fiber) in several small emphasis on high-fiber sources (>20 g fiber) in several small meals (lowmeals (low––glycemic-load meals)glycemic-load meals)

Increased exercise and low kilocalorie intake to promote weight Increased exercise and low kilocalorie intake to promote weight lossloss

Decrease inflammation with omega-3 fats, high-magnesium Decrease inflammation with omega-3 fats, high-magnesium foods, and increased antioxidant vitamins (vitamin C, beta foods, and increased antioxidant vitamins (vitamin C, beta carotene)carotene)

Moderate alcohol intake for individuals who already drinkModerate alcohol intake for individuals who already drink

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Medication Concerns in Medication Concerns in Managing Insulin Resistance Managing Insulin Resistance

Clinicians advised to monitor clients at risk for Clinicians advised to monitor clients at risk for insulin resistance who are using certain insulin resistance who are using certain medications for treatment of schizophreniamedications for treatment of schizophrenia

Antipsychotics associated with weight gain Antipsychotics associated with weight gain should be avoided in persons with risk for should be avoided in persons with risk for insulin resistanceinsulin resistance

Insulin-sensitizing medications may be Insulin-sensitizing medications may be appropriate to reduce signs and symptoms of appropriate to reduce signs and symptoms of PCOSPCOS

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Practical Dietary AdvicePractical Dietary Advice

Judge these meals according to the Dietary Guidelines and what you know about

reducing metabolic syndrome risk

Breakfast: banana, corn flakes, whole milk, sugar, toast with butter and jelly

Lunch: hot dog on roll, mustard and relish, chocolate chip cookies, cola

Dinner: cheeseburger on roll, French fries, coleslaw, milkshake