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Objectives Discuss metabolic syndrome and its impact on overall health An Overview Assess laboratory findings of Metabolic associated with metabolic Syndrome syndrome Stephanie Blackburn, MHS, MLS(ASCP)CM Relate metabolic syndrome with chronic disease

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Metabolic Syndrome “Metabolic” “Syndrome” Collection of cardiovascular risk Pattern of factors that accelerate the onset Refers to symptoms biochemical of heart disease, stroke, and Type 2 that together processes diabetes mellitus are involved in characteristic the body’s of a specific normal disorder or functioning disease

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Leading causes of death (CDC)

According to National Heart, Lung, 1. Heart disease and Blood Institute, “ a person with 2. Cancer metabolic syndrome is twice as 3. Chronic lower respiratory disease likely to develop heart disease and five times as likely to develop 4. Accident diabetes as someone without 5. Stroke metabolic syndrome” 6. Alzheimer’s disease 7. Diabetes

http://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm

1 7 8 History of Metabolic Syndrome 1947 Atherosclerosis Risk factors for diabetes observed in 1920s Upper Gout body Diabetes “Metabolic syndrome” coined in obesity 1950s Better understood in 1970s Kidney stones

9 10 Early 1950s 1977 – Metabolic Syndrome Term described association Low- between obesity, diabetes calorie diet Improvements: mellitus, high triglycerides, high Diabetes uric acid, and fatty liver disease Cholesterol Combination  increased risk for Low- Triglycerides atherosclerosis carb diet Later, described association between hyperlipidemia, obesity, gout, diabetes, and hypertension

11 12 1978 Metabolic Syndrome Combination of risk factors for Dysmetabolic syndrome myocardial infarction & obesity Described risk factors as Hypertriglyceridemic waist “constellation abnormalities” Glucose intolerance Insulin resistance syndrome Hyperinsulinemia High triglycerides Obesity syndrome High glucose High cholesterol Syndrome X

2 13 14 “Syndrome” Who is at risk? Cluster of conditions that occur Posses at least 3 of the following: together Central obesity Men waist: >40 in. Metabolic syndrome Women waist: >35 in.  Various conditions that occur Triglycerides: ≥ 150 mg/dl together that increase risk of heart HDL-C: <40 mg/dl (male), <50 disease, stroke, and diabetes mg/dl (female) Hypertension: 130/85 mmHg FPG: ≥ 100 mg/dl

15 16 Other risk factors: Prevalence

Age ~40% of those over age 60 Characteristic Male Female Race 20-39 years 20.3 % 15.6% Mexican American at highest risk 40-59 years 40.8 % 37.2 % Obesity Over 60 years 51.5% 54.4 % Diabetes Family history or gestational diabetes Other diseases

http://www.cdc.gov/nchs/data/nhsr/nhsr013.pdf

17 18 Prevalence Prevalence

Characteristic Male Female Characteristic Male Female Non-Hispanic 37.2% 31.5 % Underweight and 6.8 % 9.3 % white normal weight Non-Hispanic 25.3 % 38.8 % Overweight 29.8 % 33.1 % black Obese and 65 % 56.1 % Mexican 33.2 % 40.6 % extremely obese American

http://www.cdc.gov/nchs/data/nhsr/nhsr013.pdf http://www.cdc.gov/nchs/data/nhsr/nhsr013.pdf

3 19 20 Role of obesity Body Mass Index (BMI)

“apple” vs. “pear” Measure of body fat based on height and weight Sedentary lifestyle Weight (kg) / Height (m2) > 50% U.S. population is overweight or obese OR [Weight (lbs) / Height (in)2] x 704 Children being affected

21 22 BMI Example BMI

Height = 5 ft 7 in (67 in) Underweight = <18.5 Weight = 170 lbs Normal weight = 18.5-24.9 Overweight = 25-29.9 2 [Weight (lbs) / Height (in) ] x 704 Obesity = BMI of 30 or greater (170 / 672) x 704 BMI = 26.6

http://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmicalc.htm

23 24 Calculation of BMI BMI Target value = ≤ 24.9 http://www.nhlbi.nih.gov/health/ lose 12 lbs (158) = 24.7 educational/lose_wt/BMI/bmicalc .htm Overweight = 25 – 29.9 Our 5’7” 170 lbs = 26.6 Obese = 30 – 39.9 BMI Table at http://www.nhlbi.nih.gov/health/ gain 22 lbs (192) = 30.1 educational/lose_wt/BMI/bmi_tbl. Morbidly obese = ≥ 40 htm

4 25 26 Other risk factors associated Limitations of BMI with obesity May overestimate body fat in athletes and others with muscular Hypertension High LDL Low HDL build

High blood Family history High TG of heart May underestimate body fat in glucose disease older persons and others who have lost muscle Inactivity Smoking

27 Obesity prevalence, 1992

Weight Diabetes

30 Obesity prevalence, 2007 Obesity prevalence, 2015

http://www.cdc.gov/obesity/data/prevalence-maps.html

5 31 32 Why increased incidence of Insulin Resistance obesity in U.S.? Insulin Hormone that aids in regulation of blood glucose Lifestyle Environment Insulin resistance  Inability of cells to respond to insulin- stimulated glucose uptake  Blood glucose levels rise, promoting storage as fat and glycogen = weight gain. Genes

33 Insulin Resistance

“Inadequate” Compensatory Insulin Response Hyperinsulinemia

Type 2 Diabetes Metabolic Syndrome Heart Disease Retinopathy Hypertension Nephropathy Stroke Neuropathy

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Diabetes Statistics in U.S. (2014) Fasting 2 hrs. post Glycated >29 million diabetics plasma prandial hemoglobin glucose (mg/dl) (%) 1 in 4 do not know (mg/dl)

86 million pre-diabetics Normal ≤100 <140 <5.7 15-30% will develop Pre- 101-125 140-199 5.7-6.4 T2DM within 5 yrs. diabetic Diabetic ≥126 ≥200 ≥6.5

http://www.cdc.gov/Features/DiabetesFactSheet/

6 37 38 Increased numbers of diabetes Diabetes Statistics diagnoses (1980-2014)

Cardiovascular disease death rates about 1.7x higher in diabetics

About 20% people over 40 with metabolic syndrome have T2DM

http://www.cdc.gov/diabetes/statistics/prev/national/figpersons.htm

39 40 Triglycerides Cholesterol Triglycerides are fat! LDL-C HDL-C

 “Bad” cholesterol  “Good” cholesterol Ideally, <150 mg/dl  Primarily  Scavenger composed of  Primarily cholesterol composed of  Ideally <100 mg/dl protein  Ideally <50 mg/dl (women) & <40 mg/dl (men)

41 42 Other conditions associated Signs & Symptoms with metabolic syndrome: Large waistline is only obvious sign Excessive blood clotting If diabetic  may be symptomatic  Excessive thirst Constant, low-grade inflammation throughout body  Increased urination  Fatigue Hypertension  Researchers unsure if these  Headache conditions cause metabolic  Dizzy spells syndrome or worsen it  Nose bleeds

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When to seek medical advice Laboratory Assessment Lipid profile If you have at least one risk factor – Prefer 9-12 hr. fasting period you may have others but not know it Observe: TG >150 mg/dl HDL <40 or 50 mg/dl LDL >100 mg/dl

45 46 Laboratory Assessment Laboratory Assessment Fasting glucose >100 mg/dl Proinflammatory state Elevated CRP, cytokines, & fibrinogen Insulin Decreased adiponectin Ordered with glucose or GTT concentration Levels high in patients with insulin resistance Procoagulant state May measure C-peptide, as alternative Increased PAI-1 Increased platelet aggregation

47 48 Study by American Heart Study by American Heart Association Association

Participants categorized by diet Analyzed diet of 9514 participants  Western-pattern diet Ages 45 – 64 Refined grains Red meat Processed meat Eggs 66 item food frequency Fried foods Soda questionnaire  Prudent pattern diet Vegetables Poultry Fruit Whole grains Fish & seafood Low fat dairy

8 49 50 Study by American Heart Study by American Heart Association Association RESULTS: Assessed associations with 40% participants had 3 or more risk individual foods: fried foods, factors for metabolic syndrome sweetened drinks, diet soda, nuts, and coffee Western diet adversely associated with metabolic syndrome (18% greater risk) Follow up after nine years HOWEVER No evidence that prudent diet was beneficial

51 52 Study by American Heart Association Literature Review (2013): RESULTS: Hamburgers, hot dogs, & processed Association between low-grade meat → 26% greater risk chronic inflammation, diet, and Fried foods → 25% greater risk metabolic syndrome Diet soda → 34% greater risk Dairy products → beneficial → 13% lower risk Sweetened beverages, coffee, & nuts → no association

Ahluwalia, N., Andreeva, V.A., Kesse-Guyot, E., & Hercberg, S. (2013). Dietary patterns, inflammation, and the metabolic syndrome. Diabetes & Metabolism, 39, 99-110.

53 54 Results of Literature Review: Sugar, Obesity, & Diabetes

Healthy diet  reduces inflammation Sugar-sweetened beverages & incidence of metabolic syndrome (SSBs)  Due to weight control Soft drinks, fruit drinks, energy drinks, vitamin water Unhealthy diet  high levels of Sucrose, high fructose corn syrup, & cytokines & CRP fruit juice concentrate  Prolonged inflammation may induce insulin Largest contributor to added sugar resistance, dyslipidemia  leads to intake in U.S. diet metabolic syndrome & associated complications

Ahluwalia, N., Andreeva, V.A., Kesse-Guyot, E., & Hercberg, S. (2013). Dietary patterns, inflammation, and the Malik, V.S. & Hu, F. B. (2012). Sweeteners and risk of obesity and type 2 diabetes: The role of sugar-sweetened metabolic syndrome. Diabetes & Metabolism, 39, 99-110. beverages. Current Diabetes Reports, 12, 195-203.

9 55 56 Sugar, Obesity, & Diabetes SSB & Obesity Study of 50,000 women Weight Increased SSB consumption  gain Gained ~17 lbs over 8 yrs. Decreased SSB consumption  SSB gained ~ 6 lbs over 8 yrs. Further studies confirmed findings SSB most strongly associated with T2DM 4 yr. weight change, after potato chips & potatoes

Malik, V.S. & Hu, F. B. (2012). Sweeteners and risk of obesity and type 2 diabetes: The role of sugar-sweetened Malik, V.S. & Hu, F. B. (2012). Sweeteners and risk of obesity and type 2 diabetes: The role of sugar-sweetened beverages. Current Diabetes Reports, 12, 195-203. beverages. Current Diabetes Reports, 12, 195-203.

57 58 SSB & Type 2 Diabetes SSB & Metabolic Syndrome 310,819 participants High SSB consumption (≥1/day) Risk for development of T2DM associated with inc risk of: Highest SSB intake  26% greater risk Hypertension 1 serving SSB/day  15% increased Hypertriglyceridemia risk Low levels of HDL-C 50,000 women (same as previous High levels of LDL-C study) Higher waist circumference 1 SSB/day  83% inc risk for T2DM

Malik, V.S. & Hu, F. B. (2012). Sweeteners and risk of obesity and type 2 diabetes: The role of sugar-sweetened Malik, V.S. & Hu, F. B. (2012). Sweeteners and risk of obesity and type 2 diabetes: The role of sugar-sweetened beverages. Current Diabetes Reports, 12, 195-203. beverages. Current Diabetes Reports, 12, 195-203.

59 60 Are diet soda’s the answer? Artificial Sweeteners Increasing consumption of Attractive alternative to sugar artificial sweeteners  Virtually no calories Aspartame Sucralose Widely used in processed foods, Saccharin drinks, etc.

  Sugar substitutes inc. risk of Cautiously approved by AHA & ADA weight gain, metabolic to combat obesity, metabolic syndrome, T2DM, & CVD syndrome, and diabetes

Swithers, S. E. (2013). Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends in Endocrinology and Metabolism, 24(9), 431-441.

10 61 62 Concerns about artificial Back to sugar? sweeteners: Sugar in natural form can be “I am drinking diet coke, so it’s nutritious okay to have a cake”

Refined, concentrated sugar in Change the way we taste food large amounts is not so good

Crave more sweets

63 64 Treatment Treatment for Heart- healthy metabolic eating Exercise syndrome 30-60 minutes moderately intensity Aiming exercise EVERY DAY Quitting for smoking healthy Heart- weight Weight loss healthy Losing 10% excess body weight lifestyle lowers blood pressure, improves insulin resistance, and decreases risk of diabetes Physical Manage activity stress 250 lb person  lose 25 lbs

65 66 Treatment Treatment We are Eat healthy! what we Balanced diet eat! Stop smoking! Reduce calories Smoking worsens insulin resistance Reduce saturate fat Smoking increased LDL and lowers Increase fruits & vegetables HDL Use monounsaturated or Nicotine is a potent vasoconstrictor polyunsaturated oils & primary cause of heart disease Canola, olive, peanut Safflower, sunflower

11 67 68 Treatment Goals of If lifestyle changes do not work, Reduce risk medications may be prescribed: of coronary Treatment Blood pressure heart disease Triglycerides Cholesterol Blood sugar Prevent Aid in weight loss onset of T2DM

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Routine Clinical Trials Prevention doctor visits National Heart, Lung, and Blood

Make Institute (NHLBI) supports research Do not healthy smoke aimed at learning more about Heart- choices healthy metabolic syndrome lifestyle Strong commitment for the

Manage prevention/treatment of heart, Exercise stress lung, and blood diseases

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NHBLI Clinical Trials More info about clinical trials:

 How tobacco exposure and abdominal obesity affect adolescents’ risk of developing metabolic http://clinicalresearch.nih.gov syndrome www.clinicaltrials.gov

 The effect of two diets on the treatment of www.nhlbi.nih.gov/studies/index.htm adolescents who have heart disease risk factors www.researchmatch.org

 How certain medicines can help treat metabolic syndrome

 The effects of sugar-sweetened beverages on cholesterol, triglycerides, and blood sugar levels

12 73 74 In conclusion… The number of people with metabolic syndrome continue to rise AND

Metabolic syndrome may soon become the leading risk factor for heart disease

SO…

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